abstract
"Lichen planus is a chronic, inflammatory, immune-mediated dermatosis affecting the patient's skin, scalp, mucous membranes, and nails. Drug-induced lichen planus is described after the administration of antimalarials, ß-blockers, methyldopa, NSAIDs, penicillamines, and sodium aurothiomalate. The use of biologicals such as adalimumab, etanercept, and infliximab has also been linked with the appearance of lichenoid eruptions in the recent past. In this case, we report on a patient developing oral and cutaneous lichen planus after the administration of dupilumab. The lichenoid lesions occurred after 11 months of the drug's administration and involved the buccal walls, trunk, and extremities. Dupilumab had been administered in an effort to counter severe atopic dermatitis exacerbations. Dupilumab is associated with a downregulation of T-helper 2 cell activation by blocking the Interleukin-4/Interleukin-13 pathway, so leading to a TH1/TH2 imbalance. This imbalance may cause a shift toward a TH1-mediated immune response and be an explanation for the drug-induced lichen planus. Dupilumab was discontinued, and the patient was treated with oral corticosteroids and UVB phototherapy, leading to a significant improvement in the lichen planus lesions."
"Infliximab (IFX) is a chimeric human-murine monoclonal antibody that prevents tumor necrosis factor alpha (TNF-α) activation by binding to both soluble and transmembrane forms of TNF-α. Antagonists of TNF (anti-TNF agents) can cause drug-induced liver injury (DILI). We present a non-anti-TNF naïve patient suffering from severe Crohn's disease who developed DILI with a hepatocellular pattern, without jaundice, after two infusions of an IFX biosimilar."
"One third of patients with acute severe ulcerative colitis (ASUC) are steroid-refractory.
To review the different options for the management of steroid-refractory ASUC, including not only the standard treatment (cyclosporine and infliximab), but also most recently developed agents (such as vedolizumab, ustekinumab and tofacitinib).
We performed a bibliographic search to identify studies focusing on the treatment of steroid-refractory ASUC.
Cyclosporine and infliximab currently represent the mainstays of salvage therapy and they are generally considered comparable. However, long-term persistence is higher in infliximab therapy, and many clinicians prefer to use infliximab given its ease of use. However, cost of cyclosporine is lower. Sequential rescue therapy after cyclosporine or infliximab failure (with infliximab and cyclosporine, respectively) could be considered in referral centers for highly selected cases. Tofacitinib, due to its rapid effect, represents an attractive rescue option mainly in biologic-experienced patients. The good safety profile of vedolizumab and ustekinumab makes them ideal candidates for use as maintenance therapy in combination with cyclosporine as induction therapy, especially for patients previously exposed to anti-TNFs or thiopurines.
Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also play a role. Tofacitinib, due to its rapid effect, is an attractive therapeutic rescue option. Vedolizumab and ustekinumab, as maintenance therapy in combination with the fast-acting cyclosporine as induction therapy, may represent a promising bridging strategy, especially in patients with previous failure to thiopurines and/or anti-TNF agents."
"Biological agents cross the placenta, resulting in detectable blood levels in the neonate. Neonatal vaccinations are essential to prevent serious infections.
To review the effectiveness and safety of vaccines in children exposed to biological drugs in utero and/or those whose mothers received biological agents during lactation.
A systematic bibliographic search was performed.
Infants exposed in utero to anti-TNFs, vedolizumab or ustekinumab mount adequate serological responses to vaccines. No relevant adverse events for non-live inactivated vaccines have been reported in newborns exposed in utero to biologics. Studies assessing the safety of live-attenuated vaccines administered to infants exposed to biologics in utero have not observed, in general, serious adverse events. However, although no severe complications have been reported with rotavirus live vaccination, several fatal disseminated tuberculosis infections after administration of the BCG live vaccine in infants exposed to anti-TNFs in utero have been reported. Infliximab, adalimumab, and probably also vedolizumab and ustekinumab treatments, are considered compatible with breastfeeding, although minuscule amounts of these biologics have been detected in breast milk of treated nursing mothers. Based on the literature available, the benefits from breastfeeding while receiving infliximab (or any other anti-TNF) and at the same time adhering to national infant immunization programs probably outweigh any hypothetical risk for the infant.
Vaccines seems to be effective in infants exposed to biologics in utero. Inactivated vaccines are probably safe, whereas live-attenuated vaccines should be avoided while the children have detectable levels of biological drugs. Vaccines (non-live and live) are probably safe in children breastfed by mothers treated with biologics."
"Anti-TNF biologic therapies such as infliximab (INF) have revolutionised the treatment of inflammatory bowel diseases (IBD). However, serious adverse effects due to systemic administration can significantly impact patient quality of life, limiting their success. Oral nanomedicines propose an innovative solution to provide local delivery to inflamed gastrointestinal tissues, thereby limiting systemic exposure and enhancing therapeutic efficacy. This study aimed to examine the potential of INF nanomedicines for IBD treatment with a focus on nanoparticle size to modulate the targeting of INF to the epithelial barrier.
Healthy and inflamed in vitro models of the intestinal epithelial barrier were established to examine the cell interaction of PLGA-PEG NPs of varying particle sizes and polydispersities. INF-loaded NPs were prepared by electrostatic interaction of INF with NPs and examined for their therapeutic efficacy in the inflamed epithelial cell barrier model.
NP interaction was significantly enhanced in the inflamed cell barrier model, with increased transport observed for 130 - 300 nm NPs and accumulation of larger NPs (∼600 nm) at the barrier. Delivery of INF directly to the inflamed barrier by ∼600 nm NPs accelerated recovery of barrier integrity and reduced inflammatory cytokine secretion and cytotoxicity in comparison to treatment with INF alone.
Results from this study show that NP particle size can be used to differentially target and treat the inflamed intestinal barrier. Oral INF nanomedicines of modulated size present a novel strategy for the local, targeted treatment of IBD."
"The combination of infliximab and immunosuppressant therapy is a standard management strategy for patients with Crohn's disease. Concerns regarding the implications of long-term combination therapy provided the rationale for a formal clinical trial of treatment de-escalation. Our aim was to compare the relapse rate and the time spent in remission over 2 years between patients continuing combination therapy and those stopping infliximab or immunosuppressant therapy.
This multicentre, open-label, randomised controlled trial was performed in 64 hospitals in seven countries in Europe and Australia. Adult patients with Crohn's disease in steroid-free clinical remission for more than 6 months, on combination therapy of infliximab and immunosuppressant therapy for at least 8 months were randomly assigned (1:1:1) to either continue combination therapy (combination group), discontinue infliximab (infliximab withdrawal group), or discontinue immunosuppressant therapy (immunosuppressant withdrawal group). Randomisation was stratified according to disease duration before start of first anti-TNF treatment (≤2 or >2 years), failure of immunosuppressant therapy before start of infliximab, and presence of ulcers at baseline endoscopy. The patient number and group of each stratum were assigned by a central online randomisation website. Treatment was optimised or resumed in case of relapse in all groups. Participants, those assessing outcomes, and those analysing the data were not masked to group assignment. The coprimary endpoints were the relapse rate (superiority analysis) and time in remission over 2 years (non-inferiority analysis, non-inferiority margin 35 days). Analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT02177071, and with EU Clinical Trials Register, EUDRACT 2014-002311-41. The trial was completed in April, 2021.
Between Nov 2, 2015, and April 24, 2019, 254 patients were screened. Of these, 211 were randomised and 207 were included in the final analysis (n=67 in the combination group, n=71 in the infliximab withdrawal group, and n=69 in the immunosuppressant withdrawal group). 39 patients had a relapse (eight [12%] of 67 in the combination group, 25 [35%] of 71 in the infliximab withdrawal group, six [9%] of 69 in the immunosuppressant withdrawal group). 2-year relapse rates were 14% (95% CI 4-23) in the combination group, 36% (24-47) in the infliximab withdrawal group, and 10% (2-18) in the immunosuppressant withdrawal group (hazard ratio [HR] 3·45 [95% CI 1·56-7·69], p=0·003, for infliximab withdrawal vs combination, and 4·76 [1·92-11·11], p=0·0004, for infliximab withdrawal vs immunosuppressant withdrawal). Of 28 patients who had a relapse and were retreated or optimised according to protocol, remission was achieved in 25 patients (one of two in the combination group, 22 of 23 in the infliximab withdrawal group, and two of three in the immunosuppressant withdrawal group). The mean time spent in remission over 2 years was 698 days (95% CI 668-727) in the combination group, 684 days (651-717) in the infliximab withdrawal group, and 706 days (682-730) in the immunosuppressant withdrawal group. The difference in restricted mean survival time in remission was -14 days (95% CI -56 to 27) between the infliximab withdrawal group and the combination group and -22 days (-62 to 16) between the infliximab withdrawal group and the immunosuppressant withdrawal group. The 95% CIs contained the non-inferiority threshold (-35 days). We recorded 31 serious adverse events, in 20 patients, with no difference in frequency between groups. The most frequent serious adverse events were infections (four in the combination group, two in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group) and Crohn's disease exacerbation (three in the combination group, four in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group). No death nor malignancy was recorded.
In patients with Crohn's disease in sustained steroid-free remission under combination therapy with infliximab and immunosuppressant therapy, withdrawal of infliximab should only be considered after careful assessment of risks and benefits for each patient, whereas withdrawal of immunosuppressant therapy could generally represent a preferable strategy when considering treatment de-escalation.
European Union's Horizon 2020."
"The release of inflammatory cytokines, namely tumor necrosis factor-α (TNF-α), plays an important role in the pathogenesis of cardiomyopathy. TNF-α increases in plasma and in myocardium of heart failure patients. We aimed to investigate the role of TNF-α inhibitor (infliximab; IFX) in regulating dilated cardiomyopathy (DCM) induced in rats. DCM was induced in rats by doxorubicin (DOX; 3.5 mg. kg"
"Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients.
Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination.
Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R
Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response.
JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care."
"The lifetime risk of symptomatic hand osteoarthritis (OA) is 39.8%, with one in two women and one in four men developing the disease by age 85 years and no disease-modifying drug (DMOAD) available so far. Intra-articular (IA) therapy is one of the options commonly used for symptomatic alleviation of OA disease as it can circumvent systemic exposure and potential side effects of oral medications. The current narrative review focuses on the efficacy and safety profiles of the currently available IA agents in hand OA (thumb-base OA or interphalangeal OA) such as corticosteroids and hyaluronic acid (HA), as well as the efficacy and safety of IA investigational injectates in phase 2/3 clinical trials such as prolotherapy, platelet-rich plasma, stem cells, infliximab, interferon-? and botulinum toxin, based on the published randomized controlled trials on PubMed database. The limited published literature revealed the short-term symptomatic benefits of corticosteroids in interphalangeal OA while long-term data are lacking. Most of the short-term studies showed no significant difference between corticosteroids and hyaluronic acid in thumb-base OA, usually with a faster onset of pain relief in the corticosteroid group and a slower but greater (statistically insignificant) pain improvement in the HA group. The majority of studies in investigational agents were limited by small sample size, short-term follow-up, and presence of serious side effects. In addition, we reported higher accuracy rates of drug administrations under imaging guidance than landmark guidance (blind method), and then briefly describe challenges for the long-term efficacy and prospects of IA therapeutics."
"Takayasu arteritis is a systemic vasculitis of the large vessels and mainly affects Japanese and Southeast Asian women in the second and third decades of life. Inflammatory infiltrate affects the full thickness of the vessel wall, inducing progressive lumen stenosis and occlusion. The main biomarkers of disease activity are the ESR, CRP and serum levels of circulating cytokines. This case report describes the clinical history of a young woman with Takayasu disease with high serum levels of IgA at onset. IgA remained elevated with persistence of disease activity, and normalized only when the patient was treated with an anti-TNF agent (infliximab), which also induced a clinical response in the vasculitis. IgA levels, together with other inflammatory parameters, may be considered a biomarker of disease activity.
This case report highlights the need to increase the number of humoral markers used to assess disease course in Takayasu arteritis (TA).IgA may be considered a biomarker of TA disease activity.Serum IgA levels may be helpful to identify TA patients not responding to traditional therapy."
"Multicentric reticulohistiocytosis (MRH) is categorized as a rare non-Langerhans cell histiocytosis most commonly seen in women in the fourth to fifth decade of life. This systemic inflammatory condition affects multiple organ systems and can result in severe joint destruction which can progress to arthritis mutilans. To date, various underlying malignancies have been discovered in patients with MRH including breast, gastric, thymic, hepatic, and melanoma. There has been 1 case of underlying renal cell carcinoma reported in a patient diagnosed with MRH. Additionally, there is no consistently recognized treatment for MRH described in the literature. The rarity of the disease contributes to the difficulty in defining a standardized treatment. We present the case of a patient with extensive joint and skin involvement who was successfully treated with infliximab and methotrexate, experienced clinical improvement, and was later diagnosed with clear cell renal cell carcinoma. The synergistic effects of infliximab and methotrexate, in combination with the low side-effect profile, appear to be promising in the setting of MRH and in our patient resulted in the resolution of symptoms and cutaneous manifestations. We suggest this regimen as an effective combination therapy. We emphasize thorough and continuous screening for underlying malignancy associated with MRH, despite clinical improvement or negative malignancy work-up upon initial diagnosis."
"Ixekizumab is one of the three biologic agents including Secukinumab and Brodalumab that targets the Interleukin-17 (IL-17) pathway to reduce inflammation in psoriasis and ankylosing spondylitis. In this report we present the case of 42-year-old woman, who was diagnosed with psoriasis and psoriatic arthritis. One week after first administration of Ixekizumab, she developed diffuse abdominal pain, bloody diarrhea (7-8 stools/day) and fever. Following imaging (colonoscopy, computed tomography) and laboratory investigations, she was diagnosed with acute severe ulcerative colitis complicated with toxic megacolon. The medical treatment (first corticotherapy, then infliximab) has failed and the patient needed emergency colectomy. Based on the immunological mechanisms and the observation from other studies, Ixekizumab should be considered an etiology for new-onset inflammatory bowel disease."
"SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications.
This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC].
In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks.
This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications."
"Exposure-outcome relationship data show that higher infliximab concentrations are associated with better outcomes in patients with Crohn's disease (CD). However, most of these data were derived from adult patients on maintenance therapy. We aimed to investigate the association of infliximab concentrations during and early after induction therapy of infliximab with short-term and long-term clinical outcomes in a pediatric CD population.
We conducted a post hoc analysis of the REACH trial which included pediatric patients with moderate-to-severe CD treated with infliximab (n = 103). The investigated outcomes were early clinical remission (CR) defined as a pediatric CD activity index score of ≤ 10, assessed at week 10, and long-term clinical response (LTCR) defined as a decrease from baseline in the pediatric CD activity index score of at least 15 points, with a total score of ≤ 30 and no need for drug discontinuation, assessed at weeks 30 and 54.
Based on multivariable logistic regression analysis, higher week 10 infliximab concentrations were independently associated with CR at week 10 (odds ratio: 1.54; 95% confidence interval: 1.06-2.22; P = 0.022) and LTCR at week 30 (odds ratio: 1.62; 95% confidence interval: 1.12-2.36; P = 0.010). Receiver operating characteristic analysis identified week 10 infliximab concentration thresholds of ≥7.1 μg/mL and ≥6.5 μg/mL to be associated with CR at week 10 and LTCR at week 30, respectively.
Higher postinduction infliximab concentrations are associated with both short-term and long-term favorable clinical outcomes in pediatric patients with CD. Tailoring dosing during induction to achieve higher infliximab exposure may lead to better outcomes in pediatric patients with CD."
"To predict primary failure of infliximab (IFX) therapy in Crohn's disease (CD) and to identify patients who maintain long-term effectiveness to IFX is currently not feasible. Some genetic variations are proposed as potential biomarkers.
We assessed a set of single nucleotide polymorphisms (SNPs) in genes related to the IFX mechanism of action and the presence of HLA-DQA1 * 05 allele on the primary response and long-term durability in CD patients.
A multi-centre cross-sectional study of IFX-exposed adult patients with CD was undertaken. Treatment persistence and time to failure were co-primary endpoints. DNA from the 131 patients was genotyped. Association between SNPs and clinical variables with IFX persistence was assessed.
Failure to IFX was documented in 65 (49.6%) out of 131 patients. IFX persistence was associated either with carrying the TT genotype in ADAM17 rs10929587 (ORa=0.2; 95%CI=0.1-0.8; p = 0.021), or the CC genotype in SLCO1C1 rs3794271 (ORa=0.2; 95%CI=0.1-0.7; p = 0.008), according to multivariate logistic regression. In contrast, previous bowel resection increased the risk of IFX failure (ORa=2.8; 95%CI=1.1-7.3; p = 0.025). Cox regression analysis confirmed these findings and also identified IL23R rs10489629-TT (HRa 0.41; 95%CI=0.22-0.75; p = 0.004) and concomitant immunosuppressants (HRa 0.46; 95%CI=0.27-0.77; p = 0.003) as protection from IFX failure. However, no association between HLA-DQA1 * 05 allele and persistence of IFX therapy was found, with similar failure rates among carriers and non-carriers (52.8% vs. 47.4%, respectively; p = 0.544).
SNPs rs10929587-TT in ADAM17, rs10489629-TT in IL23R and rs3794271-CC in SLCO1C1, together with no previous bowel surgery and concomitant immunosuppression, were identified as protection from failure to IFX."
"Tumor necrosis factor (TNF) is a cytokine that regulates immunity by binding to the cytokine receptor (TNFR), which has a role in treating inflammatory, neoplastic, and autoimmune diseases. Medications, including etanercept, infliximab, and adalimumab, are examples of TNF-alpha blockers. Adalimumab is a fully human immunoglobulin monoclonal antibody approved for use in the treatment of psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, and hidradenitis suppurativa according to the American College of Rheumatology. However, there are few reports of cases where its administration was associated with skin reactions. In the present paper, we report a case of a psoriatic male patient who developed a cutaneous reaction of the face following treatment with adalimumab."
"To describe two cases of Behçet's retinitis lesions in the macula causing sloughing of retinal tissue forming a full-thickness macular hole. This was a case series study. Case 1 was a 26-year-old presented, known case of Behçet's disease, presented with a large area of retinitis involving the center of the macula with overlying vitritis. One day after the initiation of treatment, vitritis improved, but the retinitis patch sloughed and created a full-thickness macular hole. Case 2 was a 31-year-old male, known case of Behçet's uveitis, who presented vitritis and multiple retinitis patches involving the macula of the left eye. Two weeks after infliximab infusion, the inflammation resolved with medical management, however, the retinitis patch was complicated by a full-thickness macular hole with an inferior rhegmatogenous retinal detachment. Retinitis at the macula can be complicated by a full-thickness macular hole."
"A 20-year-old male Behçet uveitis (BU) patient presented with visual acuities (VAs) of hand movement in OD and counting fingers at 1 m in OS following treatment with corticosteroid monotherapy elsewhere. He had active intraocular inflammation OU along with macular hole and retinal detachment in OS. Infliximab (IFX) was started and vitreoretinal surgery was performed. He had infusion reaction with IFX, hepatotoxicity and depression with interferon, and resistance to adalimumab and tocilizumab therapies. Cytomegalovirus retinitis developed in OD following intravitreal dexamethasone implant and endophthalmitis developed in OS. At the 33"
"SDRIFE is a rare cutaneous eruption characterized by symmetrical intertriginous dermatitis, caused by delayed Type-IV immune reaction, with several reported drug-triggers.
We present a case of SDRIFE associated with infliximab in a 70-year-old female with rheumatoid arthritis, and review cases of SDRIFE associated with TNF-inhibitors.
A literature review about SDRIFE cases associated with TNF-inhibitors was performed. Articles published in English from inception to January 6th, 2022, restricted to humans, and directly related to this review were included.
Ours is the third reported case of SDRIFE associated with TNF-inhibitors, and second with infliximab. SDRIFE can occur anytime during treatment with TNF-inhibitors, and presents with similar clinical and histopathological features as SDRIFE secondary to other drugs. No systemic manifestations have been reported, and the rash resolves after discontinuation of the TNF-inhibitor without any long-term sequelae.
SDRIFE is benign, and an accurate diagnosis and discontinuation of the responsible drug remain the cornerstone of management."
"Carriers of the human leucocyte antigen variant HLADQA1*05 (rs2097432) are at risk of developing antibodies against infliximab and adalimumab with reduced tumor necrosis factor (TNF) antagonist persistence. The impact of proactive therapeutic drug monitoring (PTDM) on this association has been barely assessed.
We conducted a retrospective single-center cohort study including patients with inflammatory bowel disease starting anti-TNF therapy between January 2017 and March 2021. Proactive therapeutic drug monitoring was defined as periodic drug level measurement (≥2 determinations during the first year of treatment and ≥1/annual determination during the following years), regardless of clinical condition, followed by dose optimization. Variables associated with treatment persistence were assessed with multivariable Cox regression analysis.
A total of 112 patients were included, 52 (46.4%) HLA-DQA1*05 carriers, with a median follow-up of 73.9 (interquartile range, 35.4-133.1) weeks. Combination therapy with thiopurines was more frequent among HLA-DQA1*05 noncarriers (28 [46.7%] vs 12 [23.1%]; P = .01). Clinical remission rates at week 14 (77.9% vs 73.9%; P = .69) and 56 (73.2% vs 68.4%; P = .64) were similar between HLA-DQA1*05 noncarriers and carriers. Drug persistence was higher among HLA-DQA1*05 carriers (hazard ratio [HR], 0.32; 95% confidence interval, 0.14-0.71; P = .01). Multivariable Cox regression analysis identified systemic steroids at anti-TNF initiation (HR, 4; 95% confidence interval, 1.7-9.7) as a risk factor and HLA-DQA1*05 carriers (HR, 0.31; 95% confidence interval, 0.12-0.81) as a protective factor of treatment cessation.
In adult patients with PTDM, a positive HLA-DQA1*05 genotype does not associate a higher risk of treatment cessation nor worse clinical outcomes.
This is a retrospective cohort study including 112 inflammatory bowel disease patients starting anti-TNF therapy under proactive therapeutic drug monitoring (PTDM). The HLA-DQA1*05 carriers did not present lower drug persistence or remission rates, suggesting PTDM overcomes the reduced treatment survival expected in HLA-DQA1*05 carriers."
"Update the available evidence comparing biologic disease-modifying antirheumatic drugs (bDMARDs) in combination with conventional synthetic disease-modifying antirheumatic drugs (CsDMARDs) to bDMARDs in monotherapy in patients with rheumatoid arthritis.
Research was limited to randomized controlled trials. Major outcome: ACR 20 response criteria at 24 weeks.
clinical and radiographic criteria at week 24, 52 and 104.
23 trials (6358 patients), including seven bDMARDs and one other molecule: Anbainuo (anti-TNF-R). No study satisfied our search criteria for anakinra, certolizumab and infliximab. Compared to bDMARD monotherapy, combination therapy gives a better ACR 20 at 24 weeks (RR: 0.88 (0.84-0.94)) in fixed and random effect models, and this result is sustained at 52 and 104 weeks. The results were mostly similar for all other outcomes without increasing the risk of adverse effects.
This meta-analysis confirms the superiority of combination therapy over monotherapy in rheumatoid arthritis, in accordance to the usual guidelines."
"A 53-year-old man who had a history of ulcerative colitis (UC) for 2 years underwent colonoscopy as regular follow-up. The results showed an elevated lesion in the descending colon, which was diagnosed as plasmablastic lymphoma (PBL) based on pathological findings. In situ hybridization for the Epstein-Barr virus-encoded RNA probe was positive. Fluorescence in situ hybridization revealed rearrangement of the MYC gene. He had been taking prednisolone, 5-aminosalicylic acid, azathiopurine, and ustekinumab at the diagnosis of PBL and had multiple prior therapies for UC including infliximab, tacrolimus, and tofacitinib due to steroid dependence. PBL is a rare aggressive B cell lymphoma initially described in the oral cavity of human immunodeficiency virus positive patients and it is suspected to have an association with immunocompromised status of patients. The number of cases of PBL in inflammatory bowel disease (IBD) patients is extremely rare. All these patients were administered immunosuppressive therapy including thiopurines or biologics. IBD patients with immunosuppressive therapy have a higher potential for developing lymphoproliferative disorders. Clinicians should be aware of the risk of lymphoma, including PBL."
"Since Fc-gamma receptors (FcgRs) are involved in the degradation of IgG complexes, we assessed whether a modification in FcgRs' affinity to Fc portion, caused by single nucleotide polymorphisms such as rs1801274-R131H FcgRIIa, rs396991-F158V FcgRIIIa and NA1/NA2-FcgRIIIb, might impact clearance of therapeutic monoclonal antibodies and thus, serum drug levels and the development of anti-drug antibodies.
A cross sectional, multicentral and non-interventional study was conducted in Tunisian RA patients treated with rituximab (RTX), etanercept (ETA), infliximab (IFX) and adalimumab (ADL). Serum drug level (SDL) of the different biologics and ADA against them were measured. All patients were genotyped for the three FCGR SNPs.
A total of 81 patients were included: 47 were under TNF-inhibitors (18 ETA, 13 ADL and 16 IFX) and 34 were under RTX. Regardless of the type of biotherapy, SDL was in therapeutic range, in 35 patients (43.2%) of whom only one was treated with RTX. Fourteen patients (22.2%) developed ADA but none of the patients treated with ETA had detectable ADA levels. There was no association between SDL positivity and FCGR polymorphisms. However, the high affinity FCGR2A 131 H/H receptor was statistically more prevalent in patients with detectable ADA treated with ADL, IFX and RTX (p=0.018). The same result was obtained in mAb TNFi subgroup (n=29, p=0.022) as well as in patients treated only with IFX (n=16, p=0.029).
Our work supports the hypothesis of an impact of FCGR SNPs on biologics' immunogenicity, particularly FCGR R131H polymorphism, but further studies with larger cohorts needs to be undertaken to confirm these results."
"Despite new and better treatments for juvenile dermatomyositis (JDM), not all patients with moderate severity disease respond adequately to first-line therapy. Those with refractory disease remain at higher risk for disease and glucocorticoid-related complications. Biologic disease-modifying antirheumatic drugs (DMARDs) have become part of the arsenal of treatments for JDM. However, prospective comparative studies of commonly used biologics are lacking.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM biologics workgroup met in 2019 and produced a survey assessing current treatment escalation practices for JDM, including preferences regarding use of biologic treatments. The cases and questions were developed using a consensus framework, requiring 80% agreement for consensus. The survey was completed online in 2020 by CARRA members interested in JDM. Survey results were analyzed among all respondents and according to years of experience. Chi-square or Fisher's exact test was used to compare the distribution of responses to each survey question.
One hundred twenty-one CARRA members responded to the survey (denominators vary for each question). Of the respondents, 88% were pediatric rheumatologists, 85% practiced in the United States, and 43% had over 10 years of experience. For a patient with moderately severe JDM refractory to methotrexate, glucocorticoids, and IVIG, approximately 80% of respondents indicated that they would initiate a biologic after failing 1-2 non-biologic DMARDs. Trials of methotrexate and mycophenolate were considered necessary by 96% and 60% of respondents, respectively, before initiating a biologic. By weighed average, rituximab was the preferred biologic over abatacept, tocilizumab, and infliximab. Over 50% of respondents would start a biologic by 4 months from diagnosis for patients with refractory moderately severe JDM. There were no notable differences in treatment practices between respondents by years of experience.
Most respondents favored starting a biologic earlier in disease course after trialing up to two conventional DMARDs, specifically including methotrexate. There was a clear preference for rituximab. However, there remains a dearth of prospective data comparing biologics in refractory JDM. These findings underscore the need for biologic consensus treatment plans (CTPs) for refractory JDM, which will ultimately facilitate comparative effectiveness studies and inform treatment practices."
"CMAB008 is a monoclonal antibody developed as a biosimilar to infliximab (Remicade
The population pharmacokinetic model was developed on the basis of intensive pharmacokinetic data from a phase 1 study in healthy male subjects and combined intensive and sparse pharmacokinetic data from a phase 3 study in patients with RA.
A two-compartment model with first-order elimination adequately described CMAB008 and Remicade
The pharmacokinetic characteristics were similar between CMAB008 and Remicade
ClinicalTrials.gov identifiers NCT04779892, NCT03478111."
"Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that can cause cartilage and bone damage as well as a disability. Various cytokines play an essential role in disease formation such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, IL-17, and macrophages; osteoclast is also activated by the cytokines, which cause bone degradation. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterized risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and using conventional, biological, and new non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favorable, many still do not respond to current therapies. The biologics have changed the disease progression over the past few decades, such as TNF-alpha inhibitors (infliximab, etanercept, adalimumab, golimumab, certolizumab), IL-1 inhibitors (anakinra), IL-6 inhibitors (tocilizumab), CD20 inhibitors (rituximab), and cytotoxic T-lymphocyte associated antigen (CTLA)-4 inhibitors (abatacept). In treatment with biologics, only little is known if ""biologic-free"" remission is possible in patients with sustained remission following intensive biological therapy. Infliximab and etanercept, in the long run, develop the drug antibody. This article has reviewed the action of the cytokine on joints and biological drug's action in blocking the cytokine degradation effect, benefits of biologics, and adverse effects in the long and short term. They are also effective alone or in combination with other drugs."
"Oral manifestations of IBD can be specific or nonspecific, due to intestinal malabsorption or induced by pharmacological treatments. Oral manifestations may precede the diagnosis of IBD or interfere with timely diagnosis and treatment. The paradigm of treatment for oral lesions in patients with IBD is based on treating and controlling the intestinal manifestations of the underlying disease as well as local methods of treatment can be used. Here, we report a case of a patient with the oral manifestation of IBD, who responded to treatment with infliximab. The patient was admitted with complaints of long-term nonhealing ulcers of the lips and oral cavity, odynophagia, and there were no intestinal manifestations at that time. The appearance of the disease in 2008 with lesions of the oral cavity, however, Crohn's disease was diagnosed in 2016. The patient began therapy with azathioprine and prednisolone, and later developed hormone dependence and osteoporosis. In 2020, against the background of immunosuppressive therapy, the patient has an exacerbation, especially increased symptoms from the lesion of the oral cavity. In 2020 was started therapy with vedolizumab, with slight improvement. Due to the ineffectiveness of the latter's therapy, therapy with monoclonal antibodies (infliximab) was started in February 2021. Currently, patient is in clinical, laboratory, and endoscopic remission."
"Immune checkpoint inhibitors have transformed the treatment of cancer. Nonetheless, multiple immune-related adverse events have been reported, including checkpoint inhibitor colitis. Severe colitis can be complicated by ileus, megacolon, intestinal perforation, and death. Current appropriate treatment includes steroids, followed by antitumor necrosis factor biologic therapy, infliximab. Alternatively, vedolizumab and fecal microbiota transplantation have reported efficacy for refractory cases. In this study, we present the first case report of a patient with steroid-refractory checkpoint inhibitor-induced colitis due to pembrolizumab for Stage IV anaplastic thyroid carcinoma successfully treated with ustekinumab after failure of infliximab, vedolizumab, and fecal microbiota transplantation. This may lead to a better understanding of treatment options for refractory checkpoint inhibitor colitis."
"Biologics are recommended to treat paediatric ulcerative colitis (UC) that is chronically active or steroid-dependent despite aminosalicylic acids (5-ASA) and thiopurine treatments. Anti-tumour necrosis factor inhibitors (Anti-TNF inhibitors) are the agents of choice and vedolizumab could be considered as second-line biologic therapy.In the current case, we aim to describe a successful long-term treatment with vedolizumab in a 9-year-old boy with severe UC and primary non-response to infliximab. Concomitant azathioprine was used, and steroid refractoriness was also detected. Drug and anti-drug antibody levels were negative after infliximab induction so a switch to a 6-week-induction vedolizumab regimen followed by a maintenance regimen as a monotherapy was decided. The clinical response and tolerability to vedolizumab allowed long-term disease remission. Vedolizumab is currently non-authorised to treat paediatric patients and there is limited data on long-term treatments to date. This case contributes to the literature by adding evidence on the long-term efficacy and safety of vedolizumab in paediatric UC."
"Assess the efficiency and cost-effectiveness of infliximab, cyclosporine and tacrolimus for the treatment of ulcerative colitis (UC).
A literature search identified studies that investigated infliximab, cyclosporine or tacrolimus compared with placebo in UC patients. Short-term, long-term remission rates and response rates were employed to assess efficacy. Odds ratios with 95% confidence intervals were analyzed. A Markov model was constructed to simulate the progression in a cohort of patients with UC, with an over 10 years of time horizon, with a discount rate of 3%, and established threshold of €30,000/quality-adjusted life-year (QALY) or ¥82442/QALY.
Results of network meta-analysis showed that the order was cyclosporine, tacrolimus, infliximab and placebo from high rate to low with regard to short-term clinical response. The comparison between infliximab versus cyclosporine achieved an incremental cost effectiveness ratio (ICER) of €184435/QALY and ¥531607/QALY, with a 0.34893 QALYs difference of efficacy, and an incremental cost of €64355 and ¥185494. Tacrolimus versus cyclosporine reached an ICER of €44236/QALY and ¥57494/QALY, with a difference of 0.40963 QALYs in efficacy, and a raising cost to €18120 and ¥23551. The probabilistic sensitivity analysis shows that cyclosporine would be cost-effective in the 75.8% of the simulations, tacrolimus in the 24.2%, and infliximab for the 0%.
Infliximab, cyclosporine and tacrolimus as salvage therapies are efficacious. For long-term of clinical remission, the order of pharmacological agents was tacrolimus, infliximab and cyclosporine from high efficacy to low while no significant difference is seen. In cost-effectiveness analysis, the cyclosporine versus infliximab or tacrolimus is expected to be at best."
"The standard therapy for acute severe ulcerative colitis (ASUC) is intravenous corticosteroids; however, 30% of ulcerative colitis (UC) patients do not recover with corticosteroids alone. Few studies have reported the efficacy and safety of tofacitinib for ASUC with steroid resistance. We report a case series of successful first-line treatment consisting of tofacitinib (20 mg/day) administered to ASUC patients with steroid resistance.
Patients diagnosed with ASUC at our institution between October 2018 and February 2020 were retrospectively evaluated. They were administered a high dose of tofacitinib (20 mg) after showing no response to steroid therapy in a dose of 1-1.5 mg/kg/day.
Eight patients with ASUC, 4 (50%) men, median age 47.1 (range 19-65) years, were included. Four patients were newly diagnosed, and the median UC duration was 4 (range 0-20) years. Six of the 8 patients were able to avoid colectomy. One patient (patient 2) had no response; however, remission was achieved after switching from tofacitinib to infliximab. One patient (patient 6) with no response to tofacitinib underwent total colectomy. Only one patient (patient 4) experienced an adverse event, local herpes zoster, treated with acyclovir without tofacitinib discontinuation.
Clinical remission without serious adverse events can be achieved with high probability and colectomy can be avoided by first administering high-dose tofacitinib to steroid-resistant ASUC patients. Tofacitinib may be one of the first-line treatment options for steroid-resistant ASUC."
"This is the English version of Japanese guidance for use of biologics for psoriasis (the 2022 version). As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti-tumor necrosis factor-α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti-interleukin (IL)-12/IL-23p40 antibody, which was launched in Japan in 2011. Moreover, after 2015, three IL-17 inhibitors, the IL-17A antibody preparations secukinumab and ixekizumab, and an anti-IL-17 receptor antibody preparation brodalumab were marketed. Furthermore, after 2018, the anti-IL23p19 antibody preparations guselkumab and risankizumab, the TNF inhibitor certolizumab pegol, the IL-23 inhibitor tildrakizumab, and the anti-IL-17A/F antibody bimekizumab were marketed. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors, and patient background factors, sharing such information with patients. The followings can be listed as points to be considered for the selection of biologics: drug effects (e.g., strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g., infections, administration-related reactions, and relationships with other comorbidities), convenience for patients (e.g., hospital visit intervals, self-injection, maintenance therapy at clinics, feasibility of drug discontinuation/re-administration), and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above-mentioned factors."
"Immune checkpoint inhibitors (ICIs) can induce a wide range of immune-related adverse events (irAEs), potentially affecting any organ. ICI-induced colitis is a frequently reported irAE, whereas enteritis is rare and not well documented.
We are presenting a patient with metastatic melanoma who developed severe ICI-induced enterocolitis multirefractory for glucocorticoids, infliximab and vedolizumab, partially responding to faecal microbiota transplantation and final complete response to tofacitinib.
This case supports that tofacitinib may be an(other) effective agent in managing multirefractory ICI-induced diarrhoea caused by colitis and/or enteritis."
"To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet's disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies.
This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy.
A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies.
This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. (ClinicalTrials.gov identifier: NCT02505568)."
"Sulfasalazine is commonly used to treat pediatric ulcerative colitis (UC). Sulfasalazine can be compounded into a suspension form which is beneficial for children with difficulty swallowing a pill. Despite being utilized for over 40 years, there is a lack of published data on the efficacy and safety of sulfasalazine suspension in children with UC. Recently, third-party payors have begun refusing to pay for sulfasalazine suspension due to lack of data.
In this retrospective study, we reviewed the electronic medical records of patients ages <18 years diagnosed with UC from June 1999-December 2019 at Boston Children's Hospital and treated with sulfasalazine suspension as a first-line agent. We obtained demographics, clinical and endoscopic data to measure outcomes at one year and long term.
Of 57 patients treated with sulfasalazine suspension, 52 (91%) had a follow-up and 26/52(50%) remained in steroid-free remission at one year. Two patients were switched to sulfasalazine tablets due to nonmedical reasons and eleven (21%) required rescue treatment (two Infliximab, one Tacrolimus, eight 6MP/Azathioprine) within a year. Three required colectomy within a year and five in long term. Four (8%) developed non-serious adverse reactions and switched to 5-Aminosalicylates (5-ASA) by one year. The median duration of long term follow up was 36 months (range,2- 205 months) with 28 requiring treatment escalation in long term.
Sulfasalazine suspension is a safe and effective treatment for UC in children with difficulty swallowing a pill. The one-year remission rate on this treatment is comparable to 5-ASA utilized in children."
"Although concurrent occurrence of spondyloarthritis (SpA) and ulcerative colitis (UC) is sometimes seen, the profiles of cytokines have been poorly understood in UC-associated SpA. We herein report a case of UC-associated SpA successfully treated with infliximab. Profiles of cytokines in the serum and colonic mucosa were characterized by an enhanced expression of IL-6 but not TNF-α. Successful induction of remission by infliximab was associated with the downregulation of IL-6 expression but no significant alteration in TNF-α expression. These findings suggest that some cases of UC-associated SpA might be driven by IL-6, and infliximab might be effective in cases lacking enhanced TNF-α responses."
"Immune checkpoint inhibitors (ICIs) are a new class of antitumor drugs that have been approved to treat a variety of malignant tumors. However, the occurrence of immune related adverse events (irAEs) has become an important reason for terminating treatment. ICIs sometimes lead to diarrhea and colitis, with severe enterocolitis potentially causing the hemorrhage of the lower gastrointestinal tract and colonic perforation. ICI-associated colitis is primarily treated with glucorticosteroids and/or agents targeting tumor necrosis factor-α. Here, we describe a case of severe ICI-associated colitis due to anti-programmed cell death ligand 1 (PD-L1) (durvalumab) treatment for small cell lung cancer with liver metastasis. The patient exhibited a poor response to rescuable therapy, and eventually received a laparoscopic subtotal colectomy and ileostomy. The data presented here will contribute to optimizing current treatment strategies for patients with severe ICI-associated colitis.
A 71-year-old man was admitted for a second course of anti-PD-L1 + IP (durvalumab + irinotecan + cisplatin) treatment to manage lung cancer with liver metastasis, diagnosed 1 mo previously. Four days after the second dose, the patient developed abdominal pain and bloody diarrhea. Due to the anti-PD-L1 medication history and colonoscopy findings of the patient, he was diagnosed with a colitis associated with ICI treatment. After treatment with sufficient glucocorticoids and two courses of infliximab, the patient developed severe lower gastrointestinal bleeding. After adequate assessment, the patient was treated by laparoscopic surgery, and was discharged in stable condition.
The early screening and hierarchical management of irAEs need the joint participation of a multidisciplinary team. For ICI-related colitis with ineffective medical treatment, timely surgical intervention could prevent the death of patients."
"The abscess is a common complication of Crohn's disease (CD), with the perianal form more frequent than gluteal or presacral which is relatively rare. There are few case reports of gluteal abscess combined with presacral abscess caused by CD and the treatment has not been established. A 21-year-old male was admitted with right buttock and lower back pain with a duration of 3 months. He had a history of CD in the small intestine diagnosed 10 months previously. He had poor compliance and had not returned for follow-up care during the previous 6 months. Abdominopelvic CT indicated newly developed multiple abscess pockets in right gluteal region, including piriformis muscle and presacral space. Additionally, fistula tracts between small bowel loops and presacral space were observed. Patient's CD was moderate activity (273.12 on the Crohn's Disease Activity Index [CDAI]). Treatment was started with piperacillin/ tazobactam antibiotic but patient developed a fever and abscess extent was aggravated. Therefore, surgical incision and drainage was performed and 4 Penrose drains were inserted. Patient's pain and fever were resolved following surgery. Infliximab was then administered for the remaining fistulas. After the induction regimen, multiple fistula tracts improved and patient went into remission (CDAI was -0.12)."
"Prospective data are lacking on evolution of trough levels, effectiveness, acceptance rate and patient satisfaction after switch from the adalimumab originator to a biosimilar in patients with inflammatory bowel disease.
Patients in clinical remission or stable response and treated with adalimumab originator in 2 Belgian centers were offered to participate in this phase IV, prospective trial in which patients were switched to adalimumab biosimilar SB5. The primary outcome was the description of adalimumab trough levels over time. Secondary outcomes were secondary loss of response, disease activity, patient satisfaction score and drug persistence over 12 months.
The study included 110 patients. Mean baseline adalimumab trough level was 9.21 μg/ml. Concentration remained within the therapeutic range over time. No changes were observed in disease activity scores nor in biochemical parameters over time. The acceptance rate of switch was 84.6%. By month 12, 74.5% was still treated with SB5. The most frequent reason for discontinuation was occurrence of adverse events. 50% of these adverse events were injection site pain. The local discomfort was only significant the first 30 minutes after injection. Satisfaction with the decision to switch to SB5 was high and remained stable over time.
After being well informed the great majority of patients treated with the adalimumab originator is willing to switch to biosimilar SB5. In our study, there was a persistence rate of 75% over one year. The trough levels remained within the therapeutic range and no change in disease activity was seen over time."
"In axial spondyloarthritis (axSpA) inflammation of the sacroiliac joints and spine is associated with local extracellular matrix (ECM) remodeling of affected tissues. We aimed to investigate the association of ECM metabolites with treatment response in axSpA patients treated with TNF-α inhibitory therapy for 46 weeks.
In a prospective clinical study of axSpA patients (n=55) initiating a TNF inhibitor (infliximab, etanercept, or adalimumab), serum concentrations of formation of type I (PRO-C1), type III (PRO-C3), and type VI (PRO-C6) collagen; turnover of type IV collagen (PRO-C4), and matrix-metalloproteinase (MMP)-degraded type III (C3M) collagen, MMP-degraded type IV (C4M), type VI (C6M), and type VII (C7M) collagen, and cathepsin-degraded type X collagen (C10C), MMP-mediated metabolite of C-reactive protein (CRPM), citrullinated vimentin (VICM), and neutrophil elastase-degraded elastin (EL-NE) were measured at baseline, week 2, week 22, and week 46.
Patients were mostly males (82%), HLA-B27 positive (84%), with a median age of 40 years (IQR: 32-48), disease duration of 5.5 years (IQR: 2-10), and a baseline Ankylosing Spondylitis Disease Activity Score (ASDAS) of 3.9 (IQR: 3.0-4.5). Compared to baseline, PRO-C1 levels were significantly increased after two weeks of treatment, C6M levels were significantly decreased after two and 22 weeks (repeated measures ANOVA, p=0.0014 and p=0.0015, respectively), EL-NE levels were significantly decreased after 2 weeks (p=0.0008), VICM levels were significantly decreased after two and 22 weeks (p=0.0163 and p=0.0374, respectively), and CRP were significantly decreased after two and 22 weeks (both p=0.0001). Baseline levels of PRO-C1, PRO-C3, C6M, VICM, and CRP were all associated with ASDAS clinically important and major improvement after 22 weeks (ΔASDAS ≥1.1) (Mann-Whitney test, p=0.006, p=0.008, p<0.001, <0.001, <0.001, respectively), while C6M, VICM and CRP levels were associated with ASDAS clinically important and major improvement after 46 weeks (ΔASDAS ≥2.0) (p=0.002, p=0.044, and p<0.001, respectively). PRO-C1 and C6M levels were associated with a Bath AS Disease Activity Score (BASDAI) response to TNF-inhibitory therapy after 22 weeks (Mann-Whitney test, p=0.020 and p=0.049, respectively). Baseline levels of PRO-C4 and C6M were correlated with the total SPARCC MRI Spine and Sacroiliac Joint Inflammation score (Spearman's Rho ρ=0.279, p=0.043 and ρ=0.496, p=0.0002, respectively).
Extracellular matrix metabolites were associated with ASDAS response, MRI inflammation, and clinical treatment response during TNF-inhibitory treatment in patients with axSpA."
"Children with Crohn's disease have lower response rates to infliximab, lower infliximab levels, and higher infliximab clearance on weight-based dosing than adults. We hypothesize infliximab clearance is a predictive of later outcomes on infliximab in children with Crohn's disease.
In this single-center retrospective study, data were collected from charts on diagnosis, anthropometry, routine labs, infliximab therapeutic drug monitoring, infliximab dosing, disease activity, and other treatments. With these data we generated a population pharmacokinetic model using non-linear mixed effects modeling and calculated infliximab clearance for each patient over time. Patients were classified as in remission, responder-only or non-responder at 5, 10 and 16 months. Regression and ROC analyses were used to assess for early predictors of remission and response to infliximab.
Eighty-five subjects were included, with a median follow-up of 22.3 months (IQR 10.1-36.8). Our pharmacokinetic model showed infliximab clearance was positively associated with CRP and weight, while negatively associated with albumin. In regression analyses, early infliximab clearance was the only significant, consistent predictor of remission. A 0.1 L/day increase in infliximab clearance predicted remission with an OR between 0.179 and 0.426. Differences in dosing did not account for differences in outcome. Infliximab clearance alone had moderate predictive accuracy of remission, with an AUC between 0.682 and 0.738.
Early infliximab clearance is strongly associated with remission in children with Crohn's disease. It may be useful as a marker of response in proactive therapeutic drug monitoring to guide early dose optimization and/or changes in treatment for betterment of long-term outcomes."
"Septic arthritis (SA) is a serious complication occurring in the joints, and its risk increases with immunosuppressive therapy. This study investigated whether tumour necrosis factor (TNF)-inhibitors increase the risk of SA in patients with ankylosing spondylitis (AS) and seropositive rheumatoid arthritis (SPRA).
We searched the South Korean Health Insurance Review and Assessment Service database for incident cases of AS and SPRA between 2010 and 2020. SA was defined using the diagnostic code M00 and hospital admission. Cox-proportional hazards analysis was conducted to compare the incidence of SA according to TNF-inhibitor (infliximab, etanercept, adalimumab/golimumab) use during follow-up.
Of the 145,129 patients analysed, 1,170 (0.8%) developed SA during the follow-up period. Older age; male sex; SPRA diagnosis; comorbidities of hypertension (HTN), diabetes mellitus (DM), and chronic pulmonary disease (CPD); and infliximab and etanercept use increased the incidence of SA in the overall population. However, in patients with AS, only age and renal disease were predictors of SA, and TNF-inhibitors did not increase the incidence of SA. Meanwhile, patients with SPRA treated with TNF-inhibitors were prone to SA regardless of TNF-inhibitor type, and age, HTN, DM, and CPD were associated with SA. The incidence of SA was prominent after the first year of commencing TNF-inhibitor therapy, for both AS and SPRA.
TNF-inhibitors increase the incidence of SA, specifically in patients with SPRA, but not AS. Importantly, age, comorbidities, and the early time period after starting TNF-inhibitors were associated with SA, that should be considered simultaneously when initiating TNF-inhibitor therapy."
"there is increasing evidence that proactive therapeutic drug monitoring in induction is useful to improve the control of inflammatory bowel disease (IBD), although it remains controversial. The primary objective of the study was to assess the short-term outcomes of proactive Bayesian therapeutic drug monitoring (TDM) during induction, to optimize infliximab (IFX) maintenance dose.
retrospective observational cohort of IBD patients > 18 years. They were divided into two cohorts, standard therapy group (ST-group), with clinically based dose adjustment, and monitoring group (iTDM-group), with pharmacokinetic parameters calculated by Bayesian prediction at week 6 and individualized dosage regimens thereafter. In patients with an infliximab trough level (ITL) at week 6 below the optimal therapeutic range, the dose adjustment was performed at the first maintenance dose.
a total of 153 patients were included, 40 in the iTDM-group. Median ITL at week 6 during the induction period was 12.8 µg/ml (IRQ: 12.7) in this group. Only 16 patients (40.0 %) had ITL ≥ 15 µg/ml. Half of the patients (50.3 %) received intensified maintenance therapy during the study period (57.5 % iTDM vs 47.8 % ST, p = 0.291). The proportion of patients achieving primary response at week 14 was 51.8 %. When comparing the two groups, this proportion was higher in the iTDM group (74.3 % vs 44.2 %, p = 0.002). With regards to the variable ""poor clinical outcomes"" at week 26, this proportion was lower in the iTDM group (3.3 % iTDM vs 21.1 % ST, p = 0.024).
proactive therapeutic drug monitoring using Bayesian approach is associated with higher primary response rates and fewer short-term complications."
"We describe the case of a 69-year-old male with Crohn's disease (CD), treated with infliximab and undergoing intestinal resection. The surgery and postoperative period were unremarkable, with no CD-related symptoms. Two months after surgery and two weeks after the introduction of infliximab, he was admitted due to acute onset diffuse abdominal pain, hematochezia and arthralgia. On physical observation on admission, he showed signs of arthritis of the left knee. Laboratory tests revealed renal failure with nephrotic proteinuria, slightly low complement (C3) and IgA elevation. Remaining autoimmunity and viral panel were negative. Abdominal examination showed duodenum and thickening of the proximal wall of the jejunum. Biopsies excluded active CD. Colon and ileum mucosa were normal. The patient met EULAR criteria for Henoch-Schönlein purpura and was started on prednisolone with response. Although no clear trigger was pointed out, we switched anti-TNF to ustekinumab. We present this case given its endoscopic exuberance, and because of the high index of suspicion to make the diagnosis in adult patients with previous inflammatory bowel disease. The distinction between this vasculitis and CD is of utmost importance, given the therapeutic implications."
"Patients with rheumatic diseases taking immunosuppressive medications might be at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the effectiveness of using combined conventional and biological disease-modifying anti-rheumatic drugs(bDMARDs) in managing rheumatic diseases, there have been concerns that taking biological agents may have an additive effect on getting infected with COVID-19. This study evaluates the impact of taking biological agents on altering the chance of getting infected with SARS-CoV-2 in rheumatoid and lupus patients compared to traditional DMARDs.
We carried out a cross-sectional survey study from February 2020 to January 2021 on patients diagnosed with lupus and rheumatoid arthritis disease. COVID-19 infection was confirmed by the presence of symptoms and signs of the disease and para-clinical findings such as lymphopenia and elevated C-reactive protein (CRP) and positive chest CT scan or polymerase chain reaction (PCR) of COVID-19.
Out of 591 patients included in this study, 422 (71.4%) had rheumatoid arthritis (RA), and 169 (28.6%) had systemic lupus erythematosus (SLE). Among them, 56 (9.5%) cases were diagnosed with COVID-19 infection. No association was found between age, gender, or type of rheumatological diseases and SARS-CoV-2. There was a significant association between COVID-19 infection and treatment with biological drugs (
This study develops a better understanding of the risk of immunosuppressive medications for SARS-CoV-2 infection. Patients treated with conventional and biological medicine had a higher disease risk than those taking exclusively conventional drugs. However, more studies are required to deliberate the relation of the reviewed factors with the severity of COVID-19."
"In our clinical experience, more than half of patients do not present a complete response to biologic drugs, or drug loses its efficacy over time. Plasma determinations of drug and anti-drug antibodies levels are an objective tool for optimisation in these patients; however, established therapeutic ranges are not suitable, so the objective of this study was to study these patients and optimise their healthcare. We have made a retrospective, observational study, using data of plasma levels of drugs and anti-drugs antibodies of infliximab, adalimumab or Etanercept, we summarise all data and make a study of sensitivity, specificity, positive and negative predictive value on current therapeutic ranges. We have found a statistically significant association between subtherapeutic levels and therapeutic failure in psoriasis treated with infliximab and adalimumab. New ranges were found with higher sensitivity than the established ones, we propose 2-10 µg/mL therapeutic range for infliximab, 3-11 µg/mL for adalimumab, and 1-7 µg/mL for etanercept. In conclusion, levels of drug and anti-drug antibodies are a decisive tool for predicting therapeutic response. The current therapeutic ranges may have minimum values that are excessively high, owing to which lowering them significantly increases the sensitivity of the test in all cases, and negative predictive value in the case of etanercept. Further prospective studies are needed to prove the usefulness of these new ranges."
"there is currently limited research examining the QoL of patients with Ulcerative colitis (UC) following treatment of acute severe colitis (ASUC).
to examine the long-term QoL of ASUC patients enrolled in the CONSTRUCT trial following treatment of UC with infliximab or ciclosporin and to compare the differences in the QoL between the two drug treatments over time.
The CONSTRUCT trial examined the cost and clinical effectiveness of infliximab and ciclosporin treatments for acute severe UC. We collected QoL questionnaire data from patients during the active trial period up to 36 months. Following trial completion, we contacted patients postannually for up to a maximum of 84 months. We collected QoL data using a disease-specific (CUCQ, or CUCQ+ for patients who had colectomy surgery) or generic (EQ5D-3L) questionnaire. We analysed QoL scores to determine if there was any difference over time and between treatments in generic or disease-specific QoL.
Following initial treatment with infliximab and ciclosporin, patients experienced a statistically significant improvement in both the generic and disease-specific QoL at three months. Generic scores remained fairly static for the whole follow-up period, reducing only slightly up to 84 months. Disease-specific scores showed a much sharper improvement up to 2 years with a gradual reduction in QoL up to 84 months. Generic and disease-specific QoL remained higher than baseline values. There was no significant difference between treatments in any of the QoL scores.
Both infliximab and ciclosporin improve QoL following initial treatment for ASUC. QoL scores remain higher than at admission up to 84 months post-treatment."
"Subcutaneous infliximab and vedolizumab formulations have been developed for maintenance therapy in inflammatory bowel disease. The objective of this study was to explore the inflammatory bowel disease patient's acceptance for switching from intravenous infliximab or vedolizumab to subcutaneous, as well as to describe the causes of refusal or, conversely, the factors associated with acceptance.
Patients were prospectively recruited between June 2021 and March 2022 during their infusion of infliximab or vedolizumab in the Medical Day Hospital of Nancy University Hospital. Adult patients with an established diagnosis of inflammatory bowel disease in clinical remission were eligible for inclusion in this study if they had been treated with intravenous infliximab or vedolizumab for at least six months.
One hundred and thirty patients were included in this study. Thirty-six patients (27.7%) received vedolizumab and ninety-four patients (72.3%) received infliximab. Median duration of treatment at inclusion was 7.0 years [3.0-11.0]. In this cohort, 77.7% of patients accepted the switch from intravenous infliximab or vedolizumab to subcutaneous. The main reasons for patient's refusal for switching from intravenous to subcutaneous formulation were fear of loss of efficacy, a more spaced-out medical follow-up, increased frequency of administration, and self-administered injection. A short duration of treatment was associated with a high switch acceptance rate (odd ratio (OR) (95% confidence interval (CI)) = 0.9 (0.8-0.9); 
A large majority of the patients included accepted the switch of their treatment with infliximab or vedolizumab from the intravenous form to the subcutaneous form. This study identified one predictor influencing the acceptance rate in inflammatory bowel disease population: short treatment duration. Subcutaneous infliximab and vedolizumab hold potential for greater patient flexibility by self-administration, reducing travel and hospital attendance for infusion."
"Coronary atherosclerosis is a chronic pathological process that involves inflammation together with endothelial dysfunction and lipoprotein dysregulation. Experimental studies during the past decades have established the role of inflammatory cytokines in coronary artery disease, namely interleukins (ILs), tumor necrosis factor (TNF)-α, interferon-γ, and chemokines. Moreover, their value as biomarkers in disease development and progression further enhance the validity of this interaction. Recently, cytokine-targeted treatment approaches have emerged as potential tools in the management of atherosclerotic disease. IL-1β, based on the results of the CANTOS trial, remains the most validated option in reducing the residual cardiovascular risk. Along the same line, colchicine was also proven efficacious in preventing major adverse cardiovascular events in large clinical trials of patients with acute and chronic coronary syndrome. Other commercially available agents targeting IL-6 (tocilizumab), TNF-α (etanercept, adalimumab, infliximab), or IL-1 receptor antagonist (anakinra) have mostly been assessed in the setting of other inflammatory diseases and further testing in atherosclerosis is required. In the future, potential targeting of the NLRP3 inflammasome, anti-inflammatory IL-10, or atherogenic chemokines could represent appealing options, provided that patient safety is proven to be of no concern."
"Post-marketing surveillance is essential to evaluate the risk/benefit profile of drugs; however, pharmacovigilance studies comparing persistence and safety of biologic therapies in patients with inflammatory bowel disease (IBD) are scant. The aim of this study was to prospectively investigate persistence together with safety profiles of biologics in a cohort of patients diagnosed with Crohn's Disease (CD) or ulcerative colitis (UC) followed by the IBD unit of Messina and treated with infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST) from 2017 through 2021. Descriptive and treatment persistence analyses with predictors for discontinuation and occurrence of adverse drug reactions (ADRs) were performed. A total of 675 IBD patients were enrolled. A higher persistence rate was noted for UST and ADA in the first year (83.8% and 83.1%, respectively) and for IFX in the fifth year of treatment (58.1%). GOL, VED, and UST-all used as second/third-line therapies-seemed to have a higher risk of non-persistence than IFX (in order HR: 2.19; CI 95%: 1.33-3.61, 1.45; 1.04-2.04, 2.25; 1.25-4.07) as well as switchers and those who had at least one ADR (18.1; 13.22-24.68 and 1.55; 1.20-1.99, respectively). The reported ADRs, which were generally mild-moderate, were largely known. However, real-world data should be implemented to further study undetected safety concerns, including risk of malignancy."
"To compare the efficacy of TNF inhibitors (adalimumab (ADA) and infliximab (IFX)) vs tocilizumab (TCZ) in patients with refractory cystoid macular edema (CME) due to Behçet's disease (BD).
Multicenter study of patients with BD-associated CME refractory to conventional and/or biological immunosuppressive drugs. From a cohort of 177 patients treated with anti-TNF and 14 patients treated with TCZ, we selected those with CME at baseline. We analyzed the evolution of macular thickness (main outcome), best-corrected visual acuity (BCVA) and intraocular inflammation (Tyndall and vitritis) from baseline up to 4 years in the 3 groups mentioned.
49 patients and 72 eyes with CME were included. ADA was used in 25 patients (40 eyes), IFX in 15 (21 eyes) and TCZ in 9 (11 eyes). No statistically significant baseline differences were observed between the 3 groups except for a lower basal BCVA in TCZ group and a higher basal degree of intraocular inflammation in ADA group. Most patients from all groups had received several conventional immunosuppressive drugs. In addition, most patients in the group of TCZ had also received anti-TNF agents. Biological therapy was used in monotherapy (n=8) or combined with conventional immunosuppressive drugs (n=41). Macular thickness progressively decreased in the 3 groups, with no signs of CME after 1 year of treatment. Similarly, BCVA improvement and inflammatory intraocular remission was achieved in all groups.
Refractory CME associated with BD uveitis can be effectively treated either with ADA, IFX or TCZ. Furthermore, TCZ is effective in patients resistant to anti-TNF therapy."
"Tumor necrosis factor inhibitors (TNFis) can induce antidrug antibody (ADA) formation and loss of therapeutic response. However, the utility of ADA testing and the association between ADAs and treatment response in patients with noninfectious uveitis (NIU) is not well understood.
To assess the frequency of ADAs and their association with drug levels and clinical response in patients with NIU treated with adalimumab or infliximab.
This retrospective cross-sectional study included patients diagnosed with NIU who received adalimumab or infliximab and underwent testing for serum drug level and ADAs at the National Eye Institute from September 2017 to July 2021.
Serum drug level testing with reflex testing for ADA levels was performed.
The main outcome was the association between drug levels and ADAs, clinical response, and concurrent antimetabolite use in patients treated with TNFis for NIU.
Of 54 patients included in the study, 42 received adalimumab (mean [SD] age, 43.6 [19.6] years; 25 [59.5%] female) and 12 received infliximab (mean [SD] age, 42.7 [20.4] years; 7 [58.3%] male). In the adalimumab group, mean (SD) drug level was 9.72 (6.82) μg/mL, mean (SD) ADA level was 84.2 (172.9) arbitrary units/mL, and ADA frequency was 35.7% (15 of 42 patients). Mean drug level was lower in those with ADAs compared with those without ADAs (mean [SD], 2.8 [2.6] μg/mL vs 13.6 [5.2] μg/mL; difference: 10.8 μg/mL; 95% CI, 8.3-13.2 μg/mL; P < .001). There was a higher mean drug level with concurrent antimetabolite use compared with monotherapy (mean [SD], 11.0 [7.3] μg/mL vs 6.8 [4.5] μg/mL; difference: -4.2 μg/mL; 95% CI, -8.7 to 0.2 μg/mL; P = .06). Multivariable modeling showed that a 1-arbitrary unit increase in ADAs was associated with a -0.02 μg/mL (95% CI, -0.01 to -0.34 μg/mL) difference in mean drug level (P < .001). Favorable clinical response was associated with a threshold drug level above 2.7 μg/mL or an antibody level below 15.2 μg/mL. The mean (SD) drug level in the infliximab group was 27.02 (18.15) μg/mL, and no ADAs were detected.
In this study, 35.7% of adalimumab-treated patients with NIU had ADAs. The presence of ADAs was associated with lower drug levels, and higher ADA levels were associated with increased risk of TNFi treatment failure. Although limited by the retrospective design, our results suggest that therapeutic drug monitoring may be considered among patients experiencing therapy failure to help exclude ADAs as a potential cause of treatment failure."
"Inflammatory bowel disease poses significant social and economic burdens. We assessed the budget impact of including the recently approved subcutaneous (SC) formulation of vedolizumab as maintenance therapy (MT) in patients with ulcerative colitis (UC) in France.
A decision-analytic model was developed from a French payer's perspective over 5 years to assess budget impact of including vedolizumab SC as MT for UC following induction therapy with vedolizumab intravenous (IV), by subtracting outcomes of a 'world without vedolizumab SC' from a 'world with vedolizumab SC.' Comparators included approved therapies: infliximab (branded/biosimilar), adalimumab (branded/biosimilar), golimumab, ustekinumab, and vedolizumab IV. The model predicts drug, medical, and total costs, including indirect costs in a scenario analysis. A one-way sensitivity analysis explored the impact of varying individual parameters.
Including vedolizumab SC as MT following vedolizumab IV induction yielded total cost savings of €59,176,842 (biologic-naïve) and €22,004,135 (biologic-experienced) versus a world without vedolizumab SC. Including indirect costs yielded cost savings in biologic-naïve (€62,600,716) and biologic-experienced (€24,314,915) populations in a world with vedolizumab SC.
Introducing vedolizumab SC as MT after IV induction is expected to have substantial cost savings to a health plan from a French payer's perspective versus a world without vedolizumab SC."
"Behcet's disease (BD) is a multisystem immune-mediated inflammatory disorder that occasionally involves the gastrointestinal tract. Reports on gastrointestinal involvement of BD are relatively rare, of which gastroduodenal involvement is particularly rare. Endoscopic features of gastroduodenal lesions are unknown, and treatment strategies have not been established. In this report, we present the case of a 72-year-old female with gastrointestinal BD who presented with extensive gastroduodenal ulcers and hematemesis that were resistant to colchicine and corticosteroid treatment, which were subsequently successfully treated with infliximab. We also review the current literature on the gastroduodenal involvement of BD. Although rare, the case highlights the importance of being aware of upper gastrointestinal manifestations of BD, as well as demonstrating the potential of infliximab to treat corticosteroid-resistant cases."
"To study the efficacy and long-term effects of infliximab and adalimumab in patients with active refractory non-infectious intermediate, posterior, or panuveitis (NIPPU).
Retrospective, longitudinal study.
Included were 61 patients (104 eyes) of whom 34 were males (55.74%). Mean age at diagnosis of uveitis was 26.5 ± 16.14 years. All patients had active uveitis at baseline (time of initiation of biological therapy). Median interval between the start of conventional immunomodulatory therapy (IMT) to the introduction of biological therapy was 13.0 (IQR 26.0) months. Ocular inflammation was effectively controlled in 92 eyes (88.46%). The most commonly used TNF-α inhibitor was adalimumab in 47 patients (77%). Mean follow-up time after baseline was 40 ± 34.08 months. In the year preceding the institution of TNF-α inhibitors, the average number of flares was 1.5 ± 1.1/year and it decreased to 0.08 ± 0.29/year in the first year after baseline (
Anti-TNF-α therapy was successful in controlling refractory NIPPU in the majority of cases. It significantly reduced flare rate, exerted steroid-sparing effects, and preserved visual potential. Adalimumab use, better initial visual acuity, and earlier introduction of anti-TNF- α therapy were associated with a lower risk of visual loss."
"Glucocorticoids are the primary treatment choices for sarcoidosis. However, some patients are resistant to corticosteroids or have side effects and may not respond to alternative treatments added to reduce corticosteroid therapy. Evidence has demonstrated the critical role of Infliximab [anti-tumor necrosis factor (TNF)-α] which is a chimeric IgG1 monoclonal antibody in the pathogenesis of granulomatous inflammation. In this paper, we present a patient who improved clinically and radiologically with infliximab treatment, which was initiated due to the development of serious side effects associated with corticosteroids; however, following unresponsiveness to other therapeutic drugs initiated due to relapse, restarted infliximab, and developed an early hypersensitivity reaction. With infliximab, the frequency of early-type hypersensitivity reactions is 2-3%. In such cases, drug desensitization is an effective and safe treatment option. Different desensitization protocols have been defined with infliximab, and the frequency of reactions during desensitization has been reported as 29%, especially in the last step. With the desensitization protocol we have modified, patients with a history of early-type hypersensitivity reaction with infliximab will have the chance to take this effective drug more safely and effortlessly."
"Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason.
A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars.
153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild.
No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed."
"The primary end point of the pivotal phase III study of infliximab (IFX) s.c. demonstrated non-inferiority of s.c. to i.v. IFX, based on 28-joint DAS-CRP (DAS28-CRP) improvement at Week (W) 22 (NCT03147248). This post-hoc analysis investigated whether numerical differences in efficacy outcomes at W30/54 were statistically significant, using conservative imputation methods.
Patients with active RA and inadequate response to MTX received IFX i.v. 3 mg/kg at W0 and W2 (induction) and were randomised (1:1) to IFX s.c. 120 mg every 2 weeks or i.v. 3 mg/kg every 8 weeks thereafter (maintenance). Patients randomised to IFX i.v. switched to IFX s.c. from W30-54. This post-hoc analysis compared efficacy outcomes for s.c. and i.v. groups pre-switch (W30) and post-switch (W54) using last observation carried forward (LOCF) and non-responder imputation (NRI) methods.
Of 343 randomised patients, 165 (IFX s.c.) and 174 (IFX i.v.) were analysed. At W30, significantly improved outcomes were identified with s.c. vs i.v. IFX for DAS28-CRP/DAS28-ESR/Clinical Disease Activity Index (CDAI)/Simplified Disease Activity Index (SDAI) scores (LOCF); ACR/good EULAR responses, DAS28-CRP/Boolean remission, and DAS28-CRP/DAS28-ESR/CDAI/SDAI low disease activity and remission (LOCF and/or NRI); and minimal clinically important difference in HAQ score (LOCF and NRI). After switching to IFX s.c. from IFX i.v., fewer significant between-group differences were identified at W54.
IFX s.c. showed improved efficacy at W30 compared with IFX i.v., and the reduced between-group difference in efficacy outcomes at W54 after switching supports the results suggesting benefits of IFX s.c. compared the IFX i.v. at W30.
ClincialTrials.gov, http://clinicaltrials.gov, NCT03147248."
"Small fiber neuropathy (SFN) may present as complication in sarcoidosis.(1) SFN can potentially result into a large range of symptoms with a high impact on quality of life.(2) Although treatment of the underlying disease of SFN is paramount, little research has been performed to investigate SFN improvement as consequence of sarcoidosis treatment. This retrospective study investigates whether there is an association between the anti-inflammatory effects of infliximab and SFN-symptoms Methods: The Small Fiber Neuropathy Screening List (SFNSL) was used to measure changes in SFN symptoms during infliximab treatment. Maximal standardized uptake value (SUVmax) from Fluordeoxyglucose Positron Emission Tomography (FDG-PET) was used as a measure for inflammatory activity.
36 sarcoidosis patients were eligible for analysis. SFNSL-score showed a mean decrease of -1,9 points (p = 0.446). SUVmax did improve with a mean of -3.7 (p<0.001). No correlation between a decrease of SUVmax and SFNSL screening list could be found (p=0.610).
Our data reveal no association between anti-inflammatory effect of infliximab and SFN-related symptoms in patients with sarcoidosis, which contradicts previous case-reports and case-series.(3-6) Given the major negative impact of SFN-related symptoms on the quality of life in patients with sarcoidosis, it is necessary that the possible beneficial effect of anti-inflammatory therapy will be further addressed in future prospective studies.1."
"The importance and pathophysiology of transmural healing in patients with Crohn's disease (CD) remains to be verified. We aimed to examine the association between serum concentrations of biologics and transmural remission evaluated via magnetic resonance enterography (MRE).
We enrolled patients with CD who received maintenance biologics 1 year after induction and prospectively followed up for at least 1 year after baseline laboratory, endoscopic and MRE examination. We evaluated the relationship between baseline factors including the presence of transmural remission and patient prognosis, as well as between serum concentrations and transmural remission.
We included 134 patients. Of them, 65, 31, 27, and 11 patients received infliximab, adalimumab, ustekinumab, and vedolizumab, respectively. Those who achieved transmural remission showed a lower risk of hospitalization and surgery than those who did not achieve remission (P < 0.01). Adjusted hazard ratios of transmural remission for predicting hospitalization and surgery was 0.11 and 0.02, respectively, which was lower than that of clinical remission, biochemical remission, and endoscopic remission. Regarding serum concentrations, the median concentration was higher in patients with transmural remission than in patients with transmural activity for all agents (P < 0.01 for infliximab, P = 0.04 for adalimumab, P < 0.01 for ustekinumab, P = 0.08 for vedolizumab).
Transmural remission was the best predictor for prognosis in CD patients who received maintenance biologic therapy. High drug concentration levels were associated with transmural remission confirmed via MRE."
"Anti-tumor necrosis factor-alpha agent (anti-TNF-α) is considered an effective third-line therapy for refractory sarcoidosis,studies observing the efficacy of anti-TNF-α agents show conflicting results.
We performed an up-to-date systemic meta-analysis to determine effectiveness and further elucidate the role of anti-TNF-α in the treatment of sarcoidosis.
A systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis, published up to April 10, 2022. The study was registered in the international prospective register of systematic reviews (PROSPERO) under ID: CRD42022364614.
Clinical trials written reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis were included.
Statistical analyses were performed with Comprehensive Meta-Analysis software, and the random-effects model was used. The combined overall treatment success was determined for patients with pulmonary and extrapulmonary sarcoidosis.
Overall treatment success rate wasdefined as no disease progression or improvement in symptoms.
Eight clinical trial articles were included in the meta-analysis; four used Infliximab, two Etanercept, one Adalimumab, and one Ustekinumab and Golimumab. The mean age of participants was 48.5 years. The duration of drug therapy ranged from 14 to 45 weeks. We found a combined overall treatment success rate, defined as no disease progression or improvement in symptoms, of 69.9% (95% CI 35.0-90.9, I2: 70%) in the pulmonary sarcoidosis group and 74.5% (95% CI 36.3-93.7, I2: 90%) in the extrapulmonary sarcoidosis group. There was no evidence of publication bias in either group.
Treatment of refractory sarcoidosis with anti-TNF-α agents was effective in both pulmonary and extrapulmonary sarcoidosis, with a slightly higher efficacy seen in extrapulmonary sarcoidosis. Further randomized controlled trials should be conducted to determine the effects of anti-TNF-α agents as a part of the management strategy of sarcoidosis. Patients with pulmonary sarcoidosis should be studied separately from patients with extrapulmonary sarcoidosis to adjust for confounding results."
"Characterization of therapeutic monoclonal antibodies (mAbs) represents a major challenge for analytical sciences due to their heterogeneity associated with post-translational modifications (PTMs). The protein glycosylation requires comprehensive identification, which could influence on the mAbs' structure and their function. Here, we demonstrated high-resolution tandem mass spectrometry with an ultra-high-performance liquid chromatography for characterization and comparison between biologics and biosimilar of infliximab at an advanced level. Comparing the N- and O-glycopeptides profiles, a total of 49 and 54 glycopeptides was identified for each product of the biologics and biosimilar, respectively. We also discovered one novel N-glycosylation site at the light chain from both biopharmaceuticals and one novel O-glycopeptide at the heavy chain from only biosimilar. Site-specific glycopeptide analysis process will be a robust and useful technique for evaluating therapeutic mAbs and complex glycoprotein products."
"In Crohn's disease, combination therapy with infliximab and azathioprine is more effective than either drug alone but is associated with a higher risk of therapy-related complications. Though therapy de-escalation can reduce risks and save costs, it is associated with a risk of Crohn's disease relapse.
We aimed to study the cost-effectiveness of de-escalation strategies in Crohn's disease patients in remission on infliximab and azathioprine.
We constructed a decision tree with Markov models for continuation of infliximab and azathioprine, discontinuation of azathioprine followed by its re-introduction in case of relapse, discontinuation of azathioprine followed by infliximab dose intensification without azathioprine reintroduction in case of relapse and discontinuation of infliximab. Third-party payers' perspective with a willingness-to-pay threshold of $100,000/quality-adjusted life years was used. Markov cycle length was 3 months, and the study period was 5 years. A 35-year-old patient with Crohn's disease in clinical remission on azathioprine 150 mg daily and infliximab 5 mg/kg every 8 weeks was used for base-case analysis.
Azathioprine withdrawal followed by its reintroduction upon relapse was the dominant strategy as it was the most effective and least expensive approach on base-case analysis. It was also cost-effective in 99.3% of Monte Carlo trial simulations. AZA withdrawal without IFX dose intensification upon relapse was the least effective and the most expensive strategy.
Azathioprine withdrawal is the most effective and least costly de-escalation strategy in CD patients in remission on combination therapy if AZA re-introduction is performed upon CD relapse."
We report the first described case of pulmonary tularaemia in the pediatric patient receiving infliximab for ulcerative colitis. We highlight the importance of considering Francisella tularensis in diagnostically challenging cases of persistent respiratory symptoms to facilitate early diagnosis and adequate therapy. The TCR-γδ 
"To answer the following question: In patients with primary autoimmune inner ear disease (AIED), (population) what impact do disease-modifying antirheumatic agents (DMARDs) (intervention) when compared with no treatment or corticosteroids (comparison) have on auditory and vestibular outcomes (outcome)?
Systematic review and meta-analysis.
According to PRISMA guidelines, PubMed, Scopus, CINAHL, and Cochrane Library databases were searched from inception to March 10, 2022.
Studies of patients receiving DMARDs for the treatment of AIED were selected for review. Case reports, phase I/II trials, studies of patients with secondary AIED, and studies of AIED patients receiving solely corticosteroids were excluded.
Primary outcomes were pure-tone audiometry and speech discrimination scores at baseline and after DMARD treatment. Secondary outcomes were rates of subjective audiovestibular complaints and rates of adverse reactions. No objective vestibular outcomes underwent meta-analysis.
Mean differences were calculated using RevMan 5.4. Heterogeneity was assessed with the Q test and I2 statistic. Pooled prevalence rates of audiovestibular symptoms were expressed as a percentage with 95% confidence intervals.
Ten studies with a total of 187 patients were included. Treatments included methotrexate, etanercept, azathioprine, anakinra, cyclophosphamide, rituximab, and infliximab. Mean treatment duration was 10.8 ± 22.2 months and mean follow-up was 13.7 ± 8.1 months. The pure-tone audiometry and speech discrimination scores mean differences between baseline and post-DMARD were -2.1 [-4.1, -0.1] dB and 13.9 [8.5, 19.4] %, respectively. Seven studies reported 38 adverse events, four of which were classified as serious.
DMARDs showed statistically significant improvement in auditory outcomes, as well as subjective symptoms, with relatively low rates of adverse events. They warrant further exploration to better compare with corticosteroids."
"Immune checkpoint inhibitors (ICIs) have been proven to be very effective in the treatment of multiple cancers. They have a unique side-effect profile distinct from conventional chemotherapy that can manifest as immune-related adverse events (irAEs). With expanding ICI use, clinicians will increasingly encounter irAEs, and thus adequate physician knowledge on their recognition and management is crucial.
To assess physician knowledge of irAEs due to ICIs, an online survey was administered to resident physicians in internal medicine (IM), emergency medicine, and family medicine (FM), as well as to faculty physicians in IM and FM.
We sent the survey to 413 physicians and received responses from 155 (38%), of which 110 were residents and 45 were faculty. Pembrolizumab was identified as an ICI by 79% of physicians, nivolumab by 64%, and ipilimumab by 55%. Twenty-five percent incorrectly thought infliximab and adalimumab were ICIs. Most physicians (93%) were able to identify the gastrointestinal tract as an irAE site, whereas only 57% and 67% were able to identify cardiovascular and renal systems as irAE sites, respectively. A total of 59% believed steroids negatively affect efficacy of ICIs and should be used with caution to treat irAEs, 65% incorrectly thought endocrinopathies due to irAEs are usually reversible, and 45% of FM residents considered antibiotics as the mainstay of treatment in ICI-mediated colitis. On a self-rated scale from 0 to 100, the median comfort level for all physicians in recognizing irAEs was 15 and for treatment of irAEs was 10.
Significant knowledge gaps exist among residents and faculty physicians across multiple specialties regarding the recognition and treatment of irAEs due to ICIs. Given that these physicians are usually the first point of contact with patients, physician education on identification and treatment of irAEs is needed. Early detection of these toxicities is critical for their resolution."
"Inflammatory Bowel Diseases (IBD) are chronic nonspecific intestinal inflammatory diseases with a relapsing-remitting course, including Ulcerative Colitis (UC) and Crohn's Disease (CD). Combination therapy has been proposed as a strategy to enhance treatment efficacy in IBD. The aim of this study is to summarize current evidence and perspectives on combination therapies in IBD.
Electronic databases such as PubMed, Ovid Embase, Medline, and Cochrane CENTRAL were searched to identify relevant studies.
Current evidence supports that the combination of infliximab and thiopurines is more effective than monotherapy in inducing and maintaining remission in IBD. Data on the combination of other biological agents such as adalimumab, vedolizumab, ustekinumab, and immunosuppressors is lacking or showed conflicting results. Vedolizumab seems a potentially effective maintenance regimen after calcineurin inhibitors-based rescue therapy in acute severe ulcerative colitis (ASUC). Dual Targeted Therapy, which is the combination of two biological agents and/or small molecules, might be a reasonable choice in patients with concomitant IBD and extraintestinal manifestations, or in patients with medical-refractory IBD who lack valid alternatives. Some safety concerns such as adverse events (serious and opportunistic infections) and malignancies (lymphoma and nonmelanoma skin cancer) were raised in combination therapies.
Combination therapies seem to be effective in some IBD patients such as refractory IBD patients or patients with extraintestinal manifestations, but it might be associated with an increased risk of adverse events and malignancies."
"Immune checkpoint inhibitors (ICI) have become a pillar of cancer therapy for many people around the world. However, up to two-thirds of all patients undergoing ICI therapy will have immune-related adverse events (irAEs), including immune-checkpoint inhibitor colitis (ICIC). This review summarizes the most valuable and currently available information about the mechanism, diagnosis, and management of ICIC.
Recent findings include several developments on the leading theories for the mechanisms of ICIC such as the role of the gut microbiome. New emerging therapy strategies include tocilizumab, ustekinumab, mycophenolate mofetil, and calcineurin inhibitors.
The occurrence of irAEs remains a limiting factor for the use of immunotherapy in cancer treatment. Prompt diagnosis of ICIC with endoscopy and histologic confirmation can lead to early utilization of known effective treatments such as corticosteroids, infliximab, vedolizumab, and other emerging therapy strategies. We summarize the key points of this review article in our abstract video, Supplemental Digital Content 1, http://links.lww.com/COG/A44."
"Colorectal cancer (CRC) is among the best examples for depicting the relationship between inflammation and cancer. The introduction of new therapeutics targeting inflammatory mediators showed a marked decrease in the overall risk of CRC, although their chemopreventive potential is still debated. Specifically, a monoclonal antibody that blocks tumor necrosis factor (TNF), infliximab, increases CRC risk in inflammatory bowel disease patients. To address the axis between TNF and CRC development and progression, we depleted the "
"Takayasu arteritis (TA) is a large vessel vasculitis rarely reported in children and infants. Most articles on pediatric TA have not focused on infants. We present the largest case series of infantile TA aiming to identify its demographic and clinical characteristics and compare them with existing data on older children.
We conducted an international multicentre retrospective cohort study. Epidemiological and clinical data were collected from patients' charts from six rheumatology centers. All patients met both the EULAR/PReS 2008 criteria and the 1990 ACR/EULAR criteria and were diagnosed with TA at age <5 years.
Twelve patients were included (50% female). Median age of symptom onset was 11 months, with a diagnostic delay of 4 months. The most common symptoms at presentation were hypertension, blood pressure differences between limbs, and fever. The most commonly involved arteries were the abdominal aorta and renal artery. Medications included steroids, conventional and biological disease-modifying antirheumatic drugs, and other immunosuppressive therapies. Half of the patients received biologic agents of which infliximab had the highest complete remission rate (40%). Other medications resulting in complete remission were cyclophosphamide (40%) and methotrexate (38%). Invasive procedures were required for 58% of patients. The most common complications were cardiac (50%), stroke (42%), and serious infections (33%). No patients died.
This study presents the largest series of infantile TA. Compared with other reported series on older children, infants with TA have more severe disease and were more likely to receive biologic agents, develop complications, and require invasive interventions."
"Only one head-to-head comparison of advanced treatments in moderately to severely active ulcerative colitis (UC) has been published; therefore, there remains a need for further comparisons.
The relative treatment effects of filgotinib and adalimumab, golimumab, infliximab, tofacitinib, ustekinumab and vedolizumab were estimated using a network meta-analysis (NMA).
Systematically identified studies (MEDLINE, Embase and Cochrane Library; searched: inception-May 2019, updated November 2020) investigating treatments for moderately to severely active UC were re-evaluated for inclusion in a Bayesian NMA (fixed-effects model). Relative treatment effects were estimated using different permutations of patient population (biologic-naïve or biologic-experienced), treatment phase (induction or maintenance) and outcomes (MCS response/remission or endoscopic mucosal healing).
Seventeen trials (13 induction; 9 maintenance) were included in the NMA; 8 treatment networks were constructed. Most targeted therapies were superior to placebo in terms of MCS response/remission and endoscopic mucosal healing; filgotinib 200 mg was similar to most other treatments. Infliximab 5 mg/kg was superior to filgotinib 200 mg (biologic-naïve; induction) for MCS response/remission (mean relative effect, 0.34 [95% credible interval: 0.05, 0.62]). Filgotinib 200 mg was superior to adalimumab 160/80/40 mg for MCS response/remission (biologic-experienced; induction; - 0.75 [- 1.16, - 0.35]), and endoscopic mucosal healing (biologic-naïve; maintenance; - 0.90 [- 1.89, - 0.01]); and to golimumab 50 mg every 4 weeks (biologic-naïve; maintenance; - 0.46 [- 0.94, 0]) for MCS response/remission.
The current treatment landscape benefits patients with moderately to severely active UC, improving key outcomes; filgotinib 200 mg was similar to current standard of care in most outcomes."
"Cartilage tissue engineering is a promising strategy for treating cartilage damage. Matrix formation by adipose-derived stem cells (ADSCs), which are one type of seed cell used for cartilage tissue engineering, decreases in the late stage of induced chondrogenic differentiation 
To improve the chondrogenic differentiation efficiency of ADSCs 
Tumor necrosis factor-alpha (TNF-α) inhibitor was added to chondrogenic culture medium, and then Western blotting, enzyme linked immunosorbent assay, immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B (NF-κB) signaling pathway.
In this study, we found that the levels of TNF-α and matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs. TNF-α then bound to its receptor and activated the NF-κB pathway, leading to a decrease in cartilage matrix synthesis and secretion. Blocking TNF-α with its inhibitors etanercept (1 μg/mL) or infliximab (10 μg/mL) significantly restored matrix formation.
Therefore, this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs, and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage."
"Inflammatory bowel diseases (IBDs) are chronic diseases that demand continuous interaction between patients and healthcare providers. Quality of care (QoC) is a factor that contributes to a patient's adherence to treatment and its success.
To evaluate QoC in patients from a single IBD reference center.
This cross-sectional study included 133 patients from a single Brazilian IBD public health center. QoC was evaluated through the QoC Through the Eyes of Patients with IBD (QUOTE-IBD) questionnaire (based on patient perspectives), which measures eight dimensions of care. We compared QoC among patients with Crohn's disease and ulcerative colitis and analyzed the clinical and psychological factors associated with QoC satisfaction. Clinical evaluations assessed disease characteristics, quality of life, anxiety, and depression levels.
Sixty-nine patients with Crohn's disease and 64 with ulcerative colitis were interviewed. The mean age was 37.26 years ± 13.05 years, and 63.91% of the patients were women. The mean duration of the disease was 8.44 years ± 7.59 years, where most patients were in remission (70.31% of patients with ulcerative colitis and 62.32% with Crohn's disease). The total QoC score of the sample was 8.61 years ± 1.31 points, indicating that the QoC provided by the center was unsatisfactory. According to univariate logistic regression, patients with Crohn's disease had higher satisfaction rates than those with ulcerative colitis [odds ratio (OR): 2.746; 95% confidence interval (CI): 1.360-5.541; 
Patients from the IBD public center reported good doctor-patient relationships, but had problems related to the healthcare structure. Evaluation of healthcare centers is of paramount to improve QoC for the patients involved."
"Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), are chronic, systemic autoimmune diseases. As the incidence of IBD rapidly increases in Asia, increasing attention has been paid to developing additional treatment strategies. Presently, the end point of therapy is achieving clinical and endoscopic remission through the blockade of inflammatory cascades. Recent studies have shown that monoclonal antibodies (mAbs) use for precise molecular targeting of inflammatory pathways has a promising effect on IBD, especially moderate-to-severe CD and UC. Since the 1997 report on the use of infliximab (a monoclonal antibody against tumor necrosis factor alpha [TNF-α]) in patients with CD, mAbs have expanded therapeutic options and have also complicated initial management options and subsequent treatment. This review comprehensively summarizes the clinical reports and studies related to the use of mAbs for the treatment of IBD in Asian countries and regions in recent years thus demonstrating the current status of mAbs use in Asia. In addition, the differences in the use of mAbs for the treatment of IBD between the Asia and the West are expounded. Ultimately, it is hoped that this review will provide new insights and a scientific basis for the clinical application of mAbs."
"Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection.
CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual.
Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p<0·0001), BA.1 (107·3 [86·40-133·2] vs 648·9 [523·5-804·5]; p<0·0001), and BA.4/5 (40·63 [31·99-51·60] vs 223·0 [183·1-271·4]; p<0·0001) variants. Breakthrough infection was significantly more frequent in patients treated with infliximab (119 [13·7%; 95% CI 11·5-16·2] of 871) than in those treated with vedolizumab (29 [7·0% [4·8-10·0] of 417; p=0·00040). Cox proportional hazards models of time to breakthrough infection after the third dose of vaccine showed infliximab treatment to be associated with a higher hazard risk than treatment with vedolizumab (hazard ratio [HR] 1·71 [95% CI 1·08-2·71]; p=0·022). Among participants who had a breakthrough infection, we found that higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and, hence, a longer time to breakthrough infection (HR 0·87 [0·79-0·95]; p=0·0028).
Our findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies.
Royal Devon University Healthcare NHS Foundation Trust; Hull University Teaching Hospital NHS Trust; NIHR Imperial Biomedical Research Centre; Crohn's and Colitis UK; Guts UK; National Core Studies Immunity Programme, UK Research and Innovation; and unrestricted educational grants from F Hoffmann-La Roche, Biogen, Celltrion Healthcare, Takeda, and Galapagos."
"This study evaluated the existence of anti-drug antibodies (ADAs) before and 52 weeks after switching from intravenous infliximab (IFX) to intravenous CT-P13 in patients with rheumatoid arthritis (RA).
We performed a prospective observational study. Twenty-eight patients (7 males and 21 females) received intravenous CT-P13 after intravenous IFX, and the clinical data were collected from medical records. Rheumatoid factor (RF) and anti-CCP antibody were examined at baseline. At baseline and 52 weeks after the start of CT-P13 treatment, the Disease Activity Score based on the 28-joint count and the levels of C-reactive protein, matrix metalloproteinase-3, and ADA, as well as the erythrocyte sedimentation rate were evaluated. ADAs were measured using an enzyme-linked immunosorbent assay kit.
Seven (25%) and 6 (21.4%) cases were positive for ADAs at baseline and 52 weeks after, respectively. One case became newly positive for ADAs at week 52. Two of the ADA-positive cases became ADA-negative 52 weeks after. The ADA-positive group showed significantly higher RF values at baseline than the ADA-negative group (p = 0.03). No difference was observed between the ADA-positive group and the ADA-negative group regarding other clinical parameters.
The positive rate of ADAs did not increase after switching from intravenous IFX to intravenous CT-P13. Among the patients with ADAs, a high level of RF was observed at baseline."
"Determining the relative cost-effectiveness between advanced therapeutic options for ulcerative colitis (UC) may optimize resource utilization. We evaluated total cost per response, cost per remission, and cost of safety events for patients with moderately-to-severely active UC after 52 weeks of treatment with advanced therapies at standard dosing.
An analytic model was developed to estimate costs from the US healthcare system perspective associated with achieving efficacy outcomes and managing safety outcomes for advanced therapies approved for the treatment of UC. Numbers needed to treat (NNT) for response and remission, and numbers needed to harm (NNH) for serious adverse events (SAEs) and serious infections (SIs) were derived from a network meta-analysis of pivotal trials. NNT for induction and maintenance were combined with drug regimen costs to calculate cost per clinical remission. Cost of managing AEs was calculated using NNH for safety outcomes and published costs of treating respective AEs.
Costs per remission were $205,240, $249,417, $267,463, $365,050, $579,622, $750,200, and $787,998 for tofacitinib 10 mg, tofacitinib 5 mg, infliximab, vedolizumab, golimumab, adalimumab, and ustekinumab, respectively. Incremental costs of SAEs and SIs collectively were $136,390, $90,333, $31,888, $31,061, $20,049, $12,059, and $0 for tofacitinib 5 mg, golimumab, adalimumab, tofacitinib 10 mg, infliximab, ustekinumab, and vedolizumab (reference), respectively.
Tofacitinib was associated with the lowest cost per response and cost per remission, while vedolizumab had the lowest costs related to SAEs and SIs. Balancing efficacy versus safety is important when evaluating the costs associated with treatment of moderate-to-severe UC."
"This study aimed to assess the cost-effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) for treating patients with psoriatic arthritis who failed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).
A decision tree and Markov model were constructed to capture long-term costs and outcomes from a societal perspective. Patients with psoriatic arthritis who failed 2 previous csDMARDs were modeled over a 3-month cycle with a lifetime horizon. Clinical probabilities were derived from a published meta-analysis. Prices of bDMARDs were proposed by pharmaceutical companies. Other costs and utilities were based on data in Thailand. All costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratio and a series of sensitivity analyses were performed.
All 11 bDMARDs (3 infliximab originator and biosimilars, 2 etanercept originator and biosimilar, golimumab, 2 secukinumab 150 mg and 300 mg, 3 adalimumab biosimilars) gained better quality-adjusted life-years (QALYs) with more costly than csDMARDs. Infliximab had the highest QALYs compared with other bDMARDs. Only secukinumab 150 mg showed the incremental cost-effectiveness ratio below the Thai threshold of 5152 US dollars per QALY. Cost of bDMARDs was the most influential factor.
At the current price, secukinumab 150 mg shows the value for money in the Thai context. Price negotiation is of great importance for other bDMARDs."
"Along with the rising prevalence of inflammatory bowel disease (IBD) [Crohn's disease (CD) and ulcerative colitis (UC)], biological therapies need an update/insight.
This review included randomized controlled trials (RCTs) from PubMed database (2000-October 2022) of approved biologics and small molecules with primary outcome analysis on efficacy (clinical response/remission/mucosal healing) and/or adverse events (AEs). Considered for this review under biologics classes are TNF-α inhibitors, leukocyte trafficking inhibitors, and anti IL-12/IL-23; and under small molecules are Janus-kinase inhibitors, and sphingosine-1-phosphate receptor modulators.
In CD, clinical response and remission were better with tofacitinib (61.23%) and infliximab (44.86%), respectively, in the induction phase, and these were better with ustekinumab in the maintenance phase. In UC, the maximum rate of response, remission, and mucosal healing were obtained with infliximab during the induction phase (67.49%, 35.99%, and 60.25%, respectively). During the maintenance phase, response rate was better with ustekinumab, but remission and mucosal healing were better with vedolizumab. The combined percentage of AEs was highest with infliximab (174.45%) and least with ozanimod (23.04%), and most commonly belonged to the 'infection and infestation system organ class (SOC).' These efficacy and safety analyses will help in the optimization of biologic treatment in IBD."
"During the COVID-19 pandemic, the focus of many health care systems shifted in order to prioritize and allocate resources toward treating those affected by COVID-19. What this has meant for other patient populations remains unclear. We aimed to determine if there have been changes to acute care access for patients with inflammatory bowel disease (IBD) during the COVID-19 pandemic.
A retrospective cohort study was performed in IBD patients seen during (March 1, 2020 to August 31, 2020) and before (March 1, 2019 to August 31, 2019) the COVID-19 pandemic. IBD-related emergency room (ER) access, hospitalization, inpatient care and follow-up and post-discharge ER access were assessed.
A total of 1229 participants were included. A higher proportion of patients accessed ER during the pandemic (44.6% versus 37.2%, 
These data highlight the need for ER services and hospitalization amongst IBD patients during the COVID-19 pandemic. This suggests that a return to pre-pandemic IBD care infrastructure is needed to mitigate the need for acute care access."
"Chronic inflammatory disorders after ileal pouch-anal anastomosis (IPAA) surgery are common. These include chronic pouchitis (CP), Crohn's disease (CD) of the pouch, prepouch ileitis (PI) and rectal cuff inflammation (cuffitis). The aim of this study was to evaluate the efficacy of biologic therapies in treating these disorders.
Systematic review of all published studies from inception to August 1, 2021 was performed to investigate the efficacy of biologic therapies for post-IPAA chronic inflammatory disorders. The primary outcome was the efficacy of biologic therapies in achieving complete clinical response in patients with IPAA.
A total of 26 studies were identified including 741 patients. Using a random-effect model, the efficacy of infliximab in achieving complete clinical response in patients with CP was 51% (95% CI, 36 to 66), whereas the efficacy of adalimumab was 47% (95% CI, 31 to 64). The efficacies of ustekinumab and vedolizumab were 41% (95% CI, 06 to 88) and 63% (95% CI, 35 to 84), respectively. In patients with CD/PI, the efficacy of infliximab in achieving complete clinical response was 52% (95% CI, 33 to 71), whereas the efficacy of adalimumab was 51% (95% CI, 40 to 61). The efficacies of ustekinumab and vedolizumab were 42% (95% CI, 06 to 90) and 67% (95% CI, 38 to 87), respectively. Only one study involved patients with cuffitis.
Ustekinumab, infliximab, vedolizumab and adalimumab are effective in achieving complete clinical response in post-IPAA surgery chronic inflammatory disorders. More studies are needed to determine the efficacy of biologics in cuffitis."
"Herein we investigate the difference between Kawasaki disease (KD) with and without a recent history of SARS-CoV-2 infection.
We compared the clinical characteristics of patients with KD during the SARS-CoV-2 pandemic in a single children's hospital in Korea. Fifty-two patients were enrolled and divided into group 1 (with a history of COVID-19, 
The median age of patients was significantly higher in group 1 than in group 2 (53 months [IQR, 24-81] vs. 15 months [IQR, 6-33], 
Post-COVID KD showed a stronger inflammatory response than KD-alone, with no differences in cardiac complications."
"Monoclonal antibodies against tumor necrosis factor-alpha (TNF-α) have been used successfully in the treatment of sarcoidosis, but optimal duration of their use is unclear. Published studies have consistently suggested that withdrawal of therapy typically results in prompt disease relapse. The aim of this study is to identify and characterize patients with sarcoidosis in whom medication-free disease remissions were induced and sustained following treatment with and subsequent discontinuation of anti-TNF-α antibodies.
A retrospective chart review was conducted to identify patients satisfying three criteria: (1) histopathological documentation of sarcoidosis; (2) disease remission induced by anti-TNF-α antibodies, since discontinued; and (3) subsequent maintained clinical, radiological, and laboratory remission for at least one year without ongoing immunomodulatory medications.
Eight patients whose sarcoidosis remained in medication-free remissions were identified. The duration of remissions ranged from 22 to 132 months. All patients had previously had inadequate response to corticosteroid therapy and at least one steroid-sparing agent, prompting the use of anti-TNF-α antibodies. Before anti-TNF-α therapy was discontinued, all eight patients had been able to remain off systemic corticosteroid therapy for at least a year (range 12-130 months).
These observations suggest that in select sarcoidosis patients, anti-TNF-α antibodies may induce prolonged medication-free remissions. The sustained capacity to remain off corticosteroids during anti-TNF-α therapy may be a favorable prognostic indicator for maintained disease remission. These findings may help to develop principles for optimal utilization of these agents and to shed light onto the potential pathogenic role of TNF-α in this disease."
"Although biological agents have revolutionized the management of inflammatory bowel diseases (IBDs), a significant proportion of patients show primary non-response or develop secondary loss of response. Therapeutic drug monitoring (TDM) is advocated to maintain the efficacy of biologic agents. Reactive TDM can rationalize the management of primary non-response and secondary loss of response and has shown to be more cost-effective compared with empiric dose escalation. Proactive TDM is shown to increase clinical remission and the durability of the response to a biologic agent. However, the efficacy of proactive and reactive TDM has been questioned in recent studies and meta-analyses. Hence, we need a different approach to TDM, which addresses inflammatory burden, the individual patient, and disease factors. Bayesian approaches, which use population pharmacokinetic models, enable clinicians to make better use of TDM for dose adjustment. With rapid improvement in computer technology, these Bayesian model-based software packages are now available for clinical use. Bayesian dashboard systems allow clinicians to apply model-based dosing to understand an individual's pharmacokinetics and achieve a target serum drug concentration. The model is updated using previously measured drug concentrations and relevant patient factors, such as body weight, C-reactive protein, and serum albumin concentration, to maintain effective drug concentrations in the serum. Initial studies have found utility for the Bayesian approach in induction and maintenance, in adult and pediatric patients, in clinical trials, and in real-life situations for patients with IBD treated with infliximab. This needs confirmation in larger studies. This article reviews the Bayesian approach to therapeutic drug monitoring in IBD."
"Golimumab (GLM) is an anti-tumor necrosis factor (TNF)-α antibody preparation known to be less immunogenic than infliximab (IFX) or adalimumab. Few reports on GLM in pediatric patients with ulcerative colitis (UC) are available. This study aimed to review the long-term durability and safety of GLM in a pediatric center.
The medical records of 17 pediatric patients (eight boys and nine girls) who received GLM at the National Center for Child Health and Development were retrospectively reviewed.
The median age at GLM initiation was 13.9 (interquartile range 12.0-16.3) years. Fourteen patients had pancolitis, and 11 had severe disease (pediatric ulcerative colitis activity index ≥65). Ten patients were biologic-naïve, and 50% achieved corticosteroid-free remission at week 54. Two patients discontinued prior anti-TNF-α agents because of adverse events during remission. Both showed responses to GLM without unfavorable events through week 54. However, the efficacy of GLM in patients who showed primary nonresponse or loss of response to IFX was limited. Four of the five patients showed non-response at week 54. Patients with severe disease had significantly lower corticosteroid-free remission rate at week 54 than those without severe disease. No severe adverse events were observed during the study period.
GLM appears to be safe and useful for pediatric patients with UC. Patients with mild to moderate disease who responded to but had some adverse events with prior biologics may be good candidates for GLM. Its safety and low immunogenicity profile serve as favorable options for selected children with UC."
"A 23-year-old man diagnosed with Crohn's disease (CD) was treated with infliximab. He developed new-onset sore throat and dysphagia during admission, and nasopharyngoscopy revealed epiglottic ulceration. Laryngeal ulceration was considered as an extraintestinal manifestation of CD owing to treatment failure with antibiotics and hydrocortisone. This strongly suggested that laryngeal ulceration was a complication of CD because of the rapid improvement in the symptoms and lesions after prednisolone administration. Furthermore, this treatment process demonstrated the superior anti-inflammatory effect of prednisolone over that of hydrocortisone and supported the assumption of inflammation related to CD."
"Crohn's disease (CD) is a chronic inflammatory condition affecting any part of the gastrointestinal tract. Current therapies involve pharmacological efforts to dampen inflammation. Biologics are recommended for patients with steroid-dependent or steroid-refractory disease; however, little is known about current biologic use in real-world settings in Japan.
This observational, longitudinal, cohort study utilized the Japan Medical Data Center (JMDC) database to analyze claims data of patients who were prescribed ≥1 biologic (adalimumab, infliximab, or ustekinumab) following a new CD diagnosis made between January 2009 and January 2019. We primarily assessed the type of first-line treatment prescribed within 6 months of a patient's first CD diagnosis.
Of the 1,346 eligible patients, the most common prescriptions were 5-aminosalicylic acid (5-ASA) monotherapy (26.8%), 5-ASA plus biologic combination (26.3%), and biologic monotherapy (12.9%). First-line biologics were prescribed within 6 months of initial CD diagnosis in 61.1% of patients, either alone or in combination with other therapies. As an individual first-line treatment, the proportion of patients receiving prescriptions of infliximab was high (66.3%) and steroids, low (1.3%). Patients who had a procedure to inspect the small intestine, such as endoscopy (n = 508), were mostly treated with a nonbiologic therapy (74.8%), whereas those who had not (n = 838), mostly received biologics (alone or in combination, 82.8%) as a first-line treatment.
In this study, we discovered the typical treatment pattern of patients with CD who received biologics and are registered in the JMDC database in Japan. Biologics were commonly used in the early phase of CD treatment. Treatment with traditional approaches such as steroids and nutritional therapy with evaluation for small intestine lesions, before turning to the use of biologics, may be prudent for achieving optimal outcomes."
"Monoclonal antibodies (mAbs) represent a dynamic class of biopharmaceutical products, as evidenced by an increasing number of market authorizations for mAb innovator and biosimilar products. Stability studies are commonly performed during product development, for instance, to exclude unstable molecules, optimize the formulation or determine the storage limit. Such studies are time-consuming, especially for mAbs, because of their structural complexity which requires multiple analytical techniques to achieve a detailed characterization. We report the implementation of a novel methodology based on the accelerated stability assessment program (ASAP) in order to model the long-term stability of mAbs in relation to different structural aspects. Stability studies of innovator infliximab and two different biosimilars were performed using forced degradation conditions alongside in-use administration conditions in order to investigate their similarity regarding stability. Thus, characterization of post-translational modifications was achieved using liquid-chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and the formation of aggregates and free chain fragments was characterized using size-exclusion chromatography-multi-angle light scattering (SEC-MALS-UV/RI) analysis. Consequently, ASAP models were investigated with regard to free chain fragmentation of mAbs concomitantly with N57 deamidation, located in the hypervariable region. Comparison of ASAP models and the long-term stability data from samples stored in intravenous bags demonstrated a relevant correlation, indicating the stability of the mAbs. The developed methodology highlighted the particularities of ASAP modeling for mAbs and demonstrated the possibility to independently consider the different types of degradation pathways in order to provide accurate and appropriate prediction of the long-term stability of this type of biomolecule."
"Limited information exists regarding drug survival of biologics among psoriasis patients in Malaysia. This study aimed to determine the drug survival of biologics in Malaysian psoriasis patients, the reasons for drug discontinuation and to identify the predictor of drug survival.
A retrospective review of case notes on adult psoriasis patients treated with biologics in Hospital Sultanah Aminah Johor Bahru Malaysia, between January 2006 and December 2020. Drug survival was analysed using the Kaplan-Meier method.
By December 2020, 100 patients with 154 treatment courses of biologics were included in the study. Male to female ratio was 1:1. The mean age at onset was 31.36 ± 11.72 years. Ustekinumab was the most frequently prescribed biologics (39%), followed by adalimumab (29.2%), secukinumab (14.9%), etanercept (13%), and infliximab (3.2%). Overall median drug survival for biologics was 25 months (interquartile range [IQR]= 12.0-.0). The median drug survival for ustekinumab was 35 months (IQR, 12-93); followed by 25 months (IQR, 12.0-), 18 months (IQR, 7-85), 17 months (IQR, 11-43), and 8 months (IQR, 1-10) for secukinumab, adalimumab, etanercept, and infliximab, respectively. The main reason for drug discontinuation was loss of efficacy (26%), inadequate funding (14.3%), loss to follow-up (10.4%), adverse events (4.5%), and patients' request (1.3%).
Our study shows ustekinumab has the best long-term drug survival among biologics in Malaysian patients with psoriasis in real-life setting. Further study is required to evaluate the long-term drug survival for newer biologics."
"To evaluate the efficacy of infliximab (IFX, 5-10 mg/kg) (Group 1) and tocilizumab (TCZ, 4-8 mg/kg) (Group 2) infusions in non-infectious retinal vasculitis (RV) using Angiographic Scoring for the Uveitis Working Group fluorescein angiography (FA) scoring system.
Records of 14 patients (24 eyes) in Group 1 and 8 patients (11 eyes) in Group 2 were retrospectively evaluated to assess visual acuity (VA), anterior chamber cell and flare, vitreous haze, central subfield thickness (CST), and FA scoring at baseline and 6 months of follow-up. The measurements were employed to grade in each group.
In Group 1 and 2, respectively, there was no underlying disease in 9 (60%) and 3 (42.9%) patients. Three (42.9%) patients in Group 2 had juvenile idiopathic arthritis (JIA) as the most common identified cause. Mean improvement in VA (log MAR) and CST were 0.04 ± 0.14 and 40.3 ± 78.5 µm in Group 1; 0.04 ± 0.09 and 47.3 ± 82.3 µm in Group 2, respectively. Mean FA scores were significantly reduced from 12.4 ± 5.2 and 11.6 ± 4.4 at baseline to 6.4 ± 5.0 and 5.8 ± 3.9 at 6-month in Group 1 and 2, respectively. In Group 2, 9 eyes of 6 patients (75%) had the history of IFX use prior to TCZ initiation. There was no significant safety concern requiring treatment discontinuation during the follow-up in either group.
IFX and TCZ infusions showed statistically significant improvement of non-infectious RV as shown by ASUWOG FA Scoring System. TCZ, as well as IFX, appeared to be effective treatment options for non-infectious RV."
"To clarify the differences in MRI findings between rheumatoid arthritis (RA) patients treated with Certolizumab pegol (CZP) and Infliximab (IFX).
The study included RA patients who received CZP or IFX, and were examined with low-field MRI (compacTscan; cMRI) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumor necrosis factor (TNF) inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow edema (BME), and synovitis.
Ten cases in CZP and 18 cases in IFX group were compared. The biologic DMARDs-naïve rate in the IFX group was significantly higher than in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group there was no significant change. Synovitis score was significantly decreased in both groups after 6 months.
The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX."
"Rheumatoid vasculitis (RV) is a rare but potentially devastating complication of rheumatoid arthritis (RA). It typically occurs in patients with extra-articular manifestations. Here we reported a case of PUK with nodular episcleritis and pulmonary nodules that occurred in the same patient without joint involvement.
A 43-year-old Chinese woman, exhibited a partial crescent-shaped marginal corneal ulcer in the right eye at admission and the ulcer developed rapidly into nearly 360-degree ulcers in both eyes within one week. Nodular episcleritis was observed in the right eye. Conjunctival biopsy revealed vasculitis. Her rheumatoid factor (RF) and anti-cyclic citrullinated protein antibody were positive, while anti-neutrophilic cytoplasmic antibody (c-ANCA) and anti-protease 3 were negative. Pulmonary nodules were found, without joint involvement. The ocular condition did not relieve under the topical and systemic use of corticosteroids, or under other immunosuppressive agents until the infliximab therapy. PUK recurrence was observed after the discontinuation of infliximab.
Rapidly deteriorated PUK with nodular episcleritis and pulmonary nodules occurred in the same patient is a special case of RA without joint involvement. This case reinforces the concept that RV may be the initial sign of RA. Infliximab can be used to prevent further progress of RA-related PUK in some refractory cases."
"The use of immune-modifying biological agents has markedly changed the clinical course and the management of Inflammatory bowel diseases (IBDs). Active post-marketing surveillance programs are fundamental to early recognize expected and unexpected adverse events (AEs), representing a powerful tool to better determine the safety profiles of biologics in a real-world setting.
This study aimed to identify the occurrence of AEs and therapeutic failures linked to biological drugs used in gastroenterology units during a prospective pharmacovigilance program in Southern Italy. Patients affected by IBDs and treated with a biologic agent, from 1 January 2019, to 31 December 2021 (study period) in three gastroenterology units were enrolled.
Overall, 358 patients with a diagnosis of active Crohn's disease or ulcerative colitis satisfying inclusion criteria have been enrolled. Infliximab (IFX) was the most administered drug at the index date (214; 59.8%), followed by Adalimumab (ADA; 89; 24.9%), Golimumab (GOL; 37; 10.3%), Vedolizumab (VDZ; 17; 4.7%) and Ustekimumab (UST; 1; 0.3%). Seventy-three patients (20.4%) experienced at least one AE, while 62 patients (17.3%) had therapeutic ineffectiveness. No serious AEs were reported in the follow-up period in the enrolled patients. AEs have been described with IFX (50/214; 
Based on the low rate of AEs observed and withdrawal from treatment, our data seem to corroborate the favorable beneficial/risk profile of biologics for IBDs."
"Surgery remains an important treatment modality in the multidisciplinary management of patients with Crohn's disease (CD). To illustrate the recent advances in the management of postoperative CD we outline the contemporary approach to treatment: diagnosing disease recurrence using endoscopy or noninvasive methods and risk stratification underlying decisions to institute treatment. Endoscopic scoring indices are being refined to guide treatment decisions by accurately estimating the risk of recurrence based on endoscopic appearance. The original Rutgeerts score has been modified to separate anastomotic lesions from lesions in the neoterminal ileum. Two further indices, the REMIND score and the POCER index, were recently developed with the same intention. Noninvasive monitoring for recurrence using a method with high negative predictive value has the potential to simplify management algorithms and only perform ileocolonoscopy in a subset of patients. Fecal calprotectin, intestinal ultrasound, and magnetic resonance enterography are all being evaluated for this purpose. The use of infliximab for the prevention of postoperative recurrence is well supported by data, but management decisions are fraught with uncertainty for patients with previous exposure to biologics. Data on the use of ustekinumab and vedolizumab for postoperative CD are emerging, but controlled studies are lacking."
"To describe the clinical course and management of a patient with bilateral retinal vasculitis associated with cold agglutinin disease (CAD) treated with obinutuzumab and infliximab.
A 69-year-old Hispanic woman was referred to a tertiary Uveitis Clinic with progressively worsening blurry vision, right eye (OD) worse than left eye (OS). Past ocular history was significant for epiretinal membranes in both eyes (OU). Past medical history was notable for non-specific joint disease, primarily affecting her knees bilaterally, and pulmonary symptoms (e.g., dyspnea, productive cough) of unclear etiologies one year before presentation. She had been evaluated by rheumatologists and pulmonologists and was placed on low doses of prednisone and methotrexate. Upon examination, her visual acuity was 20/40 in OD and 20/25 in OS. Anterior segment exam was unremarkable with no cell or flare in OU. Dilated fundus examination was notable for 0.5+ vitreous haze in OU and mild vessel attenuation in OU. Wide-angle fluorescein angiography (FA) revealed mild bilateral periphery peri-vasculature leakage in OU. Initial blood evaluations revealed decreased hematocrit, and positive anti-nuclear antibody. Her peripheral smear disclosed 3+ agglutination. She was initially treated with mycophenolate mofetil 1000 mg twice daily and prednisone 20 mg then referred to hematology. Further work up revealed high-titer cold agglutinin and positive thermal amplitude screen at 30 °C. Bone marrow examination demonstrated a chronic lymphocytic leukemia (CLL)-like monoclonal B-cell lymphocytosis. Anti-CD20 monoclonal antibody therapy with obinutuzumab was started in an effort to treat the underlying CLL clone and address the associated ocular vasculitis related to CAD. Three months later, after eight cycles of obinutuzumab, the patient's best- corrected visual acuity (BCVA) continued to be stable at 20/30 in OD and 20/20 in OS. However, FA showed persistent diffuse perivascular leakage. Intravenous infliximab with concurrent intravenous methylprednisolone infusions were started. After two cycles of treatment, FA showed significantly improved perivascular leakage. Visual acuity remained stable at 20/25 in OU.
Ocular involvement in CAD is rare. The index case is the first report of retinal vasculitis in a patient with CAD. Our report not only describes the unique course of CAD-related retinal vasculitis, but also introduces and underscores a successful therapeutic plan."
"A delivery system consisting of bone marrow mesenchymal stem cells (MSCs) loaded with polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles (SPIONs) was constructed to treat a rat model of cisplatin (Cis)-induced nephrotoxicity with 1/10 of the common dose of anti-tumor necrosis factor-alpha (TNF-α) antibodies (infliximab).
Morphology, size, crystallinity, molecular structure, and magnetic properties of uncoated and PEG-coated SPIONs were analyzed. A delivery system consisting of MSCs containing infliximab-labeled PEG-coated SPIONs (Infliximab-PEG-SPIONs-MSCs) was generated and optimized before treatment. Fifty female Wistar rats were divided into five equal groups: Group 1: Untreated control; Group 2 (Cis): Rats were administered Cis through intraperitoneal (i.p.) injection (8 mg/kg) once a week for 4 weeks; Group 3 (Infliximab): Rats were injected once with infliximab (5 mg/kg), i.p. 3 days before Cis administration; Group 4 (Cis + MSCs): Rats were injected with Cis followed by an injection of 2 × 10
With the support of the constructed MSCs-SPIONs infliximab delivery system, it will be possible to track and monitor cell homing after therapeutic application. This infliximab-loading system may help overcome some challenges regarding drug delivery to the target organ, optimize therapeutics' efficacy, and reduce the dose. The outcomes of the current study provide a better understanding of the potential of combining MSCs and antibodies-linked nanoparticles for the treatment of nephrotoxicity. However, further investigation is recommended using different types of other drugs. For new approaches development, we should evaluate whether existing toxicity analysis and risk evaluation strategies are reliable and enough for the variety and complexity of nanoparticles."
"Hydroxychloroquine is effective for treating a number of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine is generally safe and may be prescribed to pregnant women. Although current guidelines recommend initiating hydroxychloroquine when considering pregnancy, the drug can cause adverse effects such as acute generalized exanthematous pustulosis, which should be carefully evaluated. A 30-year-old pregnant woman with systemic lupus erythematosus at 16+5 gestational weeks was referred to our tertiary centre for persistent proteinuria and alopecia. Tacrolimus was initiated and the dose of prednisone was increased. At 20+3 weeks of gestation, hydroxychloroquine was administered to allow for a dose reduction of prednisolone. Proteinuria gradually improved as the pregnancy course stabilized. At 27+1 weeks of gestation, generalized pustular exanthema developed, presumably due to hydroxychloroquine. After analysis of the clinical course and skin lesions, she was considered to have either acute generalized exanthematous pustulosis or generalized pustular psoriasis. Despite discontinuing hydroxychloroquine, the skin lesions worsened dramatically, and infliximab therapy was required. After one course of infliximab treatment, exanthema gradually subsided. The final diagnosis was acute generalized exanthematous pustulosis, based on the clinical course and pathological findings. At 30 weeks, the pyothorax developed because of the pyogenic skin lesion and the compromised immune system, and long-term antibiotic therapy was required until 32+4 weeks, after which, she underwent caesarean section. Although introducing hydroxychloroquine is occasionally necessary during pregnancy, it is preferable to initiate hydroxychloroquine in the preconception period and not after pregnancy because of the possible adverse effect which can alter perinatal prognosis. Rheumatologists should consider the potential risks of hydroxychloroquine."
"Thyroid-associated ophthalmopathy (TAO), also known as thyroid eye disease (TED) or Graves' orbitopathy (GO), is a complex autoimmune condition causing visual impairment, disfigurement, and harm to patients' physical and mental health. The pathogenesis of TAO has not been fully elucidated, and the mainstream view is that coantigens shared by the thyroid and orbit trigger remodeling of extraocular muscles and orbital connective tissues through an inflammatory response. In recent years, cytokines and the immune responses they mediate have been crucial in disease progression, and currently, common evidence has shown that drugs targeting cytokines, such as tocilizumab, infliximab, and adalimumab, may be novel targets for therapy. In this review, we summarize the research development of different cytokines in TAO pathogenesis in the hope of discovering new therapeutic targets."
"The propensity for some monoclonal antibodies (mAbs) to aggregate at physiological and manufacturing pH values can prevent their use as therapeutic molecules or delay time to market. Consequently, developability assessments are essential to select optimum candidates, or inform on mitigation strategies to avoid potential late-stage failures. These studies are typically performed in a range of buffer solutions because factors such as pH can dramatically alter the aggregation propensity of the test mAbs (up to 100-fold in extreme cases). A computational method capable of robustly predicting the aggregation propensity at the pH values of common storage buffers would have substantial value. Here, we describe a mAb aggregation prediction tool (MAPT) that builds on our previously published isotype-dependent, charge-based model of aggregation. We show that the addition of a homology model-derived hydrophobicity descriptor to our electrostatic aggregation model enabled the generation of a robust mAb developability indicator. To contextualize our aggregation scoring system, we analyzed 97 clinical-stage therapeutic mAbs. To further validate our approach, we focused on six mAbs (infliximab, tocilizumab, rituximab, CNTO607, MEDI1912 and MEDI1912_STT) which have been reported to cover a large range of aggregation propensities. The different aggregation propensities of the case study molecules at neutral and slightly acidic pH were correctly predicted, verifying the utility of our computational method."
"Successful uptake of biosimilars in rheumatology is limited by lack of real-world evidence regarding effectiveness of biosimilar-to-biosimilar switching. We investigated infliximab biosimilars CT-P13-to-GP1111 switching among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA).
Observational cohort study from the DANBIO registry. Patients were classified as originator-naïve or originator-experienced. Retention rates of 1-year GP1111 treatment were explored (Kaplan-Meier). We identified baseline factors (at the time of switch) associated with withdrawal of GP1111 (multivariable Cox-regression analyses with HRs including originator treatment history). Changes in subjective and objective measures of disease activity 4 months before and after the switch were assessed in individual patients.
Of 1605 patients (685 RA, 314 PsA and 606 AxSpA, median disease duration was 9 years, 37% in Clinical Disease Activity Index/Ankylosing Spondylitis Disease Activity Score remission), 1171 were originator-naïve. Retention rates at 1-year were 83% (95% CI: 81% to 85%) and 92% (95% CI: 90% to 95%) for the originator-naïve and originator-experienced, respectively. GP1111 retention rates were higher in originator-experienced compared to originator-naïve with RA (HR=0.4 (95% CI: 0.2 to 0.7)) and PsA (HR=0.2 (95% CI: 0.1 to 0.8)), but not significantly for AxSpA: HR=0.6 (95% CI: 0.3 to 1.2). Lower disease activity was associated with higher retention. Changes in disease activity preswitch and postswitch were close to zero.
This real-world observational study of more than 1600 patients with inflammatory arthritis showed high 1-year retention following a nationwide infliximab biosimilar-to-biosimilar switch. Retention was higher in originator-experienced and in patients with low disease activity, suggesting outcomes to be affected by patient-related rather than drug-related factors."
"A 77-year-old patient with ulcerative colitis (UC) was transferred to our department because of worsening bloody diarrhea and abdominal pain, which was consistent with a UC flare. Two days after admission, she complained of cough and high fever. The polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive, and a computed tomography showed pneumonia in the left lobe, consistent with coronavirus disease 2019 (COVID-19) pneumonia. However, frequent bloody diarrhea and abdominal pain due to the UC flare persisted; therefore, an additional immunosuppressive agent needed to be considered. We initiated infliximab biosimilar (IFX-BS), and her abdominal symptoms improved. However, they deteriorated after the second IFX-BS infusion. After confirming that the patient was negative for SARS-CoV-2 by PCR, we administered a combination of azathioprine and IFX-BS. The combination treatment improved her intestinal symptoms without worsening COVID-19 pneumonia. She has remained in remission for over a year since her discharge."
"Recent studies have emphasized the early use of infliximab (IFX) in pediatric patients with inflammatory bowel disease. Standard dosing of 5 mg/kg/dose may not be sufficient to achieve optimal clinical outcomes. The aim of our study was to compare short-term outcomes with standard dosing of IFX to higher, nonstandard dosing of IFX for induction therapy.
Retrospective study of 162 pediatric patients receiving either standard (5-6 mg/kg, n = 90) or nonstandard (>6 mg/kg, n = 72) dosing of IFX during induction was performed. Patient demographics, clinical outcomes, and laboratory data were collected. Need for dose escalation during the first 6 months, combination therapy with immunomodulators, and steroid-free progression were investigated.
Clinical remission rates between the 2 groups were significantly different, with patients receiving nonstandard dosing demonstrating higher rates (58% vs 78%; p = 0.012). Use of combination therapy with immunomodulators was significantly different between standard and nonstandard groups (80% vs 48%; p < 0.001). Numeric trend in need for IFX dose escalation in the first 6 months was seen between standard and nonstandard groups (54% vs 39%, respectively; p = 0.087). Post-induction IFX trough concentrations, rates of antibody development, drug discontinuation, and infusion reaction were similar.
Nonstandard induction dosing of IFX was associated with higher rates of clinical remission, despite similar rates of serum IFX trough concentrations. There was a numeric trend towards the standard group requiring dose escalation within the first 6 months of therapy. Patients given nonstandard dosing may achieve superior clinical outcomes compared with those on standard dosing."
"Patients with various cancers benefit from immune checkpoint inhibitors. However, immune checkpoint inhibitor-induced adverse events have also been reported, such as colitis. Prednisolone is the first-line treatment for immune-related adverse events, but second-line therapy for patients refractory to steroids has not been established. Furthermore, the inflammatory cytokine expression pattern in the intestinal mucosa of patients with steroid-refractory immune-related colitis remains unclear. We present the case of a 48-year-old man diagnosed with immune-related colitis and pancreatitis induced by pembrolizumab for advanced lung cancer. First, we administered 50 mg/day of prednisolone, and the patient's abdominal symptoms improved. However, the pancreatic enzyme levels did not return to normal. Furthermore, the patient's diarrhea worsened and hematochezia appeared at a 40 mg/day prednisolone dose. A mucosal cytokine analysis identified a low interleukin-10 messenger RNA level, which has been associated with a poor response to prednisolone. Thus, we administered 5 mg/kg of infliximab; the patient's diarrhea and hematochezia immediately improved, and the pancreatic enzyme levels returned to normal. Infliximab was administered three times every 2 weeks. After, the patient's colitis and pancreatitis did not recur. To our knowledge, this is the first report demonstrating the effectiveness of infliximab for immune-related colitis and pancreatitis."
"Acute severe ulcerative colitis is a rapidly progressive severe form of colitis that can occur in 20-30% patients with ulcerative colitis. Early recognition, hospitalization at centers with experience and expertise and multidisciplinary treatment is the cornerstone of appropriate management of this condition. After excluding infections and other differentials, patients should be started on parenteral corticosteroids to control inflammation. ASUC patients are at high risk for thromboembolic complications and hence DVT prophylaxis is ideally started as soon as possible in the emergency room and continued throughout hospitalization. Objective criteria should be applied to assess improvement and identify patients who are unlikely to improve without second line/rescue therapy as early as 72 hours on steroid therapy. Infliximab and cyclosporine are the most used options for second line therapy and should be administered under direction by gastroenterologists. Disease progression despite aggressive treatment or non-response to second line therapy, complications such as megacolon, perforation, hemorrhage can occur requiring colectomy as a salvage option in those patients."
"As the third year of the SARS-CoV-2 pandemic approaches, COVID-19 continues to cause substantial morbidity and mortality due to waning vaccine efficacy and the emergence of new, highly contagious subvariants and better therapies are urgently needed.
Hospitalized patients who develop hypoxia due to SARS-CoV-2 infection are typically treated with an antiviral agent, remdesivir, as well as an immunomodulator, dexamethasone, but mortality rates for severe COVID-19 remain unacceptably high. Mounting evidence suggests a second immunomodulator added to the standard of care may benefit some hospitalized patients; however, the optimal treatment remains controversial.
On 2 June 2022, the United States National Institutes of Health reported results from a large, randomized placebo-controlled clinical trial known as ACTIV-1. The study found a mortality benefit and substantially improved clinical status for adults hospitalized with COVID-19 who were treated with infliximab, a chimeric monoclonal antibody that binds to and inhibits TNF-α, and is widely used to treat a variety of autoimmune conditions, including rheumatoid arthritis, Crohn's disease, and ulcerative colitis. This manuscript reviews what is known about infliximab as an immunomodulator for patients with COVID-19 and explores how this agent may be used in the future to address the SARS-CoV-2 pandemic."
"Infliximab (INF) is intravenously used for the clinical treatment of rheumatoid arthritis. However, it can cause serious side effects, which are mainly associated with systemic exposure and high doses. Here, we developed a modified hydrophobic ion-pairing complexes (INF HIPC) through the sequential introduction of bovine lactoferrin (BLF) and hyaluronic acid (HA) with opposite charges into the INF solution. INF and BLF were found to be not only integrally responsible for the structural integrity of HIPC but also were determined to have respective biological activities by binding human tumor necrosis factor-alpha (hTNF-α) or promoting the proliferation of osteoblasts. The INF HIPC had good stability, high drug-loading efficiency, and long-term retention effects. Whether via knee joint injection or intravenous injection, INF HIPC resulted in lower hTNF-α levels and less cartilage destruction than INFs in the transgenic mouse model. At the same time, INF HIPC could reduce toxicity based on body weight changes in transgenic mice. Our findings provide a simple and promising avenue to develop advanced delivery systems for other antibodies and macromolecules."
"Inflammatory bowel disease (IBD) is a condition that affects most of the digestive tract. There is no report of fertility reduction in medically managed IBD women compared with the general population. On the other hand, active IBD can lead to significantly decreased fertility. Over the previous 2 decades, anti-tumor necrosis factor (anti-TNF) has been an effective treatment for managing patients with IBD, increasing the use of infliximab and adalimumab in clinical practice. However, it is unclear which biologics are better for pregnant women with IBD.
We conducted a systematic review and meta-analysis for the risk of adverse pregnancy outcomes following treatment with infliximab and adalimumab in women with IBD.
Bibliographic databases were retrieved from their inception to July 2022. The results were adverse pregnancy outcomes, including congenital malformations and spontaneous abortion.
A total of 8 studies included 527 pregnant women with IBD. Of these, 343 received infliximab, and 184 received adalimumab therapy. Compared to adalimumab, adverse pregnancy outcomes were not increased in infliximab therapy including congenital malformations and spontaneous abortion.
Infliximab and adalimumab therapy did not show the difference of risk in adverse pregnancy outcomes in women with IBD.
http://www.crd.york.ac.uk/PROSPERO , identifier: CRD 42,021,277,869."
"Published data on the safety of biologics other than tumor necrosis factor (TNF) inhibitors during pregnancy are limited.
The aim was to detect pharmacovigilance signals for fetal and neonatal adverse drug reactions (ADRs) to biologics taken by pregnant women with autoimmune diseases.
We performed a disproportionality analysis of the World Health Organization's VigiBase
In the main analysis, the RORs were particularly high for musculoskeletal malformations with anakinra (7.18 [3.50-14.73]), canakinumab (19.54 [12.82-29.79]), and abatacept (5.09 [2.77-9.33]), and for immune system disorders with canakinumab (347.88 [217.9-555.50]) and rituximab (9.27 [2.95-29.15]). After the exclusion of reports with steroids, the ROR was significant for neonatal infections with belimumab (28.49 [5.75-141.25]).
We identified possible associations with some adverse fetal and neonatal outcomes, suggesting that vigilance is required when prescribing certain biologics during pregnancy."
"There is increasing evidence that proactive monitoring is useful in improving the control of inflammatory bowel disease, although it remains controversial. The aim of this study was to evaluate the efficacy of proactive TDM based on the Bayesian approach to optimise the IFX dose compared with the standard of care dosing in patients with IBD.
Retrospective observational cohort of inflammatory bowel disease patients>18 years. Patients were classified into two groups according to the strategy used to optimise the dose of IFX: a standard therapy group (ST-group) with clinically based dose adjustment and therapeutic drug monitoring group (TDM-group), with estimation of pharmacokinetic parameters calculated by Bayesian prediction.
A total of 153 patients were included. Of these, 75 were in the TDM-group. Clinical response at week 52 was evaluated in 114 patients. The proportion of patients who achieved clinical remission was higher in the TDM than in the ST-group (80.7% vs 61.4%, respectively, p=0.023). A total of 28 patients (24.6%) met the parameters for the composite variable 'poor clinical outcome' at week 52. The proportion of patients who reached this outcome was lower in the TDM-group than in the ST-group (12.3% vs 36.8%, respectively, p=0.002).
Proactive therapeutic drug monitoring using Bayesian approach is associated with higher secondary response and fewer long-term complications."
"The aim of our study was to describe the distinct features of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) patients and to identify risk factors for its development.
Data from the German biologics in paediatric rheumatology registry (Biologika in der Kinderrheumatologie (BiKeR)) collected between 2001 to 2021 were analysed retrospectively.
In 5009 JIA patients, 28 developed confirmed IBD before the age of 18 years: 23 (82.1%) with Crohn's disease (CD), 4 (14.3%) with ulcerative colitis (UC) and 1 (3.6%) with IBD-unclassified. The incident rate of IBD during 20 years of observation was 0.56% (0.46% for CD, 0.08% for UC, 0.02% for IBD-U), of whom 20.3% were HLA-B27 positive, 25% had enthesitis-related arthritis and 14.3% psoriatic arthritis. Within 90 days before IBD diagnosis, 82.1% (n=23) received treatment with etanercept (ETA), 39.3% (n=11) NSAID, 17.9% (n=5) systemic corticosteroids, 8 (28.6%) methotrexate (MTX), 14.3% (n=4) sulfasalazine, 10.7% (n=3) leflunomide, and 3.6% (n=1) adalimumab and infliximab, respectively. The incidence of IBD was lower in patients treated with MTX, but higher in patients treated with ETA except if ETA was combined with MTX. Also in patients on leflunomide or sulfasalazine, the IBD incidence was higher.
In our JIA cohort, an increased IBD incidence is observed compared to the general population, and the ratio of CD to UC is markedly higher hinting at a distinct phenotype of IBD. Pre-treatment with MTX seems to be protective. Treatment with ETA does not prevent IBD development and JIA patients treated with leflunomide and sulfasalazine may be at an increased risk for IBD development.An infographic is available for this article at: http://links.lww.com/MPG/C985."
"Excessive immunosuppression after kidney transplantation (KT) is often encountered in patients undergoing therapy for anti-rejection or autoimmune disease that requires further treatment using immunosuppressive medications (IMs), including biologic agents. We report a novel case wherein a kidney transplant recipient developed severe acute allograft injury and hemorrhagic cystitis at 4.5 years after KT due to adenovirus nephritis after treatment with infliximab for Crohn's disease. The diagnosis was made based on adenovirus immunohistochemistry staining and urine polymerase chain reaction tests. The patient was successfully treated by reducing IMs and administration of immunoglobulin even though allograft function was eventually partially recovered. When new immunosuppressive agents, particularly biologic agents, are initiated for other diseases in addition to maintenance IMs, the following points need to be regarded: (1) pay attention to opportunistic infections even in the late phase of KT, and (2) maintain communication with other specialists who prescribe biologics to ensure appropriate administration of IMs."
"To study the association between infliximab trough level (IFX-TL) prior to maintenance treatment and disease outcome in children with Crohn's disease (CD).
A retrospective analysis was performed on 35 children with CD who received induction therapy with infliximab (IFX) and the measurement of IFX-TL before maintenance treatment from August 2018 to November 2021. Clinical data and laboratory markers at baseline and before maintenance treatment were collected, and the association between outcome and IFX-TL was analyzed.
The clinical remission group, endoscopic remission group, and combined remission group had a significantly higher IFX-TL level than the corresponding non-remission groups (
Among children with CD receiving infliximab induction therapy, the children achieving clinical and endoscopic remission before maintenance treatment tend to have a higher level of IFX-TL. IFX-TL has a certain predictive value for clinical remission."
"The implementation of biologic therapy has improved the treatment and clinical course of patients with inflammatory bowel disease since the initial approval of infliximab for Crohn's disease in 1998. However, the efficacy and safety profiles of currently available therapies are still less than optimal in several ways, highlighting the need for novel therapeutic targets. Several new drug classes (Janus kinase inhibitors, anti-integrins, sphingosine-1-phosphate receptor modulators, anti-interleukin-23 antibodies, and stem cell therapies) are currently being studied in Crohn's disease and ulcerative colitis with promising results. This article reviews the current literature and provides an updated overview of the emerging therapies."
"Anti-tumor necrosis factor (TNF) antibodies play a major role in treating inflammatory bowel disease (IBD), both in adult and pediatric patients. While there is a large number of studies on efficacy and safety of infliximab in treating children and adolescents with ulcerative colitis (UC), data on adalimumab (ADA) are scarce.
Here, we review published case reports, cohort and real-time data, as well as the first randomized trial, ENVISION I, using ADA for treating pediatric UC. Available evidence confirms good efficacy in inducing and maintaining remission in children and adolescents with UC, with even higher response rates compared to adult UC. ENVISION I showed that in UC patients responding to ADA induction therapy, almost half of the patients remained in remission after 52 weeks of therapy on high-dosing ADA (weekly administration). As already well experienced with other biologics, dosing schemes are different between pediatric and adult patients, with children often requiring higher dosing.
Further data are required to better understand how to optimize ADA therapy. The present and still-growing evidence places subcutaneous (sc.) anti-TNF-medication as alternative first-line therapy also for pediatric UC. This is also reflected by the preference for sc. medication of adolescent patients allowing less frequent and autonomous drug administration."
"Infliximab, a chimeric monoclonal antibody against anti-tumor necrosis factor-α (TNF-α), has revolutionized the management of inflammatory bowel disease. However, a recent nested case-control study showed that anti-TNF-α therapy exposure in patients with autoimmune diseases is associated with an increased risk of inflammatory central nervous system (CNS) events. A 27-year-old man diagnosed with Crohn's disease at 17 years of age was referred to our clinic for suffering with Wernicke's aphasia and the right-hand weakness over two weeks. Nine years of treatment for Crohn's disease with infliximab anti-TNF-α therapy was well tolerated. An initial MRI revealed diffuse leptomeningeal enhancement along the bilateral cerebral sulci without any parenchymal abnormalities. Cerebrospinal fluid (CSF) and serum N-methyl-D-aspartate receptor (NMDAR) antibody testing yielded positive results. Anti-NMDAR encephalitis was diagnosed, and the patient was treated with rituximab. A follow-up brain MRI showed new multiple cerebral lesions in the left insular cortex and subcortical white matter of the left frontal and temporal gyri. Approximately 8 months after symptom onset, the CSF and serum NMDAR antibody converted to negative. Twelve months later, the patient fully recovered from anti-NMDAR encephalitis without any neurological deficits and is currently being treated with the anti-interleukin 12/23 agent ustekinumab for Crohn's disease. This is the first report of not only a patient with infliximab-associated anti-NMDAR encephalitis in Crohn's disease but also of an inflammatory non-demyelinating CNS event during long-term suppression of TNF-α. Our case highlights the need for clinicians to recognize the possibility of a paradoxical autoimmune response occurring with novel biological therapies."
"The era of biological therapy has revolutionized in the management of autoimmune rheumatic diseases. There have been conflicting results about the incidence of infections related to these drugs. The purpose of this study was to compare the spectrum and severity of infection between patients on biological disease-modifying antirheumatic drugs (bDMARDs) versus conventional disease-modifying antirheumatic drugs (cDMARDs).
This hospital-based prospective observational study was conducted in a tertiary care hospital, and a total 200 patients were enrolled in this study. Patients on either bDMARDs or cDMARDs for at least six weeks presenting with evidence of infection were included. Patients with known immunodeficiency states, multiple comorbidities, and patients on prednisolone >7.5 mg were excluded. Data was expressed as percentage and mean ± SD. Kolmogorov-Smirnov analysis was performed for checking linearity of the data, and analysis of variance (ANOVA) followed by Tukey's HSD test were used to test the significance of difference between more than two parameters in parametric data.
Rheumatoid arthritis in 58 patients (29%) were the commonest ones presenting with infections, followed by systemic lupus erythematosus in 37 patients (18.5%). 135 patients (67.5%) were on cDMARDs and 65 patients (32.5%) on bDMARDs. Respiratory tract infection in 47 (34.8%) patients was found to be the commonest infection due to cDMARDs. Incidence of infection was higher with biologics, and types of infection in patients receiving infliximab and etanercept were significantly different from that of cDMARDs. Patients receiving etanercept had higher risk of infections and re-infections, but they were milder compared to cDMARDs. A significantly higher frequency of re-infection was found in patients who had not received vaccination.
This study emphasizes that TNF-α inhibitors are significantly associated with higher risk of infections. Patients on etanercept have significantly higher but milder infections as compared to cDMARDs. Vaccination plays a pivotal role in prevention of re-infections."
This study aimed to develop a pH-responsive folic acid-grafted organic/inorganic hybrid nanocomposite system for site-selective oral delivery of therapeutic antibodies. A folic acid-grafted aminoclay (FA-AC) was prepared 
"Tumor necrosis factor-alpha inhibitor therapy for inflammatory bowel disease may be associated with paradoxical cutaneous adverse events, most commonly psoriasiform eruptions. We present the case of a pediatric female patient with Crohn's disease who developed multiple concurrent cutaneous eruptions while on infliximab treatment, including morphea, psoriasiform dermatitis, and genital lichen sclerosus. Although refractory to skin-directed treatments, all three conditions resolved upon discontinuation of infliximab, supporting their development as a paradoxical reaction to infliximab therapy."
"Evaluation of costs and short-term cost-effectiveness of infliximab plus methotrexate (IFX + MTX); triple therapy of hydroxychloquine, sulphasalazine, and methotrexate (TRIPLE); or methotrexate monotherapy (MTX) in patients with new-onset polyarticular juvenile idiopathic arthritis (JIA).
In a prospective multicenter study (ACUTE-JIA), costs and health outcomes of 60 randomized patients with new-onset disease-modifying anti-rheumatic drug (DMARD)-naïve polyarticular JIA were analyzed during the first year. A mapping algorithm was used to obtain utility values from Child Health Assessment Questionnaire (CHAQ). Wallace criteriae were used to assess clinically inactive disease (CID). Linear regression with non-parametric bootstrapping was used to adjust imbalances at baseline.
Using prices for IFX biosimilar, adjusted annual mean (SD) costs of treatment (€) were 21,164 (4158), 12,136 (5286), and 18,300 (8635) on IFX + MTX, TRIPLE, and MTX, respectively. Incremental cost-effectiveness ratio (ICER) for IFX + MTX as compared with TRIPLE or MTX were 3442 € or 678 € per additional month spent in CID. Mean (SD) quality-adjusted life years (QALYs) for IFX + MTX, TRIPLE and MTX were 0.755 (0.065), 0.725 (0.062), and 0.686 (0.124). ICER for IFX + MTX vs TRIPLE was 294,433 €, and for IFX + MTX vs MTX 31,435 € per QALY gained.
In short-term, biosimilar IFX + MTX can be considered cost-effective when compared with MTX alone. TRIPLE was cost-effective when compared with MTX and showed cost advantage when compared with IFX + MTX. Cost per time spent in CID showed similar results than ICER evaluations.
This trial was primarily registered with the Ethical Board of Helsinki District University Hospital ( https://www.hus.fi ), clinical trial number 211864, and later with ClinicalTrials.gov, number NCT01015547."
"The early outcomes of ulcerative colitis (UC) after rescue therapy with cyclosporine A (CyA) are well known. Published data on the safety of this treatment in perioperative use and data on the long-term prognosis are scarce and are investigated here.
All UC patients treated with CyA in Tampere University Hospital between 2009 and 2018 were reviewed from patient records.
A total of 182 patients were included with the median follow-up of 3.8 (range 0-13) years. Of all patients, 139 (76%) responded to CyA. A quarter of the responders achieved long-term remission and used thiopurines as maintenance therapy at the end of follow-up. Altogether 83 (46%) needed further enhancement of treatment with corticosteroids (Cs) and 57 (31%) with biologicals or small molecules. Of the nonresponders 27 (55%) were treated surgically within admission to index flare. Infliximab was used as a third-line rescue therapy for 16 patients of whom four benefitted. The overall colectomy rate in this series was 45%. When compared to Cs alone CyA did not increase the risk for severe postoperative complications in patients treated for severe treatment-refractory UC.
In conclusion, despite the good initial response to CyA, a large proportion of patients relapsed during long-term follow-up and the colectomy rates remain high. Other therapy attempts after failure of CyA merely postpone surgery in many. We therefore recommend informing patients about the possibility of surgery prior to the initiation of rescue therapy."
"Immunomodulators, particularly the thiopurines and to a lesser extent methotrexate, were standard of care for inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, for >40 years. While there has been a renaissance in available therapies with the advent of biologics and small molecules, an impetus remains for the ongoing use of thiopurines and methotrexate. This is particularly true for the maintenance of remission and when used in combination therapy with infliximab to suppress anti-biologic antibodies. This article summarizes the data behind immunomodulator use in Crohn's disease, focusing on the beneficial role these drugs still have while acknowledging their clinical limitations."
"TNF-alpha inhibitors have revolutionized the therapeutic care in chronic inflammatory diseases. Several biosimilar products were commercialized at their patent expiry, substantially decreasing the cost of treatment. This longitudinal descriptive study aimed at assessing infliximab, etanercept and adalimumab biosimilar penetration rates using data of the French National Health Data System. A total of 207,118 new or prevalent users from the date of first biosimilar commercialization in France (respectively January 2015, May 2016 and October 2018) were included in the study and followed until September 30, 2021. Biosimilars represented respectively 78%, 46% and 53% of the overall initiations, and 94%, 66% and 60% last year's initiations. A total of 46%, 19% and 17% of originator product prevalent users switched for a biosimilar during the follow-up. Biosimilar penetration rate was much higher for infliximab than for its counterparts, due to its hospital delivery modality. Biosimilar initiation and originator-to-biosimilar switch tended to be observed more in rheumatology than in the other specialties. Biosimilar use was mostly consistent across patient socio-demographic characteristics. Biosimilar initiation rate increased rapidly from their market arrival and originator-to-biosimilar switch rate remained moderate, highlighting the need and usefulness of political action and biosimilar use tracking."
"We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response.
Twenty-nine patients (15 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4β7 therapy. Biopsies were taken for fluorescein isothiocyanate-labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort.
In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn's disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7).
Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF-responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders."
"Anti-tumor necrosis factor (anti-TNF) monoclonal antibody, infliximab, is the primary therapeutic modality for patients with Crohn's disease (CD) and ulcerative colitis (UC), refractory to conventional therapy. Biosimilars of infliximab have been shown to have equivalent efficacy to originator infliximab. We compared the safety and efficacy of infliximab biosimilar with the originator in Indian patients with inflammatory bowel disease (IBD).
Patients with IBD treated with either originator or biosimilar infliximab from January 2005 to October 2020 were included in this retrospective analysis. The safety and efficacy of originator or biosimilar infliximab in inducing and maintaining clinical remission at weeks 14 and 52 for CD and UC were evaluated. Disease activity was estimated at baseline, after induction therapy, after 1 year of treatment, and during 12 months of follow-up.
In all, 137 patients (82 CD; 55 UC) were included, of whom 102 were on originator, and 35 patients received biosimilar. In biosimilar group, clinical response and remission rates at weeks 14 and 52 were 84.2%, 58% and 68.4%, 52.6% in CD and 81.2%, 56.2% and 68.7%, 62.5% in UC patients, respectively. Among patients who were on originator, clinical response and remission rates at weeks 14 and 52 were 79.4%, 46% and 57.1%, 43% in CD and 72%, 64.1% and 66.7%, 56.4% in UC patients, respectively. Thirty-three (24.1%) patients experienced adverse events; eighteen developed tuberculosis (TB), of whom 17 received originator and one patient received biosimilar.
Infliximab biosimilar is comparable to originator infliximab in terms of safety profile and its efficacy in inducing and maintaining remission in patients with IBD."
"Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency with considerable morbidity (30% to 40%). Patients with ASUC require hospitalization for prompt medical treatment, and colectomy is considered if medical therapy fails. Corticosteroids remain the primary initial therapy, although one-third of patients do not respond to treatment. Clinical data have indicated that cyclosporine, tacrolimus, and infliximab can be used to treat patients with ASUC who do not respond to intravenous corticosteroids. The effectiveness and safety of sequential therapy have recently been reported; however, the data are not convincing. Importantly, timely decision-making with rescue therapy or surgical treatment is critical to manage ASUC without compromising the health or safety of the patients. In addition, risk stratification and the use of predictive clinical parameters have improved the clinical outcome.of ASUC. Multidisciplinary teams that include inflammatory bowel disease experts, colorectal surgeons, and other medical staff contribute to the better management of patients with ASUC. In this review, we introduce current evidence and present a clinical approach to manage ASUC."
"Loss-of-response and adverse events (AE) to biologics have been linked to HLA-DQA1*05 allele. However, the clinical factors or biologic used may influence treatment duration. Our objective was to evaluate the influence of clinical and therapeutic factors, along with HLA, in biological treatment discontinuation.
A retrospective study of consecutive IBD patients treated with biologics between 2007 and 2011 was performed. Main outcome was treatment discontinuation due to primary non-response (PNR), secondary loss of response (SLR) or AE. HLA-DQA1 genotyping was done in all patients. Regression analyses were used to assess risk factors of treatment discontinuation.
One hundred fifty patients (61% male) with 312 biologic treatments were included. 147 (47%) were discontinued with a cumulative probability of 30%, 41% and 56% at 1, 2 and 5 years. The use of infliximab (p=0.006) and articular manifestations (p<0.05) were associated with treatment discontinuation. Considering cause of withdrawal, Ulcerative Colitis (UC) had a higher proportion of PNR (HR=4.99; 95% CI=1.71-14.63; p=0.003), SLR was higher if biologics had been indicated due to disease flare (HR=2.32; 95% CI=1.05-5.09; p=0.037) while AE were greater with infliximab (HR=2.46; 95% CI=1.48-4.08; p<0.001) or spondylitis (HR=2.46; 95% CI=1.78-6.89; p<0.001). According to the biological drug, HLA-DQA1*05 with adalimumab showed more SLR in cases with Crohn's disease (HR=3.49; 95% CI=1.39-8,78; p=0.008) or without concomitant immunomodulator (HR=2.8; 95% CI=1.1-6.93; p=0.026).
HLA-DQ A1*05 was relevant in SLR of IBD patients treated with adalimumab without immunosupression. In patients treated with other biologics, clinical factors were more important for treatment interruption, mainly extensive UC or extraintestinal manifestations and having indicated the biologic for flare."
"Anticancer immune-checkpoint inhibitors (ICI) can cause immune-related adverse events (irAEs), including interstitial pneumonitis, which is managed chiefly with systemic corticosteroids. When corticosteroids fail, second-line immunosuppressive therapy is indicated. Our objective was to evaluate the prevalence and outcomes of ICI-induced pneumonitis requiring second-line immunosuppressive therapy (IS).
We collected data form the REISAMIC pharmacovigilance registry and the multidisciplinary immunological toxicity board at Gustave Roussy (France). No response to steroids was called steroid-refractory pneumonitis and relapse after an initial response was defined as steroid-resistant pneumonitis.
Of the 1187 patients screened from the REISAMIC register, 48 (4%) patients had pneumonitis treated with corticosteroids. Five of them (10%) had corticosteroid refractory/resistant disease but only 2 were treated with immunosuppressive therapy. Four additional patients requiring immunosuppressive therapy identified via the immunological toxicity board were included. Immunosuppressive therapy were cyclophosphamide (n=4 pts), infliximab (n=1 pt), intravenous immunoglobulins (n=1 pt). Five of these six patients had corticosteroid-refractory disease and one had corticosteroid-resistant pneumonitis. Five patients had severe pneumonitis (Common Terminology Criteria for Adverse Events grade ≥3) at initial pneumonitis diagnosis. Two months mortality rate in patients treated with IS was 67% (4/6). Among the patients treated with IS, the two patients alive at 5 months were treated with cyclophosphamide.
Patients with ICI-pneumonitis treated by steroids received IS in 10% of cases. High mortality at 67% of patients was observed in ICI-pneumonitis after steroid failure. Cyclophosphamide could be a treatment option for pneumonitis after corticosteroid failure that requires further investigations."
"Crohn's disease (CD) is a chronic gastrointestinal granulomatous disease. When CD is complicated by abscess formation, the most quality of life of patients were seriously affected, especially those with intestinal fistula, intestinal stenosis or severe disease activity.
We present a case of a 20-year-old male with CD associated with intestinal fistula and psoas muscle abscess formation, who was successfully managed by drugs and nutrition without surgery.
Surgery is undoubtedly the most effective treatment for CD with abscesses/fistulas. Whereas, for patients sensitive to drug therapy, abscess puncture and drainage could be considered as alternative to surgery, at this time enteral nutrition, antibiotics and immunosuppressants is particularly critical.
We suggest that CD patients complicated with abscess formation in clinical, if the infection can be controlled before operation, and the abscess site is convenient for puncture and drainage, who could consider to choose comprehensive treatment like enteral nutrition, antibiotics, continuous local irrigation of the abscess cavity via the catheter and immunosuppressive agents."
"To update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA).
This systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022.
Of 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission.
The results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA."
"This study aimed to evaluate the role of microRNAs (miRNA) as biomarkers of treatment response in rheumatoid arthritis (RA) patients through a systematic review of the literature. The MEDLINE and Embase databases were searched for studies including RA-diagnosed patients treated with disease-modifying antirheumatic drugs (DMARDs) that identify miRNAs as response predictors. Review inclusion criteria were met by 10 studies. The main outcome of the study was the response to treatment, defined according to EULAR criteria. A total of 839 RA patients and 67 healthy donors were included in the selected studies. RA patients presented seropositivity for the rheumatoid factor of 74.7% and anti-citrullinated C-peptide antibodies of 63.6%. After revision, 15 miRNAs were described as treatment response biomarkers for methotrexate, anti-tumour necrosis factor (TNF), and rituximab. Among treatments, methotrexate presented the highest number of predictor miRNAs: miR-16, miR-22, miR-132, miR-146a and miR-155. The most polyvalent miRNAs were miR-146a, predicting response to methotrexate and anti-TNF, and miR-125b, which predicts response to infliximab and rituximab. Our data support the role of miRNAs as biomarkers of treatment response in RA and point to DMARDs modifying the miRNAs expression. Nevertheless, further studies are needed since a meta-analysis that allows definitive conclusions is not possible due to the lack of studies in this field."
"To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field.
An international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item.
The task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3-6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations.
These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost."
"There is limited evidence on within-country discrepancies in biosimilar uptake. This study analyzes differences in timing and diffusion of biosimilar uptake across Portuguese NHS hospitals and explores possible determinants.
We analyzed publicly accessible consumption data of originator biologic and biosimilar drugs for adalimumab, etanercept, infliximab, rituximab, and trastuzumab, by hospital and month for the years 2015-2021 (
Academic hospitals were characterized by a quicker uptake of adalimumab and infliximab biosimilars but lower shares for other drugs. A higher total consumption of biologics was related to a lower share of biosimilar uptake. A stronger participation in randomized controlled trials was linked to higher biosimilar shares and quicker uptake, except for rituximab. If all NHS hospitals had biosimilar shares equal to the highest ones, potential annual savings could reach 13.9 million euros.
The findings suggest a need for capacity-building on biosimilar prescribing, including for doctors of academic hospitals and those working in settings where high biosimilar use would be expected."
"To report a case of frosted branch angiitis presenting in a pediatric patient with unremarkable laboratory work-up apart from SARS-CoV-2 IgG antibodies.
Less than four weeks after a SARS-CoV-2 infection, a 10 year-old female presented to the emergency department with severe headache and intermittent fevers. During her hospital admission, the ophthalmology service was consulted for blurry vision. Subsequent eye examination revealed frosted branch angiitis. The patient initially received intravenous corticosteroids but was escalated to plasmapheresis to achieve resolution of her symptoms. Outpatient maintenance therapy consisted of an oral Prednisone taper and Infliximab infusion.
This case represents a unique ocular manifestation of COVID-19, as recent SARS-CoV-2 was the sole identifiable cause of the patient's frosted branch angiitis. Additionally, this patient required plasmapheresis to control disease progression."
"A 46-year-old man with myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable underwent myeloablative bone marrow transplantation from an HLA-DR-1-antigen-mismatched related donor while receiving tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. However, grade III acute GVHD of the gut occurred on day 20 and was treated with prednisolone (PSL) and oral beclomethasone dipropionate while continuing MMF. Subsequently, he presented with progressive epigastric pain. Endoscopy demonstrated multiple stomach and duodenal deep ulcers. The ulcers were suspected to be GVHD; thus, the PSL dose was increased and infliximab was administered; however, the ulcers exacerbated, resulting in repeated perforations and hemorrhagic shock. Furthemore, MMF was suspected as the cause of refractory ulcers and was discontinued on day 156, which resolved the ulcers after 6 months. MMF-induced gastrointestinal (GI) injury resembles anti-inflammatory drug-related ulcers and upper and lower GI tract GVHD, respectively. MMF-induced GI injury has been reportedly resolved after discontinuing or reducing the MMF dose. Several reports suggested that refractory upper GI ulcers and rectal sparing colitis were associated with MMF toxicities rather than GVHD in hematopoietic stem cell transplantations. Physicians should be aware that MMF can induce severe GI injury."
"This is a case implying a serious infectious complication risk during intensive severe ulcerative colitis treatment. A 26-year-old man developed diarrhea and bloody stool who was diagnosed with ulcerative colitis in 2018. He was managed with 5-aminosalicylic acid, but intolerance reaction resulted in discontinuation of treatment. He relapsed with severe abdominal pain and bloody stools in February 2019. He was referred to our department for intensive therapy. He had been treated with steroids, tacrolimus, granulocyte and monocyte apheresis, infliximab or tofacitinib, which temporarily improved his clinical symptoms. However, his medical condition could not be controlled. Hand-assisted laparoscopic subtotal colectomy was then performed in October 2019. He developed intermittent fever on postoperative day 3. Enhanced computed tomography (CT) revealed multiple deep vein thromboses and pulmonary embolism. Antibiotics and anticoagulation therapy were initiated, but postoperative day 13 CT showed multiple pulmonary cavities containing fluids and air, which were diagnosed as pulmonary abscess. His intermittent fever was over 38.0°C. Severe cough and hemoptysis lasted 3 weeks, the clinical symptoms and laboratory data then gradually improved after the fourth week."
"A woman in her 30s was diagnosed with ulcerative colitis (UC) 4 years ago and treated with tacrolimus, azathioprine, and prednisolone 5mg (PSL). Skin ulcers appeared on the right lower leg during the course of treatment, diagnosed as pyoderma gangrenosum (PG). The patient initially improved with an increased PSL and infliximab dose, but then developed multiple skin ulcers and folliculitis throughout her body. She was transferred to our hospital for PG exacerbation treatment. She developed fever after transfer and contrast-enhanced computed tomography showed multiple abscesses in the lungs and kidneys. PSL was decreased and infliximab was discontinued. Antibiotic therapy and granulocyte/monocyte apheresis (GMA) were started. Fever persisted even after antibiotic treatment, and her general condition did not improve. A right renal abscess puncture was performed. Pus was sterile. A sterile abscess associated with PG was suspected. The PSL dose was increased to 1mg/kg and infliximab restarted. Thereafter, the patient's general condition improved, and both lung and renal abscesses contracted. Skin ulcer epithelialization was also observed. Abdominal symptoms were mild during the course of the disease, and colonoscopy showed only a localized ulcerative lesion in the rectum. The patient was later transferred to the department of dermatology at our hospital for PG treatment. Aseptic abscesses are caused by neutrophil infiltration without infection and have been reported to be associated with neutrophilic dermatosis and inflammatory bowel disease. UC-associated aseptic abscess is rare. This is only the sixth case in Japan. Aseptic abscesses can occur in various sites, including subcutaneous and deep organs, but this is the first kidney abscess case. In previous reports, PSL, infliximab, colchicine, and infliximab+GMA were used for aseptic abscesses associated with UC. They all showed abscess reduction. Aseptic abscesses associated with PG should be considered if abscess lesions occur during the course of UC, and a treatment strategy including enhanced immunosuppression should be considered."
"Budd-Chiari syndrome (BCS) is considered a rare but serious complication of Behçet's disease (BD). This study was performed to define the prevalence, clinical and biological features, treatment, and clinical course of BSC associated with BD in a Moroccan population. We retrospectively analyzed the medical records of 1578 patients fulfilling the international diagnostic criteria for BD, including those with BSC. Eighteen male and 3 female patients, with a mean age of 36 ± 8.6 years. The inferior vena cava was involved in 81% (n = 17) of cases. All forms of BCS were noted: the chronic form in 52.4% (n = 11), the subacute form in 38% (n = 8), and the fulminant form (2 cases). Ascites was the main clinical sign and was present in 62% of patients (n = 13). Other venous thromboses (superior vena cava and lower limbs) were associated with BSC in 52.4% of patients (n = 11). Arterial involvement was noted in 28.6% (n = 6). Cardiac manifestations were present in 19% (n = 4) of the patients. All the patients received anticoagulants associated with corticosteroids. Immunosuppressants were used in 95% (n = 20). One patient received infliximab. Severe complications were noted in 38% (n = 8) of patients (digestive bleeding, confusion, infections and liver failure). Four patients have died during the study period. BCS in patients with BD is not uncommon and can be life threatening. It is frequently associated with other vascular manifestations that can be difficult to treat, particularly in the presence of pulmonary artery aneurysms. Prognosis improved with the use of immunosuppressants. Biologics can be promising in the early stages."
"This study aimed to investigate the effect of infliximab on orthodontic tooth movement in rats.
Sixty male Sprague-Dawley rats were randomly divided into two groups: saline group and infliximab group. The two groups of rats received weekly intraperitoneally injection of saline or infliximab (5 mg/kg), respectively. After four weeks of injection, five rats in each group were euthanized and orthodontic appliances were placed in the other twenty-five rats each. On days 1, 3, 7, 14 and 21, five rats from each group were euthanised. Maxillae of all the rats were collected and examined by micro-computed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, and immunohistochemical staining of tumour necrosis factor (TNF)-α, receptor activator of nuclear factor κB ligand (RANKL), receptor activator of nuclear factor κB (RANK), and osteoprotegerin (OPG). All data were analysed with Mann-Whitney test.
Infliximab inhibited orthodontic tooth movement and decreased osteoclastogenesis on the compression side during orthodontic tooth movement. The elevated TNF-α level, induced by orthodontic force, was decreased by infliximab. Furthermore, infliximab reduced the expression of RANKL and RANK, while increased the expression of OPG on the compression side.
Infliximab inhibits orthodontic tooth movement by reducing levels of TNF-α, RANKL, and RANK, while increasing level of OPG, and decreasing osteoclastogenesis on the compression side of periodontium."
"Immune checkpoint inhibitors are widely used in various cancers as a standard treatment. However, while various immune-related adverse events related to immune checkpoint inhibitors have been reported, there are few reports of lower urinary tract symptoms.
The patient was a 60-year-old man with primary lung cancer who was receiving long-term nivolumab therapy. He was referred to our department due to the sudden onset of glans penile pain and micturition pain. We suspected non-bacterial cystitis as an immune-related adverse event caused by nivolumab and were able to treat it by administering prednisolone. While his symptoms and findings on cystoscopy recurred during prednisolone therapy, we were able to treat him again by administering an additional dose of infliximab.
A few reports have described cases of immune checkpoint inhibitor-induced cystitis for which prednisolone was effective. This report is the first to describe cystitis as a steroid-resistant immune-related adverse event."
"Tumor necrosis factor (TNF) inhibitors have been used in the treatment of cardiac sarcoidosis, infliximab being the most commonly used. We have previously reported a case of effective treatment of cardiac sarcoidosis using adalimumab.
To describe our experience of using adalimumab in the treatment of cardiac sarcoidosis.
We conducted a retrospective study to evaluate patients with cardiac sarcoidosis who received adalimumab treatment at the University of Illinois Health between 2011 and 2022. The outcome was evaluated by assessing safety, tolerability, and ability to taper systemic corticosteroids therapy following initiation of adalimumab.
Seven patients met the inclusion criteria. Clinical responses to adalimumab were universally positive. Corticosteroid therapy was discontinued in five patients and the dose was reduced in two patients. Furthermore, adalimumab was well tolerated, and no adverse events were reported.
Adalimumab was safe and well-tolerated in seven patients with cardiac sarcoidosis seen at our medical center and exhibited corticosteroid-sparing effects. Our observation further warrants large prospective studies to evaluate the safety and efficacy of adalimumab in the treatment of cardiac sarcoidosis."
"In 2020, the European Medicines Agency approved infliximab subcutaneous (SC) for the treatment of inflammatory bowel disease. This new mode of infliximab administration will reduce outpatient visits and costs of intravenous (IV) administration. This article describes a budget impact analysis of introducing infliximab SC to the Big-5 European (E5) market (Germany, France, Italy, Spain and UK) for 5 years, from the healthcare payer's perspective.
A prevalence-based budget impact model was developed to examine the financial impact of infliximab SC. ""World with"" versus ""world without"" infliximab SC scenarios were compared, including the potential administration costs of IV administration.
Introducing infliximab SC in patients with Crohn's disease (CD) for 5 years resulted in cost savings of €42.0 million in the UK, €59.4 million in Germany, and €46.4 million in France and Italy, but increased budget expenditure in Spain by €3.8 million. For ulcerative colitis (UC), cost savings of €42.7 million in the UK, €44.9 million in Germany, €44.3 million in France, and €53.0 million in Italy occurred, but with no savings in Spain for 5 years. Cost-savings per patient was calculated by diving the net budget saving by number of treatment eligible patients. Maximum and minimum saving per patient per year ranged between €38.25 and €575.74 in CD, both from Germany, and €105.06 (France) and €647.25 (Germany) in UC.
Healthcare payers in the UK, Germany, France, and Italy, but not in Spain, will make budget savings by using infliximab SC for the treatment of inflammatory bowel disease."
"Acute generalized exanthematous pustulosis (AGEP) is a rare dermatological manifestation of the adverse drug reaction that occurs for a varied duration after the receipt of certain drugs. It manifests as an acute onset of generalized exanthematous pustular reaction with an edematous base. It has a characteristic clinical presentation and rapid resolution soon after the removal of the offending drug. The unique histological finding is that of single-cell necrosis of keratinocytes with edema of papillary dermis accompanied by components of vasculitis and/or exocytosis of eosinophils. Management consists of moist antiseptic dressings, topical steroids, infliximab, the use of systemic steroids if needed, and avoiding antibiotics as much as possible. Here, we present a case of AGEP in a setting of usages of antibiotics like vancomycin, cefepime, and ceftriaxone in a patient with cutaneous lymphoma that resolved after withdrawal of the offending antibiotics."
"Different classes of medication have been reported in the literature to be associated with an increased risk of gastrointestinal perforation. However, little is known about the risk of drug-induced perforated appendicitis.
We analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS), a large national database of reported adverse events associated with post-market FDA-approved medications from January 2011 to October 2021. Patients of any age group with appendiceal perforation were included. Duplicated reports and other anatomical areas of gastrointestinal tract perforation outside the appendix were excluded.
During the study period, 474 event cases met inclusion criteria, of which 284 were females. Most reports of perforation occurred in patients 40-49 years (
Findings from the FAERS database highlight the risk of appendiceal perforation in the context of different classes of drugs. Larger pharmacovigilance studies are needed to confirm these observations."
"Perianal fistulising Crohn's disease (pfCD) is a disabling phenotype of Crohn's disease (CD) with suboptimal outcomes. We assessed neutrophil extracellular traps (NETs) in perianal fistulas and implicated their roles in pfCD healing.
Patients with complex pfCD who developed preplaced seton drainage were recruited during the verified maintenance of remission in CD. Fistula tracts were sampled during definitive surgery plus seton removal. Patient demographics, CD classification, medication strategy, and healing of pfCD were recorded. RNA sequencing was applied for transcriptomic profile analysis. NETs components, including myeloperoxidase (MPO), neutrophil elastase (NE), and citrullinated histone H3 (CitH3), were identified using immunofluorescence. Serum infliximab (IFX), anti-IFX antibodies, and tissue levels of IFX, adalimumab (ADA), MPO and CitH3 were determined using enzyme-linked immunosorbent assays. Peptidyl arginine deiminase IV (PAD4), tumour necrosis factor (TNF)-α, and NE were detected using immunohistochemistry. Gene expression levels of PAD family members were assessed with qPCR.
Twenty-one patients were included, 15 of whom adopted IFX as maintenance treatment. RNA-seq revealed difference in neutrophil associated pathways between unhealed and healed fistulas. NETs components (MPO/NE/CitH3) were detectable in the fistulas and were parallel with the PAD4 levels. Eleven of 21 (52%) patients experienced complete healing of the pfCD 108 weeks post-operatively. Fistula NETs were significantly increased in patients with unhealed pfCD. Increased NETs were associated with abundant TNF-α production and the absence of IFX in fistulas.
NETs exist in pfCD fistulas, which are associated with unhealed post-operative fistulas in pfCD, suggesting their prognostic roles in pfCD."
"Loss of response to infliximab or adalimumab in ulcerative colitis occurs frequently, and dose escalation may aid in regaining clinical benefit. This study aimed to systematically assess the annual loss of response and dose escalation rates for infliximab and adalimumab in ulcerative colitis.
A systematic search was conducted from August 1999 to July 2021 for studies reporting loss of response and dose escalation during infliximab and/or adalimumab use in ulcerative colitis patients with primary response. Annual loss of response, dose escalation rates, and clinical benefit after dose escalation were calculated. Subgroup analyses were performed for studies with 1-year follow-up or less.
We included 50 unique studies assessing loss of response (infliximab, n = 24; adalimumab, n = 21) or dose escalation (infliximab, n = 21; adalimumab, n = 16). The pooled annual loss of response for infliximab was 10.1% (95% confidence interval [CI], 7.1-14.3) and 13.6% (95% CI, 9.3-19.9) for studies with 1-year follow-up. The pooled annual loss of response for adalimumab was 13.4% (95% CI, 8.2-21.8) and 23.3% (95% CI, 15.4-35.1) for studies with 1-year follow-up. Annual pooled dose escalation rates were 13.8% (95% CI, 8.7-21.7) for infliximab and 21.3% (95% CI, 14.4-31.3) for adalimumab, regaining clinical benefit in 72.4% and 52.3%, respectively.
Annual loss of response was 10% for infliximab and 13% for adalimumab, with higher rates during the first year. Annual dose escalation rates were 14% (infliximab) and 21% (adalimumab), with clinical benefit in 72% and 52%, respectively. Uniform definitions are needed to facilitate more robust evaluations.
Annual loss of response in ulcerative colitis was 10% for infliximab and 13% for adalimumab, with higher rates during the first year. Annual dose escalation was higher than loss of response, with clinical benefit for 72% (infliximab) and 52% (adalimumab)."
"Although short-term clinical trials have demonstrated that switching from infliximab (INF) bio-originator to its biosimilar is safe with no significant loss of efficacy, there are limited real-world data comparing their patterns of use and adherence.
Using 2015-2018 IBM Marketscan data, we established 4 cohorts of patients with at least one administration or pharmacy claim for INF bio-originator or biosimilar in 2017, including INF naïve biosimilar users, INF prevalent biosimilar users, INF naïve bio-originator users, and INF prevalent bio-originator users, defined according to their prior use of INF from 2015 to their first INF administration in 2017. The proportion of days covered (PDC) was calculated for patients with at least 6, 12, or 18 months of follow-up time. Factors associated with optimal adherence (PDC > 80%) were evaluated using log-binomial models.
We identified 96 INF naïve biosimilar users, 223 INF prevalent biosimilar users, 2,149 INF naïve bio-originator users, and 10,970 INF prevalent bio-originator users. At the end of 18 months of follow-up, 64% of INF prevalent bio-originators, 48% of INF naïve biosimilars, 41% of INF naïve bio-originators, and 36% of INF prevalent biosimilars had optimal adherence. Depression, previous hospitalization, and greater use of prior biologics were negatively associated with adherence, whereas IBD diagnoses (referent to RA) and age 55-64 (referent to < 35) were positively associated with high adherence.
INF prevalent users had higher adherence in our analyses than INF naïve users. However, further studies with larger sample size are needed to evaluate INF biosimilar users' adherence."
"Dosing of tumour necrosis factor-α inhibitors (TNFis) is not personalized causing interindividual variation in serum drug levels; however, dose optimization is not widely implemented. We hypothesized that some patients are overdosed; thus, drug prescription could be reduced by therapeutic drug monitoring (TDM).
Independent of disease activity, 239 adults treated for rheumatoid arthritis (n = 99), psoriatic arthritis 15 (n = 48), or spondyloarthritis (n = 92) were recruited for a 48-week prospective, randomized open-label trial. Standard care alone or plus TDM was applied in chronic arthritis patients treated with infliximab (IFX), (n = 81), etanercept (ETN) (n = 79), or adalimumab (ADA) (n = 79). Serum TNFi trough levels assessed at inclusion and every 4 months determined patients within/outside predefined therapeutic intervals, supporting change in prescription or drug switch. The primary endpoint was reduced drug prescription.
Compared to standard care, TDM reduced prescribed IFX [-12% (95% confidence interval -20, -3); p = 0.001] and ETN (-15% (-29, 1); p = 0.01], and prolonged the interdosing intervals of ETN [+235% (38, 432); p = 0.02] and ADA [+28% (6, 51); p = 0.04]. Time to drug switch was accelerated (χ2 = 6.03, p = 0.01). No group differences in adverse events, disease activity, or self-reported outcomes were shown, indicating equally sustained remission.
TDM reduced prescription of IFX, ETN, and ADA and identified patients benefiting from accelerated drug switch, thereby minimizing treatment failure, risk of toxicity, and unnecessary adverse events."
"Biologic drugs have greatly improved treatment outcomes of inflammatory joint diseases, but a substantial proportion of patients either do not respond to treatment or lose response over time. Drug immunogenicity, manifested as the formation of anti-drug antibodies (ADAb), constitute a significant clinical problem. Anti-drug antibodies influence the pharmacokinetics of the drug, are associated with reduced clinical efficacy, and an increased risk of adverse events such as infusion reactions. The prevalence of ADAb differs among drugs and diseases, and the detection of ADAb also depends on the assay format. Most data exist for the tumor necrosis factor-alpha inhibitors infliximab and adalimumab, with a frequency of ADAb that ranges from 10 to 60% across studies. Measurement of ADAb and serum drug concentrations, therapeutic drug monitoring, has been suggested as a strategy to optimize therapy with biologic drugs. Although the recent randomized clinical Norwegian Drug Monitoring (NOR-DRUM) trials show promise towards a personalized medicine prescribing approach by therapeutic drug monitoring, several challenges remain. A plethora of assay formats, with widely differing properties, is currently used for measuring ADAb. Comparing results between different assays and laboratories is difficult, which complicates the development of cut-offs necessary for guidelines and the implementation of ADAb measurements in clinical practice. With the possible exception of infliximab, limited data on clinical relevance and cost effectiveness exist to support therapeutic drug monitoring as a routine clinical strategy to monitor biologic drugs in inflammatory joint diseases. The aim of this review is to provide an overview of the characteristics and prevalence of ADAb, predisposing factors to ADAb formation, commonly used assessment methods, clinical consequences of ADAb, and the potential implications of ADAb assessments for everyday treatment of inflammatory joint diseases."
"Immune check-point inhibitors-induced colitis (ICPIs-induced colitis) is one of the immune-related side effects. Steroids and Infliximab are commonly used to treat it. The patients of our report were treated by Vedolizumab.
The two patients went to the doctor with bloody stools and were treated by Sintilimab and Camrelizumab, respectively, for their malignant tumors. They were diagnosed as ICPIs-induced colitis based on endoscopic and histologic examination. The original immunotherapy was ceased while the anti-inflammatory therapy was introduced. The patients' colitis symptoms disappeared after the treatment and no recurrence was found during the follow-up period. The unique feature about the case reports is that Vedolizumab combined with short-term corticosteroids had achieved good therapeutic effects.
For the symptoms of bloody diarrhea after the ICPIs treatment of cancer, the possibility of ICPIs-induced colitis should be considered. Vedolizumab combined with short-term corticosteroids may be appropriate for the treatment."
"Tumor necrosis factor (TNF) inhibitors improved clinical outcomes for patients with psoriasis but are limited by their high cost. There are several biosimilar options approved for the treatment of psoriasis which provides a lower-cost alternative and the potential to increase treatment availability for both biologically naïve and bioexperienced patients. Numerous phase III randomized controlled trials (RCTs) have investigated the effects of switching from biologics to biosimilars; biosimilars had comparable safety and efficacy to their reference products. Real-world evidence may provide complementary information on the expected performance of biosimilars. In this literature review, we analyzed data from real-world studies on switching from biologics for psoriasis to their biosimilars. Effectiveness and safety profiles were comparable when switching from biologics to biosimilars of adalimumab, etanercept, and infliximab. These studies are limited by their sample sizes, duration of follow-up, and single-arm designs without control groups. Based on available real-world evidence, patients may safely and effectively undergo switching to biosimilar therapies for the treatment of psoriasis."
"Corticosteroids are a mainstay of the treatment of moderately severe relapses of ulcerative colitis, yet almost 50% of patients do not respond fully to these and risk prolonged steroid use and side effects. There is a lack of clarity about the definitions of steroid resistance, the optimum choice of treatment, and patient and health-care professional treatment preferences.
The overall aim of this research was to understand how steroid-resistant ulcerative colitis is managed in adult secondary care and how current practice compares with patient and health-care professional preferences.
A mixed-methods study, including an online survey, qualitative interviews and discrete choice experiments.
NHS inflammatory bowel disease services in the UK.
Adults with ulcerative colitis and health-care professionals treating inflammatory bowel disease.
We carried out a survey of health-care professionals (
The survey and the discrete choice experiments with patients and health-care professionals are limited by their relatively small sample sizes. The qualitative studies are subject to selection bias. The timing of the different substudies, both before and during the COVID-19 pandemic, is a potential limitation.
We have identified factors influencing treatment decisions for steroid-resistant ulcerative colitis and the characteristics to consider when choosing treatments to evaluate in future randomised controlled trials. The findings may be used to improve discussions between patients and health-care professionals when they review treatment options for steroid-resistant ulcerative colitis.
This research highlights the need for consensus work to establish an agreed definition of steroid resistance in ulcerative colitis and a greater understanding of the optimal use of tofacitinib and surgery for this patient group. A randomised controlled trial comparing infliximab with tofacitinib is also recommended.
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in 
Steroids are one of the main treatments for ulcerative colitis; however, steroids work well for only about 50% of people who take them. There are many other treatments that can be given when steroids do not work, but evidence is limited about how these treatments are best used. To carry out better research about the best treatment options and to improve clinical practice in the future, this study aimed to find out how adults with steroid-resistant ulcerative colitis are managed in hospital and why patients and health-care professionals prefer different treatments. The study combined various methods of research, including an online survey of health-care professionals ("
"Acute pancreatitis (AP), a complex inflammatory disease of the pancreas, is associated with increased morbidity and mortality. Currently, no specific therapies are approved for its treatment, and management is primarily based on supportive care. Despite enhanced understanding of AP pathogenesis, patients remain at significant risk owing to a lack of targeted drug treatments. Therefore, there is an urgent need for effective pharmacological therapeutic measures which may inhibit the early systemic inflammation, thereby preventing subsequent organ failure. This narrative review summarizes the available treatment options for AP and highlights the potential drug classes and pharmacologic therapies including those under clinical development. Although, several therapies targeting different aspects of AP pathogenesis have been investigated, some therapies with promising preclinical activity have been rendered ineffective in clinical trials. Other novel drug classes or molecules including dabigatran (anticoagulant), ulinastatin (protease inhibitor), infliximab (monoclonal antibody), spautin-A41 (autophagy inhibitor), and CM4620-Injectible Emulsion (calcium channel inhibitor) await further clinical assessment. Alternative treatment options using stem cells and nanoparticles are also being explored and may hold promise for AP therapy. However, challenges for exploring targeted treatment approaches include disease complexity, timing of therapeutic intervention, and establishing appropriate clinical endpoints. Understanding the role of specific biomarkers may help in identifying appropriate targets for drug discovery and facilitate determining relevant clinical study endpoints to monitor disease severity and progression, thereby aiding in design of more precise therapies with improved clinical outcomes."
"Ulcerative colitis often leads to gastrointestinal bleeding and venous thromboembolism (VTE). At present, there is no clear conclusion about anticoagulant therapy for these patients. Treatment for ulcerative colitis usually includes 5-aminosalicylic acid, corticosteroid, and biologics. Acute ulcerative colitis, usually caused by infection, is usually severe and can be life-threatening.
We report the development of VTE in a patient with severe acute ulcerative colitis who experienced gastrointestinal bleeding following hormonal therapy. The patient's indicators suggested that his blood was hypercoagulable and that his prognosis was poor.
Patients with ulcerative colitis are prone to form VTE. The use of corticosteroids during treatment increases the risk of thrombus. Anticoagulation strategy for patients with ulcerative colitis after gastrointestinal bleeding is a problem that needs to be discussed."
"Many patients with inflammatory bowel disease (IBD) are treated with anti-tumor necrosis factor (TNF) therapies, of which infliximab (IFX) is most commonly used. Loss of response (LOR) to anti-TNF therapy due to immunogenic failure accounts for 20% of subsequent medical intervention and is defined, using a drug sensitive assay, as low or undetectable concentration of drug with high titers of anti-drug antibodies (ADAb). We performed a systematic review to investigate the use of a drug tolerant assay during both induction and maintenance to monitor patients treated with anti-TNFs. After the search on PubMed, 90 publications were reviewed. Most ADAb detection methods are drug sensitive, cannot detect ADAb in the presence of drug, and therefore cannot be used close to drug administration, when the drug concentration is too high. To overcome this major limitation, several drug-tolerant techniques have been developed and will be discussed in this review. Using drug-tolerant assays ADAb against infliximab (IFX) or adalimumab (ADM) can be detected during induction and predict primary non-response or LOR. Drug sensitive assays do not allow detection of ADAb during the induction phase as IFX or ADM concentration is typically high."
"The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biologics disease-modifying antirheumatic drugs (bDMARDs) have been demonstrated to be effective for both the skin and joints, as well as for slowing radiographic progression. However, there has been a lack of direct comparisons of bDMARDs. To evaluate the comparative effects of bDMARDs in preventing radiographic progression in psoriatic arthritis, we conducted a systematic review and network meta-analysis. On March 7 2022, a search for relevant randomized trials was conducted on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Our outcomes included radiographic non-progression, a mean change in the total radiographic score, and adverse events leading to discontinuation (DAE) at week 24. We included 11 trials on 10 bDMARDs, involving 4010 participants. Most bDMARDs were more effective than placebos in achieving radiographic non-progression, including adalimumab (odds ratio (OR) 4.7, 95% confidence interval (CI) 2.66-8.29), etanercept (OR 4.19, 95% CI 1.65-10.61), certolizumab pegol (OR 2.83, 95% CI 1.55-5.2), secukinumab 300 mg (OR 2.63, CI 1.62-4.27), infliximab (OR 2.54, CI 1.13-5.69), ixekizumab (OR 2.22, 95% CI 1.06-4.65), golimumab (OR 2.21, 95% CI 1.24-3.93), and abatacept (OR 1.54, 95% CI 1.03-2.28). A significant reduction in the total radiographic score was found in infliximab (standardized mean difference (SMD) -0.59, 95% CI -0.87, -0.3), etanercept (SMD -0.51, 95% CI -0.78, -0.23), adalimumab (SMD -0.45, 95% CI -0.64, -0.26), ixekizumab (SMD -0.37, 95% CI -0.62, -0.12), secukinumab 300 mg (SMD -0.33, 95% CI -0.50, -0.15), golimumab (SMD -0.33, 95% CI -0.58, -0.09), secukinumab 150 mg (SMD -0.25, 95% CI -0.43, -0.07), certolizumab pegol (SMD -0.23, 95% CI -0.44, -0.03), and ustekinumab (SMD -0.19, 95% CI -0.35, -0.33). No significant differences in DAE were detected between bDMARDs. In conclusion, anti-tumor necrosis factor agents (adalimumab, infliximab, and etanercept) may be preferred for treating psoriatic arthritis for their superiority in preventing radiographic progression."
"Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis α monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting."
"CT-P13 is the first subcutaneous infliximab molecule approved for the management of inflammatory bowel disease (IBD). Compared to intravenous therapy, SC infliximab offers a range of practical, micro- and macroeconomic advantages. Data from the rheumatological literature suggest that subcutaneous CT-P13 may lead to superior disease outcomes in comparison to intravenous infliximab. Existing studies in IBD have focussed on pharmacokinetic comparisons and are inadequately powered to evaluate efficacy and safety differences between the two modes of administration. However, emerging clinical trial and real-world data support comparable clinical, biochemical, endoscopic and safety outcomes between subcutaneous and intravenous infliximab in both luminal Crohn's disease and ulcerative colitis. Across the available data, subcutaneous CT-P13 provides relative pharmacokinetic stability and higher trough drug levels when compared to intravenous administration. The clinical impact of this observation on immunogenicity and treatment persistence is yet to be determined. Trough levels between the two methods of administration should not be compared in isolation as any subcutaneous advantage must be considered in the context of comparable total drug exposure and the theoretical disadvantage of lower peak concentrations compared to intravenous therapy. Furthermore, target drug levels for subcutaneous CT-P13 associated with remission are not known. In this review, we present the available literature surrounding the pharmacokinetics of subcutaneous CT-P13 in the context of therapeutic drug monitoring and highlight the potential significance of these observations on the clinical management of patients with IBD."
"Drug persistence reflects an agent's efficacy and safety in routine practice. This study was undertaken to compare the 2-year persistence rates of three biologic disease-modifying antirheumatic drugs (bDMARDs) used to treat rheumatoid arthritis (RA) and to describe their efficacy and safety profiles.
This retrospective, observational, single-center study included RA patients who had received at least one intravenous dose of infliximab, abatacept, and/or tocilizumab. Two-year drug persistence was estimated using the Kaplan-Meier method. Efficacy profiles were assessed as changes of Disease-Activity Score-28 (DAS28)-based EULAR-criteria responses.
The infliximab, abatacept, and tocilizumab groups included 40, 72, and 93 patients, respectively. Their respective 2-year persistence rates were similar: 55.0%, 45.8%, and 62.4%. Tocilizumab recipients benefited from greater improvement than those given infliximab (
Even if this retrospective work includes different biases (lack of data, recruitment bias, etc.), it highlights that the 2-year persistence rates for infliximab, abatacept, and tocilizumab in daily practice did not differ significantly, thereby confirming the long-term efficacies of these three bDMARDs. However, tocilizumab was associated with more significant DAS28 improvement at 2 years than infliximab and abatacept."
"This was a retrospective cohort study aimed at identifying parameters measured at diagnosis of pediatric IBD to predict subsequent biologic therapy, as an equivalent to an unfavorable clinical course. Identification of predictors of poor outcomes is an important issue in current ECCO guidelines on pIBD. The study population consisted of 119 children with Crohn's disease and 112 with ulcerative colitis, diagnosed and monitored for at least 1 year from 2009-2019. The population was divided into the study groups separately: 39 children with CD and 14 with UC who received biologics before the age of 18 y compared to 80 with CD and 98 with UC who did not. The combined analysis of 53 biologic therapy recipients vs. 178 non-recipients with IBD was also conducted. Logistic regression tests (OR, RR) and sensitivity, specificity, PPV, and NPV were used. Factors significantly correlated with subsequent biologic therapy were perianal disease, complicated disease behavior, high PCDAI (CD), fatigue, hypoalbuminemia, high PUCAI (UC) and fever, fatigue, hypoalbuminemia, hypoproteinemia, and elevated CRP (IBD). Marginally significant factors were ileocecal disease, elevated serum IgA, anemia, and L4a-L4b coexistence. Apart from parameters already accepted as POPO (B2/3, perianal disease), interesting observations are the significance of IgA, L4a-L4b in CD, and hypoalbuminemia in UC."
"This study aims to measure the concentration of cytokines produced during the inflammation process to investigate if there are any differences in response to treatment of pediatric Crohn's disease and to determine if the initial tumor necrosis factor-alpha (TNF-α) level affected the trough concentration of infliximab (IFX).
This study included 30 pediatric patients with moderate-to-severe Crohn's disease. At the time of diagnosis, blood samples were collected for the measurement of cytokines (IL-6, TNF-α, IL-17A, and IL-10). Blood samples were extracted from patients who had begun IFX treatment to measure the IFX trough concentration immediately before the fourth dose administration.
All cytokines (TNF-α, IL-6, IL-10, and IL-17A) were significantly higher in patients who did not achieve clinical or biochemical remission than in those who did (
Measuring cytokines at the time of diagnosis can be used to predict the treatment response. Measuring the initial TNF-α concentration may help to predict the treatment response to IFX. When the initial TNF-α concentration is greater than 27.6 pg/mL, a higher dose of IFX may be more appropriate than routinely administering 5 mg/kg of IFX to maintain the therapeutic concentration."
"Over the past two years, the entire medical community has taken up the fight against the new coronavirus infection. At the initial encounter with COVID-19, it seemed that this virus mainly affects the respiratory system. Still, with long-term observation, it turned out that the consequences of this disease can be much more severe and associated with lung damage and thromboembolic complications, and be a trigger for autoimmune diseases. According to the literature, after suffering COVID-19, some patients debuted systemic lupus erythematosus, hemolytic anemia, thrombocytopenia, developed GuillainBarr syndrome, vasculitis, and multiple sclerosis, and a case of autoimmune hepatitis (AIH) was described in foreign literature. AIH is a fairly rare disease, the prevalence of which in Europe is 1618 cases per 100 thousand inhabitants, affecting mainly women. It is known that chemicals and drugs (minocycline, diclofenac, methyldopa, infliximab, etanercept), viruses (HAV, HEV, EBV, HCV, CMV), environmental factors can serve as triggers of the autoimmune process in the liver. This article presents two clinical cases of AIH that developed after suffering a new coronavirus infection, which we consider as the initial provoking factor of autoimmune inflammation. Given the rarity of AIH, the description of new triggers is of clinical interest. It may be useful for doctors of different specialties since they faced drug-induced liver damage against the background of antiviral and immunobiological therapy. In the domestic literature, there have not yet been any publications devoted to the debut of AIH in adults after coronavirus infection.
В течение последних 2 лет все медицинское сообщество встало на борьбу с новой коронавирусной инфекцией. При первичном столкновении с COVID-19 казалось, что этот вирус поражает преимущественно респираторную систему, но при длительном наблюдении выяснилось, что последствия этой болезни могут быть куда более тяжелыми, сопряженными с поражением легких и тромбоэмболическими осложнениями, а также являться пусковым механизмом для аутоиммунных заболеваний. Согласно литературным данным после перенесенного COVID-19 у некоторых пациентов дебютировали системная красная волчанка, гемолитическая анемия, тромбоцитопения, развивались синдром ГийенаБарре, васкулиты и рассеянный склероз, также в зарубежной литературе описан случай аутоиммунного гепатита (АИГ), который является достаточно редким заболеванием, распространенность которого в Европе составляет 1618 случаев на 100 тыс. жителей, поражает преимущественно женщин. Известно, что в качестве триггеров аутоиммунного процесса в печени могут послужить химические вещества и лекарства (миноциклин, диклофенак, метилдопа, инфликсимаб, этанерцепт), вирусы (HAV, HEV, EBV, HCV, CMV), факторы внешней среды. В данной статье представлены два клинических примера АИГ, развившегося после перенесенной новой коронавирусной инфекции, которая рассматривается нами в качестве первоначального провоцирующего фактора аутоиммунного воспаления. Учитывая редкость АИГ, описание новых триггеров вызывает клинический интерес, может оказаться полезным для врачей разных специальностей, так как ранее в основном сталкивались с лекарственно-индуцированным поражением печени на фоне противовирусной и иммунобиологической терапии. В отечественной литературе пока не встречалось публикаций, посвященных дебюту АИГ у взрослых после коронавирусной инфекции."
"Intestinal stricture and obstruction are rare complications of ulcerative colitis (UC). Currently, there are only a few studies on the treatment of UC with intestinal stenosis, however there are no reports on the treatment of UC with benign intestinal stenosis with ustekinumab (UST).
A 22-year-old woman was admitted to our hospital due to a 3-year history of recurrent bloody mucous in stool with intermittent abdominal pain and distension developed in the past month. She was steroid-dependent and had developed a secondary loss of response to infliximab.
She was diagnosed with UC combined with incomplete intestinal obstruction due to stenosis. The stricture had a mixed pattern with both inflammatory and fibrotic components, with the former covering a larger section of the intestine.
The patient was given UST for 56 weeks.
The patient's symptoms subsided after treatment with UST. The ulcers healed, and the stenosis was reduced.
UST is effective against UC with benign intestinal stenosis. It is thought that UST inhibits the production of transforming growth factor-β and interleukin-17, leading to the suppression of myofibroblast proliferation, ultimately alleviating intestinal stenosis."
"The aim of this study was to assess how 6-thioguanine nucleotide (6-TGN) levels and use of oral methotrexate relate to the pharmacokinetics of biologics.
This was a prospective cohort study including patients with inflammatory bowel diseases on maintenance doses of infliximab, vedolizumab, or ustekinumab on monotherapy or combination with a thiopurine or oral methotrexate. We collected 6-TGN concentrations, biomarker levels, and clinical and endoscopic disease activity. The primary outcomes were infliximab, vedolizumab, and ustekinumab concentrations as well as anti-drug antibodies (ADAs).
A total of 369 patients were recruited (113 infliximab, 133 vedolizumab, and 123 ustekinumab). Patients with 6-TGN levels ≥146 pmol per 8 × 10
Achieving higher 6-TGN levels or the use of methotrexate improved the pharmacokinetics of infliximab. Conversely, these data do not support the use of combination therapy to augment pharmacokinetics with vedolizumab or ustekinumab."
"Psoriasis is a chronic, immune-mediated inflammatory disease for which no definitive cure exists and patients difficult to treat with moderate to severe psoriasis often require life-long therapy. In general, the use of any biologic agent as monotherapy allows a long-term efficacy, however survival response may progressively decrease over time. We report real-world long lasting response data in psoriatic patients on treatment with anti-TNFα evaluating those on the same anti-TNFα agent (infliximab, etanercept, adalimumab) from January 2011 and December 2013 to December 31, 2021 as monotherapy. On 210 treated patients, 69 were found to maintain the same anti-TNFα agent. The median survival rate for etanercept, infliximab and adalimumab was 10, 9.6, and 9.5 years respectively and the efficacy rate was similar (mean PASI96). Our results demonstrate that anti-TNFα agents are a long-term effective and safe therapeutic option for a satisfying proportion (33%) of patients with moderate-to-severe chronic plaque psoriasis. Further long-term real life studies are needed to better understand which are the causes of drug failure or persistent response and why these may occur at different time intervals in patients on the same drug."
"The pathogenesis of severe COVID-19 is due, in part, to dysregulation of the human immune system in response to SARS-CoV-2 infection. Immune cells infected with SARS-CoV-2 can trigger a hyperinflammatory response of both the adaptive and innate immune system that has been associated with severe disease, hospitalization, and death, and better treatment options are urgently needed.
A mainstay of therapy for COVID-19 involves an antiviral agent, remdesivir, in combination with a systemic corticosteroid, dexamethasone.
The addition of a second immunomodulator, such as an interleukin-6 inhibitor or a Janus kinase inhibitor, has been associated with clinical benefit in a subset of patients with moderate-to-severe disease, but their use remains controversial. This manuscript reviews what is known about the approach to treatment of severe COVID-19 and examines how immunomodulators such as infliximab and abatacept may alter clinical management and COVID-19 research in the years ahead based on the results of randomized, controlled trials."
"Axial spondyloarthritis, often known as ankylosing spondylitis (AS), is an inflammatory condition that mostly affects the axial skeleton. Axial spondyloarthritis is further subdivided into non-radiographic and radiographic AS. For radiographic axial spondyloarthritis, the male-to-female ratio is two to one, while for non-radiographic axial spondyloarthritis, it is one to one, often manifesting in the third decade of life. Effective treatment for AS includes non-steroidal anti-inflammatory medications (NSAIDs) and TNF blockers. All articular symptoms of AS have been seen to improve significantly when treated with TNF inhibitors such as Etanercept, Adalimumab, Infliximab, Certolizumab, and Golimumab. Upadacitinib, has proven to be significantly efficacious in the management of active non-radiographic axial spondyloarthritis (nr-axSpA), with MRI-based or blood tests displaying objective evidence of inflammation, an increased C-reactive protein, and an unsatisfactory response to Non-steroidal anti-inflammatory drug (NSAIDs). the lack of oral therapy options, and the stigma associated with surgical intervention makes it crucial to offer an unambiguous treatment choice, especially in light of the disease's strong heredity. Thus, Upadacitinib's usage in the treatment of nr-axSpA and its clinical trial is a significant step toward the availability of an internationally-approved medicine for the treatment of nr-axSpA."
"To assess treatment patterns and initial and maintenance dosing of biologics over 3 years in pediatric patients with ulcerative colitis (UC) or Crohn's disease (CD), utilizing data from the ImproveCareNow registry.
Pediatric patients diagnosed with UC or CD and aged 2-17 years were included in the study. Descriptive statistics were employed to summarize baseline demographics. The proportion of patients on medication for UC or CD were analyzed at the baseline visit, 1-year, and 3-year time points (Cohort 1). Biologic maintenance dosage was calculated only for patients who had data for dose and weight at all-time points (Cohort 2).
In Cohort 1 (UC = 1784; CD = 4720), baseline treatment in UC included corticosteroid, 5-ASA, and 6-MP/AZA; at 1-year and 3-year time points, treatment with 5-ASA and corticosteroid decreased, whereas 6-MP/AZA and anti-TNFs increased. In CD, baseline treatment included corticosteroid, anti-TNF, 6-MP/AZA, and methotrexate; use of corticosteroids decreased, whereas the use of methotrexate and anti-TNFs increased over 3 years. In Cohort 2 (UC = 350; CD = 1537), at first maintenance dose, UC patients on infliximab received a mean dose of 10.5 mg/kg/8 wk, adalimumab (weight < 40 kg and ≥40 kg) 1.3 mg/kg/2 wk and 0.8 mg/kg/2 wk, and vedolizumab 6.9 mg/kg/8 wks. At the first maintenance dose, CD patients on infliximab received a mean dose of 8.1 mg/kg/8 wk, adalimumab (weight < 40 kg) 1.1 mg/kg/2 wk, adalimumab (weight ≥ 40 kg) 0.8 mg/kg/2 wk, and vedolizumab 10.5 mg/kg/8 wks.
The use of corticosteroids was common at the initial visit in patients. Anti-TNFs remain the most used class of biologics, however, reported doses in our study were substantially higher than the standard dosing guidelines."
"The clinical symptoms of an immune checkpoint inhibitor (ICI)-induced colitis are similar to those of ulcerative colitis. ICI-induced colitis, like ulcerative colitis, may be complicated by other colitis, such as "
"The FDA approved adalimumab, an anti-tumor necrosis factor alpha agent, for the treatment of moderate to severe pediatric ulcerative colitis (UC) in February 2021. There are no real-world publications, however, on adalimumab as the first-line biologic in pediatric UC, a form of chronic inflammatory bowel disease (IBD).
A retrospective review was conducted to characterize the clinical courses of nine patients with moderate to severe pediatric UC who received adalimumab as their first biologic and had documented drug monitoring trough levels.
Seven of the nine patients, or 78%, were switched from adalimumab to another therapy due to continued symptoms or steroid-dependence at an average of 5 months from initiation. Six of these seven patients, or 86%, had adalimumab drug trough levels in the consensus therapeutic range. Three patients were successfully switched to infliximab.
Both the Crohn's disease-based dosing and the new FDA-approved pediatric UC dosing of adalimumab were ineffective in inducing remission in the majority of patients in our case series. This study indicates that further real-world observations are needed to optimize and position adalimumab in the treatment paradigm of moderate to severe pediatric UC."
"The treatment guidelines for acute Kawasaki disease (KD) have been revised several times. Moreover, the criterion used to define coronary artery abnormalities (CAAs) has changed from the coronary artery's internal diameter to the Z-score. Treatment for KD and methods for evaluating CAAs vary between hospitals, so we investigated the actual status of acute KD treatment and development of CAAs under the 2012 Japanese treatment guidelines for acute KD.
The 24th Japanese Nationwide Survey on Kawasaki Disease yielded 2618 patients who developed KD in the Kinki area in 2016. We sent a secondary questionnaire to each participating hospital and used the resulting data to investigate the frequency of CAAs according to Z-score, treatment by KD treatment stage, and predictors of CAAs.
The response rate was 80.0%. The data for 1426 patients without major data deficiencies were examined. The frequency of CAAs was 3.0% when based on coronary artery internal diameters and 8.8% when based on Z-scores. Intravenous immunoglobulins combined with corticosteroids were administered as an initial treatment in 12.8% of cases and as a second-line treatment in 16.8% of cases. Corticosteroids, cyclosporine A, infliximab, and plasma exchange were used at similar frequencies for third-line treatment. A pretreatment maximum coronary artery Z-score of ≥1.9 and age <1 year were associated with significantly higher incidences of CAAs.
Using the Z-score resulted in a threefold increase in the number of patients diagnosed with CAAs. A pretreatment maximum coronary artery Z-score of ≥1.9 and age <1 year are useful predictors of CAAs."
"Uveitis is a major manifestation of Behçet disease (BD) and potentially has a high morbidity. This article reviews recently published data on BD uveitis.
A set of classification criteria and a diagnostic algorithm have been developed for BD uveitis. Recent reports have confirmed male predominance and posterior segment inflammation in the majority of BD uveitis patients. A high uveitis attack severity score, fluorescein angiographic leakage at the posterior pole, and disruption of outer retinal layers on optical coherence tomography (OCT) predict poor visual outcome. OCT-angiography studies have suggested subclinical changes of retinal capillaries in patients with or without ocular involvement. In a randomized controlled trial, interferon-α was superior to cyclosporine. Favorable outcomes were reported with earlier initiation, optimization, and withdrawal of infliximab after remission. Adalimumab as first-line was superior to conventional therapy.
Classification criteria will be used to select a homogeneous group of patients for research and the diagnostic algorithm may help ophthalmologists predict the probability of BD uveitis based on ocular findings. Fluorescein angiography and OCT are the routine imaging modalities. Clinical relevance of OCT-angiography is unclear. Interferon-α, infliximab, and adalimumab have proven superior efficacy compared to conventional therapy."
"Behcet's disease is a systemic autoimmune disorder occasionally associated with otological manifestations, including sensorineural hearing loss. We are reporting a case of Behcet's disease, which was complicated by sensorineural hearing loss and managed successfully with anti-TNF agent Infliximab."
"The introduction of biological treatments has revolutionized the management of moderate-to-severe psoriasis. Multiple clinical trials have established the efficacy of biological agents in the treatment of moderate-to-severe psoriasis. Nevertheless, there are no clear indications for optimal monitoring intervals during treatment.
Collect and analyze laboratory evaluation data from patients receiving biological therapy to provide a better understanding of the need for laboratory investigations before and during treatment with biological agents, and to analyze adverse events and other factors.
Retrospective cohort SETTINGS: Tertiary care center in Riyadh, Saudi Arabia.
Data were collected from the electronic medical records of patients attending the dermatology, rheumatology, and gastroenterology clinics from June 2014 to June 2019. The laboratory parameters of patients who have received one of the TNF-alpha inhibitors (adalimumab, etanercept, or infliximab) were collected starting at baseline and up to at least one year from treatment initiation.
The time points at which patients developed significantly abnormal laboratory results during treatment with one of the TNF-alpha inhibitors.
250 patients RESULTS: Most patients were treated with adalimumab (38.4%); a similar proportion (38%) with infliximab, whereas only 23.6% were treated with etanercept. The majority of the significant abnormal laboratory results occurred at baseline, 3-6 and 9-12 months. Most abnormalities were among patients using infliximab, followed by etanercept, and then adalimumab. The median number of laboratory abnormalities for dermatology patients was significantly lower than that for gastroenterology patients (
Because dermatology patients showed a lower median number of laboratory abnormalities than patients treated by other specialties in our study, we believe that dermatology patients require less frequent laboratory monitoring. Therefore, we recommend laboratory evaluation at baseline, after 3-6 months, 1 year from the beginning of treatment, and annually thereafter for patients using TNF-alpha inhibitor agents. However, more frequent testing might be warranted according to patient comorbidities, concomitant medications, and physician judgment.
Single center and retrospective design.
None."
"Anti-tumour necrosis factor (anti-TNF) therapies are the most commonly used biologics for inflammatory bowel disease (IBD), but for patients with a comorbidity, newer agents may be a more appropriate treatment choice.
To investigate the impact of comorbidities in patients with IBD, on first-line biologic prescribing habits of IBD-specialist healthcare practitioners in the UK.
IBD-specialist physicians and nurses were asked to answer an online survey, considering different prescribing scenarios in ulcerative colitis (UC) and Crohn's disease (CD). Respondents could indicate a preference for anti-TNFs or newer biologics, both in the absence and presence of 10 common comorbidities.
A total of 120 IBD-specialist healthcare professionals (HCPs) completed the survey. In the absence of comorbidities, anti-TNFs were favoured; infliximab was the preferred first-line biologic in both UC and CD (43% and 37% of respondents, respectively). On introducing comorbidities, the largest shift in prescribing behaviour was for vedolizumab, with preference increasing by 27% and 21%, compared with infliximab, which fell by 14% and 9% in UC and CD, respectively. Chronic/recurring infection (46%), congestive heart failure (≤44%) and malignancies (≤43%) were the most commonly selected comorbidities for vedolizumab treatment.
Clinicians adapt their biologic prescribing habits in patients with IBD with comorbidities, considering known contraindications and precautions. A preference for vedolizumab is evident in many cases, however, for several comorbid scenarios, including demyelinating disorders, chronic obstructive pulmonary disease and malignancy, anti-TNFs are prescribed despite known risks. It is important that continual re-evaluation of the IBD treatment landscape is undertaken by HCPs, in alignment with recommendations in published guidelines."
"Immune checkpoint inhibitors (ICIs) are a new class of cancer pharmacotherapy consisting of antibodies that block inhibitory immune regulators such as cytotoxic T lymphocyte antigen 4, programmed cell death 1 and programmed death-ligand 1. Checkpoint blockade by ICIs reactivates a tumor-specific T cell response. Immune-related adverse events can occur in various organs including skin, liver, and gastrointestinal tract. Mild to severe colitis is the most common side effect with some experiencing rapid progression to more serious complications including bowel perforation and even death. Prompt diagnosis and management of ICI-induced colitis is crucial for optimal outcome. Unfortunately, its clinical, endoscopic and histopathologic presentations are non-specific and overlap with those of colitis caused by other etiologies, such as infection, medication, graft-"
"Crohn's disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents."
"Psoriatic arthritis (PsA) is a heterogeneous chronic musculoskeletal disease, affecting up to 30% of people with psoriasis. Research into PsA pathogenesis has led to the development of targeted therapies, including Tumor Necrosis Factor inhibitors (TNF-i). Good response is only achieved by ~60% of patients leading to 'trial and error' drug management approaches, adverse reactions and increasing healthcare costs. Robust and well-validated biomarker identification, and subsequent development of sensitive and specific assays, would facilitate the implementation of a stratified approach into clinical care. This review will summarise potential genetic biomarkers for TNF-i (adalimumab, etanercept and infliximab) response that have been reported to date. It will also comment upon the importance of managing clinical confounders when understanding drug response prediction. Variants in multiple gene regions including TNF-A, FCGR2A, TNFAIP3, TNFR1/TNFR1A/TNFRSF1A, TRAIL-R1/TNFRSF10A, FCGR3A have been reported to correlate with TNF-i response at various levels of statistical significance in patients with PsA. However, results were often from heterogenous and underpowered cohorts and none are currently implemented into clinical practice. External validation of genetic biomarkers in large, well-documented cohorts is required, and assessment of the predictive value of combining multiple genetic biomarkers with clinical measures is essential to clinically embed pharmacogenomics into PsA drug management."
"Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the apocrine glands primarily affecting the axillae, perineum, and inframammary regions. It is characterized by painful, inflamed cutaneous lesions causing nodules, sinus tracts, and abscesses. Cervicofacial HS is an atypical presentation of HS in the head and neck region and is scarcely reported in the literature. We present a 34-year-old male who developed a large facial swelling overlying the left inferior mandibular border. Management included surgical incision and drainage, antibiotic therapy, followed by infliximab (Remicade). The purpose of this case report was to highlight the presentation, pathophysiology, interdisciplinary approach to treatment and follow-up of patients with cervicofacial HS, and finally, review the cervicofacial HS literature."
"Cerebrovascular disease is rarely reported in neurosarcoidosis and constitutes one of its least well-described forms, though recognition for it has grown in the last decade with recent studies estimating a higher frequency of occurrence than previously known.
Patients with ischemic stroke were included if the mechanism was directly attributable to sarcoidosis of the CNS. Patients were excluded if an alternative stroke etiology was of equal or higher likelihood than CNS sarcoidosis.
Neurologic disease was the initial presenting manifestation of sarcoidosis in 8/11 (72.7%), and ischemic stroke was an inaugural manifestation of sarcoidosis in 4/11 (36.4%). Small vessel disease was the predominant ischemia subtype (10/11, 90.9%) with pontine perforating vessels (6/11, 54.5%) and lenticulostriate arteries (3/11, 27.3%) being the vasculature most often affected. Vessels with a more rostral supratentorial distribution were uncommonly affected. Common neuroinflammatory accompaniments included leptomeningitis (10/11, 90.9%) and cranial nerve disease (3/11, 27.3%). Recurrent strokes occurred in 8/11 (72.7%), and recurrent neuroinflammation occurred in 7/11 (63.6%). Antiplatelet drugs were used in 6/11 (54.5%) patients. Most (10/11, 90.9%) required at least two lines of immunosuppression to achieve inflammatory disease remission in this context; infliximab was the most successfully employed immunosuppressant (7/8 treatment courses, 87.5%). Recurrent strokes occurred in 8/11 (72.7%) patients, and a second inflammatory attack occurred in 7/11 (63.6%) patients. The presenting median modified Rankin Scale score of 4.0 improved to 2.0 over a median period of follow-up of 52.0 months.
Ischemic strokes in neurosarcoidosis occur in a caudal-to-rostral distribution, tend to affect small caliber blood vessels that lack collateral blood flow, and typically associate with inflammatory leptomeningeal disease. The risk for relapse in the forms of stroke or neuroinflammation are high in this neurosarcoidosis phenotype."
"The optimal treatment strategy for cardiac sarcoidosis has not been standardized. We examined the effectiveness of three prednisone-tapering treatment regimens for cardiac sarcoidosis.
We retrospectively reviewed prednisone-tapering treatment regimens for cardiac sarcoidosis that contained prednisone alone (P), prednisone plus methotrexate (P-M), and prednisone plus infliximab containing regimens (P-I). We defined the success of each regimen as the ability to lower the daily prednisone dose to 7.5 mg or less for 6 or more months without developing an adverse cardiac event. We also examined the lowest effective daily prednisone dose achieved without developing an adverse cardiac event.
We identified 61 treatment regimens in 33 cardiac sarcoidosis patients that were analyzed. The success rate of prednisone-tapering regimens was significantly different P: 8/30, 27%; P-M: 3/23, 13%; P-I: 6/8, 75%., p = 0.04. The lowest effective daily prednisone dose for the regimens was also significantly different: P: 14.1 ± 10.1 mg; P-M: 16.9 ± 9.4 mg; infliximab: 7.8 ± 4.9 mg, (p = 0.03); by both measures the success was greatest with the P-I regimen.
For the treatment of cardiac sarcoidosis, prednisone-tapering regimens containing infliximab are superior to those containing prednisone alone or prednisone plus methotrexate in terms of reaching 7.5 mg/day of prednisone for more than 6 months and achieving the lowest effective prednisone."
"Recently, the extraintestinal manifestations of Crohn's disease (CD) have attracted more and more attention, among which interstitial lung disease (ILD) is a rare extraintestinal manifestation. Clinical presentation is polymorphic and pathogenesis remains unclear. The purpose of this article is to elaborate on these rare extraintestinal manifestations of CD, and the importance of short-term chest computed tomography (CT) for differential diagnosis is emphasized.
A 27-year-old male patient, who is a student, presented with chief complaints of ""loose stools for 4 months, intermittent low-grade fever for 1 month"". The next day, he developed a high fever with a body temperature of 39.8°C. A chest CT scan revealed multiple patellar ground glass shadows which suggested ILD. In the time of Corona virus disease (COVID-19), novel coronavirus pneumonia was first suspected according to the patient's history and symptoms, but laboratory examinations did not confirm. Colonoscopy showed multiple ulcers between the sigmoid colon to the terminal ileum, and pathology found epithelioid granuloma in submucosa. Moreover, a total gastrointestinal CT angiography showed that segmental leaping thickening of the bowel. Based on the above results, we ultimately made a diagnosis of CD. After using systemic steroid therapy, his fever was quickly relieved, and a follow-up chest CT showed that multiple patellar ground glass shadows were almost completely absorbed. Then, infliximab was used, and a repeat colonoscopy showed that intestinal ulcers were significantly improved.
ILD is a rare extraintestinal manifestation of CD and reveals the excellent response to systemic steroid therapy. Manifestations of pulmonary disease associated with IBD are polymorphic; therefore; clinicians should be more vigilant regarding IBD-related ILD, especially when infectious causes have been excluded in the time of COVID-19. For those with ILD related to IBD, a short-term follow-up CT would be crucial."
"Infliximab has been recommended by the American Society of Clinical Oncology (ASCO) guidelines for the treatment of steroid-refractory immune checkpoint inhibitor-related pneumonia (CIP), but clinical evidence remains insufficient. In order to improve the level of diagnosis and treatment and rational use of infliximab in the treatment of CIP, a successful case is reported and the relevant literature is reviewed.
We report a 67-year-old male patient with small cell lung cancer (SCLC) who was admitted to hospital with rapidly worsening dyspnea and bilateral interstitial lung following PD-1 inhibitor (tislelizumab) combined with chemotherapy and radiation therapy. According to the comprehensive judgment of the patient's medical history, clinical symptoms, imaging manifestations, laboratory tests, exclusion of infection, heart failure and treatment response, the diagnosis of grade 4 CIP was made. The patient's condition did not improve after high-dose glucocorticoid and immunoglobulin therapy. After infliximab was added, the clinical manifestations and imaging were significantly improved, oxygenation index also gradually return to normal, then the patient was discharged smoothly.
This report suggests that infliximab should be considered when high-dose glucocorticoids combined with immunoglobulin are ineffective for severe CIP. At the same time, this case indicates that inflammatory factors, especially tumor necrosis factor (TNF-α), may be prospective in predicting the efficacy of infliximab in the treatment of steroid-refractory CIP."
"Recent trials support the clinical efficacy and safety of subcutaneous infliximab (IFX) or vedolizumab (VDZ) for Inflammatory Bowel Disease (IBD). We evaluated the uptake and rationale for choosing to switch from intravenous infusions to subcutaneous injections.
Retrospective analysis of all adult patients receiving standard dosing IFX or VDZ maintenance therapy to investigate uptake of subcutaneous injections and the rationale for switching to subcutaneous injections.
Of 232 eligible patients (total = 258: IFX = 190, VDZ = 68, and no longer eligible = 26), 58% of patients on IFX and 59% of patients on VDZ chose to switch to subcutaneous treatment. Age, sex, diagnosis, drug, line of treatment, and duration of treatment were not predictors for willingness to switch. Questionnaire responses (
Switch uptake rates were 58%, with 90% of patients eligible to switch. Switch decision was influenced by time savings for patients but not by other patient-related factors."
"Inflammation is the main cause of corneal and retinal damage in an ocular alkali burn (OAB). The aim of this study was to investigate the effect of tauroursodeoxycholic acid (TUDCA) on ocular inflammation in a mouse model of an OAB. An OAB was induced in C57BL/6j mouse corneas by using 1 M NaOH. TUDCA (400 mg/kg) or PBS was injected intraperitoneally (IP) once a day for 3 days prior to establishing the OAB model. A single injection of Infliximab (6.25 mg/kg) was administered IP immediately after the OAB. The TUDCA suppressed the infiltration of the CD45-positive cells and decreased the mRNA and protein levels of the upregulated TNF-α and IL-1β in the cornea and retina of the OAB. Furthermore, the TUDCA treatment inhibited the retinal glial activation after an OAB. The TUDCA treatment not only ameliorated CNV and promoted corneal re-epithelization but also attenuated the RGC apoptosis and preserved the retinal structure after the OAB. Finally, the TUDCA reduced the expression of the endoplasmic reticulum (ER) stress molecules, IRE1, GRP78 and CHOP, in the retinal tissues of the OAB mice. The present study demonstrated that the TUDCA inhibits ocular inflammation and protects the cornea and retina from injury in an OAB mouse model. These results provide a potential therapeutic intervention for the treatment of an OAB."
"Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn's disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD."
"After market exclusivity ends for biologic drugs, biosimilars-follow-on versions made by other manufacturers-can compete with lower prices. Biosimilars have modestly reduced prescription drug spending for US payers, but it is unclear whether patients have directly experienced any savings. In this study we assessed whether availability of biosimilar infliximab was associated with lower out-of-pocket (OOP) costs, using claims from a national data set of commercially insured patients from 2014 to 2018. We used two-part models, adjusting for patient demographics, clinical characteristics, insurance plan type, and calendar month. Compared with the reference biologic, there was no difference in the percentage of biosimilar claims with OOP costs (30.1% vs. 30.8%; adjusted odds ratio (aOR) 0.98, 95% confidence interval (CI), 0.84-1.15, P = 0.84) or the average nonzero OOP cost (median $378 vs. $538, adjusted mean ratio (aMR) 0.97, 95% CI, 0.80-1.18, P = 0.77). The percentage of claims with OOP costs was lower after biosimilar competition (30.7% vs. 35.0%, aOR 0.96, 95% CI, 0.94-0.99, P = 0.003), but average nonzero costs increased (median $534 vs. $520, aMR 1.04, 95% CI, 1.01-1.07, P = 0.004). Thus, early biosimilar infliximab competition did not improve affordability for patients. Policymakers need to better assure that competition in the biosimilar market translates to lower costs for patients using these medications."
"This analysis evaluates the association between baseline patient-reported symptom (PRS) severity in Crohn's disease (CD), including abdominal pain, stool frequency, general well-being, and achievement of clinical and endoscopic outcomes. We compared baseline PRS to baseline endoscopic scores for the prediction of endoscopic remission (ER).
This post hoc analysis of 2 clinical trials of infliximab in CD included 601 patients and evaluated baseline PRS variables (abdominal pain, stool frequency, and general well-being) as measured by the Crohn's disease activity index and their association with 6-month clinical remission (CR) (Crohn's Disease Activity Index<150), corticosteroid-free CR, and week 26/54 ER (absence of mucosal ulceration). Logistic regression models assessed the relationships between PRS and outcomes of interest. Receiver operating characteristic curve analyses compared the sensitivity and specificity of the different baseline PRS compared with baseline endoscopic scores for achievement of ER at weeks 26 and 54.
No difference was found comparing patients with higher baseline PRS to those with lower PRS in achieving 6-month CR, 6-month corticosteroid-free CR, or week 26/54 ER. Modified multiplier of the SES-CD (MM-SES-CD) at baseline demonstrated a significant ability to predict week 54 ER (area under the curve, 0.71; 95% CI 0.65-0.78; P=0.017).
Baseline PRS in CD is not prognostic of clinical or endoscopic response. In contrast, active endoscopic disease as measured by the MM-SES-CD, more accurately predicts endoscopic outcomes. Endoscopic scores such as the MM-SES-CD may be considered for selection criteria and as a primary outcome of interest in CD trials, with PRS as a co-primary or secondary endpoint."
"Although reports of gastrointestinal perforation after immune-related adverse events (irAE) enteritis are rare, the anti- vascular endothelial growth factor (VEGF) effect of bevacizumab may be involved in gastrointestinal perforation. We report a rare case of gastrointestinal perforation in a patient with hepatocellular carcinoma treated with atezolizumab/bevacizumab combination therapy and infliximab before steroid use.
A 72-year-old man, who received seven courses of atezolizumab/bevacizumab for hepatocellular carcinoma due to hepatitis B, was admitted to our department with idiopathic abdominal pain and diarrhea (grade 2 [G2]). Computed tomography (CT) and colonoscopy confirmed edema in the gastrointestinal tract. Perforation of the jejunum was observed in a CT performed on the third day and an emergency operation was performed. Intraoperative findings showed severe edema of the jejunum and leakage of feces into the abdominal cavity. The patient was diagnosed with irAE enteritis comprehensively with severe wall thickening on CT and colonoscopy, negative stool culture, and pathological findings of CD8-positive cells. Infliximab was administered before initiating steroids, to prevent reperforation. The enteritis improved by the 22nd day; however, CT performed on the 35th day of illness showed relapse of gastrointestinal wall thickening and G2 diarrhea symptoms; therefore, prednisolone (PSL) 60 mg/day was started on the 36th day of illness. After introducing PSL, enteritis did not reoccur, and the patient was discharged on the 63rd day of illness after admission.
There are no reports of gastrointestinal perforation by atezolizumab/bevacizumab for hepatocellular carcinoma, and prior administration of infliximab. We therefore report the clinical course and management."
"Pneumocystis jirovecii pneumonia (PJP) is a very rare, potentially life-threatening pulmonary fungal infection that occurs in immunocompromised individuals including patients with inflammatory bowel disease (IBD). Our aim was to describe immunosuppressive treatment exposure as well as the outcome in IBD patients with PJP.
PJP cases were retrospectively collected through the COllaborative Network For Exceptionally Rare case reports of the European Crohn's and Colitis Organization. Clinical data were provided through a case report form.
18 PJP episodes were reported in 17 IBD patients (10 ulcerative colitis and 7 Crohn's disease). The median age on PJP diagnosis was 55 years (IQR, 40-68 years). Two PJP (11.1%) occurred in patients on triple immunosuppression, 10 patients (55.6%) had double immunosuppressive treatment, 4 patients (22.2%) had monotherapy and 2 PJP occurred in absence of immunosuppressive treatment (one in a human immunodeficiency virus patient and one in a patient with a history of autologous stem cell transplantation). Immunosuppressive therapies included steroids (n=12), thiopurines (n=10), infliximab (n=4), ciclosporin (n=2), methotrexate (n=1) and tacrolimus (n=1). None of the patients diagnosed with PJP had received prophylaxis. All patients were treated by trimethoprim/sulfamethoxazole or atovaquone and an ICU stay was required in 7 cases. Two patients (aged 71 and 32 years) died, and one patient had a recurrent episode 16 months after initial treatment. Evolution was favourable for the others.
This case series reporting potentially fatal PJP highlights the need for adjusted prophylactic therapy in patients with IBD on immunosuppressive therapy."
"Ankylosing spondylitis (AS), a type of chronic spondyloarthritis, significantly increases patients' risk of cervical spine fracture. We describe the anesthetic management of a 32-year-old male with AS who was scheduled to have bilateral mandibular third molar extractions under general anesthesia. To minimize the potential for cervical spine damage, a laryngeal mask airway was used for airway management while the patient's head was held firmly during surgery. Additionally, he developed a postoperative surgical infection that was attributed to his continued immunotherapy with infliximab. In patients with AS, postoperative infection control as well as cervical spine protection throughout the perioperative period is important."
"Patient-reported outcome (PRO) data have assumed increasing importance in the care of patients with rheumatoid arthritis (RA), yet physician-derived disease activity measures, such as Clinical Disease Activity Index (CDAI), remain the most accepted metrics to assess disease activity. The possibility that newer longitudinal PRO data might be used as a proxy for the CDAI has not been evaluated.
Using data from a large pragmatic trial, we evaluated patients with RA initiating golimumab intravenous or infliximab. The classification target was low disease activity (LDA) (CDAI ≤10) at the first visit between months 3 and 12. Data were randomly partitioned into training (80%) and test (20%) data sets. Multiple machine learning (ML) methods (eg, random forests, gradient boosting, support vector machines) were used to classify CDAI disease activity category, conduct feature selection, and assess feature importance. Model performance evaluated cross-validated error, comparing different ML approaches using both training and test data.
A total of 494 patients were analyzed, and 36.4% achieved LDA. The most important classification features included several Patient-Reported Outcomes Measurement Information System measures (social participation, pain interference, pain intensity, and physical function), patient global, and baseline CDAI. Among all ML methods, random forests performed best. Overall model accuracy and positive predictive values for all ML methods were approximately 80%.
ML methods coupled with longitudinal PRO data appear useful and can achieve reasonable accuracy in classifying LDA among patients starting a new biologic. This approach has promise for real-world evidence generation in the common circumstance when physician-derived disease activity data are not available yet PRO measures are."
"Generalized pustular psoriasis (GPP) is a rare severe variant of psoriasis that is characterized by the abrupt widespread onset of small pustules accompanied by systemic manifestations of inflammation. It can arise in patients with a history of psoriasis as well as in those without, sometimes due to medication initiation or withdrawal, pregnancy, or infection. Generalized pustular psoriasis is thought to be driven primarily by innate immunity and unrestrained IL-36 cytokine activity. Recent genetic analyses have identified 3 genetic mutations that are associated with GPP-IL36RN, CARD14, and AP1S3-though these mutations only account for a minority of cases. There are many cutaneous pustular diseases that must be ruled out in the evaluation of a patient with suspected GPP, especially acute generalized exanthematous pustulosis (AGEP), and histologic analysis is the cornerstone of diagnosis. Although the quality of evidence to generate treatment recommendations for GPP is limited, management often includes utilization of systemic agents and/or biologics, usually with adjunctive topical treatment. Accumulating evidence suggests that biologic agents, especially infliximab, may be considered as first-line treatment of GPP, especially in severe acute cases, due to their abrupt onset of action and favorable side-effect profiles compared with oral systemic agents."
"Medicare patients in the United States may face high out-of-pocket (OOP) costs for specialty inflammatory bowel disease (IBD) medications.
We conducted a study of Medicare OOP costs for specialty IBD medications between 2020 and 2022 and compared them to incomes of typical Medicare beneficiaries.
In 2022, median OOP costs ranged from 6.4% to 59.2% of annual income for a Medicare patient with approximately median income. Inflation-adjusted OOP costs for most medications increased between 2020 and 2022 though decreased for infliximab and its biosimilars.
OOP costs may limit many Medicare beneficiaries' access to specialty IBD medications."
"Infliximab is an effective drug for the treatment of Crohn's disease. As a rare and unique adverse effect of infliximab, hypertension should be paid enough attention in clinical work. At present, there is no relevant case report. We report a case of a 38-year-old man with Crohn's disease who had no history of hypertension and developed hypertension symptoms during infliximab treatment.
The patient was treated with 5 mg/kg infliximab on August 27, 2020. From August 27, 2020 to October 20, 2020, the patient underwent 3 treatment sessions. After each injection of infliximab, the patient's blood pressure became elevated, accompanied by dizziness and symmetrical numbness of both lower limbs. Amlodipine benazepril tablets were given orally to control blood pressure. Under close monitoring, 5 mg/kg infliximab was used again. After 10 min of infusion, blood pressure rose to 160/118 mmHg. Infusion was discontinued immediately, after which blood pressure decreased to normal. Adrenal computed tomography did not indicate adrenal hyperplasia or space occupying lesions, and the detection of hypertension related indicators in standing and supine position was abnormal. Since follow up, the patient has stopped using infliximab and has had no hypertension-related symptoms, even without antihypertensives. Measured blood pressure was within the normal range.
Hypertension, as one of the rare adverse reactions of infliximab in the treatment of Crohn's disease, should be paid enough attention."
"Therapeutic drug monitoring (TDM) is effective in optimizing the efficacy of infliximab in patients with inflammatory bowel disease (IBD). An affordable way of monitoring is in high demand. This study evaluated the analytical and clinical performances of the newly available Remsima monitor kits and compared them with the established enzyme-linked immunosorbent assay kits. The trough level of infliximab in patients with IBD treated with an infliximab originator (Remicade) or biosimilar compounds (Remsima and Remaloce) was measured using a Remsima® Monitor Drug Level (Remsima) kit at the Samsung Medical Center, Seoul, Korea. Twenty-six plasma samples were collected immediately before the infusion of infliximab from 18 patients with IBD (Remicade, n = 8; Remsima, n = 6; and Remaloce, n = 4). The intra-assay intraclass correlation coefficient (ICC) of the RIDA and Remsima kits was 0.951 (95% CI = 0.908-0.976) and 0.990 (95% CI = 0.981-0.995). The inter-assay ICC of infliximab trough level between the RIDA and Remsima kits was very high (R = 0.971; 95% CI = 0.935-0.987), and the mean difference between the kits was 1.458 (95% limits of agreement = -3.302 to 6.219). The intra- and inter-assay reliabilities of all types of infliximab did not show significant differences. Qualitative stratification revealed substantial similarities between the kits (weighted kappa = 0.798). This study indicated that the Remsima kit was reproducible and highly correlated with the RIDA kit."
"The use of biologics in paediatric-onset inflammatory bowel disease (PIBD) is rapidly changing.
To identify the incidence and prevalence of biologic use within Scottish PIBD services, and to describe patient demographics and outcomes for those patients who required escalation of therapy beyond anti-tumour necrosis factor alpha (anti-TNFα) agents METHODS: We captured a nationwide cohort of prospectively identified patients less than 18 years of age with PIBD (A1 phenotype; diagnosed <17 years of age) within paediatric services over a 4.5-year period (1 January 2015-30 June 2019). All patients who received infliximab, adalimumab, vedolizumab or ustekinumab during the study period and/or received their first dose of these biologics were audited retrospectively.
Scotland-wide PIBD-prevalence cases increased from 554 to 644 over the study period. A total of 495 incident new-start biological therapies were commenced on 403 PIBD patients: 295 infliximab (60%), 161 adalimumab (32%), 24 vedolizumab (5%) and 15 ustekunumab (3%). The proportion of new-start biologics changed with infliximab initiation rates decreasing (87%-54%) while adalimumab (13%-31%), vedolizumab (0%-9%) and ustekinumab (0%-6%) all increased. The incidence rate (first dose of new biologic not including biosimilar switch) increased from 6.9% to 8.1% over the study period and point prevalence rates (any biologic use) increased from 20.2% to 43.5% - an average annual percentage increase of 20%. Biosimilar penetration of new-start anti-TNFα agents increased from 3% to 91%. Demographics and outcomes of those patients receiving vedolizumab and ustekinumab were similar.
Complete accrual of Scottish nationwide biologic usage within paediatric services demonstrates a rapidly changing, inexorably increasing PIBD biologics landscape."
"The early prediction of intravenous corticosteroid (IVCS) resistance in acute severe ulcerative colitis (ASUC) patients remains an unresolved challenge. This study aims to construct and validate a model that accurately predicts IVCS resistance.
A retrospective cohort was established, with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020. The primary outcome was IVCS resistance. Classification models, including logistic regression and machine learning-based models, were constructed. External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University.
A total of 129 patients were included in the derivation cohort. During index hospitalization, 102 (79.1%) patients responded to IVCS and 27 (20.9%) failed; 18 (14.0%) patients underwent colectomy in 3 months; 6 received cyclosporin as rescue therapy, and 2 eventually escalated to colectomy; 5 succeeded with infliximab as rescue therapy. The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and C-reactive protein (CRP) level at Day 3 are independent predictors of IVCS resistance. The areas under the receiver-operating characteristic curves (AUROCs) of the logistic regression, decision tree, random forest, and extreme-gradient boosting models were 0.873 (95% confidence interval [CI], 0.704-1.000), 0.648 (95% CI, 0.463-0.833), 0.650 (95% CI, 0.441-0.859), and 0.604 (95% CI, 0.416-0.792), respectively. The logistic regression model achieved the highest AUROC value of 0.703 (95% CI, 0.473-0.934) in the external validation.
In patients with ASUC, UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance. We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC. A nomogram based on the logistic regression model might aid in the management of ASUC patients."
"Anti-TNFα are recommended for preventing Crohn's disease (CD) postoperative recurrence (POR) in patients with risk factors. However, few data exploring anti-TNFα efficacy in patients with preoperative anti-TNFα failure are available so far.
The aim of the present study was to compare the efficacy of anti-TNFα with other biologics and immunosuppressants to prevent POR in this setting.
Consecutive CD patients who underwent bowel resection between January 2010 and December 2019 after failure of at least one anti-TNFα were retrospectively included among three tertiary centers if they started a postoperative medical prophylaxis within the three months after index surgery. The main outcome was to compare rates of objective recurrence (endoscopic or radiological recurrence in absence of colonoscopy) between patients treated with an anti-TNFα agent or another treatment as prevention of POR.
Among the 119 patients included, 71 patients received an anti-TNFα (26 infliximab, 45 adalimumab) and 48 another treatment (18 ustekinumab, 7 vedolizumab, 20 azathioprine and 3 methotrexate) to prevent POR. Rates of objective recurrence at two years were 23.9% in patients treated with anti-TNFα and 44.9% in the others (p = 0.011).
Anti-TNFα remained an effective option to prevent POR for patients operated upon with previous anti-TNFα failure."
"Although extraintestinal manifestations of inflammatory bowel disease (IBD) are well documented, myocarditis has only rarely been reported as an extraintestinal manifestation, and it can be fatal. The various clinical presentations and causes of myocarditis in IBD patients complicate making a correct and timely diagnosis.
Here we report a 15-year-old boy who presented with myocarditis as the initial presentation of a relapse of ulcerative colitis. In reviewing the literature for cases of myocarditis complicating IBD, we found 21 other cases, allowing us to expand our understanding of the clinical presentation, diagnosis, management, and outcomes of this rare condition. The most frequent diagnostic clues for myocarditis in IBD patients are dyspnea, chest pain, tachycardia, raised cardiac biomarkers, and abnormalities on trans-thoracic echocardiography. Additionally, we discuss the etiology of myocarditis in IBD patients, which include an extraintestinal manifestation, the adverse effects of mesalamine and infliximab, selenium deficiency, and infection, to help provide a framework for diagnosis and management.
Myocarditis as an extraintestinal manifestation of IBD can be life-threatening. Trans-thoracic echocardiogram and cardiac magnetic resonance may assist its diagnosis."
"Kawasaki disease is a systemic vasculitis with a risk of developing coronary artery lesions if left untreated. Kawasaki disease can be diagnosed clinically with classical symptoms (conjunctivitis, rash, lymphadenopathy, mucositis, edema of hands and feet), but predicting the risk of developing coronary artery aneurysm remains challenging. The coronary sequelae of Kawasaki disease have significant morbidity and mortality and are the second most common cause of acquired cardiac disease in children. Several genetic and immune factors are involved in the inflammation of coronary artery lesions in Kawasaki disease. Inositol trisphosphate 3-Kinase (ITPKC), Foxp3+, circular RNAs, mannose-binding lectin 2 (MBL2), complement factor H (CFH), kininogen 1 (KNG1), serpin family C member 1 (SERPINC1) and fibronectin 1 (FN1) are the essential genes identified in the pathogenesis of coronary artery lesions in Kawasaki disease. The addition of methylprednisolone to a combination of aspirin and intravenous immunoglobulins and biological agents like anakinra, etanercept, infliximab, and immunosuppressants like cyclosporine prevents the occurrence of coronary artery aneurysms in Kawasaki disease. Since the coronary artery lesions form the second most common cause of acquired cardiac disease in children and the incidence of myocardial infarction is a late complication, the risk stratification for coronary artery aneurysms and follow-up protocols for the prevention of cardiac thrombosis were proposed by the American Heart Association in 2017."
"To compare the persistence, retention rate and prescription pattern  of original infliximab and infliximab CT-P13 in biologic- naïve patients with ulcerative colitis.
This was an ambispective study of biologic-naive patients with  ulcerative colitis who received non-simultaneous first-line treatment with  Remicade ® (infliximab) and Remsima® (infliximab CT-P13) over a 10-year  study period (2012-2021). Data on their age, weight, persistence, retention  rate and on whether they required intensification or deintensification  throughout the study period was collected. The real patient/year cost of  Remicade® and Remsima® was determined individually based on the amounts  administered during the study period.
27 biologic-naive patients were treated with Remicade® and 53 with  Remsima®. Neither patient group presented with differences in terms of  weight and age. Persistence (median ± interquartile range) with Remicade ®  was 42.49 ± 57.48 months, as compared to 27.50 ± 58.50 months for  Remsima®, without significant differences (p = 0.455). The retention rate at  6, 12, and 24 months was 81%, 63%, and 33%, respectively, for the Remicade® group and 71%, 47%, and 37%, respectively, for the Remsima® group. Nine subjects in the Remicade® group vs 11 patients in the Remsima ® group were intensified. Regarding deintensification, five patients treated with  Remicade® were deintensified, as compared with 7 patients on Remsima®.  Savings obtained with the use of Remsima® amounted to 203,649 €, which  would allow treating an additional 118 patients with biosimilar infliximab for  one year.
There are no significant differences in persistence, retention, and number of intensifications or deintensifications between  iologicnaïve patients treated with Remicade® and those treated with  Remsima®, the latter being an effective, safe and economical alternative for  the treatment of ulcerative colitis.
Comparar la persistencia, tasa de retención y pauta de prescripción de infliximab original e infliximab CT-P13 en pacientes naive a biológicos con colitis ulcerosa.Método: Estudio ambispectivo de pacientes naive a biológicos en colitis ulcerosa que recibieron tratamiento en primera línea con Remicade® (infliximab) y Remsima® (infliximab CT-P13) de forma no  simultánea durante un periodo de estudio de 10 años (2012-2021). Se  tomaron datos de su edad, peso, persistencia, tasa de retención y si precisó de  intensificación o desintensificación a lo largo del periodo de estudio. Se  determinó el coste paciente/año real de Remicade® y Remsima® de forma  individualizada en función de las administraciones durante el periodo del  estudio.
Un total de 27 pacientes naive a biológicos fueron tratados con  Remicade® y 53 con Remsima®. Ambos grupos de pacientes no presentaron diferencias en cuanto al peso y edad. La persistencia (mediana ±  rango intercuartílico) con Remicade® fue de 42,49 ± 57,48 meses frente a  27,50 ± 58,50 meses para Remsima®, sin demostrar diferencias significativas (p = 0,455). La tasa de retención a los 6, 12 y 24 meses fue del  81%, 63% y 33%, respectivamente, para el grupo de Remicade®, y del 71%, 47% y 37%, respectivamente, para el grupo de Remsima®. En el grupo de pacientes tratados con Remicade®, 9 pacientes fueron intensificados frente a  11 pacientes en el grupo de Remsima®. En cuanto a las desintensificaciones, 5  pacientes que recibieron tratamiento con Remicade® fueron  desintensificados frente a 7 pacientes en tratamiento con Remsima®. El ahorro obtenido con el uso de Remsima® fue de 203.649 €, que equivaldría a tratar a  118 pacientes adicionales con infliximab biosimilar durante un año.
No existen diferencias significativas en la persistencia, tasa de  retención y número de intensificaciones y desintensificaciones entre los  pacientes naive que fueron tratados con Remicade® y aquellos tratados con  Remsima®, siendo una alternativa eficaz, segura y económica en el  tratamiento biológico de la colitis ulcerosa."
"There are concerns regarding anti-TNF-induced lupus (ATIL) in patients with inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis about the incidence, the clinical characteristics and serological characteristics of ATIL secondary to anti-TNF agents in IBD patients.
Electronic databases were searched to identify relevant studies. Primary outcomes were the pooled ATIL incidence rates in IBD patients treated with anti-TNF agents. Secondary outcomes were the pooled clinical symptoms incidence rates, autoantibodies incidence rates and clinical resolution rates in IBD patients treated with anti-TNF agents.
Ten studies were included in this meta-analysis. The pooled ATIL incidence rate in IBD patients treated with anti-TNF-α agents was 2.5%. The pooled ATIL incidence rate in UC and CD patients treated with anti-TNF-α agents was 1.5% and 1.8%, respectively. The pooled ATIL incidence rate in IBD patients treated with IFX and ADA was 4.5% and 0.2%, respectively. The pooled arthritis, mucocutaneous symptom, myalgia and fatigue incidence rate in IBD patients treated with anti-TNF-α agents was 87.2%, 29.4%, 23.9% and 41.8%, respectively. The pooled ANA rate in IBD patients treated with anti-TNF-α agents was 97.3%. The pooled anti-dsDNA antibody rate in IBD patients treated with anti-TNF-α agents was 73.9%.
ATIL has a low prevalence in IBD patients treated with anti-TNF agents. ATIL occurs more frequently in CD patients than in UC patients. Arthritis, fatigue and mucocutaneous lesions were found to be common symptoms of ATIL. Patients with ATIL were more likely to develop ANA and anti-dsDNA."
"This exploratory analysis investigated the potential use of the multibiomarker disease activity (MBDA) score to support biosimilarity assessments using data from two randomised controlled trials (RCTs) of biosimilar infliximab (IFX-qbtx) and biosimilar adalimumab (ADL-afzb) versus EU-sourced infliximab (Remicade; IFX-EU) and adalimumab (Humira; ADL-EU) reference products, respectively, both conducted in adult patients with active rheumatoid arthritis.
In one study, patients (N=650) were randomised 1:1 to IFX-qbtx or IFX-EU (3 mg/kg intravenous at weeks 0, 2 and 6, then every 8 weeks). In the other, patients (N=597) were randomised 1:1 to ADL-afzb or ADL-EU (40 mg subcutaneous every other week). All treatments were given with MTX. Mean values of MBDA scores were calculated at baseline (BL), based on the concentrations of 12 serum proteins using the Vectra disease activity algorithm, and at timepoints throughout treatment period 1 (TP1) of the IFX (weeks 6, 14, 30) and ADL (weeks 6, 12, 26) studies. Data were summarised using descriptive statistics for the intent-to-treat population, without imputation for missing data.
At BL, mean (±SD) MBDA scores were 61.3 (±12.5) and 58.8 (±13.2) for IFX-qbtx (n=236) and IFX-EU (n=248), respectively, and 57.2 (±14.44) and 58.3 (±15.34) for ADL-afzb (n=292) and ADL-EU (n=293), respectively. Mean MBDA scores were highly comparable between IFX-qbtx and IFX-EU and between ADL-afzb and ADL-EU at all measured timepoints during TP1 in each study.
These RCTs are the first to incorporate MBDA score as an exploratory assessment of biosimilarity. MBDA scores may provide objective, quantitative evidence of biosimilarity using an assessment of disease activity that is independent of the potential subjectivity inherent in joint counts, or in patient or physician global assessments.
NCT02222493 and NCT02480153."
"Surgery in Crohn's disease may be the cause of short bowel syndrome that may lead to kidney dysfunction. Dual biologic therapy is rarely needed to control activity. We present a case of a 61-year-old steroid dependent (A2L1B3p) female who had undergone surgery on three occasions: ileocecal resection (resection of 15 cm of terminal ileum); resection of right and left colon up to sigmoid; proctectomy with intersphincteric resection along with ileostomy due to a rectovaginal fistula. She had been previously treated with prednisone, azathioprine, methotrexate, infliximab and adalimumab but the treatment was discontinued owing to adverse effects. Vedolizumab was started, showing good control of the luminal activity but the rectovaginal fistula recurred. Treatment changed to ustekinumab, the fistula activity was controlled but the mucosa activity recurred. 11 months after commencing with ustekinumab, vedolizumab was added to the treatment and complete remission was achieved for three years. Simultaneously, the patient developed renal dysfunction derived from the short bowel syndrome that led to chronic kidney failure. In the face of potential renal replacement therapy, a new therapy with 2.5 mg/sc/d teduglutide was started achieving stable figures of creatinine and normalization of the glomerular filtration rate."
"CD4+ T-cell activation through recognition of Human Leukocyte Antigen II (HLAII)-presented peptides is a key step in the development of unwanted immune response against biotherapeutics, such as the generation of anti-drug antibodies (ADA). Therefore, the identification of HLAII-presented peptides derived from biotherapeutics is a crucial part of immunogenicity risk assessment and mitigation strategies during drug development. To date, numerous CD4+ T-cell epitopes have been identified by HLAII immunopeptidomics in antibody-based biotherapeutics using either their native or aggregated form. Antibody-target immune complexes have been detected in patients with ADA and are thought to play a role in ADA development by enhancing the presentation of CD4+ T-cell epitopes at the surface of antigen presenting cells (APCs). The aim of this study was to investigate the effect of biotherapeutic antibody-target immune complexes on the HLAII peptide presentation of biotherapeutics in human primary monocyte-derived dendritic cells (DCs). The trimeric tumor necrosis factor (TNF) and its biotherapeutic antagonists infliximab (INFL), adalimumab (ADAL), and a single armed Fab' were used as a model system. The HLAII immunopeptidome of DCs loaded with antagonists or their immune complexes with TNF was analyzed by trapped ion mobility time-of-flight mass spectrometry (timsTOF MS) leading to the identification of ~ 12,000 unique HLAII-associated peptides per preparation. Anti-TNF sequences were detected at a median of 0.3% of the total immunopeptidome, against a majority background of peptides from endogenous and media-derived proteins. TNF antagonist presentation spanned the variable and constant regions in a widespread manner in both light and heavy chains, consistent with previously discovered HLAII peptides. This investigation extends the collection of observed HLAII peptides from anti-TNF biotherapeutics to include sequences that at least partially span the complementary determining regions (CDRs), such as the LCDR1 for both INFL and ADAL. Although antagonist presentation varied significantly across donors, peptides from both bivalent antagonists INFL and ADAL were more highly presented relative to the Fab'. While TNF immune complexes did not alter overall HLAII presentation, a moderate increase in presentation of a subset of peptide clusters was observed in the case of INFL-TNF, which included HCDR2, HCDR3 and LCDR2 sequences."
"Diagnosis of breast cancer in a patient with Crohn's disease (CD) is uncommon. However, cytotoxic chemotherapy might help control CD during the treatment period. Here, we report a case of CD relapse during treatment with neoadjuvant chemotherapy (NAC) for bilateral breast cancer. A 39-year-old woman with CD controlled by infliximab and mesalazine was diagnosed with bilateral breast cancer. Infliximab treatment was discontinued temporarily so that the patient could receive NAC. However, her CD symptoms intensified during chemotherapy, and after her symptoms improved after a one-time administration of infliximab, the remainder of NAC was completed with a corticosteroid. Bilateral breast conservation surgery was performed. Histopathological examination revealed partial response of the left breast cancer and no residual cancer in the right breast. Breast irradiation and hormone therapy were added and no signs of recurrence have been observed for 5 years. CD has been well controlled with adalimumab and mesalazine."
"A 68-year-old man presented in late summer 2021 with fever, myalgias, generalized weakness, dizziness, and headache. Past medical history included rheumatoid arthritis treated with infliximab, congestive heart failure with preserved ejection fraction, and recent travel to Alaska. He was febrile, tachycardic, and tachypneic on admission. Physical exam and admission labs were overall unremarkable. On day 4, he complained of shortness of breath and central chest discomfort. Troponin was mildly elevated, electrocardiogram was unremarkable, and echocardiogram showed new global wall motion abnormalities and ejection fraction of 40%, which was 55% months prior. Serum West Nile IgM antibodies resulted positive near the end of hospitalization. Testing for SARS-CoV-2, influenza as well as multiple other viral, bacterial, and fungal organisms was negative. Overall, the patient recovered clinically including improvement in ejection fraction on echocardiogram with conservative management. West Nile virus (WNV) is associated with a myriad of symptoms and complications, most notably, neuroinvasive disease. However, cardiomyopathy secondary to WNV as illustrated in this case has been infrequently described. Clinicians should be aware of this potential rare complication in patients with WNV to improve rapid detection and treatment of myositis, associated cardiomyopathy, and related complications."
"Mucosal healing (MH) has become a therapeutic end point for Crohn's disease (CD). The purpose of this study was to identify potential risk factors responsible for a lower probability of mucosal healing in CD. It also aimed to create and validate a noninvasive tool for predicting mucosal healing in CD to aid clinical decision-making.
We established a derivation cohort diagnosed with CD, in which endoscopic examination was performed before and after treatment at the First Affiliated Hospital of Nanjing Medical University between January 2010 and June 2021. Patient data including demographic and clinical characteristics and treatment details were collected. The achievement of mucosal healing (without ulceration on endoscopic examination) after treatment was the endpoint observed during follow-up. We performed logistic regression analysis to identify factors associated with mucosal healing. These factors were used to develop a model (CD mucosal healing prediction nomogram) to predict mucosal healing in CD. External validation was performed using a new cohort of 60 patients from the Second Affiliated Hospital of Soochow University between January 2012 and June 2021.
A total of 331 patients were included in the derivation cohort. We found the following factors to be independently associated with mucosal healing after treatment: disease course <11 months, ulcer size <0.5 cm, Harvey-Bradshaw Index score <9, infliximab treatment, and non-exclusive use of 5-aminosalicylic acid. The model incorporating these factors achieved good discrimination, calibration, and clinical decision curve analysis results on internal validation (C-index: 0.788, 95% confidence interval [CI]: 0.74-0.84). The external validation cohort also demonstrated good discrimination (C-index: 0.785, 95% CI: 0.68-0.90) and calibration.
The CD mucosal healing prediction nomogram model demonstrated good reliability and validated. It can potentially be developed into a simple and clinically useful tool for predicting mucosal healing in CD."
"Therapeutic monitoring of infliximab is limited by the time lag between drug-level measurement and dose adjustment, along with the cost of dose escalation. Strategies for dose reduction in stable patients on maintenance infliximab at supratherapeutic levels are uncertain. This study determined the feasibility of a pharmacist-driven strategy for immediate dose adjustment using a sliding scale at the point of care in stable patients with inflammatory bowel disease on maintenance therapy.
Adult patients with stable disease undergoing maintenance therapy with infliximab infusions, 5 mg/kg every 8 weeks, were prospectively studied. Trough drug levels were assessed by a rapid assay (and later by ELISA) at all infusions for up to 12 months with immediate but quantitatively small dose adjustment according to a sliding scale targeting a therapeutic range of 3-7 µg/mL. Disease activity was assessed both clinically and biochemically.
The rapid assay and ELISA detected similar infliximab levels, and the strategy added approximately 30 min to the duration of infusion events. Only 20% of 48 patients (77% with Crohn's disease) had baseline trough infliximab concentrations within the therapeutic range. This value increased threefold after 24 and 48 weeks of interventions. One in two patients had baseline supratherapeutic levels and most were brought into the therapeutic range without discernible impact on disease activity by one dose adjustment, but two or three adjustments were generally needed for 29% of patients with sub-therapeutic levels. Overall, drug costs were reduced by 4%.
Immediate dose adjustment following infliximab rapid assay performed by a pharmacist using a sliding scale is a feasible strategy. Supratherapeutic infliximab levels can be safely and quickly brought into the therapeutic range using small dose adjustments without impacting disease activity, offsetting (at least partly) costs associated with dose escalation."
"Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care.
We conducted a master protocol investigating immunomodulators for potential benefit in treatment of participants hospitalized with Covid-19 pneumonia. We report results for infliximab (single dose infusion) versus shared placebo both with standard of care. Primary outcome was time to recovery by day 29 (28 days after randomization). Key secondary endpoints included 14-day clinical status and 28-day mortality.
A total of 1033 participants received study drug (517 infliximab, 516 placebo). Mean age was 54.8 years, 60.3% were male, 48.6% Hispanic or Latino, and 14% Black. No statistically significant difference in the primary endpoint was seen with infliximab compared with placebo (recovery rate ratio 1.13, 95% CI 0.99-1.29; p=0.063). Median (IQR) time to recovery was 8 days (7, 9) for infliximab and 9 days (8, 10) for placebo. Participants assigned to infliximab were more likely to have an improved clinical status at day 14 (OR 1.32, 95% CI 1.05-1.66). Twenty-eight-day mortality was 10.1% with infliximab versus 14.5% with placebo, with 41% lower odds of dying in those receiving infliximab (OR 0.59, 95% CI 0.39-0.90). No differences in risk of serious adverse events including secondary infections.
Infliximab did not demonstrate statistically significant improvement in time to recovery. It was associated with improved 14-day clinical status and substantial reduction in 28-day mortality compared with standard of care.
ClinicalTrials.gov ( NCT04593940 )."
"Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients.
We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments, and related AE. We analyzed the frequency, type, and risk factors for AE necessitating drug discontinuation.
A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least 1 drug-related AE that required drug cessation. Immunomodulators [methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)] followed by tumor necrosis factor (TNF)-alpha antagonists [adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)] accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE [odds ratio = 2.50, 95% confidence interval (1.50-4.17)] in all pediatric IBD patients.
Drug-related AE necessitating discontinuation are common in pediatric and adolescent IBD patients. Caution needs to be taken in the case of concomitant drug use."
"Measuring of serum infliximab (IFX) induction concentrations might reduce primary non-response rates in inflammatory bowel diseases (IBD), but optimal target concentrations are unclear. We investigated whether IFX induction concentrations predict short-term endoscopic response at week 12 or treatment persistence at week 52.
Sixty-nine IBD patients (Crohn's disease, n=24; ulcerative colitis, n=45) received standard IFX induction of 5 mg/kg bodyweight at weeks 0, 2, and 6. Responders continued maintenance therapy and underwent follow-up until week 52 or treatment discontinuation. We measured IFX concentrations at weeks 2, 6, and 12, and evaluated treatment response around week 12 with endoscopy or with clinical scores and fecal calprotectin. Using the receiver operating characteristic analysis, we determined optimal IFX concentration thresholds associated with treatment response. We further compared IFX induction concentrations between patients persisting on IFX at week 52 and patients discontinuing treatment due to insufficient response.
Responders (74%, 51 out of 69 patients) had significantly higher median IFX concentrations than non-responders at weeks 6 (25.06 vs. 19.68 µg/ml; P = 0.04) and 12 (18.03 vs. 10.02 µg/ml; P = 0.03), but not at week 2 (33.12 vs. 34.20 µg/ml; P = 0.97). Optimal IFX concentration thresholds for induction response were 21.33 and 5.13 µg/ml at weeks 6 and 12, respectively. Fifty-three patients continued IFX maintenance therapy until week 52. Induction concentrations failed to predict persistence on IFX therapy at week 52.
Higher IFX induction concentrations predict endoscopic short-term response. However, induction concentrations failed to predict long-term persistence on IFX treatment."
"Infliximab is a tumour necrosis factor-alpha inhibitor that is used to treat children with refractory Kawasaki disease (KD). Our purpose was to evaluate the safety and impact of infliximab versus intravenous immunoglobulins on the incidence of coronary artery aneurysms (CAAs) and treatment resistance in children with refractory KD.
The Medline/PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials and clinical trials registries were searched to December 2021. Randomized controlled trials (RCTs) comparing infliximab as second-line therapy to a second dose of intravenous immunoglobulin (IVIG) in children with refractory KD, reported in abstract or full text, were included. Studies were selected and assessed for risk of bias by two reviewers. Data were extracted and pooled using conventional random-effects meta-analysis. The certainty of evidence was assessed using the GRADE system.
A total of 199 participants from four RCTs were included. The pooled risk ratio (RR) for the incidence of treatment resistance in patients treated with infliximab was 0.40 (95% confidence interval [CI] 0.25-0.64). For incidence of CAAs RR was 1.20 (95% CI 0.54-2.63), the incidence of adverse effect ""infusion reactions"" RR was 0.48, (95% CI 0.12-1.92) and for ""infections"" RR was 0.55 (95% CI 0.27-1.12). Overall, the GRADE strength of evidence for the primary outcomes was low. Evidence on the duration of fever and inflammatory biomarkers was sparse, heterogeneous and inconclusive.
Moderate-certainty evidence indicates that infliximab may reduce the incidence of treatment resistance in children with refractory KD. However, the limited strength of evidence warrants further research."
"Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR).
In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission.
Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNFα in prior anti-TNFα agent failures. No differences were found according to type of adverse events or severe adverse events.
Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNFα in TNFα failures."
"Studies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19).
This multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021.
A total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn's disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset (1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, 
Regardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD."
"/objectives Several biological disease-modifying anti-rheumatic drugs (bDMARDs) have been widely used for the management of rheumatoid arthritis (RA). These drugs target different molecules important for the pathophysiology of RA; however, only a few studies have compared the effects of these biological drugs on cytokines and bone metabolic markers. The main aim of this study is to clarify the effects of bDMARDs with different modes of action on the cytokine and bone metabolic marker levels in patients with RA.
Patients with RA who were initiated on infliximab, tocilizumab, or abatacept as the first bDMARD were prospectively enrolled in this study. Serum cytokine and bone metabolic marker levels were measured longitudinally, and changes in their levels were compared.
A total of 174 patients were enrolled in this study, with 55, 70, and 49 patients in the infliximab, tocilizumab, and abatacept groups, respectively. At six months, despite the similar clinical effectiveness of the three drugs, changes in the cytokine and bone metabolic marker levels were distinct; interferon-γ and tumor necrosis factor-α levels were significantly increased with infliximab, interleukin-6 levels were increased with tocilizumab, and interleukin-1β and interleukin-8 levels were increased with abatacept treatment. Bone-specific alkaline phosphatase and osteocalcin levels increased more significantly with tocilizumab than with infliximab, while osteopontin and osteonectin levels decreased with infliximab treatment.
bDMARDs with different modes of action exert different effects on the cytokine and bone metabolic marker levels in patients with RA."
"Dear Editor, After the coronavirus disease 2019 (COVID-19) pandemic affected the whole world, rheumatologists began to think about how COVID-19 will progress in patients with inflammatory conditions. High cytokine levels play a role in the pathophysiology of COVID-19 infection. Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine known to have a key role in the pathogenesis of chronic immune-mediated diseases. AntiTNF therapy may cause an increase in active tuberculosis, other granulomatous diseases, and serious infections [1]. According to many studies, rheumatological diseases have not been identified as a risk factor for severe COVID-19 infection [2]. Should significantly increased cytokine levels during COVID-19 infection make us consider anticytokine therapies that may be used in the treatment of patients with COVID-19 a risk? We aimed to explore whether the frequency of COVID-19 infection increased, the effect of comorbidities on the frequency of infection, and whether the severity of the disease and need for intensive care support increased in patients who used anti-TNF agents. We performed a retrospective case-control study between March and December 2020 in Sakarya University Training and Research Hospital. Retrospectively, we evaluated whether there was a difference in the frequency and severity of COVID-19 in our patients diagnosed with ankylosing spondylitis (AS), 77 of whom were using anti-TNF and 49 of whom didn't use anti-TNF. Hospitalization and intensive care unit (ICU) requirements were evaluated as endpoints. In the anti-TNF group, patients used adalimumab, etanercept, certolizumab, infliximab, and golimumab. Patients were questioned at an outpatient clinic in person or by phone. Seventy-seven patients with AS using anti-TNF agents (58 males, 19 females) and 49 patients with AS (38 males, 11 females) not using anti-TNF agents were included in the study (p = 0.943). Mean age of patients using antiTNF agents was 41.53 ± 10.38, and mean age of patients not using anti-TNF agents was 42.94 ± 10.86 (p = 0.468). Thirty-three (42.9%) patients were smokers in the antiTNF group, while 23 (46.9%) patients were smokers in the group not using TNFi (p = 0.791). There was 12 pack-year smoking in the anti-TNF group, and 14 pack-year smoking in not using TNFi (p = 0.623). The frequency of diabetes mellitus (DM), hypertension (HT), amiloidosis, familial mediterranean fever (FMF), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD) was similar in both groups (p = 0.403, p = 0.999, p = 0.521, p = 0.999, p = 0.999, respectively). Six patients using TNFi and 3 patients not using TNFi recovered from COVID-19 infection. However, this result was not statistically significant (p = 0.999). One patient using anti-TNF was hospitalized but with no need for admission to the ICU (p = 0.999). All 9 patients recovering from COVID-19 were male (p = 0.113). There were 2 (22.2%) smokers in the SARS-CoV-2 positive group and 54 (46.2%) smokers in SARS-CoV-2 negative group (p = 0.297). There was 37.5 pack-year smoking in SARS-CoV-2 positive group, and 12 pack-year smoking in SARS-CoV-2 negative group (p = 0.151). Nobody has comorbidities (DM, HT, amiloidosis, FMF, CAD, COPD) in SARS-CoV-2 positive group. There were patients with DM (5.1%), HT (15.4%), amiloidosis (1.7%), FMF (1.7%), CAD (0.9%) and COPD (0.9%) in SARS-CoV-2 negative group (p = 0.999, p = 0.356, p = 0.999, p = 0.999, p = 0.999, p = 0.999, respectively). Having comorbidities was not detected to be associated with frequency of COVID-19. 31 (40.3%) patients were using adalimumab, 25 (32.5%) patients were using etanercept, 13 patients were using (16.9%) certolizumab, 6 (7.8%) patients were using golimumab, and 2 patients (2.6%) were using infliximab in TNF group. Six patients using anti-TNF (2 adalimumab, 1 etanercept, 1 golimumab,2 infliximab) and 3 nonuser patients recovered from COVID-19 (p = 0.999). No statistically significant difference was found between SARS-CoV-2 positive and negative patients in terms of the types of anti TNF they used. Patients were called in March 2020, and they were advised to terminate their anti-TNF therapy, when the COVID-19 pandemic began. Among those who used antiTNF, 2 (33.3%) people who had COVID-19 and 38 (53.5%) people who did not have COVID-19 interrupted treatment (p = 0.419). Anti-TNF users who did not have COVID-19 stopped taking the treatment for an average of 3 months (min 2-max 4 months) starting from March 2020, and the patients who had COVID-19 (p = 0.102) stopped taking the treatment for 1.5 months (min 1-max 2 months). Duration of interrupting TNFi was not significant for the risk of COVID-19. Comorbidities, older age, and the presence of active disease have been associated with worse outcomes in previous studies [3]. In our study, the anti-TNF using and the nonuser groups were similar according to age, sex, and comorbidities. Although comorbidities in COVID-19 are associated with severe disease in the literature, we did not find a significant difference in our study. This result is probably related to our insufficient number of patients. As a result, we found that the use of anti-TNF did not increase the frequency and severity of COVID-19. In a recently published multicenter study, it was stated that the use of biological DMARDs in patients with inflammatory rheumatic diseases was not significantly associated with a worse outcome of COVID-19. But unlike our study, having no comorbidities was associated with a decreased risk of a worse outcome [4]. There are currently studies investigating the therapeutic utility of infliximab and adalimumab in hospitalized COVID-19 patients [5]. The results of these studies are very important. The usability of TNFi in treatment and at which stage of the disease anti-TNF agents can be used are wondered. We will see the course of the disease all over the world after the administration of the COVID-19 vaccines, but we still need more information about effective and safe treatment.
The authors declare that there is no conflict of interest.
The authors did not receive support from any organization for this work."
"In Korea, infliximab was approved for use in children with ulcerative colitis (UC) in October 2012.
To compare the clinical course of UC before and after the introduction of biological agents, and to compare with the IBSEN study.
Patients under 18 years of age, who were diagnosed with UC and followed from January 2003 to October 2020, were included in the study. Group A (
After 2 years of treatment, colonoscopy evaluation revealed different outcomes in the two treatment groups. Remission was confirmed in 14 patients (29.2%) of Group A, and in 31 patients (50.0%) of Group B (
The incidence of relapse has decreased and the steroid-free period has increased after the introduction of the biological agent. The clinical course also showed a different pattern from that of IBSEN study. The active use of biological agents may change the long-term disease course in moderate to severe pediatric UC."
"Described as early as Hippocrates in his ""Third Book of Endemic Diseases,"" Behçet's Disease (BD), also known as ""The Silk Road Disease"" following its initial demographics, consists of a triad of recurrent oro-genital ulcers and associated uveitis. Current demographics and rising percentages of patients seen far beyond the Silk Road in Ocular Inflammatory Disease and Uveitis Clinics list BD uveitis as one of the frontliners of non-infectious autoinflammatory eye diseases. Clinical features of BD and juvenile-onset BD are detailed alongside various approaches in classification and suggested algorithms for diagnosis that are outlined in this review. With the ongoing Human Microbiome Project and studies such as the MAMBA study, the role of the human microbiome in BD is highlighted in the pathophysiology of BD to include the current research and literature perspective. Furthermore, with the advancement of recent diagnostic and investigative techniques, especially in the field of Optical Coherence Tomography (OCT), disease-related characteristics are updated to encompass SD, EDI and OCT-angiography characteristics of BD. Having entered the era of biologic therapy, the role of various specific cytokine-blocking biologic drugs, such as TNF-α inhibitors (e.g., adalimumab, infliximab), interferon α-2a inhibitors, IL-6 and IL-1 inhibitors are presented and contrasted alongside the conventional immunosuppressant drugs and the classic old gold standard: corticosteroids (systemic or local). Finally, with the ongoing SARS-CoV-2 pandemic, it was not possible to conclude the review without reviewing the latest evidence-based literature reporting BD morbidity in this era, the observed pattern and treatment recommendations as well as those related to reported post-vaccine complications and emergence of BD."
"Medications for inflammatory bowel disease (IBD) have changed dramatically over time. However, no study on long-term medication profiles has been conducted in the Chinese population.
To evaluate temporal changes in medication use and treatment patterns for Chinese patients with IBD.
A multicenter retrospective cohort study was conducted among Chinese patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) between January 1999 and December 2019. Baseline characteristics and drug prescriptions were collected. Trends in medication use and therapeutic patterns were analyzed.
In total, 3610 patients were analyzed. During follow-up, 5-aminosalicylates (5-ASA) and corticosteroids (CS) prescriptions gradually decreased, accompanied by a notable increase in immunosuppressants (IMS) and infliximab (IFX) prescriptions in patients with CD. Prescription rates of 5-ASA and CS were stable, whereas IMS and IFX slightly increased since 2007 in patients with UC. Subgroup (
Long-term treatment strategies analyses has provided unique insight into the switch from conventional drugs to IFX in Chinese patients with CD."
"Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease (IBD) however data on the efficacy and side effects of these therapies in the elderly is scant.
To evaluate retrospectively the drug sustainability, effectiveness, and safety of the biologic therapies in the elderly IBD population.
Consecutive elderly (≥ 60 years old) IBD patients, treated with biologics [infliximab (IFX), adalimumab (ADAL), vedolizumab (VDZ), ustekinumab (UST)] followed at the McGill University Inflammatory Bowel Diseases Center were included between January 2000 and 2020. Efficacy was measured by clinical scores at 3, 6-9 and 12-18 mo after initiation of the biologic therapy. Patients completing induction therapy were included. Adverse events (AEs) or serious AE were collected during and within three months of stopping of the biologic therapy.
We identified a total of 147 elderly patients with IBD treated with biologicals during the study period, including 109 with Crohn's disease and 38 with ulcerative colitis. Patients received the following biologicals: IFX (28.5%), ADAL (38.7%), VDZ (15.6%), UST (17%). The mean duration of biologic treatment was 157.5 (SD = 148) wk. Parallel steroid therapy was given in 34% at baseline, 19% at 3 mo, 16.3% at 6-9 mo and 6.5% at 12-18 mo. The remission rates at 3, 6-9 and 12-18 mo were not significantly different among biological therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability (
Current biologics were not different regarding drug sustainability, effectiveness, and safety in the elderly IBD population. Therefore, we are not able to suggest a preferred sequencing order among biologicals."
"Treatment with tumor necrosis factor α (TNFα) antagonists in IBD patients suffers from primary non-response rates of up to 40%. Biomarkers for early prediction of therapy success are missing. We investigated the dynamics of gene expression and DNA methylation in blood samples of IBD patients treated with the TNF antagonist infliximab and analyzed the predictive potential regarding therapy outcome.
We performed a longitudinal, blood-based multi-omics study in two prospective IBD patient cohorts receiving first-time infliximab therapy (discovery: 14 patients, replication: 23 patients). Samples were collected at up to 7 time points (from baseline to 14 weeks after therapy induction). RNA-sequencing and genome-wide DNA methylation data were analyzed and correlated with clinical remission at week 14 as a primary endpoint.
We found no consistent ex ante predictive signature across the two cohorts. Longitudinally upregulated transcripts in the non-remitter group comprised TH2- and eosinophil-related genes including ALOX15, FCER1A, and OLIG2. Network construction identified transcript modules that were coherently expressed at baseline and in non-remitting patients but were disrupted at early time points in remitting patients. These modules reflected processes such as interferon signaling, erythropoiesis, and platelet aggregation. DNA methylation analysis identified remission-specific temporal changes, which partially overlapped with transcriptomic signals. Machine learning approaches identified features from differentially expressed genes cis-linked to DNA methylation changes at week 2 as a robust predictor of therapy outcome at week 14, which was validated in a publicly available dataset of 20 infliximab-treated CD patients.
Integrative multi-omics analysis reveals early shifts of gene expression and DNA methylation as predictors for efficient response to anti-TNF treatment. Lack of such signatures might be used to identify patients with IBD unlikely to benefit from TNF antagonists at an early time point."
"The Japanese Society for Psoriasis Research (JSPR) has been conducting annual epidemiological surveys of patients with pustular psoriasis in Japan since 2017. This study aimed to conduct a recent epidemiological analysis of patients with pustular psoriasis who were enrolled in the JSPR from 2017 to 2020. A total of 291 patients from 131 medical institutions were enrolled, of which 47.4% (138 cases) were males and 52.6% (153 cases) were females. The mean ± standard deviation (SD) age of the patients was 57.4 ± 20.3 years (males, 61.2 ± 17.3 years; females, 54.1 ± 22.1 years). The mean ± SD age of the patients at disease onset was 48.5 ± 22.5 years (males, 50.8 ± 20.6 years; females, 46.4 ± 24.0 years). The types of pustular psoriasis observed included the von Zumbusch type (59.8%), annular pustular psoriasis (8.2%), impetigo herpetiformis (6.5%), and acrodermatitis continua of Hallopeau (4.8%), of which, the majority of the patients with impetigo herpetiformis were female. Among the patients, 58.4% were treated with oral medications and 44.0% were treated with biologics. The most common oral medication prescribed was etretinate (52.4%), followed by corticosteroids (24.7%) and cyclosporin (22.9%). The most common biologics used were IL-17 inhibitors (ixekizumab [28.1%] and secukinumab [22.7%]), followed by tumor necrosis factor (TNF) inhibitors (infliximab [15.6%]) and IL-23 inhibitors (guselkumab [14.8%] and risankizumab [10.2%]). This survey thus provides new and significant information regarding the recent perspective of pustular psoriasis, such as patient characteristics and treatment trends, in Japan."
"Biosimilars are biological agents that are highly analogous to their reference products currently approved and licensed by the U.S. Food and Drug Administration (FDA). Biosimilars possess no differences in their safety, purity, potency, or effectiveness compared to their respective reference biologic agents. The abbreviated licensure pathway 351(k) for biosimilars or agents interchangeable with FDA-approved biological agents (reference product) was formed by Congress by The Biologics Price Competition and Innovation Act (BPCI Act) of 2009. Biosimilars aim to increase the number of biologics available at more inexpensive costs when compared to their reference products, further increasing patient access to more treatment options. Similar to biologics or reference products, biosimilars are expected to meet the FDA's meticulous approval criteria, ensuring the reliability of the agent's safety, efficacy, quality, and effectiveness. The FDA approval process for biosimilars is based on data proving its prominent similarity and correlation to an already FDA-approved biologic agent (reference product) and its indications for use. No clinically meaningful differences among the biosimilar and its respective reference agent should exist. Differences exist in the regulatory provisions for the original biologic agent (reference product) and a biosimilar as the biosimilars obtain approval from FDA by their abbreviated approval pathway. Biosimilars seeking FDA approval must include data assessments demonstrating the agent's similarity to a reference product acquired from analytical investigations, animal studies, and clinical studies. Added data and analyses of the biosimilars immunogenicity, pharmacokinetics, pharmacodynamics, and data discussing the indication(s) the reference product is licensed and approved for use are also included. To date, ten biological agents: bevacizumab, etanercept, epoetin-alfa, trastuzumab, adalimumab, pegfilgrastim, filgrastim, infliximab, rituximab, and insulin glargine, have been used as reference products for the approval of 30 biosimilar agents. Biosimilars can be used in the management of various inflammatory and autoimmune diseases. Ailments such as rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis (JIA), psoriatic arthritis (PA), ankylosing spondylitis (AS), plaque psoriasis (PsO), inflammatory bowel disease (IBD): adult Crohn disease (CD), ulcerative colitis (UC), granulomatosis with polyangiitis (GPA) (Wegener granulomatosis), microscopic polyangiitis (MPA), and type 1 diabetes mellitus (DM). Filgrastim-sndz, a biosimilar of the reference product ""filgrastim,"" was the first-ever biosimilar to receive FDA approval in March 2015 and is characterized as a leukocyte growth factor indicated to reduce infections caused by febrile neutropenia in the neutropenic and immunosuppressed subjects. Other indications of biosimilars alongside inflammatory diseases include management for specific malignancies and secondary causes of anemia. In September 2017, bevacizumab-awwb was the first biosimilar that was granted FDA approval for certain cancers. A few months later, in December 2017, biosimilar trastuzumab-dkst was also granted FDA approval for specific malignancies. Cancers indicative of biosimilar therapy include non-squamous non-small cell lung cancer, metastatic colorectal cancer, metastatic renal cell carcinoma, glioblastoma, recurrent or metastatic cervical cancer, HER2 (human epidermal growth factor receptor 2) associated breast cancer, and HER2 associated gastric (metastatic) or gastroesophageal junction adenocarcinoma, chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL). To date, new biosimilars are currently still being FDA approved, with the latest approval coming on July 28, 2021, for biosimilar agent insulin glargine-yfgn, a long-acting insulin agent indicated for pediatric type 1 diabetes mellitus (DM) and adult patients with DM type 1 and DM type 2. Biosimilars agent insulin glargine-yfgn is the first insulin biosimilar agent to receive FDA approval and is also the first interchangeable agent in the class of biosimilar agents. Interchangeable products are biosimilars that meet additional criteria specified by the Biologics Price Competition and Innovation Act during the assessment and testing of the agent during its FDA approval process. Data is required demonstrating clinical results as its respective reference product in any subject treated with the interchangeable products. Data on the interchangeable products substituted with their reference product in terms of safety and efficacy of alternating back and forth have been assessed and evaluated by the FDA prior to their approval. Once an interchangeable product has been approved, it may be interchanged for their reference product without requiring additional consulting from the prescribing clinician or healthcare professional. Table 1: Summarizes all FDA approved biosimilars"
"Infliximab is usually either not detectable in breastmilk or detectable at very low levels. Absorption of the drug from milk by the infant is minimal. Follow-up of infants exposed in utero and breastfed during maternal infliximab therapy have found no adverse effects and normal development. The measurement of minute concentrations in the milk of some women raises the possibility of local immune suppression in the gastrointestinal tract, but levels were not high enough to be of concern for systemic immunosuppression.[1] Numerous experts and professional guidelines have stated that the drug is a low risk to the nursing infant and acceptable to use during breastfeeding.[2-11]"
"Infliximab is a biologic, monoclonal-antibody drug. The United States Food and Drug Administration (FDA) has approved infliximab for moderate to severely active Crohn disease in adults and children (six years and above), ulcerative colitis, active rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and chronic severe plaque psoriasis in adult patients. This activity describes the mode of action of infliximab, including adverse event profiles and other key factors, e.g., dosing, pharmacodynamics, pharmacokinetics, and monitoring, and highlights the interprofessional team's role in managing these patients."
"To evaluate the efficacy of infliximab (IFX) therapy in patients with Behçet's uveitis (BU) refractory to conventional immunomodulatory treatment (IMT).
This study, trial registration number TCTR20200806007, included cases of BU with a minimum of 18 months follow-up on IFX treatment. Demographic characteristics, ophthalmological examination findings, control of ocular inflammation with IFX, response to treatment and the rate of clinical remission were analyzed in this study.
Sixty-two eyes of 35 patients on IFX therapy were included in the study. The mean follow-up was 49.5±25.9months. The mean frequency of recurrences during the IMT was 1.47±0.78 (attacks/year), decreasing to 0.31±0.40 (attacks/year) with IFX (P<0.001). Visual acuity improved significantly in the 1st month of IFX treatment (P=0.026). Partial response to treatment was achieved in 91.4% of cases.
IFX is a safe and effective treatment in cases of BU refractory to conventional IMT."
"The emergence of biologics has improved the management of patients with rheumatic disease, mainly with spondyloarthritis (SpA). Sustained remission has become a reachable goal thanks to the treat to target strategy. Contrary to rheumatoid arthritis, data on biologic optimization among SpA patients in remission is scarce and still a subject of debate. The main objective of this systematic review was to provide the most up-to-date published literature regarding biologic tapering in axial spondyloarthritis.
This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed and Scopus, published until December 20th 2021, and tackling tapering strategies of the biologics in patients with axial SpA were included RESULTS: Fourteen studies met the inclusion criteria. They were published between 2008 and 2020. The most studied molecules were Etanercept (ETN) (n = 13), Infliximab (IFX) (n = 6), Adalimumab (ADA) (n = 5), certolizumab pegol (CZP) (n = 2), Golimumab (n = 1) and ETN biosimilar. There are no studies published regarding anti-IL 17 tapering strategy. Patient-tailored dose reduction of anti TNF-α agents was successful in preserving stable low disease activity in most of the studies with remission rates ranging between 20.2 % and 93.7 %. Complete treatment discontinuation is associated with a high risk of flares.
To conclude, published data indicate that a progressive tapering strategy for anti TNF-α therapy is successful among axial SpA in sustained remission. However, further studies with more homogenized tapering strategies are needed in order to ascertain the specific implication of each subset for a better holistic approach."
"Relapse is a problem in patients with Crohn's disease (CD) after medical therapy (including biologics) and after surgery to treat acute inflammation. It is unclear whether the recurrence rate over time is higher after surgical therapy than after continuous drug treatment.
We sought to compare clinical relapse rates and the need for re-interventions (resection or therapeutic endoscopic intervention) in patients with CD.
A meta-analysis was performed according to PRISMA guidelines.
The need for one of the three re-interventions (surgery, biologics or both) increased over time. The recurrence rates in patients after ileocecal resection were lower than the rates under biologic therapy. The odds ratio for clinical recurrence under biologics versus after surgical treatment was 2.50 (95% confidence interval [CI] 1.53-4.08, p-value < 0.001). The odds ratio for surgical recurrence under biologics versus after surgery was 3.60 (95% CI 1.06-12.3, p-value 0.041).
These findings support surgical resection as a treatment option in patients with CD with limited disease."
"Monoclonal antibodies (MAbs) have revolutionized the treatment of many chronic inflammatory diseases, including inflammatory bowel disease (IBD). IBD is a term that comprises two quite similar, yet distinctive, disorders-Crohn's disease (CD) and ulcerative colitis (UC). Two blockbuster MAbs, infliximab (IFX) and adalimumab (ADL), transformed the pharmacological approach of treating CD and UC. However, due to the complex interplay of pharmacology and immunology, MAbs face challenges related to their immunogenicity, effectiveness, and safety. To ease the burden of IBD and other severe diseases, biosimilars have emerged as a cost-effective alternative to an originator product. According to the current knowledge, biosimilars of IFX and ADL in IBD patients are shown to be as safe and effective as their originators. The future of biosimilars, in general, is promising due to the potential of making the health care system more sustainable. However, their use is accompanied by misconceptions regarding their effectiveness and safety, as well as by controversy regarding their interchangeability. Hence, until a scientific consensus is achieved, scientific data on the long-term effectiveness and safety of biosimilars are needed."
"Inflammaging is a low degree of chronic and systemic tissue inflammation associated with aging, and is intimately linked to pro-inflammatory mediators. These substances are involved in the pathogenesis of chronic inflammatory diseases and related psychopathological symptoms. When inflammation and aging affect the brain, we use the term neuro-inflammaging. In this review, we focused on the neuro-inflammatory process typical of advanced ages and the related psychopathological symptoms, with particular attention to understanding the immune-pathogenetic mechanisms involved and the potential use of immunomodulatory drugs in the control of clinical psychological signs. Inflammation and CNS were demonstrated being intimately linked in the neuro-inflammatory loop. IL-1, IL-6, TNF-a, COX and PGE are only partially responsible. BBB permeability and the consequent oxidative stress resulting from tissue damage make the rest. Some authors elaborated the ""theory of cytokine-induced depression"". Inflammation has a crucial role in the onset symptoms of psychopathological diseases as it is capable of altering the metabolism of biogenic monoamines involved in their pathogenesis. In recent years, NSAIDs as an adjunct therapy in the treatment of relevant psychopathological disorders associated with chronic inflammatory conditions demonstrated their efficacy. Additionally, novel molecules have been studied, such as adalimumab, infliximab, and etanercept showing antidepressant and anxiolytic promising results. However, we are only at the beginning of a new era characterized by the use of biological drugs for the treatment of inflammatory and autoimmune diseases, and this paper aims to stimulate future studies in such a direction."
"Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. There are few data on the efficacy and safety in clinical practice of infliximab (CT-P13) in subcutaneous formulation (SC) for the treatment of patients with IBD.
Multicenter, prospective study of patients with IBD in clinical remission, who had their treatment changed from intravenous (IV) infliximab to SC. Two groups of patients were evaluated according to whether they were on IV infliximab treatment at standard or intensified doses before the switch.
A total of 30 patients were on standard dosing and another 30 in intensified therapy. Treatment persistence in both groups at 6 months was greater than 95%. In both groups after the change, neither the biomarkers of inflammation nor the activity indices underwent significant changes at 3 and 6 months compared to the baseline value. Similarly, in both groups, infliximab trough levels showed a significant increase 3 and 6 months after the change to SC. No serious adverse events were registered.
The CT-P13 SC brings a new anti-TNF era. Achieving much higher drug levels that are constant over time opens new paths to explore the management of patients with IBD: less immunogenicity, better perianal disease control and higher achievement of mucosal healing."
"The thiopurine derivatives azathioprine (AZA), mercaptopurine (MP) and tioguanine (TG) remain standard treatment of inflammatory bowel disease (IBD). The immune suppressive effect of thiopurines is primarily based on blocking the Ras-related C3 botulinum toxin substrate 1 (Rac1) causing apoptosis of T lymphocytes by inhibition of the phosphorylated downstream transcription factor Signal Transducer and Activator of Transcription 3 (pSTAT3). A functional pharmacodynamic marker in T lymphocytes may be useful to predict therapeutic outcome of thiopurine therapy. The aim of this study was to explore whether protein levels of Rac1 and pSTAT3 in T lymphocytes may be applied as a specific pharmacodynamic marker for thiopurine therapy in IBD patients. Rac1 and pSTAT3 protein levels in T lymphocytes were explored in 57 IBD patients (median age 51 years, 56% female), subdivided into six groups based on IBD activity and its treatment: patients with active disease without IBD maintenance medication (1) or patients in remission on AZA/MP (2), TG (3), infliximab (IFX) (4), thiopurine and IFX combination-treatment (5) or without IBD medication (6). Reference values were obtained from healthy subjects. Rac1 and pSTAT3 protein levels in T lymphocytes from patients on thiopurine monotherapy (group 2 and 3) were compared to the other groups, and to healthy subjects. Absolute Rac1 and pSTAT3 protein levels showed no differences between the thiopurine monotherapy groups when compared to patients with active disease. However, the ratio of Rac1 and pSTAT3 protein levels was lower in thiopurine patients groups compared to patients with active disease. Rac1-corrected pSTAT3 protein levels may serve as a pharmacodynamic marker of thiopurine monotherapy and may be a potential tool to predict therapeutic effectiveness in IBD patients."
"Infliximab is an anti-tumour necrosis factor agent used in the treatment of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. While the use of infliximab is well established in the treatment of IBD, there are now four recently FDA-approved infliximab biosimilars that are increasingly used due to their cost-benefit for patients, institutions and payors. In addition, shortening the length of infliximab infusions from 120 min (standard infusion) to 60 min or less (rapid infusion) has been shown to safely provide further cost-benefit while also improving patient convenience. The safety of rapid infusions has been well-established for the infliximab reference product, however, there are limited data available regarding the safety of rapid infusions for infliximab biosimilars. The purpose of this study was to compare the incidence and severity of infusion reactions among patients with IBD receiving rapid infusion of infliximab reference product compared with infliximab biosimilar.
This was a retrospective analysis of electronic health record data of patients with a diagnosis of IBD receiving an infliximab reference product or infliximab biosimilar infusion between December 2020 and December 2021. Patient-level variables included demographics, immunomodulator use, IBD-related hospitalization and infliximab trough concentration and antibody levels. Infusion-related variables of interest included total number of infusions, drug, dose, dosing interval, infusion time and use of pre-medications. Infusion-related reactions were defined as safety concerns documented by the administering nurse (anaphylaxis, shortness of breath, hypotension, swelling, rash, pruritus, hives, flushing, chest pain, muscle pain, joint pain, fevers, chills, headache or hypertension) or administration of emergency medications. Fisher's exact test was used to compare reaction rates.
A total of 188 patients met inclusion criteria for analysis, and a total of 1124 infusions were administered during the study period. There were no statistically significant differences among any of the pre-specified outcomes. There were no differences in the incidence of infusion reactions among rapid infusion (60 min) infliximab and infliximab biosimilars (p = 0.863). Additionally, there were no differences in the incidence of infusion reactions among standard infusion (120 min) infliximab and infliximab biosimilars (p = 0.993). Finally, there were no differences among the rate of infusion reactions between rapid infusion of infliximab biosimilars and standard infusion of infliximab biosimilars (p = 0.536). Eight patients experienced safety issues, with three patients requiring emergency medications (1.6% of 188 patients).
Rapid infusions of infliximab biosimilars were not associated with an increase in the incidence of infusion reactions compared with: rapid infusion of infliximab reference product, standard infusion of infliximab biosimilars, or standard infusion of infliximab reference product. This should reassure clinicians that rapid infusions of infliximab biosimilars are safe in clinical practice."
"Despite recent approvals for new drugs to treat adults with Crohn's disease or ulcerative colitis, there are only two approved advanced treatment options (infliximab and adalimumab) for children with inflammatory bowel disease. There are many potential new therapies being developed for adult and paediatric inflammatory bowel disease. Moreover, regulatory agencies in both European Union and United States have processes in place to support the early planning and initiation of paediatric studies. Nevertheless, unacceptable delays in approvals for use of drugs in children persist, with an average seven-year gap, or longer, between authorisation of new inflammatory bowel disease drugs for adults and children.
A 2-day virtual meeting was held April 14-15, 2021 for multi-stakeholders (clinical academics, patient community, pharmaceutical companies, and regulators) to discuss their perspectives on paediatric drug development for inflammatory bowel disease.
The multi-stakeholder group presented, discussed and proposed actions to achieve expediting the approval of new drugs in development for paediatric inflammatory bowel disease.
Collaborative action points for all stakeholders are required to make progress and facilitate new drug development for children with inflammatory bowel disease."
"Recent literature involves many cases with lymphoma and ankylosing spondylitis (AS) with or without the use of TNF inhibitors. Herein, we report a patient, a 56-year-old Human Leukocyte Antigen-B27 (HLA-B27) positive man with four years history of AS who was still under treatment with infliximab with clinical remission. He was admitted with a new-onset, 6-week history of bloody diarrhoea with mucus, abdominal pain, fever, and weight loss. An ileocolonoscopy showed linear ileocecal valve ulcers. Histopathological findings of ileocecal valve ulcers revealed peripheral T-cell lymphoma of the small intestine. Infliximab was interrupted because of the possible progression of the lymphoma
We aimed to emphasize the underlying potential pathogenic mechanisms and to review the related literature. A literature search was conducted in the PubMed database between January 1980 and November 2020. The keywords including 'ankylosing spondylitis' and 'lymphoma' were used.
TNFi use, immunosuppression, and chronic inflammation may be related to the development of lymphoma in chronic inflammatory diseases. Ileocecal valve involvement should not be interpreted as inflammatory bowel disease, infection, or vasculitis in the presence of red flags."
"Cancer patients treated with immune check point inhibitors are at risk of developing severe colitis. However, the efficacy and safety of treatment of severe colitis is poorly understood.
To explore the safety and efficacy of infliximab and corticosteroids in severe immune-mediated enterocolitis (IMC) METHOD: We performed a nationwide retrospective cohort study on 140 cancer patients treated with infliximab due to IMC in Denmark from 2011 to 2021.
The rate of complete remission with infliximab was 52% after one dose, increasing to 73% after two or more doses. Thirteen patients (10%) required additional treatment with vedolizumab. Patients were heavily exposed to corticosteroids and received a median accumulated dose of 3978 mg (interquartile range [IQR] 2552-6414). Age- and cancer-adjusted Cox regression analysis found that a high dose of prednisolone at start of tapering ≥75 mg/day was associated with increased mortality (HR 1.67, 1.04-2.69, p = 0.035). Patients responding to infliximab experienced an improvement of symptoms after 3 days (IQR 2-4) and complete remission after 31 days (IQR 14-61). Twenty-four percent required hospitalisation for infection during treatment for IMC, lasting 7 days (median). Secondary gastrointestinal infections occurred in 16%, with Clostridioides difficile being most common (64%). Further, 10% had a thromboembolic event during the first 90 days after infliximab treatment.
Infliximab led to complete resolution of symptoms in 73% of patients with IMC. High prednisolone dose at tapering was associated with increased mortality rate and a high incidence of infections and hospitalisations in patients with severe IMC. We suggest optimised infliximab treatment before escalation of steroid doses."
"Colectomy rates following acute severe ulcerative colitis have plateaued around 20% despite intravenous corticosteroid and intensified anti-tumor necrosis factor (TNF) biologic dosing. Recent studies have shown tofacitinib to provide additional benefit in further decreasing colectomy rates among hospitalized adult patients with corticosteroid- and anti-TNF-nonresponsive ulcerative colitis. Pediatric data describing the effectiveness of tofacitinib for this indication does not yet exist. We aimed to describe the treatment courses and colectomy-free survival among pediatric patients treated with tofacitinib while hospitalized for refractory ulcerative colitis.
We performed a retrospective single-center cohort study of consecutive hospitalized pediatric patients initiating tofacitinib for refractory ulcerative colitis from 2018 to 2021. The primary outcome was 90-day colectomy-free survival. Secondary outcomes included colectomy-free clinical remission, corticosteroid independence, colectomy-free tofacitinib drug-persistence, tofacitinib-related adverse events, and postoperative complications. Baseline characteristics and details of the timing and positioning of therapies utilized during hospitalization were described. Outcomes were described using counts, percentages, and Kaplan-Meier curves.
Eleven patients met inclusion criteria. All patients demonstrated nonresponse to both intravenous corticosteroids and anti-TNF therapy prior to tofacitinib initiation. Median hospitalization length was 22 days and mean maximum pediatric ulcerative colitis activity index during hospitalization was 68. Eight of 11 patients remained colectomy-free at 90 days following hospital admission and 6 remained colectomy-free over median 182-day follow-up, including 4 of whom remained on tofacitinib.
Tofacitinib may represent a new treatment option for hospitalized pediatric patients with corticosteroid- and anti-TNF-nonresponsive ulcerative colitis. Future research is essential in determining the optimal positioning of these therapies."
"Anti-TNFα is measurable in infants exposed 
A prospective multi-center study conducted 2014-2017. Anti-TNFα levels were measured in cord blood, and at 3 and 12 months. T-cell repertoire and function were analyzed at 3 and 12 months by flow-cytometry, expression of diverse T cell receptors (TCR) and T-cell receptor excision circles (TREC) quantification assay. Serum immunoglobulins and antibodies for inactivated vaccines were measured at 12 months. Baseline clinical data were retrieved, and 2-monthly telephonic interviews were performed regarding child infections and growth.
24 pregnant females, age 30.6 (IQR 26.5-34.5) years were recruited, 20 with anti-TNFα (infliximab 8, adalimumab 12), and 4 with azathioprine treatment. Cord blood anti-TNFα was higher than maternal blood levels [4.3 (IQR 2.3-9.2) vs. 2.5 (IQR 1.3-9.7) mcg/ml], declining at 3 and 12 months. All infants had normal number of B-cells (
We found that T-cell and B-cell immunity is fully mature and immune function is normal in infants exposed "
"There are many challenging aspects of the management of cardiac sarcoidosis (CS) with corticosteroids and other immunosuppressive therapy (IST). First, it is not always clear who will benefit from therapy or when to initiate treatment. Secondly, there are no randomized controlled trials or large prospective studies to guide what medications to use, at what doses, and for how long. The European Respiratory Society (ERS) clinical practice guidelines on the treatment of sarcoidosis makes a strong recommendation for the use of immuno-suppressive therapy in CS patients with functional cardiac abnormalities, including heart blocks, dysrhythmias, or cardiomyopathy where patients are considered at-risk of adverse outcomes. Corticosteroids are the first line immunosuppressive therapy in CS however, early initiation of second-line steroid sparing medications has been advocated and there is data to suggest that concomitant initiation of therapy may be more beneficial. The use of anti-tumor necrosis factor (anti-TNF) agents (including infliximab and adalimumab) considered beneficial third-line anti-sarcoidosis treatment agents in other severe refractory manifestations of disease remains controversial."
"Multiple variables contribute to variation in patient exposure and response to tumor necrosis factor alpha antagonist biologics such as infliximab. This study aimed to assess the association between maintenance-phase infliximab concentrations and genetic variation in HLADQA1*05G>A and fragment crystallisable (Fc) fragment of IgG receptor and transporter (FCGRT) among patients with inflammatory bowel disease.
A cross-sectional study was carried out in participants with inflammatory bowel disease prescribed infliximab who were in the maintenance phase of treatment. Participants were genotyped for the presence of the FCGRT variable number tandem repeat (VNTR) and HLADQA1*05G>A (rs74291249). A point estimate of the infliximab trough concentration during the maintenance phase was determined using a standard enzyme-linked immunosorbent assay for each patient. Other variables associated with infliximab pharmacokinetics were collected.
A total of 156 participants with inflammatory bowel disease were included from 2 tertiary care centers affiliated with Western University, London, Canada. Median infliximab trough concentrations were lower in participants who carried the FCGRT VNTR 2/3 or 2/2 (4.14 µg/mL; interquartile range [IQR], 6.48 µg/mL) vs wild type individuals (7.00 µg/mL; IQR, 7.66; P = .0027). Median infliximab trough concentrations were significantly lower in participants who were HLADQA1*05G>A variant carriers (4.73µg/mL; IQR, 4.79) vs wild type individuals (7.85µg/mL; IQR, 7.44; P = .0006). A significant decrease in infliximab trough concentrations was seen in individuals who were dual carriers of variant polymorphisms in HLADQA1*05G>A and FCGRT VNTR (no variants, 8.96µg/mL; IQR, 6.84 vs one variant, 4.96 µg/mL; IQR, 4.95 vs dual variants, 0.86µg/mL; IQR, 5.82).
FCGRT VNTR and HLADQA1*05G>A are associated with lower maintenance-phase infliximab concentrations, particularly among patients who carry both variants.
HLADQA1*05G>A and FCGRT VNTR are associated with lower maintenance-phase infliximab concentrations, particularly among patients who carry both variants."
"Inflammatory bowel disease (IBD) affects a growing cohort of elderly patients. Our aim was to compare the quality of care received by elderly patients with IBD with a nonelderly adult IBD population using clinical markers including steroid-free clinical remission.
Retrospective audit of all consecutive patients attending a specialist IBD centre over a 1-year period aged >60 (elderly cohort [EC]) and 50 consecutive patients aged 30-45 years (control cohort [CC]). A follow-up survey was completed assessing current symptoms and perceptions of care.
One hundred thirty-nine patients were evaluated (89 EC, 50 CC). Steroid-free clinical remission was observed less commonly in the EC (58, 64%) compared with the CC (40, 80%) (P < 0.05). Biologics such as infliximab (15% EC vs 36% CC; P < 0.01) and adalimumab (14% EC vs 30% CC; P = 0.02) were used less frequently in the EC, whilst vedolizumab (6% EC vs 6% CC; P = 1) and ustekinumab (3% EC vs 2% CC; P = 1) were used at a similar frequency. Patients in the EC were less likely to have specialist IBD nursing contact (P < 0.01), smoking screening (P < 0.011) or influenza vaccinations (P < 0.006). IBD nurse contact was associated with significantly greater provision of the preventative care measures.
Elderly patients with IBD were less likely to experience steroid-free clinical remission or be prescribed biologics. Elderly patients were less likely to receive education with respect to preventative medicine. The models of care for the elderly need re-evaluation and greater incorporation with the multidisciplinary IBD team."
"Infliximab (IFX) biosimilar was the first biosimilar approved in Jordan in 2014, with limited evidence of its safety and effectiveness from the Middle East and North Africa (MENA) region. Thus, this study aimed to evaluate the safety and effectiveness of IFX biosimilar in active rheumatoid arthritis (RA) patients over 34 weeks by investigating (1) the adverse events (AEs), serious adverse events (SAEs), and therapy discontinuation and (2) the score changes of the 28-Joint Disease Activity Score (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ-DI).
This multicenter prospective cohort study collected clinical parameters within hospital settings every four weeks. The numbers and percentages of observed AEs and SAEs were informed. The DAS28 utilizing Erythrocyte Sedimentation Rate (ESR), HAQ-DI, and ESR were reported at baseline and 14th and 30th weeks; thus, they were reported as means (SD).
A total of 22 RA patients were enrolled and initiated IFX biosimilar, of which nine (41.0%) discontinued the study, but their data were analyzed up to the point of withdrawal. A total of 35 AEs were reported in 14 patients, including two (5.7%) SAEs. None of the participants discontinued treatment due to AEs. The mean (SD) score of DAS28-ESR significantly decreased from 6.55 (1.16) at baseline to 4.59 (1.45) at week 14 (
IFX biosimilar demonstrated safety and effectiveness in managing RA patients bringing real-world clinical support for biosimilars' role in rheumatology."
"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to the development of the novel coronavirus disease (coronavirus disease 2019 [COVID-19]). Scarce data are available regarding safety and efficacy of SARS-CoV-2 vaccination in inflammatory bowel disease (IBD) patients, which may present differences between subgroups. Lower humoral immunological response could require additional booster injections.
This is a prospective study including adult patients with IBD after complete vaccination against SARS-CoV-2 infection with BioNTech vaccine. Patients with previous SARS-CoV-2 infection were excluded. A control group with healthy individuals matched for age and sex was also analyzed. Blood samples were collected 30 days after complete vaccination to quantify immunoglobulin G (IgG) antibody titers against SARS-CoV-2 in both groups.
The final sample included 81 IBD and 32 non-IBD patients, 55 (48.7%) of them women, with a mean age of 40.2 ± 13.0 years. From IBD patients, 58 (71.6%) had Crohn's disease and 23 (28.4%) had ulcerative colitis. IBD patients had significantly lower median anti-SARS-CoV-2 IgG levels when compared with the control group (6479 [interquartile range (IQR) 1830-11883, 10 053] AU/mL vs 13 061 [IQR 2826-21427, 15 539] AU/mL; P = .003). Regarding IBD medication, significant lower levels of SARS-CoV-2 IgG antibodies when compared with control subjects were observed in patients treated with thiopurines (5423 [IQR 3109-13369, 10 260] AU/mL; P = .011), methotrexate (834 [IQR 507-3467, 4155] AU/mL; P = .002), anti-tumor necrosis factor α agents (5065 [IQR 1033-11669, 10 636] AU/mL; P = .001), and corticosteroids (548 AU/mL; P = .001). The incidence of SARS-CoV-2 infection after vaccination was also significantly higher in patients treated with these agents.
IBD patients treated with immunomodulators, anti-tumor necrosis factor α agents and corticosteroids presented significantly lower anti-SARS-CoV-2 IgG levels following complete vaccination when compared with healthy control subjects. These findings support the benefit of additional booster injections in this population.
This is a prospective study quantifying antibody titers against severe acute respiratory syndrome coronavirus 2 after complete vaccination in adult patients with inflammatory bowel disease. Immunomodulators, infliximab, and corticosteroid treatment were associated with lower antibody levels. This could support the benefit of an additional booster injection in this population."
"Immune-related adverse events due to immune checkpoint inhibitors (ICIs) are not always effectively treated using glucocorticoids and it may negatively affect the antitumor efficacy of ICIs. Interventional studies of alternatives to glucocorticoids are lacking. We examined whether interleukin-6 blockade by tocilizumab reduced ICI-induced colitis and arthritis.
Patients with solid cancer experiencing Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade >1 ICI-induced colitis/diarrhea (n=9), arthritis (n=9), or both (n=2) were recruited and treated with tocilizumab (8 mg/kg) every 4 weeks until worsening or unacceptable toxicity. Patients were not allowed to receive systemic glucocorticoids and other immunosuppressive drugs within the 14-day screening period. The primary endpoint was clinical improvement of colitis and arthritis, defined as ≥1 grade CTCAE reduction within 8 weeks. Secondary endpoints were improvements and glucocorticoid-free remission at week 24; safety; radiologic, endoscopic, and histological changes; and changes in plasma concentrations of C reactive protein, cytokines (IL-6, IL-8, and IL-17), and YKL-40.
Nineteen patients were available for efficacy analysis; one patient was excluded due to pancreatic insufficiency-induced diarrhea. Patients received treatment with pembrolizumab (n=10) or nivolumab (n=4) as monotherapy or ipilimumab and nivolumab (n=5) combined. Seven patients had been initially treated with glucocorticoids, and two of them also received infliximab. Ten patients continued ICI therapy during tocilizumab treatment. The primary endpoint was achieved in 15 of 19 (79%) patients. Additional one patient had ≥1 grade reduction at week 10, and another patient had stabilized symptoms. At week 24, ongoing improvement without glucocorticoids (n=12), including complete remission (n=10), was noted. Five patients had grades 3-4 treatment-related adverse events, which were manageable and reversible.
Tocilizumab showed promising clinical efficacy and a manageable safety profile in the treatment of ICI-induced colitis and arthritis. Our findings support the feasibility of randomized trials of immune-related adverse events.
NCT03601611."
"Mucosal healing improves clinical outcomes in patients with inflammatory bowel disease (IBD) and is associated with higher infliximab trough levels (ITLs). Transmural healing, assessed by intestinal ultrasound (IUS), is emerging as an objective target in Crohn's disease (CD) and ulcerative colitis (UC). This study explores the correlation between maintenance ITLs and sonographic transmural healing.
Patients on maintenance infliximab therapy were prospectively enrolled to undergo paired IUS examination and serum ITL. Infliximab trough levels were compared between patients with and without sonographic markers of inflammation using the Mann-Whitney U test.
A prospective cohort of 103 patients (51% male; 79 CD; 24 UC; median duration of disease 8 years) underwent IUS and serum ITL testing. Forty-one percent of CD and 66% of UC patients demonstrated sonographic healing (bowel wall thickening ≤3 mm with no increase in color Doppler signal). Crohn's disease patients with sonographic healing had higher median ITL compared with those with sonographic inflammation (4.8 μg/mL vs 3.1 μg/mL; P = .049). Additionally, the presence of hyperemia on Doppler was independently associated with lower ITL compared with those without hyperemia (2.1 μg/mL vs 4.2 μg/mL, respectively; P = .003). There was no significant association between ITL and other sonographic markers of inflammation. In UC, lower ITL was associated with hyperemia on Doppler imaging (P = .04). There was no association between ITL and sonographic healing or any other individual sonographic parameter of inflammation.
Lower maintenance infliximab levels are associated with sonographic parameters of inflammation in UC and CD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing.
Transmural healing assessed by intestinal ultrasound allows for objective assessment of disease activity. Lower maintenance infliximab levels were associated with sonographic parameters of inflammation in IBD. Further studies are needed to determine whether targeting higher infliximab levels can increase sonographic healing."
"Behçet's disease (BD) is multisystemic vasculitis with heterogeneous clinical manifestations. We describe the case of a 26-year-old man who presented with Budd-Chiari syndrome (BCS) related to BD. The patient received infliximab (IFX) due to the severity of vascular involvement. Subsequently, after IFX therapy, hospital-acquired pneumonia, trapped lung, and fungal infection of the lung and central nervous system developed as complications. The patient benefited from a second course of IFX and clinical remission was achieved following early identification and treatment of complications. Data on the presentation and prognosis of BCS related to BD are extremely limited. Our case report supports the growing evidence that anti-TNF antibody is a promising treatment for BD-related BCS.
Behçet's disease-related Budd-Chiari syndrome is a rare form of vascular involvement that severely affects mortality.Behçet's disease-related Budd-Chiari syndrome is frequently confused with idiopathic thrombosis and may be underdiagnosed.Infliximab could be a therapeutic option for refractory Behçet's disease with major vascular involvement, but the increased risk of opportunistic infections should be kept in mind."
"Biological medicines have improved patients' outcomes, but their high costs may limit access. Biosimilars, alternatives that have demonstrated high similarity in terms of quality, safety, and efficacy to an already licensed originator biological product, could increase competition and decrease prices. Given the expanding number of biosimilars, patients may switch from originator to biosimilar or among biosimilars. Randomized trials and observational studies conducted with multiple biosimilars over many disease areas confirmed the safety and efficacy of switching from originator to biosimilar. This study summarizes evidence on switching between biosimilars for which there are concerns to provide future guidance. A systematic search (MEDLINE, Embase, and Cochrane Library) for studies on anti-TNF agents, assessing clinical efficacy and safety of biosimilar-to-biosimilar switch in chronic inflammatory diseases, was performed. We retrieved 320 records and included 19 clinical studies. One study with historical control compared switching between biosimilars to maintenance of the same biosimilar. Ten were controlled cohort studies comparing switching between two biosimilars vs. switching from originator to a biosimilar or vs. multiple switches. Eight were single-arm cohort studies, where participants switched from one biosimilar to another, and the outcomes were compared before and after the switch. Overall, these studies did not highlight significant concerns in switching between biosimilars. Therefore, switching studies seem difficult to perform and unnecessary with the body of evidence suggesting no real problems in practice coupled with stringent regulatory requirements. Monitoring the use of biosimilars in clinical practice could support clinical decision-making, rational use of biological medicines, and help to further realize possible savings."
"Patients with inflammatory bowel disease (IBD) are at increased risk for life-threatening complications of Epstein-Barr virus (EBV), including lymphoproliferative diseases. These complications are likely related to inherent immune dysfunction and immunomodulating therapies often used. We aimed to determine the seroprevalence of EBV at diagnosis in our population, its impact on disease at onset, and the risk of active EBV infection.
We included patients newly diagnosed with IBD for whom an EBV serology was performed over a 2-year period. Demographic information and data on disease characteristics were collected retrospectively. Stored serum from the time of diagnosis was retrieved when available for the patients with positive EBV serology, and quantitative polymerase chain reaction testing was performed to assess the pre-treatment viral load of EBV.
One hundred twenty patients were included in the study. Fifty-three patients (44.2%) had positive EBV serology at diagnosis. Stratified by age group, the prevalence of seropositive patients was for 0 to <10 years 35%, 10 to <17 years 46%, and ≥17 years 50%. Overall, therapies started within 6 months of diagnosis were similar in both the seropositive and seronegative groups. Within the seropositive group, 66% received systemic corticosteroids, 32.1% infliximab, 5.7% adalimumab, and 5.7% azathioprine.
EBV seroprevalence is high in pediatric patients with IBD. EBV seropositivity did not seem to influence the severity of disease at onset or initial choice of therapy."
"Infliximab (IFX) is a monoclonal antibody that binds to and neutralizes TNF-α. IFX (Remicade) was approved by the U.S. Food and Drug Administration in 2006 for the treatment of severe plaque psoriasis. In 2013 two infliximab biosimilars: Remsima and Inflectra were also registered. The introduction of biosimilar drugs is associated with a significant reduction in treatment costs.
To evaluate the efficacy of treatment with biosimilar IFX with non-medical switch option in patients with plaque psoriasis under the drug program ""Treatment of moderate and severe plaque psoriasis"" of the Ministry of Health in Poland.
The group of 91 adult patients with moderate to severe plaque psoriasis, unresponsive or with contraindications to the standard treatment were qualified to the drug program (in 2016-2018). Efficacy of treatment with biosimilar IFX was evaluated using the Psoriasis Area and Severity Index, body surface area and Dermatology Life Quality Index scoring performed at week 0, 14, 46 and 94.
The mean change in PASI, DLQI, and BSA scores at week 14 was 89.92%, 93.75% and 90.91%, respectively. By week 14, 83.52% of patients achieved PASI75, 49.45% PASI ≥ 90 and 26.37% PASI100. At week 46, 84.62% of patients achieved PASI75, 54.95% PASI ≥ 90, and 21.98% PASI100. At week 94 of therapy, 80.22% of patients achieved PASI75, 48.35% PASI ≥ 90, and 18.68% PASI100. At week 94 of therapy, PASI100 was maintained by 37.5% of patients who achieved PASI100 at week 14.
94-week therapy with biosimilar infliximab results in high and sustained clinical efficacy in patients with moderate to severe psoriasis."
"Both exclusive enteral nutrition (EEN) and infliximab (IFX) are recommended as induction therapy for pediatric Crohn's disease (CD). Our aim was to compare long-term disease outcomes of patients initially received with either IFX or EEN.
Medical records of newly diagnosed, therapy naïve pediatric patients with CD received with IFX or EEN as induction therapy were retrospectively enrolled. Pediatric Crohn's disease activity index (PCDAI), Crohn's disease endoscopic index of severity (CDEIS), and other clinical data were compared pre- and postinduction therapy in two groups. The sustained remission rates and time coupled with body mass index (BMI) and height for age (HFA) changes were evaluated during more than 2-year long-term follow-up.
We collected data from 58 children with CD used IFX (23) or EEN (35) as induction remission therapy from January 2015 through June 2021 in our single-center. The median follow-up after starting IFX or EEN was 12.2 months (6.5-18.0months) and 18.9 months (7.1-30.7months), respectively. The proportion clinical and endoscopic remission in EEN (88.57% and 68.75%) was similar with that of IFX (73.91% and 80.77%) after induction therapy. No significant differences were also observed in BMI and HFA recovery between two groups. Among those who achieved clinical or endoscopic remission or endoscopic response, the sustained remission rates and time did not reveal any significant differences for those 10 patients who used 6-mercaptopurine/methotrexate (6-MP/MTX) or 14 patients who used IFX as maintenance treatment during longitudinal follow-up.
Our study suggested that EEN treatment is similar with IFX therapy in short-term outcomes, and EEN+6-MP/MTX treatment is comparable with IFX+IFX therapy in long-term outcomes."
"COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose.
VIP was a multicentre, prospective, case-control study done in nine centres in the UK. We recruited immunosuppressed patients with IBD and non-immunosuppressed healthy individuals. All participants were aged 18 years or older. The healthy control group had no diagnosis of IBD and no current treatment with systemic immunosuppressive therapy for any other indication. The immunosuppressed patients with IBD had an established diagnosis of Crohn's disease, ulcerative colitis, or unclassified IBD using standard definitions of IBD, and were receiving established treatment with one of six immunosuppressive regimens for at least 12 weeks at the time of first dose of SARS-CoV-2 vaccination. All participants had to have received three doses of an approved COVID-19 vaccine. SARS-CoV-2 spike antibody binding and T-cell responses were measured in all participant groups. The primary outcome was anti-SARS-CoV-2 spike (S1 receptor binding domain [RBD]) antibody concentration 28-49 days after the third vaccine dose, adjusted by age, homologous versus heterologous vaccine schedule, and previous SARS-CoV-2 infection. The primary outcome was assessed in all participants with available data.
Between Oct 18, 2021, and March 29, 2022, 352 participants were included in the study (thiopurine n=65, infliximab n=46, thiopurine plus infliximab combination therapy n=49, ustekinumab n=44, vedolizumab n=50, tofacitinib n=26, and healthy controls n=72). Geometric mean anti-SARS-CoV-2 S1 RBD antibody concentrations increased in all groups following a third vaccine dose, but were significantly lower in patients treated with infliximab (2736·8 U/mL [geometric SD 4·3]; p<0·0001), infliximab plus thiopurine (1818·3 U/mL [6·7]; p<0·0001), and tofacitinib (8071·5 U/mL [3·1]; p=0·0018) compared with the healthy control group (16 774·2 U/mL [2·6]). There were no significant differences in anti-SARS-CoV-2 S1 RBD antibody concentrations between the healthy control group and patients treated with thiopurine (12 019·7 U/mL [2·2]; p=0·099), ustekinumab (11 089·3 U/mL [2·8]; p=0·060), or vedolizumab (13 564·9 U/mL [2·4]; p=0·27). In multivariable modelling, lower anti-SARS-CoV-2 S1 RBD antibody concentrations were independently associated with infliximab (geometric mean ratio 0·15 [95% CI 0·11-0·21]; p<0·0001), tofacitinib (0·52 [CI 0·31-0·87]; p=0·012), and thiopurine (0·69 [0·51-0·95]; p=0·021), but not with ustekinumab (0·64 [0·39-1·06]; p=0·083), or vedolizumab (0·84 [0·54-1·30]; p=0·43). Previous SARS-CoV-2 infection (1·58 [1·22-2·05]; p=0·0006) was independently associated with higher anti-SARS-CoV-2 S1 RBD antibody concentrations and older age (0·88 [0·80-0·97]; p=0·0073) was independently associated with lower anti-SARS-CoV-2 S1 RBD antibody concentrations. Antigen-specific T-cell responses were similar in all groups, except for recipients of tofacitinib without evidence of previous infection, where T-cell responses were significantly reduced relative to healthy controls (p=0·021).
A third dose of COVID-19 vaccine induced a boost in antibody binding in immunosuppressed patients with IBD, but these responses were reduced in patients taking infliximab, infliximab plus thiopurine, and tofacitinib. Tofacitinib was also associated with reduced T-cell responses. These findings support continued prioritisation of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF and JAK inhibitors.
Pfizer."
"Behçet's disease (BD) is a relapsing systemic immune disorder, and intestinal BD is a significant cause of mortality in patients with BD. Conventional therapeutic strategies for intestinal BD showed unsatisfactory outcomes, especially in those patients with refractory subtypes. In recent years, biologic agents have exhibited promising results in this field. While the sample sizes of existing studies were limited, the results were heterogeneous.
This study aimed to observe the efficacy of different biologics in clinical symptomatic improvement and intestinal mucosal healing.
This is a study including the report of case series and meta-analysis.
This meta-analysis was conducted following the PRISMA guidelines. Free-text words and subject terms, including 'Behcet's Syndrome', 'Biologics', 'Tumor Necrosis Factor Antagonist', were used to systematically research the relevant studies in the electronic databases (PubMed, Web of Science, Embase, and Cochrane Library). All retrieved articles were from inception to July 2021, and the data from our institution were also included in this meta-analysis. A double arcsine transformation was performed to stabilize the variance of the original ratio. Heterogeneity was evaluated via 
Twelve studies were included, but only antitumor necrosis factor alpha (anti-TNF-α) agents were prescribed as biologicals for refractory intestinal BD. The symptom improvement rates at our institution ranged from 57.1 to 81.8%, and the mucosal healing rates were from 20 to 60% in different therapeutic periods. A total of 514 patients were enrolled in the meta-analysis, and the synthesized ratios showed that 59.8% (
Anti-TNF-α treatment is effective in treating refractory intestinal BD but more studies are required to evaluate the effects of new biologics for intestinal BD in the near future.
This study has been registered on PROSPERO, the ID is CRD42022329211."
"Immune checkpoint inhibitors (ICI) are known to cause immune-related adverse events (irAE) with the gastrointestinal (GI) tract among the most affected. Our knowledge of GI irAE in patients with luminal GI malignancies is poor. We aimed to characterize the incidence, clinical features, treatment, and outcomes of these GI irAEs.
This was a retrospective study of patients with malignancies involving the luminal GI tract and GI irAEs at MD Anderson Cancer Center from January 2010 to June 2020. Clinical data were collected and analyzed.
Eighteen patients with luminal GI tract malignancies treated with ICIs had evidence of GI irAEs based on clinical symptoms and/or histology. The predominant GI irAE symptom was diarrhea (78%). Ten had non-ulcerative inflammation (56%) and 5 had ulcerative inflammation (28%) on endoscopy. Histologically, 3 patients (17%) had evidence of acute inflammation, 4 (22%) had chronic inflammation, and 9 (50%) had both. Ten patients (56%) received immunosuppressant treatment, which included steroids alone (n=2, 20%), steroids with biologics (infliximab or vedolizumab) (n=7, 70%), or biologics alone (n=1, 10%), with clinical remission in all cases. Of the 6 patients who previously had stable or ICI-responsive cancer and received immunosuppressants, none developed progression of GI luminal malignancy during the study period.
GI irAEs occurred in 2.4% of patients treated with ICI for cancer involving the luminal GI tract. Immunosuppressant therapies (e.g., vedolizumab) appear to be effective for GI irAEs, showing no association with further GI luminal cancer progression, recurrence, or a subsequent poor response to ICI therapy."
"Ustekinumab (UST), an antibody against the p40 subunit of interleukin-12/23, has been proven to be effective in patients with Crohn's disease (CD). However, large, long-term comparative studies of UST against anti--tumor necrosis factor (TNF) agents are lacking. We compared the effectiveness of anti-TNF agents and UST in CD patients without prior use of biologics.
We used a large nationwide anonymized Japanese database containing administrative medical claims data and various related patient data. In a propensity score-matched cohort with similar clinical characteristics, 2-year effectiveness was compared between patients treated with infliximab or adalimumab (anti-TNF group) and those treated with UST (UST group). Primary outcomes were cumulative rates of hospitalization, surgery, and persistence.
Among 53 540 CD patients, 7047 were extracted for eligibility, of which 5665 were treated with an anti-TNF agent and 1382 with UST. After propensity score matching, the cumulative hospitalization rates were comparable between anti-TNF and UST groups (P = 0.85; 25.3% vs 26.5% at 1 year, 33.8% vs 39.8% at 2 years). The cumulative surgery rates were also comparable between these groups (P = 0.46; 5.5% vs 5.1% at 1 year, 8.3% vs 8.4% at 2 years). The persistence rate at 1 year was higher in UST group (90.8% vs 92.5%), and that at 2 years was higher in anti-TNF group (81.2% and 74.6%); however, there was no significant difference in the cumulative persistence rate (P = 0.55).
Anti-TNF agents and UST appear to have comparable effectiveness for CD patients without prior use of biologics."
"To evaluate long-term outcomes of infliximab (IFX) treatment in patients with Behçet's disease (BD)-associated uveitis.
We retrospectively analyzed the cases of patients with BD-associated uveitis treated with IFX for > 5 years. We compared the numbers of ocular inflammatory attacks, ocular disease activities, and visual acuity before and after the initiation of IFX treatment.
The 24 patients were 20 men and 4 women. Their mean age at the initiation of IFX treatment was 37.3 ± 9.2 years. The mean term from the initiation of IFX treatment was 10.3 ± 2.4 years. The average number of ocular inflammatory attacks was 5.4 ± 2.1 per 12 months before the IFX treatment and significantly lower at 0.83 ± 0.96 per 12 months after the initiation of IFX treatment (p < 0.05). We used a scoring system for BD-associated uveitis named the Behçet's disease ocular attack score 24 (BOS24) to estimate the changes in ocular disease activities between before and after initiation of IFX treatment. The average score decreased significantly from 7.58 ± 2.77 to 2.55 ± 2.74 after the initiation of IFX treatment (p < 0.05). Even after > 5 years of the treatment, both the number of ocular attacks and the BOS24 score kept decreasing. The visual acuity in 42 of 48 eyes (24 patients) was improved or maintained.
IFX was effective for controlling ocular inflammatory attacks and diminishing ocular disease activities in patients with BD-associated uveitis, and it maintained the patients' visual acuity."
"Despite the intense global research endeavour to improve the treatment of patients with COVID-19, the current therapy remains insufficient, resulting in persisting high mortality. Severe cases are characterised by a systemic inflammatory reaction driven by the release of pro-inflammatory cytokines such as IL-6 and tumour-necrosis-factor alpha (TNF-α). TNF-α-blocking therapies have proved beneficial in patients with chronic inflammatory diseases and could therefore pose a new treatment option in COVID-19. Hitherto, no results from randomised controlled trials assessing the effectiveness and safety of infliximab-a monoclonal antibody targeting TNF-α-in the treatment of COVID-19 have been published.
In this phase-2 clinical trial, patients with COVID-19 and clinical and laboratory signs of hyperinflammation will be randomised to receive either one dose of infliximab (5 mg/kg body weight) in addition to the standard of care or the standard of care alone. The primary endpoint is the difference in 28-day mortality. Further assessments concern the safety of infliximab therapy in COVID-19 and the influence of infliximab on morbidity and the course of the disease. For the supplementary scientific programme, blood and urine samples are collected to assess concomitant molecular changes. The Ethics Committee of the Friedrich Schiller University Jena (2021-2236-AMG-ff) and the Paul-Ehrlich-Institute (4513/01) approved the study.
The results of this study could influence the therapy of patients with COVID-19 and affect the course of the disease worldwide, as infliximab is globally available and approved by several international drug agencies.
The trial was registered at clinicaltrials.gov ( NCT04922827 , 11 June 2021) and at EudraCT ( 2021-002098-25 , 19 May 2021)."
"Discontinuation of anti-tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing.
This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3-4) versus complete (Mayo 0/SES-CD 0-2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use.
Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6-2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43-7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01-0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months.
The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse."
"This systematic review and meta-analysis sought to evaluate the effectiveness and safety of biologic therapy in the treatment of steroid-refractory microscopic colitis (MC).
We searched MEDLINE, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on biologic use (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) for induction and maintenance of remission in MC. We assessed clinical remission and response rates and all reported adverse events (AEs).
A total of 376 studies were screened yielding 13 articles (including four abstracts) with a combined information on 78 patients for efficacy and safety outcomes. Most studies were case series. Vedolizumab was used in five studies, adalimumab in three, and a combination of infliximab and adalimumab in five studies. The rates of remission were 66.08% (95% CI, 36.79-95.37%; I2 , 71%) at weeks 3-6 and 54.20% (95% CI, 39.39-69.01%; I2 , 0%) at weeks 12-16. Clinical response rates were 100% (95% CI, 88.04-100%; I2 , 0%) at weeks 3-6 and 67.20% (95% CI, 47.72-86.69%; I2 , 52%) at weeks 12-16. Most frequent AE was medication discontinuation with a pooled incidence of 16.1% (95% CI, 5.9-37.5%). No deaths attributable to biologic use were reported. The overall quality of evidence was very low due to the high risk of biases.
Low-quality evidence supports the short-term efficacy of biologics in budesonide refractory MC. While our findings represent the most comprehensive evaluation of biologic therapy in severe MC, further research including randomized clinical trials is needed to better define the role of specific agents and long-term therapy."
"Rheumatoid arthritis is a highly heterogeneous autoimmune disease characterized by unpredictable disease flares and significant differences in therapeutic response to available treatments. One possible reason for poor efficacy is that it cannot be treated accurately due to no optimal stratification for RA patients.
This study aims to construct an RA classification model by m6A characters and further predict response to medication.
Twenty m6A regulators were used to construct a random forest diagnosis model, and RNA-seq analysis was employed for external validation. The RNA modification patterns mediated by 20 m6A regulators were systematically evaluated in 1191 RA samples and explored different molecular clusters associated with other immune microenvironment characteristics and biological pathways. Then, we established an m6A score model to quantify the m6A modification patterns. The model was applied to patients at baseline to test the association between m6Ascore and infliximab responsiveness.
The m6A diagnosis model showed good discriminatory ability in distinguishing RA. Patients with RA were classified into three clusters with distinct molecular and cellular signatures. Cluster A displayed strongly activated inflammatory cells and pathways. Specific innate lymphocytes occupied cluster B. Cluster C was mainly enriched in prominent adaptive lymphocytes and NK-mediated cytotoxicity signatures with the highest m6A score. Patients with a low m6Ascore exhibited significantly infliximab therapeutic benefits compared with those with a high m6Ascore (p< 0.05).
Our study is the first to provide a comprehensive analysis of m6A modifications in RA, which provides an innovative patient stratification framework and potentially enables improved therapeutic decisions."
"Sequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4β7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting.
Patients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period.
Second-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001).
Compared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes."
"Cutaneous involvement is the second-most frequent extraintestinal manifestation of inflammatory bowel disease, with pyoderma gangrenosum (PG) a particularly relevant form because of its frequency, morbidity, and recurrence. The limited number of clinical trials involving PG increases the challenge to gastroenterologists in the management of this condition.
Four cases of atypical presentations of PG are reported. A 25-year-old patient with ulcerative colitis presented an extensive chronic ulcerative lesion on her left leg that was associated with significant bleeding; the intestinal disease was in remission under the use of azathioprine. The patient was on long-term use of 60 mg corticosteroid with no improvement in the skin disease; however, initiation of cyclosporine induced remission. In the second case, a 52-year-old woman was a carrier of Crohn's disease, with a history of partial colectomy. The patient's skin condition had evolved with a cutaneous lesion localized in the perineal region, buttocks, and colostomy pouch, simulating a case of impetigo, and this had been treated with antibiotic cycles without improvement. Lesion biopsy suggested a diagnosis of PG. Consequently, the patient was started on biological therapy with infliximab, and the PG regressed. In the third case, a 38-year-old woman with a history of pancolitis presented a picture of PG with an extensive and deep ulcerative lesion in the right breast. The lesion regressed after treatment with oral corticosteroid. The final case was a 44-year-old woman with Crohn's disease suffering from Crohn's disease pancolitis. The patient's condition evolved with a mixed pattern with pustules, bullae, and ulcerative lesions in the vulva, oral cavity, gluteus, right auricular region, scalp, and left flank, and was resolved by administration of adalimumab.
PG is an important and frequent manifestation of inflammatory bowel disease, with a spectrum of clinical variants, significant morbidity, and requiring a variety of therapeutic approaches."
"There has been a growing attention on using machine learning (ML) in pharmacovigilance. This study aimed to investigate the utility of supervised ML algorithms on timely detection of safety signals in the Korea Adverse Event Reporting System (KAERS), using infliximab as a case drug, between 2009 and 2018. Input data set for ML training was constructed based on the drug label information and spontaneous reports in the KAERS. Gold standard dataset containing known AEs was randomly divided into the training and test sets. Two supervised ML algorithms (gradient boosting machine [GBM], random forest [RF]) were fitted with hyperparameters tuned on the training set by using a fivefold validation. Then, we stratified the KAERS data by calendar year to create 10 cumulative yearly datasets, in which ML algorithms were applied to detect five pre-specified AEs of infliximab identified during post-marketing surveillance. Four AEs were detected by both GBM and RF in the first year they appeared in the KAERS and earlier than they were updated in the drug label of infliximab. We further applied our models to data retrieved from the US Food and Drug Administration Adverse Event Reporting System repository and found that they outperformed existing disproportionality methods. Both GBM and RF demonstrated reliable performance in detecting early safety signals and showed promise for applying such approaches to pharmacovigilance."
"Advances in drug therapy for inflammatory bowel disease (IBD) [Crohn disease and ulcerative colitis (UC)] have contributed to a decrease in the severity of these chronic and disabling conditions.
What are the milestones of the changes in the expert approach to the pharmacological management of IBD in the past century?
To determine the changes in the experts' approach to the management of regional ileitis and UC, as presented in a widely used textbook in the United States.
The chapters presenting the management of IBD in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020.
No specific interventions existed from 1927 through 1942. The pharmacological management of IBD has had 3 slightly overlapping eras starting in 1943. During the first period (1943-1951), the medical management relied on antibiotics, primarily sulfonamides and chloramphenicol. In the second (1955-75), experts recommended the use of adrenocorticotropic hormone or corticosteroids and 5-aminosalicylate. In the third era, which commenced in 1979 and is continuing to date, the pharmacological interventions have been expanded and refined to include 5 main drug classes, 5-aminosalicylates (sulfasalazine, mesalamine, and olsalazine), corticosteroids (prednisone and budesonide), immunomodulators (azathioprine, 6-mercaptopurine, cyclosporine, and tofacitinib), biologics (infliximab adalimumab certolizumab pegol, and natalizumab), and antibiotics (metronidazole and ciprofloxacin). A consensus exists that the monoclonal antibodies again tumor necrosis factor alpha are cost-effective for induction and maintenance of clinical remission in both UC (golimumab) and Crohn disease (certolizumab pegol). The newer agents ustekinumab (a monoclonal antibody to the interleukin p40 subunit) and vedolizumab (a monoclonal antibody to the homing receptor integrin complex) have also performed well.
The pharmacological management of IBD has been the focus of intense research and development in the past 60 years. The pillars of drug treatment have been 5-aminosalicylates and corticosteroids. Recent pharmacological innovations (immunomodulators and biologicals) constitute an encouraging paradigm shift in the treatment of UC and Crohn disease."
"To evaluate the efficacy of standard and optimized infliximab induction dosing in attaining corticosteroid (CS) free clinical remission at week 52 and the effect that post-induction trough levels have on long-term outcome.
Inflammatory bowel disease (IBD) patients ≤18 years commenced on infliximab between August 1, 2016, and August 1, 2018, from Vancouver, Canada, and Glasgow, Scotland, were included. The Glasgow cohort followed standard induction while the Vancouver cohort undertook induction optimization based on clinical, biomarker, and proactive infliximab trough levels. Baseline characteristics and laboratory values were documented.
In total, 140 children were included [median age 14.1 years (interquartile range (IQR) 12.0-16.0)]; 54% male. CS-free clinical remission at week 52 was higher in the optimized group compared to the standard cohort [65/78 (83%) vs. 32/62 (52%), P < 0.001]. Combined CS-free clinical and biomarker remission (CRP < 5 mg/L) was also higher in the optimized compared to the standard cohort [65/78 (83%) vs 25/62 (40%), P < 0.001]. The median post-induction trough level was higher in children who were in CS-free clinical remission at week 52 [3.6 mg/L (1.5-7.1)] vs. those who were not [2.0 mg/L (0.8-4.1), P = 0.04]. The odds of attaining a therapeutic post-induction trough level were almost 4-fold higher in the optimized group than the standard cohort (OR 3.97, 95% CI: 1.89-8.68, P < 0.001).
Standard infliximab induction resulted in less favorable long-term outcomes for pediatric IBD patients. Optimizing induction using clinical, biomarker, and proactive trough levels resulted in higher post-induction trough levels and a greater odds of attaining long-term clinical remission."
"Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects multiple joints. It is associated with psoriasis and treated with synthetic and biologic drugs.
The objective of this study was to assess the outcomes of patients who received biologic therapy with tumor necrosis factor (TNF) inhibitors in terms of effectiveness, safety, functionality, and quality of life.
A prospective observational study was performed at a single center in Belo Horizonte, Brazil.
Patients with PsA who received their first TNF inhibitor treatment were followed up for 12 months. Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index (CDAI). Functionality was measured using the Health Questionnaire Assessment (HAQ), and quality of life was evaluated using the European Quality of Life Five Dimensions (EQ-5D). Multiple linear regression was used to identify predictors of the clinical response at 12 months.
A total of 143 patients treated with adalimumab or etanercept were evaluated. Most of the clinical measures were significantly improved at 12 months. However, 31%-51% of the patients did not achieve good clinical control. No differences were observed between adalimumab and etanercept, except for poor functionality at 12 months among patients treated with etanercept. The main predictors of a worse clinical response were female sex, etanercept use, poor functionality, or lower quality of life at baseline. The main adverse reactions were alopecia, headache, injection site reaction, sinusitis, flu, dyslipidemia, and infections.
TNF inhibitor therapy was effective and safe. However, despite improvements in clinical measures, most patients did not achieve satisfactory control of the disease."
"Inflammatory bowel disease patients may suffer from extraintestinal manifestations. Although muscles, joints, and skin are the most commonly affected, respiratory involvement is more prevalent than previously believed, and the majority of these patients have no symptoms. Although the large airways are the most frequently affected, the small airways, lung parenchyma, and pulmonary vasculature may also be affected.
A 24-year-old nonsmoking Syrian female was referred to the pulmonary medicine clinic in December 2020 due to a chronic cough. Her cough had been present for the last year, it was described as scratchy, and produced small amounts of mucoid sputum occasionally. She denied any related wheeze, hemoptysis, weight loss, or night sweats. Multiple courses of antibiotics were prescribed by many doctors, also previous chest radiographs were reported as normal. She was diagnosed with ulcerative colitis in 2012 after presentation with abdominal pain and per rectal bleeding. The diagnosis was confirmed via colonoscopy and colon biopsies, with no prior surgery. Her past medications included prednisone, mesalamine, azathioprine, and infliximab. Tests, including complete blood count, C-reactive protein (CRP), fecal calprotectin, and chest X-ray, were normal.
Ulcerative colitis-associated bronchiectasis was established through history and clinical examination beside pulmonary function test, which revealed a mild obstructive pattern, and a chest computed tomography follow-up that revealed bilateral bronchiectasis.
Bronchiectasis was treated with inhaled oral steroids and sputum expectoration while she continued mesalamine and azathioprine for ulcerative colitis.
Cough improvement and sustained ulcerative colitis remission.
Identification of inflammatory bowel disease pulmonary exacerbation is probably poor, as pulmonary symptoms might emerge at any moment during the illness, and are most commonly diagnosed later in life and with the disassociation of inflammatory bowel disease activity. Pulmonologists should be involved in the care of inflammatory bowel disease patients who developed lung symptoms."
"The role of intestinal microbiota in inflammatory bowel diseases is intensively researched. Pediatric studies on the relation between microbiota and treatment response are sparse. We aimed to determine whether absolute abundances of gut microbes characterize the response to infliximab induction in pediatric inflammatory bowel disease.
We recruited pediatric patients with inflammatory bowel disease introduced to infliximab at Children's Hospital, University of Helsinki. Stool samples were collected at 0, 2, and 6 weeks for microbiota and calprotectin analyses. We defined treatment response as fecal calprotectin value <100 µg/g at week 6. Intestinal microbiota were analyzed by 16S ribosomal RNA gene amplicon sequencing using the Illumina MiSeq platform. We analyzed total bacterial counts using quantitative polymerase chain reaction and transformed the relative abundances into absolute abundances based on the total counts.
At baseline, the intestinal microbiota in the treatment responsive group (n = 10) showed a higher absolute abundance of Bifidobacteriales and a lower absolute abundance of Actinomycetales than nonresponders (n = 19). The level of inflammation according to fecal calprotectin showed no statistically significant association with the absolute abundances of fecal microbiota. The results on relative abundances differed from the absolute abundances. At the genus level, the responders had an increased relative abundance of Anaerosporobacter but a reduced relative abundance of Parasutterella at baseline.
High absolute abundance of Bifidobacteriales in the gut microbiota of pediatric patients reflects anti-inflammatory characteristics associated with rapid response to therapy. This warrants further studies on whether modification of pretreatment microbiota might improve the outcomes.
We studied absolute and relative abundances of fecal microbiota in relation to response to induction therapy with infliximab in pediatric inflammatory bowel disease. We discovered that a high absolute abundance of anti-inflammatory Bifidobacteriales at baseline associated with response."
"Tumor necrosis factor-alpha (TNF-α) neutralization has become increasingly important in the treatment of inflammatory bowel diseases (IBD). A series of monoclonal antibodies were approved in the clinic for anti-TNF-α therapy. However, a comprehensive assessment of TNF-α levels throughout the colon, which facilitates the diagnosis of IBD and predicts anti-TNF-α efficacy, remains challenging. Here, we radiolabeled infliximab with long-lived radionuclides "
"Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).
To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.
In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.
Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure."
"Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) mediates the immunity and inflammatory response in multiple ways to be intimately involved in the progression of autoimmune diseases. This study intended to explore the linkage of MALT1 with inflammation, disease activity, and its change with infliximab treatment response in Crohn's disease (CD) patients.
MALT1 in peripheral blood mononuclear cell samples from 72 active CD patients (at baseline, 2 weeks [W2], W6, and W12 after infliximab treatment), 20 remissive CD patients (after enrollment), and 20 healthy controls (after enrollment) were detected by RT-qPCR.
MALT1 was highest in active CD patients, followed by remissive CD patients, and lowest in healthy controls (p < 0.001). MALT1 was positively linked with C-reactive protein (p = 0.001), erythrocyte sedimentation rate (p = 0.014), clinical disease activity index (p = 0.003), tumor necrosis factor (TNF)-α (p = 0.006), interleukin (IL)-1β (p = 0.049), and IL-17A (p = 0.004), but not other clinical characteristics (all p > 0.05) in active CD patients. After infliximab treatment, MALT1 was decreased from baseline to W12 in active CD patients (p < 0.001), especially in responders (p < 0.001), but not in nonresponders (p = 0.053). The reduction of MALT1 at W6 (p = 0.049) and W12 (p = 0.004) was associated with a good treatment response to infliximab in active CD patients. Moreover, the response rate or MALT1 at any time point was not different between active CD patients with and without TNFi history (all p > 0.05).
MALT1 reflects aggravated inflammation and disease activity. Meanwhile, the decrement of MALT1 from baseline to W12 could reflect infliximab treatment response in CD patients."
"We aimed to model infliximab (IFX) pharmacokinetics (PK) in pediatric acute severe ulcerative colitis (ASUC) and assess the association between PK parameters, including drug exposure, and clinical response.
We studied a multicenter prospective cohort of hospitalized children initiating IFX for ASUC or IBD-unclassified. Serial IFX serum concentrations over 26 weeks were used to develop a PK model. We tested the association of PK parameter estimates with day 7 clinical response, week 8 clinical remission, week 26 corticosteroid-free clinical remission (CSF-CR) (using the Pediatric Ulcerative Colitis Activity Index), and colectomy-free survival.
Thirty-eight participants received IFX (median initial dose, 9.9 mg/kg). Day 7 clinical response, week 8 clinical remission, and week 26 CSF-CR occurred in 71%, 55%, and 43%, respectively. Albumin, C-reactive protein, white blood cell count, platelets, weight, and antibodies to IFX were significant covariates incorporated into a PK model. Week 26 non-remitters exhibited faster IFX clearance than remitters (P = .013). However, cumulative IFX exposure did not differ between clinical response groups. One (2.7%) and 4 (10.8%) participants underwent colectomy by week 26 and 2 years, respectively. Day 3 IFX clearance >0.02 L/h was associated with colectomy (hazard ratio, 58.2; 95% confidence interval, 6.0-568.6; P < .001).
At median higher-than-label IFX dosing for pediatric ASUC, baseline faster IFX CL was associated with colectomy and at week 26 with lack of CSF-CR. IFX exposure was not predictive of clinical outcomes. Higher IFX dosing may sufficiently optimize early outcomes in pediatric ASUC. Larger studies are warranted to determine whether sustained intensification can overcome rapid clearance and improve later outcomes.
gov identifier: NCT02799615."
"Ulcerative colitis (UC) is a chronic global disease, and its incidence and prevalence are increasing worldwide.
Our objective was to compare the secondary outcome of treatment with Infliximab (IFX) and Adalimumab (ADA) in the UC patients.
This was a one-year prospective observational study of moderate- to -severe UC patients treated with ADA or IFX. Patients' secondary health outcomes were measured using the EQ-5D 3L, EQ-VAS, and IBDQ-9 tools. T-test, Mann-Whitney, chi-square, and Fisher's exact tests were used to compare health-related quality of life (HRQoL) among UC patients. HRQoL predictor variables were identified by multivariate linear regression and multivariate logistic regression.
A total of 238 UC patients (patients taking IFX: 78, patients taking ADA: 160) with a mean age of 37.66 and a mean disease duration of 9.29 years were enrolled. The EQ-5D index, EQ-VAS, and IBDQ-9 scores of patients taking IFX were 0.65, 55.93 and, 37.42, respectively. Similarly, patients taking ADA were 0.68, 59.27 and, 36.61, respectively. The highest problem reports were in P/D: 86.1% and A/D: 73.5%. The main independent predictors of HRQoL were: education over 12 years (β = 0.054 [EQ-5D index], β = 13.63 [EQ-VAS], OR: 0.28 [MO], OR: 0.07 [SC]), education between 6-12 years (β = 11.23 [EQ-VAS]), and having ""other chronic diseases"" (β = -0.074 [EQ-5D index], β = -5.29 [IBDQ-9], OR: 2.84 [UA], OR: 3.80 [A/D]).
There was no significant difference between the effect of ADA and IFX on secondary health outcomes in patients with moderate-to-severe UC."
"Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as psoriasiform lesions, alopecia, lupus and, vasculitis, which more often affects the skin (small-sized vessels) and eventually other organs. In this review, we describe the clinical profile of patients with vasculitis induced by the main biological agents used in rheumatology.
We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The PubMed database was used for searching eligible articles. We included case reports, case series, and letter to the editor of patients on anti-tumor necrosis factor-alpha (anti-TNF-a) molecules, as well as tocilizumab, ustekinumab, secukinumab, rituximab, and abatacept, who had vasculitis induced by these agents.
Eighty-one articles were included for final analysis (n=89). Twenty-seven patients were using infliximab, 20 adalimumab, 18 etanercept, seven secukinumab, four certolizumab, four rituximab, three golimumab, three ustekinumab, two abatacept, and one tocilizumab. Unspecific leukocytoclastic vasculitis (LCV) was the most common type of vasculitis (n=37), followed by anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (n=16). The medication was replaced with another biological molecule in 23 cases, with only four relapses. In six cases, the biological was maintained, but vasculitis worsened/persisted in one case, being necessary drug removal.
Infections, infusion reaction, cancer, and autoimmune events are well-known side effects of biological therapy. This review demonstrates that vasculitis is another adverse effect of this type of therapy, particularly the anti-TNF-a molecules, and LCV the most reported type of vasculitis."
"The aim of our study was to assess the best medical and surgical approaches for perianal Crohn's disease (PCD) in order to identify an optimal combined medical and surgical treatment.
Medical records of all patients with PCD treated with TNFα antagonists in two referral centres between 1998 and 2018 were reviewed. Predictors of long-term outcomes were identified using a Cox proportional hazard model.
A total of 200 patients were included. Fifty-three patients (26.5%) were treated with adalimumab and 147 (73.5%) with infliximab. A combination of TNFα antagonist with an immunosuppressant and the presence of proctitis were independently associated with fistula closure. Seton was placed in 127 patients (63.5%) before starting biological therapy. Eighty patients (40%) underwent additional perineal surgery. Prior PCD surgery, seton positioning, additional perineal surgery, and additional surgery within 52 weeks of anti-TNFα treatment were associated with an increased rate of fistula closure. Finally, medical combination therapy (anti-TNFα plus immunosuppressant) along with seton placement and additional surgery within 1 year was the best management for PCD patients (p = 0.02).
Combined medical and surgical management is required for the treatment of PCD patients. Medical combination therapy associated with seton placement and additional surgery within 1 year is the best management for PCD patients."
"Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine's effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose can neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)]. Fifty-six subjects with IBD and 12 healthy subjects were recruited. Ninety percent of patients with IBD (49/56) received biologics and/or immunomodulatory therapy. Twenty-four subjects with IBD did not develop effective neutralizing capability against the Omicron variant. Seventy percent (17/24) of those subjects received anti-tumor necrosis factor therapy [10 = adalimumab, 7 = infliximab], two of which had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and more extensive studies are needed to evaluate optimal immunity."
"Precision medicine refers to a highly individualized and personalized approach to patient care. Pharmacogenomics is the study of how an individual's genomic profile affects their drug response, enabling stable and effective drug selection, minimizing side effects, and maximizing therapeutic efficacy. Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in the joints. It mainly starts in peripheral joints, such as the hands and feet, and progresses to large joints, which causes joint deformation and bone damage due to inflammation of the synovial membrane. Here, we review various pharmacogenetic studies investigating the association between clinical response to monoclonal antibody therapy and their target genetic polymorphisms. Numerous papers have reported that some single nucleotide polymorphisms (SNPs) are related to the therapeutic response of several monoclonal antibody drugs including adalimumab, infliximab, rituximab, and tocilizumab, which target tumor necrosis factor (TNF), CD20 of B-cells, and interleukin (IL)-6. Additionally, there are some pharmacogenomic studies reporting on the association between the clinical response of monoclonal antibodies having various mechanisms, such as IL-1, IL-17, IL-23, granulocyte-macrophage colony-stimulating factor (GM-CSF) and the receptor activator of nuclear factor-kappa B (RANK) inhibition. Biological therapies are currently prescribed on a ""trial and error"" basis for RA patients. If appropriate drug treatment is not started early, joints may deform, and long-term treatment outcomes may worsen. Pharmacogenomic approaches that predict therapeutic responses for RA patients have the potential to significantly improve patient quality of life and reduce treatment costs."
"Crohn's disease is one of the two most common types of inflammatory bowel disease. Current medical therapies are based on the use of glucocorticoids, exclusive enteral nutrition, immunosuppressors such as azathioprine and methotrexate, and biological agents such as infliximab, adalimumab, vedolizumab, or ustekinumab. International guidelines suggest regular disease assessment and surveillance through objective instruments to adjust and personalize the therapy, reducing the overall rates of hospitalization and surgery. Although endoscopy represents the gold-standard for surveillance, its frequent use is strongly bordered by associated risks and costs. Consequently, alternative non-invasive tools to objectify disease activity and rule active inflammation out are emerging. Alongside laboratory exams and computed tomography or magnetic resonance enterography, intestinal ultrasonography (IUS) shows to be a valid choice to assess transmural inflammation and to detect transmural healing, defined as bowel wall thickness normalization, no hypervascularization, normal stratification, and no creeping fat. Compared to magnetic resonance imaging (MRI) or computed tomography, CT scan, IUS is cheaper and more widespread, with very similar accuracy. Furthermore, share wave elastography, color Doppler, and contrast-enhanced ultrasonography (CEUS) succeed in amplifying the capacity to determine the disease location, disease activity, and complications. This review aimed to discuss the role of standard and novel ultrasound techniques such as CEUS, SICUS, or share wave elastography in adults with Crohn's disease, mainly for therapeutic monitoring and follow-up."
"Anti-TNF therapy has significantly improved disease control in rheumatoid arthritis, but a fraction of rheumatoid arthritis patients do not respond to anti-TNF therapy or lose response over time. Moreover, the mechanisms underlying non-response to anti-TNF therapy remain largely unknown. To date, many single biomarkers of response to anti-TNF therapy have been published but they have not yet been analyzed as a system of interacting nodes. The aim of our study is to systematically elucidate the biological processes underlying non-response to anti-TNF therapy in rheumatoid arthritis using the gene ontologies of previously published predictive biomarkers. Gene networks were constructed based on published biomarkers and then enriched gene ontology terms were elucidated in subgroups using gene ontology software tools. Our results highlight the novel role of proteasome-mediated protein catabolic processes ("
"Despite being in sustained and stable remission, patients with Crohn's disease (CD) stopping anti-tumour necrosis factor α (TNFα) show a high rate of relapse (~50% within 2 years). Characterising non-invasively the biological profiles of those patients is needed to better guide the decision of anti-TNFα withdrawal.
Ninety-two immune-related proteins were measured by proximity extension assay in serum of patients with CD (n=102) in sustained steroid-free remission and stopping anti-TNFα (infliximab). As previously shown, a stratification based on time to clinical relapse was used to characterise the distinct biological profiles of relapsers (short-term relapsers: <6 months vs mid/long-term relapsers: >6 months). Associations between protein levels and time to clinical relapse were determined by univariable Cox model.
The risk (HR) of mid/long-term clinical relapse was specifically associated with a high serum level of proteins mainly expressed in lymphocytes (LAG3, SH2B3, SIT1; HR: 2.2-4.5; p<0.05), a low serum level of anti-inflammatory effectors (IL-10, HSD11B1; HR: 0.2-0.3; p<0.05) and cellular junction proteins (CDSN, CNTNAP2, CXADR, ITGA11; HR: 0.4; p<0.05). The risk of short-term clinical relapse was specifically associated with a high serum level of pro-inflammatory effectors (IL-6, IL12RB1; HR: 3.5-3.6; p<0.05) and a low or high serum level of proteins mainly expressed in antigen presenting cells (CLEC4A, CLEC4C, CLEC7A, LAMP3; HR: 0.4-4.1; p<0.05).
We identified distinct blood protein profiles associated with the risk of short-term and mid/long-term clinical relapse in patients with CD stopping infliximab. These findings constitute an advance for the development of non-invasive biomarkers guiding the decision of anti-TNFα withdrawal."
"Sarcoidosis may present with many rheumatological symptoms as well as mimic and/or may occur concomitantly with many other rheumatic diseases. We examined the demographic, clinical and laboratory characteristics of patients diagnosed with sarcoidosis in the rheumatology department. This study planned as retrospective cross-sectional study. Medical records of patients who applied to our rheumatology outpatient clinic due to complain of musculoskeletal problems and then diagnosed sarcoidosis were retrospectively investigated. Joint findings, extrapulmonary involvements, and coexisting rheumatic disease were evaluated. Fifty-six patients (41.21 ± 7.83 years, 75% female) were included. The duration of the disease was 49.61 ± 29.11 months, and the follow-up period was 26.66 ± 13.26 months. All patients had pulmonary system involvement. Arthralgia was present in 91.10% of 56 patients and arthritis in 89.29% of patients. Examining the subtypes of the arthritis findings, mono-arthritis was found in 31/50 (62%) patients, oligo-arthritis in 15/50 (30%) patients, and polyarthritis in 4/50 (8%) patients. A total of 11 (19.60%) patients were diagnosed with uveitis. Excision of the mediastinal LAP was performed in a total of 37 patients (66.1%) and became the most commonly employed method. Considering the treatment distribution of the patients under followed-up, it is seen that non-steroidal anti-inflammatory treatments were used in 15 (26.8%) patients, corticosteroids in a total of 40 (71.4%) patients, methotrexate in a total of 15 patients (26.8%), azathioprine in six (10.7%) patients, hydroxychloroquine in 14 (25%) patients, and infliximab in one (1.8%) patient. As sarcoidosis is a mimicking disease, a good differential diagnosis should be made to avoid misdiagnosis and in order not to be late in diagnosis and treatment. Physicians, especially rheumatologists, should remember sarcoidosis more frequently as the disease may overlap with other rheumatological diseases and may occur with many rheumatological manifestations."
"Paradoxical reactions are immune-mediated disease exacerbations that can occur in Mycobacterium tuberculosis (TB) following initiation of treatment. They are rare, challenging to manage and often fatal. We present a case of neurotuberculosis in a young woman, complicated by a paradoxical reaction in which infliximab was trialled without success. This case demonstrates the severity of presentation that can occur in neurotuberculosis, and the complications that paradoxical reactions can present. It also highlights the difficulty of delivering palliative care within the context of communicable disease with challenges posed by both TB and the COVID-19 pandemic."
"Behcet's syndrome (BS) is a chronic, relapsing multisystemic inflammatory perivasculitis and can affect any tissue, including the nervous system. Neuro-Behcet's syndrome (NBS) most commonly affects the CNS parenchyma and presents with a subacute brainstem syndrome that includes cranial neuropathies. Here we describe a rare case of palato-pharyngo-laryngeal myoclonus as a manifestation of NBS and discuss it from a laryngology perspective.
Case report at tertiary care center. Informed consent was obtained from patient. IRB approved as non-human subjects research.
A 52-year-old male presented with a progressive history of ataxia, fatigue, apathy, dysphagia, depressed mood, dizziness, poor appetite, subjective fever and recurrent orogenital lesions. He was diagnosed with NBS and treated with methylprednisolone, followed by infliximab and methotrexate. Despite treatment, his severe spastic dysarthria, dysphagia, and aspiration worsened over the next few months, necessitating a gastrotomy tube. With concern for laryngospasm, he was referred to otolaryngology and found to have synchronous and symmetric palatal, pharyngeal, and laryngeal rhythmic myoclonus bilaterally at a frequency of 2 Hz with inappropriate vocal cord closure. Treatment with baclofen and a scopolamine patch improved his breathing and reduced choking events.
Palato-pharyngo-laryngeal rhythmic myoclonus can be a presentation of brainstem NBS in the otolaryngology clinic. We theorize perivascular disease in NBS results in a brainstem lesion in the denato-rubro-olivary tract, which results in hypertrophic olivary degeneration and subsequent activation of the inferior olives oscillatory activity, causing palato-pharyngo-laryngeal rhythmic myoclonus. Common symptoms include significant dysarthria, dysphonia, and dysphagia with concern for obstructive sleep apnea and airway compromise. Treatments include pharmacologic therapy, laryngeal botox, and tracheostomy in cases of significant airway compromise."
"To compare and rank the effect of glucocorticoid-sparing agents in giant cell arteritis (GCA), for which several drugs have been evaluated but with a benefit-risk balance that remains uncertain.
The MEDLINE and Clinical Trials databases were searched up to November 2021; all randomized controlled trials investigating glucocorticoids in GCA were included. The glucocorticoid regimen was dichotomized into short (≤6 months) or prolonged (>6 months) use. Risk of relapse and safety were estimated using network meta-analysis with frequentist random effects models.
Of the 96 records screened, 8 trials were included (572 patients). The trials compared glucocorticoids and a sparing agent: tocilizumab (2 trials), oral methotrexate (3 trials), infliximab (1 trial), etanercept (1 trial), and adalimumab (1 trial). The pooled prevalence of GCA relapse was 52.6% (95% CI, 38.1 to 66.9). The risk of relapse was significantly lower with tocilizumab compared with methotrexate (relative risk [RR], 0.41; 95% CI, 0.17 to 0.97) and prolonged (RR, 0.41; 95% CI, 0.20 to 0.83) and short (RR, 0.32; 95% CI, 0.16 to 0.66) glucocorticoid use. The risk of relapse was not significantly different with methotrexate compared with short (RR, 0.79; 95% CI, 0.48 to 1.31) and prolonged (RR, 0.95; 95% CI, 0.31 to 2.89) glucocorticoid use. The frequency of serious adverse events and serious infection was comparable between the different drugs. The certainty of the evidence was low to very low.
This meta-analysis suggests that tocilizumab may be superior to other sparing agents to prevent GCA relapse, but with a low to very low certainty of evidence, and that safety is comparable to the other drugs.
The protocol of the meta-analysis is registered in the international prospective register of systematic reviews PROSPERO (https://www.crd.york.ac.uk/prospero/; registration CRD42020112387)."
"Immunosuppressive therapy is standard for the treatment of inflammatory diseases and for minimizing rejection in transplant patients. However, immunosuppressant drugs are associated with an increased risk of certain cancers. In particular, melanoma is an immunogenic tumor and as such, is strongly influenced by the immune system. We performed this literature review to summarize the effects of commonly used immunomodulating agents on melanoma development, recurrence and progression. We outline the mechanism of action of each drug and discuss the available evidence on its influence on melanoma. Based on existing literature, we recommend avoiding the following agents in patients with a history of invasive melanoma: cyclosporine, sirolimus, natalizumab, IL-6 inhibitors, cyclophosphamide, methotrexate and the tumor necrosis factor-alpha inhibitors infliximab and etanercept. If there are no viable alternative agents, we recommend for these patients to see a dermatologist every 6 months for a thorough skin examination."
"Immune checkpoint inhibitors (ICIs) have been developed as cornerstones of cancer therapy, but the growing use of ICIs has induced immune-related adverse effects (irAEs). Immune-related colitis, which is one of the most common irAEs, generally occurs 2-4 months after ICI treatment initiation and can be life threatening. Therefore, early diagnosis and appropriate management are required. A rare autopsy case of nivolumab-related severe colitis that occurred 34 months after the start of treatment and recurred despite temporal remission with corticosteroids and infliximab is presented. Physicians should be aware of the possibility of late-onset irAEs in patients on receiving long-term ICI treatment."
"Since our last publication of algorithms for the management of perianal fistulas in patients with Crohn's disease, researchers have proposed a treat to target strategy systematic combotherapy for anal lesions, and indications for stem cell injection. In the absence robust publications, the Société Nationale Française de Coloproctologie (French National Society of Coloproctology [SNFCP]) wished to establish a group consensus using the Delphi method.
From October 2020 to January 2021, a scientific committee and panel of gastroenterologists and surgeons established answers which were submitted to the members of the SNFCP during a national conference in November 2020. Three questions were clarified and reformulated, and then submitted during a third and final round of consultation of members of the SNFCP.
The target was defined as being the response obtained in every domain (symptoms, physical and radiological evaluation) which could be considered satisfactory, without the need to intensify therapeutic management. By consensus, the time required for clinical evaluation of the efficacy of treatment was 6 months. A response on magnetic resonance imaging (MRI) should include the absence of a collection of 10 mm or more in size at 6 months, and a frank decrease or complete disappearance of hyperintensity in T1 and T2 sequences of the main tract at 12 months. Systematic association of an immunosuppressant with tumor necrosis factor inhibitors did not reach the consensus level for adalimumab (50%), but just did for infliximab (70%). The majority of the respondents considered failure of one, or even two lines of different biotherapies to be potential indications for injection of stem cells.
These findings reinforce the importance of composite targets including MRI evaluation, and underscore the need for precise timing of evaluation. Combotherapy is only recommended with infliximab. Injection of stem cells is a second- or third-line option."
"We assessed the effectiveness of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases (IBDs) treated with or without intensified intravenous regimen.
In this multicenter observational study, IBD patients in clinical remission (partial Mayo score ≤2 or Harvey-Bradshaw index ≤4) were switched to a unique dose of subcutaneous infliximab (120 mg every other week). Pharmacological and biological data were collected at baseline, visit 1 (4-8 weeks postswitch), visit 2 (8-16 weeks postswitch), and visit 3 (16-24 weeks postswitch). Relapse was defined as clinical relapse or fecal calprotectin increase ≥150 μg/g compared with baseline.
Among 184 eligible patients, 72.3% (n = 133 of 184) agreed to switch to subcutaneous infliximab. At visit 3, a relapse occurred in 10.2% (n = 6 of 59), 7.3% (n = 3 of 38), 16.7% (n = 3 of 18), and 66.7% (n = 10 of 15) (P < .001) of patients receiving 5 mg/kg every 8 weeks, 10 mg/kg every 8 weeks, 10 mg/kg every 6 weeks, and 10 mg/kg every 4 weeks, respectively. Dose escalation to 240 mg every other week led to recapture clinical remission in 93.3% (n = 14 of 15). Infliximab serum levels increased after the switch (P < .0001) except for patients receiving 10 mg/kg every 4 weeks. In multivariable analysis, 10 mg/kg every 4 weeks regimen (odds ratio, 12.4; 95% confidence interval, 1.6-98.4; P = .017) and fecal calprotectin >250 μg/g at baseline (odds ratio, 5.4; 95% confidence interval, 1.1-27.6; P = .042) had a higher risk of relapse as well as reduced (41.7%) or stable (36.8%) infliximab serum levels between baseline and visit 1 compared with increased serum levels (12.7%) (P = .020 and P = .019, respectively). Patients' acceptability (10-point scale) was improved by the switch (6.9 ± 1.6 vs 8.6 ± 1.4; P < .0001). No severe adverse event was reported.
Switching from intravenous to subcutaneous infliximab 120 mg every other week is safe and well accepted, leading to a low risk of relapse in IBD patients except for those receiving 10 mg/kg every 4 weeks requiring 240 mg every other week."
"This cross-sectional study describes changes in annual Medicare Part B spending for biologic drugs after biosimilar entry, focusing on the first 4 products to experience biosimilar competition: filgrastim, infliximab, epoetin alpha, and pegfilgrastim."
"The use of biologics poses a moderate to high risk for hepatitis B virus reactivation (HBVr) in chronic carriers.
To determine the prevalence of HBVr with TNF alpha inhibitors, ustekinumab and vedolizumab METHOD: We followed the MOOSE guidelines and conducted a comprehensive literature search. We conducted a systematic search of EMBASE (Ovid), MEDLINE (Ovid) and PubMed. The studies included patients who were chronic and occult HBV carriers with various rheumatological, dermatological or gastroenterological conditions. We used a random effects model using pooled estimates (prevalence of HBVr with 95% confidence intervals (CI)).
We included 29 studies with 1409 patients infected with HBV. The prevalence of HBVr in chronic carriers of HBV was 17.1% (95% CI: 7.0-35.9, n = 5), 16.6% (95% CI: 9.5-27.5%, n = 6), 40.5% (95% CI: 20.3-64.5%, n = 4) and 19.1% (95% CI: 7.3-41.2%, n = 2), respectively, for adalimumab, etanercept, infliximab and ustekinumab. The respective prevalence for reactivation in patients with occult HBV infection was 5.0% (95% CI: 2.8-8.7%, number of studies: n = 18), 2.6% (95% CI: 1.4-4.7%, n = 18), 4.4% (95% CI: 2.2-8.7%, n = 12) and 6.4% (95% CI: 2.2-16.8, n = 5). There were 39 HBVr (26 in chronic HBV and 13 in the occult group) without any hepatic failure or death. In the chronic HBVr group, only three of 24 patients received antiviral prophylaxis.
HBVr prevalence rates differ between the chronic carrier state and the occult carrier state. The uptake of prophylactic antiviral therapy in high-risk groups was low, contrary to clinical practice guidelines."
"The clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn's disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab.
Early serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes.
The median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 μg/mL at week 6 and 4.0 μg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission.
A threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab."
"We aimed to compare the long-term persistence between different tumor necrosis factor-alpha inhibitors (TNFis) with immune-mediated rheumatic diseases (IMRD). This study can potentially provide insights into the real-world evidence regarding safety and effectiveness of TNFi treatment in a Chinese population.
We enrolled newly diagnosed IMRD patients in this active comparator, retrospective cohort study by using National Taiwan insurance claim datasets. The drug survivals of first-line TNFi agents, including etanercept, golimumab, and adalimumab were compared. Propensity score matching was conducted to control the confounding effect from the observed covariates. The cumulative proportion of discontinuation was calculated over 5 years. The multiple-variable regression and propensity score analysis was used for confounding adjustment.
After propensity score matching, there were 2267 patients identified in each etanercept, golimumab, and adalimumab group. We observed the 5-year cumulative proportion of discontinuation was 52.80%, 45.85%, and 56.86% in etanercept, golimumab, and adalimumab, respectively. Compared with golimumab, increase of 31% (95% CI: 20-43) and 38% (95% CI: 26-50) risk of discontinuation were observed in etanercept and adalimumab. The factors including female gender, increasing age, long hospital stays, without co-medication with nonsteroidal anti-inflammatory drugs or methotrexate were associated were discontinuation of first-line TNFi treatment.
Golimumab had better drug survival than etanercept or adalimumab over 5 years of observation in Asian IMRD patients. Gender, age, longer hospital stays, concomitant use of disease-modifying antirheumatic drugs were associated with survival with TNFis."
"Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. Common symptoms at onset include lower back, abdominal or flank pain. Pain is frequently referred to the hip, to the groin and to the lateral regions of the leg, often with nocturnal exacerbations and not responding to position changes. The disease is commonly associated with signs of systemic inflammatory response (malaise, fever, and anorexia and weight loss). Glucocorticoids are considered the cornerstone of the therapy. The use of other immunosuppressive agents, including cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil and biological agents such as rituximab, tocilizumab and infliximab have been reported as a valuable option mostly in case reports, cases series and small studies. These agents allowed to reduce cumulative dose of glucocorticoids and their adverse effects. Combined therapy is preferable for all patients who suffer from significant glucocorticoid- related toxicity or in cases where glucocorticoids alone are insufficient to treat the condition."
"The objective of this study was to describe the efficacy and safety of infliximab (IFX) reintroduction in Crohn's disease (CD) after stopping for loss of response or intolerance.
We conducted a prospective multicenter observational cohort study including adult patients with clinically (CD Activity Index &gt;150) and objectively active luminal CD in whom IFX was reintroduced after at least 6 months of discontinuation. The reasons for the initial discontinuation could be a secondary loss of response or IFX intolerance. The reintroduction schedule included 3 IFX infusions at weeks 0, 4, and 8, after a systematic premedication. The primary end point was the efficacy of IFX retreatment at week 26 defined by a CD Activity Index of &lt;150 in the absence of IFX discontinuation or use of corticosteroids, surgery, or other biologic.
At week 26, 24 patients (35%) among the 69 analyzed reached the primary end point. No significant difference was observed between rates of clinical remission at week 26 in patients with prior LOR (n = 48) and those with IFX intolerance (n = 21) (35% and 33%, P = 0.87, respectively). Thirty-two acute infusion reactions were recorded in 27 patients, leading to withdrawal of IFX in 20 patients. No pharmacokinetic characteristic at baseline but detection of positive anti-drug antibodies at week 4 was predictive of IFX failure or infusion reaction at week 26.
In this first prospective cohort study, IFX retreatment was safe and effective in one-third of the patients with CD, regardless the reason of prior discontinuation. Early detection of anti-drug antibodies can predict subsequent IFX reintroduction failure and infusion reactions."
"Obesity is variably associated with treatment response in biologic-treated patients with inflammatory bowel diseases (IBD). We evaluated the association between obesity and risk of hospitalization, surgery, or serious infections in patients with IBD in new users of biologic agents in a large, multicenter, electronic health record (EHR)-based cohort (CA-IBD).
We created an EHR-based cohort of adult patients with IBD who were new users of biologic agents (tumor necrosis factor [TNF-α] antagonists, ustekinumab, and vedolizumab) between January 1, 2010, and June 30, 2017, from 5 health systems in California. Patients were classified as those with normal body mass index (BMI), overweight, or obese based on the World Health Organization classification. We compared the risk of all-cause hospitalization, IBD-related surgery, or serious infections among patients with obesity vs those overweight vs those with normal BMI, using Cox proportional hazard analyses, adjusting for baseline demographic, disease, and treatment characteristics.
Of 3,038 biologic-treated patients with IBD (69% with Crohn's disease and 76% on TNF-α antagonists), 28.2% (n = 858) were overweight, and 13.7% (n = 416) were obese. On a follow-up after biologic initiation, obesity was not associated with an increased risk of hospitalization (adjusted hazard ratio [aHR] vs normal BMI, 0.90; [95% confidence interval, 0.72-1.13]); IBD-related surgery (aHR, 0.62 [0.31-1.22]); or serious infection (aHR, 1.11 [0.73-1.71]). Similar results were observed on stratified analysis by disease phenotype (Crohn's disease vs ulcerative colitis) and index biologic therapy (TNF-α antagonists vs non-TNF-α antagonists).
In a multicenter, EHR-based cohort of biologic-treated patients with IBD, obesity was not associated with hospitalization, surgery, or serious infections. Further studies examining the effect of visceral obesity on patient-reported and endoscopic outcomes are needed."
"Secondary structural and functional abnormalities of the neurovascular unit are important pathological mechanisms following traumatic brain injury (TBI). The neurovascular unit maintains blood-brain barrier and vascular integrity through interactions among glial cells, pericytes and endothelial cells. Trauma-induced neuroinflammation and oxidative stress may act as initiating factors for pathological damage after TBI, which in turn impairs cerebral microcirculatory function. Studies have shown that the tumor necrosis factor α (TNF-α)/nuclear factor-κB (NF-κB) pathway regulates inflammation and oxidative damage, but its role in pericyte-mediated cerebral microcirculation are currently unknown. Herein, we assessed TNF-α/NF-κB signaling and inducible nitric oxide synthase (iNOS), and the effects of the TNF-α inhibitor infliximab after TBI. Whether pericyte damage is dependent on the TNF-α/NF-κB/iNOS axis was also evaluated to explore the mechanisms underlying disturbances in the microcirculation after TBI. Microglia are activated after TBI to promote inflammatory factors and free radical release, and upregulate NF-κB and iNOS expression. After lipopolysaccharide treatment, the activity of TNF-α/NF-κB/iNOS in BV2 cells was also upregulated. Inhibition of TNF-α using infliximab reduced NF-κB phosphorylation and nuclear translocation and downregulated iNOS expression, which attenuated the inflammation and oxidative damage. Meanwhile, inhibition of TNF-α reversed pericyte marker loss, and improved pericyte function and microcirculation perfusion after TBI. In conclusion, our study suggests that microglia released TNF-α after TBI, which promoted neuroinflammation and oxidative stress by activating downstream NF-κB/iNOS signals, and this led to pericyte-mediated disturbance of the cerebral microcirculation."
"Pyoderma gangrenosum (PG) is an inflammatory dermatosis characterized by the rapid progression of a painful, necrolytic ulcer with an irregular and undermined border. The prevalence of PG in patients with Crohn's disease (CD) has been estimated to be 0.7%. Here, we report a case that presented various painful skin lesions, including erythema, vesicles, plaques, and ulcers, one week before the fourth infliximab infusion for CD. PG was diagnosed and the lesions subsided after a 390-mg ustekinumab infusion for one month. It suggests that different lesions of PG may occur concomitantly in CD patients, and the therapy should be re-evaluated on time."
"The use of biologic therapy for antibiotic-refractory pouchitis is controversial, due to few studies on the subject and lack of convincing results.
To study the efficacy of biologic therapy for refractory pouchitis.
In this retrospective study, patient records at the Medical and Surgical departments in our hospital during an eleven-year period were scrutinized. 25 patients treated with biologics for refractory pouchitis were identified.
The majority of these patients (
This retrospective study suggests that biologic therapy may be effective for both idiopathic and Crohn's-like refractory pouchitis. Naïve patients seem to respond more successfully than not naïve patients. In cases without response on first-line treatment should second-line treatment be considered. Due to the high risk of adverse reactions Infliximab should be avoided to not naïve patients."
"Biologic medications are novel therapeutics in the treatment of Autoimmune Inner Ear Disease (AIED), an etiology of Sensorineural Hearing Loss (SNHL). The goal of this study is to review the currently available literature on the efficacy of biologic medications on autoimmune-mediated hearing loss and associated symptomology among patients with AIED.
A systematic review of Pubmed, Scopus, Cochrane, and Web of Science databases was conducted to identify studies investigating the impact of biologic medications on hearing outcomes. Bias assessment was independently conducted by three authors and studies were stratified based on risk of bias.
Of 174 unique abstracts screened, 12 articles met inclusion criteria for formal review. One randomized control trial, seven prospective cohort studies, and four retrospective cohort studies were included. Seven biologic medications, Etanercept, Infliximab, Adalimumab, Golimumab, Rituximab, Anakinra, and Canakinumab, were identified targeting three unique molecular targets, TNF-α, CD20, and IL-1.
The effects of biologic medications in treating SNHL was highly variable without clear efficacy of a drug or drug category, likely due to rarity of disease, multifactorial etiologies of AIED, and cohort heterogeneity. However, several medications alleviate symptoms associated with AIED, such as vertigo and tinnitus. While biologic medications may be promising therapeutics in AIED patients, the evidence is currently inconclusive. Large-scale randomized control trials and prospective cohort reviews are required to establish the efficacy of biologic medications in treating hearing loss."
"Biologicals, such as anti-tumor necrosis factor (anti-TNF), reduce cardiovascular disease (CVD) in patients with inflammatory rheumatic diseases. Impaired renal function is a known predictor of CVD and elevated in ankylosing spondylitis (AS).
To assess the effect of anti-TNF on renal function in patients with AS and whether anti-TNF use is safe in AS patients with pre-existing risk factors for renal decline.
Biological-naïve consecutive AS patients treated with etanercept or adalimumab were prospectively followed from 2005 to 2014. Renal function was determined by calculation of the estimated glomerular filtration rate (eGFR), estimated with the abbreviated modification of diet in renal disease (MDRD) formula. The effect of anti-TNF on eGFR was analyzed using mixed model analysis.
211 AS patients were followed for a median of 156 (36-286) weeks. Overall mixed model analyses showed a significant decrease of eGFR over time (β =  - 0.040, p = 0.000), although this association did not remain significant after adjustment for responding to anti-TNF, alcohol use, disease duration, body mass index (BMI), C-reactive protein (CRP), and disease activity (β =  - 0.018, p = 0.094). However, patients with pre-existing risk factors for renal decline did have a significant change in eGFR over time (β =  - 0.029, p = 0.006).
We found a significant change in eGFR over time, although this small decrease was not clinically relevant. This study further demonstrates that anti-TNF does not affect renal function in AS patients with and without existing risk factors for renal decline, which means that use of anti-TNF is safe concerning renal function in patients with AS. Key Points • Previous studies showed that biologicals, such as anti-tumor necrosis factor (anti-TNF), reduce cardiovascular disease (CVD) in patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS). • Impaired renal function is a known predictor of CVD, and also a known concern for many AS patients. • Use of anti-TNF is safe with regard to renal function in patients with AS. • The effect of anti-TNF on CVD in AS patients does not seem to be mediated by changes in renal function."
"Despite growing awareness of the nocebo effect, few studies have evaluated the nocebo effect using combined assessment of patient-reported outcome measures (PROMs), clinical indices, and objective biomarkers in inflammatory bowel disease (IBD) patients switching from originator to biosimilar medicines.
This study aimed to compare these outcomes across switch and non-switch cohorts to evaluate the nocebo effect in patients with IBD.
Parallel cohorts of IBD patients who (1) switched from originator to biosimilar (CT-P13) infliximab and (2) continued biosimilar (CT-P13) infliximab were evaluated over 32 weeks. Clinical disease activity, objective biomarkers and PROMs were assessed at baseline, and weeks 16 and 32 across both cohorts. The PROM of interest was patient-perceived disease activity evaluated using a 0-100 visual analogue scale (VAS) per the IBD-Control Questionnaire.
Of 81 patients, 47 switched from originator to biosimilar (CT-P13) infliximab. A negative change from baseline patient-reported disease control was observed across the switch cohort compared with the non-switch cohort at week 16 (mean VAS - 8.21 vs. 1.26; p = 0.03), but not at week 32 (mean VAS - 1.21 vs. 1.38; p = 0.58). Corresponding clinical and objective biomarker assessments over these timepoints were comparable across both cohorts.
This study demonstrated a temporary yet discernible nocebo effect in the first 16 weeks following non-medical switching that was not sustained at week 32. Negative patient perceptions may be overcome by a patient-inclusive approach to non-medical switching in conjunction with close clinical follow-up and disease monitoring."
"Inflammatory bowel disease (IBD) is of high medical and socioeconomic relevance. Moderate and severe disease courses often require treatment with biologics. The aim of this study was to evaluate machine learning (ML)-based methods for the prediction of biologic therapy in IBD patients using a large prescription database.
The present retrospective cohort study utilized a longitudinal prescription database (LRx). Patients with at least one prescription for an intestinal anti-inflammatory agent from a gastroenterologist between January 2015 and July 2021 were included. Patients who had received an initial biologic therapy prescription (infliximab, adalimumab, golimumab, vedolizumab, or ustekinumab) were categorized as the ""biologic group"". The potential predictors included in the machine learning-based models were age, sex, and the 100 most frequently prescribed drugs within 12 months prior to the index date. Six machine learning-based methods were used for the prediction of biologic therapy.
A total of 122,089 patients were included in this study. Of these, 15,824 (13.0%) received at least one prescription for a biologic drug. The Light Gradient Boosting Machine had the best performance (accuracy = 74%) and was able to correctly identify 78.5% of the biologics patients and 72.6% of the non-biologics patients in the testing dataset. The most important variable was prednisolone, followed by lower age, mesalazine, budesonide, and ferric iron.
In summary, this study reveals the advantages of ML-based models in predicting biologic therapy in IBD patients based on pre-treatment and demographic variables. There is a need for further studies in this regard that take into account individual patient characteristics, i.e., genetics and gut microbiota, to adequately address the challenges of finding optimal treatment strategies for patients with IBD."
"Immunosuppressants and biologicals are widely used therapeutics for various chronic inflammatory diseases (CID). To gain more detailed insight into their downstream effects, we examined their impact on serum immunoglobulin G (IgG) glycosylation. We analyzed IgG subclass-specific fragment crystallizable (Fc) N-glycosylation in patients suffering from various CID using the LC-MS approach. Firstly, we compared IgG Fc N-glycosylation between 128 CID patients and 204 healthy controls. Our results replicated previously observed CID-related decrease in IgG Fc galactosylation (adjusted "
"Muscle injuries are common in humans and are often associated with irrecoverable damage and disability. Upon muscle injury, TNF-α signaling pathways modulate the healing process and are predominantly associated with tissue degradation. In this study we assumed that TNF-α inhibition could reduce the TNF-α-associated tissue degradation after muscle injury.
Therefore, the left soleus muscle of 42 male Wistar rats was injured using a standardized open muscle injury model. All rats were treated immediately after injury either with infliximab (single i.p. injection; 10 mg/kg b.w.) or saline solution i.p. Final measurements were conducted at day one, four, and 14 post injury. The muscle force, the muscle cell proliferation, the muscle cell coverage as well as the myofiber diameter served as read out parameters of our experiment.
Systemic application of infliximab could significantly reduce the TNF-α levels in the injured muscle at day four upon trauma compared to saline treated animals. The ratio of muscle weight to body weight was increased and the twitch muscle force showed a significant rise 14 days after trauma and TNF-α inhibition. Quantification of myofiber diameter in the penumbra zone showed a significant difference between both groups at day one and four after injury, indicated by muscle hypertrophy in the infliximab group. Planimetric analysis of the injured muscle at day 14 revealed increased muscle tissue fraction in the infliximab group compared to the control animals. Muscle cell proliferation did not differ between both groups.
These data provide evidence that the TNF-α blockade positively regulates the restauration of skeletal muscles upon injury."
"Adalimumab (ADA) and infliximab (IFX) are the cornerstones of the treatment of Crohn's disease (CD). It remains controversial whether there is a difference in the effectiveness and safety between IFX and ADA for CD.
To perform a meta-analysis to compare the effectiveness and safety of ADA and IFX in CD.
PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Cohort studies were considered for inclusion. The primary outcomes were induction of response and remission, maintenance of response and remission, and secondary loss of response. Adverse events were secondary outcomes.
Fourteen cohort studies were included. There was no apparent difference between the two agents in the induction response [odds ratio (OR): 1.27, 95% confidence interval (CI): 0.93-1.74, 
ADA and IFX have similar clinical benefits for anti-tumor necrosis factor-α naïve or non-naïve CD patients. Overall adverse events rate is higher in patients in the IFX group."
"Infliximab trough level (ITL) severely affects therapeutic outcomes of Crohn's disease (CD) patients under infliximab (IFX). Recently, frontier research has focused on identifying ITL based on different therapeutic targets. Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy, studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas.
To explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy.
CD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected. ITL and inflammatory biomarkers were continuously monitored during the therapy. The Step I study was conducted from weeks 14 to 54 of IFX treatment. The Step II study was conducted from weeks 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (Crohn's disease endoscopic index of severity score > 2 points or Rutgeerts score > i1) and endoscopic remission (Crohn's disease endoscopic index of severity score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.
At week 14, low ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, 
Combination of ITL, CRP, and FCP contribute to long-term endoscopic prognosis monitoring. During IFX maintenance treatment, low ITL, high CRP level, and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up."
"Tumor necrosis factor-alpha inhibitors, including infliximab and adalimumab, are effective medical treatments for perianal fistulising Crohn's disease (CD), but not all patients achieve fistula healing.
To determine the correlation between perianal fistula healing and closure with infliximab and adalimumab trough levels.
In this multicentre retrospective study conducted across four tertiary inflammatory bowel disease centres in Australia, we identified CD patients with perianal fistulae on maintenance infliximab or adalimumab who had a trough level within twelve weeks of clinical assessment. Data collected included demographics, serum infliximab and adalimumab trough levels (mg/L) within 12 wk before or after their most recent clinical assessment and concomitant medical or surgical therapy. The primary outcome was fistula healing, defined as cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing and closure of all external fistula openings. Differences between patients who did or did not achieve fistula healing were compared using the chi-square test, 
One hundred and fourteen patients (66 infliximab, 48 adalimumab) were included. Forty-eight (72.7%) patients on maintenance infliximab achieved fistula healing and 18 (27.3%) achieved fistula closure. Thirty-seven (77%) patients on maintenance adalimumab achieved fistula healing and 17 (35.4%) achieved fistula closure. Patients who achieved fistula healing had significantly higher infliximab and adalimumab trough levels than patients who did not [infliximab: 6.4 (3.8-9.5) 
Higher maintenance infliximab and adalimumab trough levels are associated with perianal fistula healing in CD."
"Oral traumatic ulcers (OTU) are common in dental routine, and the control of proinflammatory cytokines, such as the tumor necrosis factor-alpha (TNF-α), may interfere with OTU repair. Our aim was to evaluate the role of TNF-α in the healing process of OTU in rats. Wistar male rats were divided into six groups: a control-group (treated with 0.1 mL/kg of saline) and five groups treated with anti-TNF-α infliximab (INF) at 1, 3, 5, 7, and 10 mg/kg immediately before OTU production. The animals were weighed (day 0) and euthanized on days 1, 3, 7, 14 and 21 after ulceration. The ulcers were clinically measured, and the mucosa samples were histologically (scores 0-4), histochemically (collagen assay (pircrosirius)), histomorphometrically (cell counting), and immunohistochemically (TNF-α, α-smooth-muscle-actin (α-SMA), monocyte-chemoattractive-protein-1 (MCP-1), interleukin-8 (IL-8), and fibroblast-growth-factor (FGF)) analyzed. The Evans blue assay was used to measure the vascular permeability. ANOVA-1-2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05). High doses of INF reduced the OTU area (p = 0.043), body mass loss (p = 0.023), vascular permeability (p < 0.001), and reduced delayed histologic scores (p < 0.05), polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, blood vessel counting (p = 0.006), and total (p < 0.001), type-I (p = 0.018), and type-III (p < 0.001) collagen. INF treatment reduced TNF-α immunostaining and delayed MPC-1, FGF, and α-SMA expression, with little/none influence in IL-8 immunostaining. TNF-α blockage by INF reduced acute inflammation in OTU but delayed cell migration and wound healing."
"Large gaps exist in understanding the symptomatic and functional impact of sarcoidosis, a rare multisystem granulomatous disease affecting fewer than 200,000 individuals in the United States. Smartphones could be used for prospective research, especially for rare diseases where organizing large cohorts can be challenging, given their near ubiquitous ownership and ability to track objective and subjective data with increasingly sophisticated technology.
We aimed to investigate whether smartphones could assess the quality of life (QoL) and physical activity of a large cohort of individuals with sarcoidosis.
We developed a mobile app (Sarcoidosis App) for a prospective, cross-sectional study on individuals with sarcoidosis. The Sarcoidosis App was made available on both Apple and Android smartphones. Individuals with sarcoidosis were recruited, consented, and enrolled entirely within the app. Surveys on sarcoidosis history, medical history, and medications were administered. Patients completed modules from the Sarcoidosis Assessment Tool, a validated patient-reported outcomes assessment of physical activity, fatigue, pain, skin symptoms, sleep, and lungs symptoms. Physical activity measured by smartphones was tracked as available.
From April 2018 to May 2020, the App was downloaded 2558 times, and 629 individuals enrolled (404, 64.2% female; mean age 51 years; 513, 81.6% White; 86, 13.7% Black). Two-thirds of participants had a college or graduate degree, and more than half of them reported an income greater than US $60,000. Both QoL related to physical activity (P<.001, ρ=0.250) and fatigue (P<.01, ρ=-0.203) correlated with actual smartphone-tracked physical activity. Overall, 19.0% (98/517) of participants missed at least 1 week of school or work in an observed month owing to sarcoidosis, and 44.4% (279/629) reported that finances ""greatly"" or ""severely"" affected by sarcoidosis. Furthermore, 71.2% (437/614) of participants reported taking medications for sarcoidosis, with the most common being prednisone, methotrexate, hydroxychloroquine, and infliximab. Moreover, 46.4% (244/526) reported medication side effects, most commonly due to prednisone.
We demonstrate that smartphones can prospectively recruit, consent, and study physical activity, QoL, and medication usage in a large sarcoidosis cohort, using both passively collected objective data and qualitative surveys that did not require any in-person encounters. Our study's limitations include the study population being weighted toward more educated and wealthier individuals, suggesting that recruitment was not representative of the full spectrum of patients with sarcoidosis in the United States. Our study provides a model for future smartphone-enabled clinical research for rare diseases and highlights key technical challenges that future research teams interested in smartphone-based research for rare diseases should anticipate."
"We aimed to evaluate US treatment patterns and, more specifically, switch patterns among patients with psoriasis (PsO) who initiated treatment with targeted therapy (TT) and subsequently switched to another therapy.
This retrospective study used IBM
A total of 11,526 patients with PsO were included; mean [standard deviation (SD)] age and Charlson Comorbidity Index score were 48.3 (12.8) years and 0.9 (1.43), respectively. During the follow-up, 69.2% of the patients were treated with NTT. Median time to first NTT, for those who received NTT, was 205 days (longest: adalimumab, 252 days). Among patients who switched to NTT after initiating treatment with TT, 52.6% reinitiated treatment with TT (least common: apremilast, 45.6%), with a median time to reinitiation of 106 days (longest: other biologics, 136 days). For all patients on NTT, the probability of reinitiating any TT was 60.7% at 24 months.
PsO treatment is often cyclical in nature. Patients frequently experience drug holidays or transition back to TT after using NTT. The consideration of real-world treatment patterns in future economic models may provide new insights into the clinical effectiveness and value of PsO treatments.
Psoriasis is a chronic inflammatory skin disease that affects 3.0% of adults or an estimated 7.56 million Americans. The most common type of psoriasis is called plaque psoriasis because of its appearance with red patches and silvery scales on the skin. A major concern of medical providers is that not all patients continue their treatment as prescribed. Many patients discontinue, switch, and often restart treatment. To develop effective psoriasis treatment plans for shared decision-making among medical providers and patients, it is important to look at how treatments are used in the real world. This can be done by conducting studies using insurance claims data from healthcare insurance providers. In this study, we evaluated treatment patterns and, more specifically, patterns in changes of treatment in US patients who began their psoriasis treatment with a targeted therapy (biologics or apremilast) and then changed to another therapy. We found that patients often took drug holidays (days with no treatment) and returned back to using a targeted therapy after using a non-targeted therapy (e.g., other oral therapy, topical treatment, phototherapy, or no treatment). Findings from this real-world study may support future studies on the clinical effectiveness and value of current and future treatments for psoriasis—especially within these targeted to non-targeted transitions."
"The aim of this study was to evaluate the cost effectiveness of tofacitinib versus other treatment options currently available in Colombia in naïve to biologics (first-line) and exposed to biologics (second-line) patients with moderate to severe active ulcerative colitis (UC).
A Markov model was constructed with 8-week cycles, simulating a cohort of patients in a 5-year time horizon. The health states included remission, treatment response, active UC, and colectomy. The transition probabilities for the induction and maintenance phase were obtained from a network meta-analysis, and effectiveness was measured using quality-adjusted life-years (QALYs). Unit costs were derived from official national sources.
For first line, the incremental cost-effectiveness ratio (ICER) per QALY was $883 for tofacitinib and $3619 for infliximab, compared with adalimumab. Sensitivity analysis showed that tofacitinib is cost effective in 45% of the iterations, adalimumab in 5%, and infliximab in 50%. Meanwhile, the ICER of adalimumab was $14,927 compared with tofacitinib in second-line treatment. In the sensitivity analysis, tofacitinib was cost effective in 64% of the iterations, followed by adalimumab in 36%. Infliximab and golimumab were not included due to data limitations in the network meta-analysis of second-line treatment.
The analysis suggests that in Colombia, treatment with tofacitinib for patients with moderate-to-severe UC is a cost-effective option in both lines compared with other treatment options."
"Inflammatory bowel disease (IBD) guidelines recommend tumor necrosis factor-α inhibitors (TNFis) for patients who have not responded to conventional therapy, and vedolizumab in case of inadequate response to conventional therapy and/or TNFis. Recent studies have shown that vedolizumab may also be effective in the earlier treatment lines. Therefore, we conducted cost-effectiveness analyses to determine the optimal treatment sequence in patients with IBD.
A Markov model with a 10-year time horizon compared the cost-effectiveness of different biologic treatment sequences in patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) from the UK and French perspectives. Subcutaneous formulations of infliximab, vedolizumab, and adalimumab were evaluated. Comparative effectiveness was based on a network meta-analysis of clinical trials and real-world evidence. Costs included pharmacotherapy, surgery, adverse events, and disease management.
The results indicated that treatment sequences starting with infliximab were less costly and more effective than those starting with vedolizumab for patients with UC in the United Kingdom and France, and patients with just CD in France. For patients with CD in the United Kingdom, treatment sequences starting with infliximab resulted in better health outcomes with incremental cost-effectiveness ratios (ICERs) near the threshold.
Based on the ICERs, treatment sequences starting with infliximab are the dominant option for patients with UC in the United Kingdom, and patients with UC and CD in France. In UK patients with CD, ICERs were near the assumed ""willingness to pay"" threshold. These results reinforce the UK's National Institute for Health and Care Excellence recommendations for using infliximab prior to using vedolizumab in biologics-naïve patients.
A Markov model compared the cost-effectiveness of biologic treatment sequences in patients with moderate to severe inflammatory bowel diseases from a European perspective. The results indicated that treatment sequences starting with infliximab are the dominant option than those starting with vedolizumab."
"To assess the efficacy and safety of infliximab versus placebo in the treatment of patients with juvenile-onset spondyloarthritis (JoSpA).
Phase III, randomized, double-blind, placebo-controlled trial of 12 weeks that included patients ≤ 18 years old with JoSpA not responding to nonsteroidal anti-inflammatory drugs, sulfasalazine, or methotrexate. Patients were randomly assigned 1:1 to the infusion of infliximab 5mg/kg or placebo; completers entered then an open-label extension (OLE) period of 42 weeks. The primary endpoint was the number of active joints. Secondary outcomes included the assessment of disease activity, tender entheses, spinal mobility, serum C-reactive protein (CRP), the Bath Ankylosing Spondylitis Disease Activity and Functional Index, and the Childhood Health Assessment Questionnaire (CHAQ).
We randomized 12 patients to infliximab and 14 to placebo. No significant differences were found between groups at baseline. At week 12, the mean number of active joints was 1.4 (SD 2.4) in the infliximab group and 4.1 (SD 3.0) in the placebo group (p = 0.0002). A repeated-measures mixed model analysis that included all endpoints in the study demonstrated sustained favourable outcomes of infliximab for active joints, tender joints, swollen joints, and tender enthesis counts, as well as for CHAQ and CRP (p < 0.01). Adverse events were more frequent in the infliximab group, including infections and infusion reactions, but none of them was serious.
Infliximab is efficacious for patients with JoSpA with an inadequate response to conventional treatment. No serious adverse events with the use of infliximab were observed."
"Introduction Incorporation of a plant-based diet was effective in both induction and short-term relapse prevention in Crohn's disease. Ten-year long-term relapse-free rates in Crohn's disease are around 10% to 23%. Objective We investigated whether infliximab and plant-based diet as first-line therapy enhance the long-term relapse-free rate in patients with Crohn's disease. Methods This single-group, prospective study was performed in tertiary hospitals in Japan. Remission was induced in 24 consecutive newly diagnosed adult patients with Crohn's disease during hospitalization via 3 standard infliximab infusions together with a plant-based diet. Patients were instructed to continue the diet after discharge. Scheduled maintenance infliximab infusion was not used. The primary endpoint was relapse, which was defined as the appearance of symptoms resulting in the alteration of therapeutic modality. The secondary endpoints were C-reactive protein level, plant-based diet score, and surgery. Results The median follow-up period was 8.6 years. Thirteen cases were relapse-free. The relapse-free rate evaluated by Kaplan-Meier survival analysis at 1, 2, 3, and 4 years was 79%, 66%, 57%, and 52%, respectively. There was no further reduction afterward up to 10 years. The relapse-free rate with normal C-reactive protein levels at 1 to 2 and 3 to 10 years was 57% and 52%, respectively. The plant-based diet score at 20 months and 5 years was significantly higher relative to baseline ("
"Clinical data on the efficacy and safety of non-medical switch between adalimumab(ADA) biosimilars are limited.
The aim of this study was to evaluate medium-term clinical efficacy, drug sustainability and safety comparing non-medical switches from the originator to biosimilar ADA, and between ADA biosimilars.
276 consecutive patients on maintenance ADA therapy (n = 205 Crohn's disease, n = 71 ulcerative colitis) were included. Data on clinical efficacy, biomarkers and adverse events were collected at four time points: 8-12 weeks prior switch, at baseline/switch, 8-12 weeks and 20-24 weeks after switch. Drug survival was evaluated after a median 40(IQR:35-42) weeks follow-up.
A total 174 patients underwent a non-medical switch from the originator to a biosimilar, and 102 patients had a biosimilar-to-biosimilar switch. No significant difference was found in clinical remission rates at any time point in patients switching from originator to biosimilar(87.3%/88.5%/86.5%/85.7%) or biosimilar to biosimilar(74.5%/78.4%/85.3%/79.8%). Mean C-reactive protein levels remained unchanged in both cohorts(p = 0.856 and p = 0.525). Drug survival was similar between the two cohorts with a probability of 91.6%(SE: 2.2) and 87.0%(SE:3.4) to stay on drug after 40 weeks(log-rank:0.96; p = 0.327). Five cases of injection related adverse events were reported.
Clinical benefit was sustained following non-medical switch from originator to biosimilar, or between biosimilars in adalimumab treated IBD patients."
"Monitoring plasma levels of Infliximab plays an important role in optimising treatment in patients with inflammatory bowel disease (IBD). The aim of the following study has been to determine the predictive potential of monitoring infliximab plasma levels for sustained clinical response and evaluate its usefulness to improve treatment efficacy and symptom control, in patients with IBD.
This single-centre retrospective study (2017-2019) included patients diagnosed with IBD treated with infliximab. Serum levels and the occurrence of drug-associated immunogenicity were analysed at Week 8 post-induction and 6, 12 and 24 months. Clinical parameters and inflammatory markers were recorded such as subjective global assessment (SGA), C-reactive protein (CRP) and faecal calprotectin (FC). Factors associated with early discontinuation and dose intensification of infliximab were determined.
Multivariate analysis determined that IFX concentrations>7μg/mL at week 8, and at 6 months, are associated with inflammatory remission (p=0.046, 0.045). IFX>7μg/mL at 12 months predicted remission at 18 months of treatment (p=0.006). IFX values>3μg/mL at 12 months are associated with stable SGA at 18 months (p=0.001). Such values at 18 months are associated with stable SGA at 24 months (p=0.044).
The predictive potential of monitoring IFX plasma levels as a strategy to evaluate sustained long-term clinical response was confirmed. Our results highlight the importance of its introduction into routine clinical practice to enable early identification of non-responders, treatment optimisation, relapse prevention and improve long-term therapy maintenance."
"Registry-based observational prospective study aimed at describing the use of biologic drugs in pediatric-onset scleritis. Data were collected at baseline, at 3-, 6-, 12-month follow-up and at last assessment. Scleral inflammation was graded according to Sen classification. Five patients (9 eyes) treated with adalimumab, infliximab, abatacept and secukinumab were included. All patients were previously treated with conventional immunosuppressors and glucocorticoids. Median biologic treatment duration was 28 (IQR = 118) months. At 6-months, scleritis resolved in all eyes. At 12-months, complete disease control was observed in 7/9 eyes (77.8%). The number of relapses 12 months before and after treatment initiation was 17 and 2, respectively. Mean BCVA was 0.83 (range 0.3-1.0) at baseline and 1.0 for all eyes after 12 months. Glucocorticoids had been withdrawn in 4/5 patients.In conclusion, biological agents proved to be effective in pediatric-onset scleritis, allowing a noticeable steroid-sparing effect and preserving visual function and bulbar integrity."
"There is insufficient evidence on the clinical effectiveness and safety of infliximab (IFX) treatment of Takayasu arteritis (TA) in infants.
We evaluated the therapeutic effectiveness and safety of IFX in a retrospective case series of 10 infantile TA patients. Observations included assessment of clinical symptoms, laboratory testing, and vascular imaging.
Fever was the presenting symptom for 8 of 10 infants with TA. During acute episodes, leucocyte and inflammatory indices were significantly increased. Vascular imaging showed the most commonly involved arteries to be carotid arteries, abdominal aortas, and coronary arteries (9 cases, 90%). Two weeks after initiating IFX treatment, leukocyte and platelet counts decreased and hemoglobin levels increased. There were statistically significant clinical improvements 6 weeks after starting treatment compared with before treatment (p < 0.05). Inflammatory indices decreased 2 weeks after starting IFX treatment compared with before treatment (p < 0.05). Vascular lesions began to recover within 1.5-3 months of initiating IFX therapy, and involved vessels significantly recovered within 13 months. Some arteries remained stenotic, with intimal thickening and uneven lumen wall thicknesses. The only adverse event was a treatment-responsive allergic reaction during IFX infusion in one infant.
Fever was the main manifestation of illness and was often accompanied by significantly increased inflammatory indices. IFX treatment was apparently effective and reduced or eliminated need for glucocorticoids. IFX had a reasonably good safety profile."
"We report on the incidental finding of Kaposi sarcoma of the colon in the setting of refractory ulcerative colitis treatment. The patient was under long-term immunosuppression with infliximab, vedolizumab, and prednisolone. Serologic analysis excluded human immunodeficiency virus (HIV) infection.
Wir berichten über den Zufallsbefund eines Kaposi-Sarkoms des Kolons bei schwerer therapierefraktärer Colitis ulcerosa. Die Patientin war zuvor lange immunsuppressiv mit Infliximab, Vedolizumab und Prednisolon behandelt worden. Serologische Untersuchungen schlossen eine HIV(„human immunodeficiency virus“)-Infektion aus."
"Dermatomyositis is an autoimmune disease mainly characterized by muscle and skin involvement. Its association with cancer is known but the term «paraneoplastic» remains debated. We report here the case of a 71-year-old woman with a new diagnosis of dermatomyositis with, at the same time, the discovery of a lung adenocarcinoma. Lung cancer was treated with pembrolizumab, an immune checkpoint inhibitor directed against the ""Programmed cell Death protein 1"" (PD-1) receptor. Three weeks later, the patient presented a severe flare of dermatomyositis. Administration of intravenous corticosteroids and infliximab were ineffective. Intravenous immunoglobulins were then administered, followed by subcutaneous methotrexate, with a progressive positive evolution. Flares of pre-existing autoimmune diseases are observed under immune check point inhibitors, even when the evolution of the cancer is favourable. These immune-related adverse events are often «mild to moderate» and severe immune related side effects are not more frequent when the patient has a pre-existing autoimmune disease. Treatment can be maintained in the majority of cases. However, as demonstrated in this clinical case, although immune checkpoint inhibitors are not contraindicated in autoimmune diseases, the presence of myositis requires special attention given the potential severity of flares.
: La dermatomyosite est une maladie auto-immune principalement caractérisée par une atteinte musculaire et cutanée. Son association avec le cancer est connue, mais le terme «paranéoplasique» reste débattu. Nous rapportons ici le cas d’une patiente de 71 ans avec un nouveau diagnostic de dermatomyosite et, au même moment, la découverte d’un adénocarcinome pulmonaire. La néoplasie pulmonaire a été traitée par pembrolizumab, un inhibiteur des points de contrôle immunitaire dirigé contre le récepteur «Programmed cell Death protein 1» (PD-1). Trois semaines plus tard, la patiente présentera une poussée sévère de dermatomyosite, ne répondant pas à la corticothérapie intraveineuse ni à l’infliximab. Des immunoglobulines intraveineuses sont alors administrées, suivies de méthotrexate sous-cutané, avec une évolution progressivement positive. On observe des poussées de maladies auto-immunes préexistantes sous inhibiteurs de points de contrôle immunitaire, même quand l’évolution néoplasique est favorable. Ces effets secondaires immuno-induits sont souvent «légers à modérés» et on n’observe pas plus de manifestations indésirables «sévères» lorsque le patient présente une maladie auto-immune pré-existante. Le traitement peut être maintenu dans la majorité des cas. Toutefois, comme démontré dans ce cas clinique, bien que les inhibiteurs de points de contrôle immunitaire ne soient pas contre-indiqués en cas de maladie auto-immune, la présence d’une myosite nécessite une attention particulière vu la gravité potentielle des poussées."
"Rheumatic immune-related adverse events (irAE) such as (poly)arthritis in patients undergoing immune checkpoint inhibitor (ICI) treatment pose a major clinical challenge. ICI therapy improves CD8
Peripheral CD8 obtained from ICI-treated patients with and without arthritis irAEs and from AA patients with and without a history of malignancy were stimulated in media containing 
CD8 from patients with irAE showed significantly lower frequency and expression of cell-surface molecule characteristic for activation, effector-functions, homing, exhaustion and apoptosis and reduced release of cytotoxic and proinflammatory immune mediators compared with CD8 from ICI patients who did not develop irAE. This was accompanied by a higher glycolytic rate and ATP production. Gene-expression analysis of pre-ICI-treated CD8 revealed several differentially expressed transcripts in patients who later developed arthritis irAEs. In vitro tofacitinib or infliximab treatment did not significantly change the immune-metabolic profile nor the capacity to release cytolytic mediators that inhibit the growth of the human lung cancer cell line H838.
Our study shows that CD8 from ICI-treated patients who develop a musculoskeletal irAE has a distinct immune-effector and metabolic profile from those that remain irAE free. This specific irAE profile overlaps with the one observed in CD8 from AA patients and may prove useful for novel therapeutic strategies to manage ICI-induced irAEs."
"There is a need to better understand the positioning of biologic therapies for long-term outcomes in biologic-naïve Crohn's disease (CD). We assessed the comparative effectiveness of infliximab and ustekinumab among induction responders for 1-year outcomes.
This post hoc analysis included data from 220 biologic-naïve CD participants with response to induction therapy from 2 clinical trial programs. Participants achieving 1-year clinical remission (CR) (Crohn's disease activity index <150), corticosteroid-free CR, normalization of fecal calprotectin (FC), endoscopic response (Simple Endoscopic Score for CD decrease ≥50% from baseline), and endoscopic remission (ER) (Simple Endoscopic Score for CD <3) were compared. Multivariate logistic regression evaluated the likelihood of achieving the outcomes adjusted for confounders. Propensity score matching created a cohort with similar distribution of baseline covariates.
One-year CR and corticosteroid-free CR rates were similar between infliximab-treated and ustekinumab-treated patients (CR, 66 of 110 [60.0%] vs 63 of 110 [57.3%]; adjusted odds ratio [aOR], 1.15; 95% CI, 0.67-1.98; P = .681; corticosteroid-free CR, 11 of 28 (39.3%) vs 27 of 51 [52.9%]; aOR, 0.58; 95% CI, 0.23-1.47; P = .251). Compared with ustekinumab-treated patients, infliximab-treated participants were more likely to achieve 1-year endoscopic response (43 of 92 [46.7%] vs 6 of 30 [20.0%], aOR, 3.59; 95% CI, 1.34-9.66; P = .011) and ER (31 of 92 [33.7%] vs 4 of 30 [13.3%]; aOR, 3.35; 95% CI, 1.07-10.49; P = .038). Among patients with FC ≥250 mg/kg at baseline, normalization (<250 mg/kg) at 1-year was similar between groups. Similar results were observed within the propensity matched population for all analyses.
Treatment with infliximab and ustekinumab among induction responders achieved 1-year CR with similar efficacy, but infliximab may confer greater benefit for endoscopic outcomes. Findings should be interpreted with caution as our analyses were unpowered.
In this post hoc analysis of biologic-naïve CD patients, treatment with infliximab and ustekinumab among induction responders achieved 1-year clinical remission with similar efficacy, but infliximab may confer greater benefit for endoscopic outcomes."
"A 45-year-old man with a 10-year history of biopsy-proven, steroid-dependent sclerosing mesenteritis failed/was intolerant to tamoxifen, azathioprine, colchicine, cyclophosphamide, and methotrexate. He developed osteoporosis, diabetes, and bilateral cataracts. He responded to infliximab but was diagnosed with mesenteric large B-cell lymphoma 6 months after treatment initiation. He achieved remission from lymphoma after chemotherapy, but the sclerosing mesenteritis remained poorly controlled. He was treated with ustekinumab (520 mg intravenously followed by 90 mg subcutaneously every 8 weeks), leading to complete steroid-free remission. He remains symptom and cancer-free 24 months after starting ustekinumab."
"Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management.
Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis.
The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis.
Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management."
"Real-life data on the efficacy of ustekinumab as first-line therapy for the treatment of luminal Crohn's disease (CD) compared with anti-tumor necrosis factor (anti-TNF) agents are lacking. We compared the clinical response rates at 3 months in 2 cohorts of biologic-naïve patients treated by ustekinumab and anti-TNF agents.
Biologic-naïve patients starting either ustekinumab or an anti-TNF agent for luminal CD between 2016 and 2019 in 2 tertiary centers were retrospectively included. The primary endpoint was clinical response at 3 months, defined as a Harvey-Bradshaw Index <4 or a 3-point drop in the score without steroids, need for CD-related surgery, or treatment discontinuation owing to failure or intolerance. Patients treated with ustekinumab were matched to patients receiving anti-TNF agents by a propensity score algorithm.
We included 156 patients starting anti-TNF agents (95 adalimumab and 61 infliximab) and 50 ustekinumab. After matching, clinical response rates at 3 months were 64% and 86% in the ustekinumab and anti-TNF groups, respectively (P = .01). At 12 months, in multivariate analysis adjusted for disease duration, location, concomitant immunosuppressant and steroids, and symptoms, clinical remission was independently associated with the biological therapy received (odds ratio, 2.6 for anti-TNF agent vs ustekinumab; P = .02). With a median follow-up duration of 40 (interquartile range, 23-52) months, no difference was observed in terms of time to drug withdrawal (P = .29) or safety.
This retrospective real-world data suggest that an anti-TNF agent as a first-line biological therapy is associated with higher rates of response at 3 months than ustekinumab in patients with CD.
We conducted a retrospective real-world study to compare the efficacy of biologics in Crohn’s disease. Our data suggest that an anti-tumor necrosis factor agent as a first-line biological therapy is associated with higher rates of response at 3 months than ustekinumab in Crohn’s disease."
"Ulcerative colitis (UC) classically presents with abdominal pain, hematochezia, or diarrhea. However, it can present atypically in pediatric and pregnant patients, posing a diagnostic challenge. A healthy, 16-year-old primigravida presented at 18 weeks and six days of gestation with sudden-onset altered mental status and severe anemia. Hematochezia began about 12 hours after admission. She underwent extensive workup, leading to an endoscopic and histopathologic diagnosis of UC, and achieved prenatal remission with high-dose steroids and infliximab. Her pregnancy, however, was complicated by severe preeclampsia, and her child's post-delivery course was medically complex from an unrelated etiology. Pregnancy-onset inflammatory bowel disease (IBD) in the pediatric population is an uncommon but important consideration. Early diagnosis, treatment, and counseling are vital to achieve results comparable to those of patients without IBD."
"Clinically overt granulomatous involvement of the nervous system (i.e. neurosarcoidosis) can be seen in up to 10% of patients with sarcoidosis. Establishing a diagnosis of neurosarcoidosis is often challenging due to the heterogeneity of clinical presentations that are sometimes nonspecific, and inaccessibility of tissue confirmation. Recommended treatments are based on expert opinions that are derived from clinical experience and limited data from retrospective studies, as data from randomized controlled studies are limited.
In this article, we comprehensively review all available literature on epidemiology, clinical presentations, diagnosis, treatment, and outcomes of neurosarcoidosis. We also offer our opinions on diagnostic approach and treatment strategy.
Given the invasive nature and the limited sensitivity of biopsy of the nervous system, diagnosis of neurosarcoidosis is usually made when ancillary tests (such as magnetic resonance imaging and cerebrospinal fluid analysis) are compatible, and alternative diagnoses are reasonably excluded in patients with established extraneural sarcoidosis. Several factors must be taken into consideration to formulate the initial treatment strategy, including the extent of the disease, severity, functional impairment, comorbidities, and patient's preference. In addition, treatment regimen of neurosarcoidosis should be formulated with an emphasis on long-term strategy."
"There are numerous biological therapies and small molecules licensed for luminal Crohn's disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this in a network meta-analysis.
We searched the literature to 1 July 2022, judging efficacy according to induction of clinical remission, clinical response and maintenance of clinical remission, and according to previous exposure or non-exposure to biologics. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs, ranking drugs according to p-score.
We identified 25 induction of remission trials (8720 patients). Based on failure to achieve clinical remission, infliximab 5 mg/kg ranked first versus placebo (RR=0.67, 95% CI 0.56 to 0.79, p-score 0.95), with risankizumab 600 mg second and upadacitinib 45 mg once daily third. However, risankizumab 600 mg ranked first for clinical remission in biologic-naïve (RR=0.66, 95% CI 0.52 to 0.85, p-score 0.78) and in biologic-exposed patients (RR=0.74, 95% CI 0.67 to 0.82, p-score 0.92). In 15 maintenance of remission trials (4016 patients), based on relapse of disease activity, upadacitinib 30 mg once daily ranked first (RR=0.61, 95% CI 0.52 to 0.72, p-score 0.93) with adalimumab 40 mg weekly second, and infliximab 10 mg/kg 8-weekly third. Adalimumab 40 mg weekly ranked first in biologic-naïve patients (RR=0.59, 95% CI 0.48 to 0.73, p-score 0.86), and vedolizumab 108 mg 2-weekly first in biologic-exposed (RR=0.70, 95% CI 0.57 to 0.86, p-score 0.82).
In a network meta-analysis, infliximab 5 mg/kg ranked first for induction of clinical remission in all patients with luminal CD, but risankizumab 600 mg was first in biologic-naïve and biologic-exposed patients. Upadacitinib 30 mg once daily ranked first for maintenance of remission."
"Restorative proctocolectomy with IPAA is the procedure of choice when colectomy is needed for medically refractory ulcerative colitis. Pouchitis is one of the most common complications among patients who have undergone IPAA and represents a spectrum of disease varying in both phenotype and clinical course.
This study aimed to assist clinicians and surgeons in the treatment of both acute and chronic pouchitis, including newer therapies and future directions.
Diagnosis is made by endoscopy of the pouch with biopsy because other conditions may produce similar symptoms such as increased stool frequency, abdominal cramps, and urgency. Pouchitis is classified by duration (acute versus chronic), disease pattern (infrequent, relapsing, and continuous), and response to antibiotics (responsive, dependent, and refractory). The Pouchitis Disease Activity Index may be used to measure disease activity. The management of pouchitis is guided by the disease phenotype. Acute episodes are treated with an initial 2-week course of antibiotics (typically ciprofloxacin or metronidazole), although patients with relapsing or chronic pouchitis may require long-term antibiotic treatment or the cycling of different antibiotics. Certain probiotics may also be used for maintenance therapy in those with chronic symptoms. For patients with chronic antibiotic refractory pouchitis, oral budesonide, immunosuppressive agents (azathioprine), or biologic therapy (infliximab, adalimumab, vedolizumab, and ustekinumab) may be required for both induction and maintenance with close monitoring for potential side effects. In rare cases, diverting ileostomy or pouch excision may be required.
Pouchitis represents a spectrum of disease phenotypes, ranging from acute antibiotic responsive pouchitis to chronic antibiotic refractory pouchitis. The management of pouchitis is primarily directed by the disease phenotype."
"Few Saudi studies have examined adverse drug reactions (ADRs) in patients with rheumatoid arthritis (RA) receiving intravenous (IV) originator biologics. Therefore, this study aimed to evaluate the prevalence, types, and predictors of ADRs following long-term IV originator biologic use in patients with RA.
This retrospective, single-center study included adult patients with RA who received IV originator biologics between 2015 and 2020. Medical records were reviewed and data regarding ADRs were collected and evaluated for causality using the Naranjo scale. Binary logistic regression analysis was performed to identify the odds for and factors associated with developing ADRs for each biologic.
A total of 129 patients (87.6% women) with a mean (standard deviation) age of 54 (13) years were included in this study. A total of 1963 doses of tocilizumab (38.76%), rituximab (38.76%), abatacept (13.95%), and infliximab (8.53%), were administered during the study period. ADRs with a Naranjo score ≥ 1 were experienced by 103 (78%) patients, with an average of 2.2 events per patient. Infection (26.6%) and skin and mucous membrane disorders (14.18%) were the most commonly reported ADRs. Abatacept was associated with a significantly higher risk of multiple ADRs than the other biologics (adjusted odds ratio: 3.145, 95% confidence interval 1.004-9.854, p = 0.049).
There was a high prevalence of ADRs among patients with RA receiving biologics. Abatacept was associated with a greater risk of multiple ADRs than other biologics. Infection was the most common ADR. Future multicenter longitudinal studies are warranted."
"Crohn's disease (CD) is characterized by excessive protease activity and extracellular matrix (ECM) remodeling. To date, 30-50% of patients experience non-response to anti-TNF-α treatment. This study aimed to assess whether serological biomarkers of ECM turnover could monitor or predict response to infliximab (IFX) induction therapy in patients with and without a surgical history.
Serum biomarkers of type I (C1M), III (C3M), IV (C4M), and VI (C6Ma3) collagen degradation, type III (PRO-C3) and VI (PRO-C6) collagen formation, basement membrane turnover (PRO-C4), and T-cell activity (C4G), were measured at baseline and week 14, in 63 patients with CD undergoing IFX induction therapy. Patients were stratified according to surgical history.
C4M was elevated at baseline in responders with a surgical history (
Baseline levels of a serological biomarker for type IV collagen degradation associated with response to IFX induction therapy, and biomarkers of type III and VI collagen formation may be used to monitor response at the end of induction therapy in patients with a surgical history. Biomarker ratios of type IV collagen turnover demonstrated promising results in monitoring treatment response in patients without a surgical history."
"There is limited information regarding disease-modifying antirheumatic drug (DMARD)-dependent risks of overall, incident, and recurrent herpes zoster (HZ) during first-line biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) treatment among patients with seropositive rheumatoid arthritis (RA) in terms of HZ risk.
A total of 11,720 patients with seropositive RA who were prescribed bDMARD or tofacitinib between January 2011 and January 2019 from the Korean Health Insurance Review & Assessment Service database were studied. A multivariate Cox proportional hazards regression model was adopted to evaluate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the risk of HZ dependent on the choice of first-line bDMARDs or tsDMARD, including etanercept, infliximab, adalimumab, golimumab, tocilizumab, rituximab, tofacitinib, and abatacept.
During the 34,702 person-years of follow-up, 1686 cases (14.4%) of HZ were identified, including 1372 (11.7%) incident and 314 (2.7%) recurrent HZs. Compared with that of the abatacept group, tofacitinib increased the overall risk (aHR, 2.46; 95% CI, 1.61-3.76; P<0.001), incidence (aHR, 1.99; 95% CI, 1.18-3.37; P=0.011), and recurrence (aHR, 3.69; 95% CI, 1.77-7.69; P<0.001) of HZ. Infliximab (aHR, 1.36; 95% CI, 1.06-1.74; P=0.017) and adalimumab (aHR, 1.29; 95% CI, 1.02-1.64; P=0.032) also increased the overall HZ risk. Moreover, a history of HZ was found to be an independent risk factor for HZ (aHR, 1.54; 95% CI, 1.33-1.78; P<0.001).
HZ risk is significantly increased in RA patients with a history of HZ after the initiation of bDMARDs or tsDMARD. The risk of incident and recurrent HZ was higher after tofacitinib treatment in patients with RA than that after treatment with bDMARDs. Individualized characteristics and history of HZ should be considered when selecting bDMARDs or tsDMARD for RA patients considering HZ risks."
"Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD.
Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study.
Geometric mean (SD) anti-S RBD antibody concentrations increased in both groups following a third dose of an mRNA-based vaccine. However, concentrations were lower in patients treated with infliximab than vedolizumab, irrespective of whether their first two primary vaccine doses were ChAdOx1 nCoV-19 (1856 U/mL (5.2) vs 10 728 U/mL (3.1), p<0.0001) or BNT162b2 vaccines (2164 U/mL (4.1) vs 15 116 U/mL (3.4), p<0.0001). However, no differences in anti-S RBD antibody concentrations were seen following third and fourth doses of an mRNA-based vaccine, irrespective of the combination of primary vaccinations received. Post-third dose, anti-S RBD antibody half-life estimates were shorter in infliximab-treated than vedolizumab-treated patients (37.0 days (95% CI 35.6 to 38.6) vs 52.0 days (95% CI 49.0 to 55.4), p<0.0001).Compared with vedolizumab-treated, infliximab-treated patients were more likely to experience SARS-CoV-2 breakthrough infection (HR 2.23 (95% CI 1.46 to 3.38), p=0.00018) and reinfection (HR 2.10 (95% CI 1.31 to 3.35), p=0.0019), but this effect was uncoupled from third vaccine dose anti-S RBD antibody concentrations. Reinfection occurred predominantly during the Omicron wave and was predicted by SARS-CoV-2 antinucleocapsid concentrations after the initial infection. We did not observe persistent oropharyngeal carriage of SARS-CoV-2. Hospitalisations and deaths were uncommon in both groups.
Following a third dose of an mRNA-based vaccine, infliximab was associated with attenuated serological responses and more SARS-CoV-2 breakthrough infection and reinfection which were not predicted by the magnitude of anti-S RBD responses, indicative of vaccine escape by the Omicron variant.
ISRCTN45176516."
"No multi-national prospective study of drug-induced liver injury (DILI) has originated in Europe. The design of a prospective European DILI registry, clinical features and short-term outcomes of the cases and controls is reported.
Patients with suspected DILI were prospectively enrolled in the United Kingdom, Spain, Germany, Switzerland, Portugal and Iceland, 2016-2021. DILI cases or non-DILI acute liver injury controls following causality assessment were enrolled.
Of 446 adjudicated patients, 246 DILI patients and 100 had acute liver injury due to other aetiologies, mostly autoimmune hepatitis (n = 42) and viral hepatitis (n = 34). DILI patients (mean age 56 years), 57% women, 60% with jaundice and 3.6% had pre-existing liver disease. DILI cases and non-DILI acute liver injury controls had similar demographics, clinical features and outcomes. A single agent was implicated in 199 (81%) DILI cases. Amoxicillin-clavulanate, flucloxacillin, atorvastatin, nivolumab/ipilimumab, infliximab and nitrofurantoin were the most commonly implicated drugs. Multiple conventional medications were implicated in 37 (15%) and 18 cases were caused by herbal and dietary supplements. The most common single causative drug classes were antibacterials (40%) and antineoplastic/immunomodulating agents (27%). Overall, 13 (5.3%) had drug-induced autoimmune-like hepatitis due to nitrofurantoin, methyldopa, infliximab, methylprednisolone and minocycline. Only six (2.4%) DILI patients died (50% had liver-related death), and another six received liver transplantation.
In this first multi-national European prospective DILI Registry study, antibacterials were the most commonly implicated medications, whereas antineoplastic and immunomodulating agents accounted for higher proportion of DILI than previously described. This European initiative provides an important opportunity to advance the study on DILI."
"Kawasaki disease (KD) is an acute and febrile systemic vasculitis that occurs during childhood. Infliximab (IFX) is a chimeric monoclonal antibody that binds to tumor necrosis factor-α. Although IFX therapy is a useful option for refractory KD, vaccine-associated infections may develop after therapy. In Japan, IFX therapy is recommended after a duration of at least 3 months after live vaccinations or at least 6 months after Bacillus Calmette-Guérin (BCG) in children with KD. However, the appropriate duration between live vaccinations and IFX therapy is unclear.
We investigated children who developed KD within 3 months after live vaccinations or within 6 months after BCG. Clinical characteristics, side effects of therapies and efficacy of live vaccinations were retrospectively investigated.
Forty-eight patients developed KD within 3 months of live vaccinations or within 6 months after BCG. Eight patients underwent IFX therapy. There were no apparent vaccine-associated infections. The patients who underwent IFX acquired protective IgG antibody titers in the 5 of 6 live vaccines.
Safe and appropriate duration between live vaccinations and IFX therapy for KD patients could be shorter in the future, although more studies are warranted to establish the safe duration."
"Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting.
A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents.
The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively.
Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups."
"Vaccination has been effective in preventing COVID-19 infections and related mortality. However, waning immunity after two-dose vaccination prompted health authorities to recommend a third dose of COVID-19 vaccine to boost immunity. The aim of our study was to assess willingness to receive a third (booster) dose among patients with inflammatory bowel disease (IBD).
A cross-sectional study was performed at an IBD tertiary care center. Patients were recruited at the infusion room from 1 January 2022 to 31 March 2022. The primary outcome was the prevalence of a third (booster) dose of the BNT162b2 vaccine in infliximab- or vedolizumab-treated patients with IBD. The secondary outcome evaluated whether the prevalence of a third (booster) dose of the BNT162b2 vaccine differed based on type of COVID-19 vaccine, gender, age, type of biologic therapy, and citizenship.
In total, 499 patients with IBD were included in this study. The median age was 34.5 years, and 60% had ulcerative colitis (UC). Among the study participants, 302 (60.5%) patients were vaccinated with BNT162b2, and 197 (39.5%) were vaccinated with ChAdOx1 nCoV-19. Of the total number of participants, 400 (80.2%) were receiving infliximab, and 99 (19.8%) were receiving vedolizumab. Overall, 290 (58.1%) of the included patients were willing to receive the third (booster) dose. Patients vaccinated with BNT162b2 were more likely to be willing to receive a booster dose compared to patients vaccinated with ChAdOx1 nCoV-19 (201 (66.5%) vs. 103 (52.0%), 
The percentage of patients with IBD willing to receive or having already received a third (booster) dose of BNT162b2 vaccine was lower compared to the general population. In addition, patients who received two doses of BNT162b2 vaccines were more likely to be willing to receive a third (booster) dose compared to patients who received ChAdOx1 nCoV-19. Patients treated with infliximab were more likely to be willing to receive a third (booster) dose of COVID-19 vaccine."
"The advent of monoclonal antibodies (mAbs) has revolutionized the management of many immune-mediated diseases such as inflammatory bowel disease (IBD). Infliximab and adalimumab were the first mAbs approved for the management of IBD, and are still commonly prescribed for the treatment of both Crohn's disease (CD) and ulcerative colitis (UC). Although mAbs have demonstrated high effectiveness rates in the management of IBD, some patients fail to respond adequately to mAbs, resulting in disease progression and the flare-up of symptoms.
The objective was to explore the predictors of treatment failure among IBD patients on infliximab (INF) and adalimumab (ADA)-as demonstrated via colonoscopy with a simple endoscopic score (SES-CD) of ≥1 for CD and a Mayo score of ≥2 for UC-and compare the rates of treatment failure among patients on those two mAbs.
This was a prospective cohort study among IBD patients aged 18 years and above who had not had any exposure to mAbs before. Those patients were followed after the initiation of biologic treatment with either INF or ADA until they were switched to another treatment due to failure of these mAbs in preventing the disease progression. Univariate and multiple logistic regressions were conducted to examine the predictors and rates of treatment failure.
A total of 146 IBD patients (118 patients on INF and 28 on ADA) met the inclusion criteria and were included in the analysis. The mean age of the patients was 31 years, and most of them were males (59%) with CD (75%). About 27% and 26% of the patients had penetrating and non-stricturing-non-penetrating CD behavior, respectively. Patients with UC had significantly higher odds of treatment failure compared to their counterparts with CD (OR = 2.58, 95% CI [1.06-6.26], 
Infliximab was shown to be more effective in the management of IBD, with lower incidence rates of treatment failure in comparison to adalimumab."
"Previous studies have consistently revealed that both local and systemic inflammations are the key to the onset and progression of osteoarthritis (OA). Thus, anti-inflammatory biologic agents could potentially attenuate the progression of OA. We conducted this meta-analysis to examine the efficacy and safety of ant-inflammatory biologic agents among OA patients.
Five databases were searched for randomized controlled trials (RCTs) comparing biologics with placebo or each other in OA patients. Data of pain, physical function, stiffness, and adverse events (AEs) were extracted for a conventional and a Bayesian network meta-analysis.
15 studies with data for 1566 patients were analyzed. In the conventional meta-analysis, etanercept (SMD -0.47; 95% CI -0.89, -0.05) and infliximab (SMD -2.04; CI -2.56, -1.52) were superior to placebo for knee pain. In the network meta-analysis, infliximab was superior to all the other biologic agents in improving pain (vs. hyaluronic acid (SMD -22.95; CI -34.21, -10.43), vs. adalimumab (SMD -21.71; CI -32.65, -11.00), vs. anakinra (SMD -24.63; CI -38.79, -10.05), vs. canakinumab (SMD -32.83; CI -44.45, -20.68), vs. etanercept (SMD -18.40; CI -29.93, -5.73), vs. lutikizumab (SMD -25.11; CI -36.47, -14.78), vs. naproxen (SMD -30.16; CI -41.78, -17.38), vs. tocilizumab (SMD -24.02; CI -35.63, -11.86) and vs. placebo (SMD -25.88; CI -34.87, -16.60)). No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs.
The findings suggest that infliximab may relieve pain more than other biological agents in OA patients. No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. The results must be interpreted cautiously; therefore, further randomized controlled trials are warranted."
"Psoriasis is an autoimmune disease in which the disturbed dependencies between lymphocytes, dendritic cells, keratinocytes and neutrophils play the most important role. One of them is the overproduction of neutrophil extracellular traps (NETs). The release of NETs can be induced by pathogens, as well as antibodies and immune complexes, cytokines and chemokines, including TNFα. The first step of the NET creation is the activation of peptidyl arginine deiminase 4 (PAD-4). PAD-4 seems to be responsible for citrullination of histones and chromatin decondensation, but the data on PAD-4 in NETs is inconclusive. Thus, the current study aimed to determine PAD-4 and TNFα levels in the serum of psoriatic patients by ELISA and observe the response of these factors to systemic (anti-17a, anti-TNFα and methotrexate) therapies. Increased levels of both PAD-4 and its main stimulus factor TNFα in pre-treatment patients have been reported along with the concentrations of proteins correlated with disease severity (PASI, BSA). Before treatment, the irregularities in the case of anti-nuclear antibodies level (ANA) were also observed. All of the applied therapies led to a decrease in PAD-4 and TNFα levels after 12 weeks. The most significant changes, both in protein concentrations as well as in scale scores, were noted with anti-TNFα therapy (adalimumab and infliximab). This phenomenon may be associated with the inhibition of TNFα production at different stages of psoriasis development, including NET creation. The obtained data suggest the participation of PAD-4 in the activation of neutrophils to produce NETs in psoriasis, which may create opportunities for modern therapies with PAD inhibitors. However, further exploration of gene and protein expression in psoriatic skin is needed."
"In cases of sepsis, the immune system responds with an uncontrolled release of proinflammatory cytokines and reactive oxygen species. The lungs, kidneys, and liver are among the early impacted organs during sepsis and are a direct cause of mortality. The aim of this study was to compare the effects of infliximab (IFX) and celecoxib (CLX) on septic rats that went through a cecal ligation and puncture (CLP) surgery to induce sepsis. This study included four groups: sham, CLP (untreated), and CLP-treated with CLX or IFX. The administration of ""low dose"" CLX or IFX was performed after 2 h following the induction of sepsis. Twenty-four hours following the induction of sepsis, the rats were sacrificed and blood samples were collected to evaluate kidney, liver, and lung injuries. MDA and NOx content, in addition to SOD activity and GSH levels, were evaluated in the tissue homogenates of each group. Tissue samples were also investigated histopathologically. In a separate experiment, the same groups were employed to evaluate the survival of septic rats in a 7-day observation period. The results of this study showed that treatment with either CLX or IFX ameliorated the three organs' damage compared to septic-untreated rats, decreased oxidative stress, enhanced the antioxidant defense, and reduced serum cytokines. As a result, a higher survival rate resulted: 62.5% and 37.5% after the administration of CLX and IFX, respectively, compared to 0% in the CLP group after 7 days. No significant differences were observed between the two agents in all measured parameters. Histopathological examination confirmed the observed results. In conclusion, CLX and IFX ameliorated lung, kidney, and liver injuries associated with sepsis through anti-inflammatory and antioxidant actions, which correlated to the increase in survival observed with both of them."
"Ulcerative colitis (US) is a chronic disease of unknown etiology. It is incurable and its clinical course is intermittent, characterized by periods of remission and relapse. The prevalence and incidence of the disease has been increasing worldwide. The update presented herein includes the participation of healthcare professionals, decision-makers, and a representative of the patients, all of whom declared their conflicts of interest. Answerable clinical questions were formulated, and the outcomes were graded. The information search was conducted on the Medline/PubMed, Embase, Epistemonikos, and LILACS databases, and covered grey literature sources, as well. The search was updated on November 30, 2020, with no restrictions regarding date or language. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification system was implemented to establish the strength of the recommendation and quality of evidence. A formal consensus was developed, based on the RAND/UCLA methodology and the document was peer reviewed. The short version of the Clinical Practice Guidelines for the Treatment of Ulcerative Colitis in the Adult Population is presented herein, together with the supporting evidence and respective recommendations. In mild-to-moderate UC, budesonide MMX is an option when treatment with 5-ASA fails, and before using systemic steroids. In moderate-to-severe UC, infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib can be used as first-line therapy. If there is anti-TNF therapy failure, ustekinumab and tofacitinib provide the best results. In patients with antibiotic-refractory pouchitis, anti-TNFs are the treatment of choice."
"Bipolar disorder (BD) is characterized by a pro-inflammatory biotype, and is a major cause of cardiovascular disease (CVD), consequently causing elevated rates of morbidity and mortality among individuals with BD.
The present study is based on a 12-week clinical trial assessing the antidepressant effects of adjunctive infliximab treatment in BD. Generalized estimating equation (GEE) models were used to evaluate CVD risk in people with BD following adjunctive infliximab treatment at baseline and week 12. Participants (baseline: n = 40; endpoint: 33) were randomized for an infliximab-treatment or placebo group. CVD-risk was calculated using Framingham risk scores (FRS), mean arterial blood pressure (MAP) and total cholesterol (TC).
There was no main effect of treatment on FRS in infliximab-treated participants compared to controls (p = 0.408). Similarly, there were no significant differences in MAP between the infliximab-treated and control group (p = 0.796). The effect of treatment on TC was not significant (p = 0.130), however, an evaluation across time suggested the main effect of the group was significant at week 0 (p = 0.01), but not week 12 (p = 0.219).
Cardiovascular disease was not an outcome of the original clinical trial, and our participant group did not have a high CVD-risk at baseline.
There were no significant treatment effects of infliximab on FRS, MAP and TC. The current study highlights the complexity of immune-system targets that influence CVD in psychiatric populations. Future studies should include a large scale, combinatorial omnibus biomarker approach to evaluate the immune and vascular link in BD."
"Primary nonresponse to infliximab in patients with ulcerative colitis (UC) is common. However, there are currently no effective biomarkers for this prediction. This study aimed to identify potential predictors for precision anti-tumor necrosis factor-alpha treatment in patients with UC. Four GPL570 datasets (GSE14580, GSE12251, GSE23597, and GSE16879) were included in this study. Sixty-nine differentially expressed genes (DEGs) were identified, while 67 were up-regulated and two were down-regulated by comparing the gene expression in response samples with the nonresponse samples. Gene Ontology analysis showed that DEGs were mostly enriched in neutrophil-mediated immunity, neutrophil activation, neutrophil activation involved in the immune response, neutrophil degranulation, and leukocyte migration. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that these DEGs were mostly enriched in cytokine-cytokine receptor interactions and interleukin (IL)-17 signalling pathways. After protein-protein interaction network analysis, verification by test set, and confirmation of clinical UC samples, S100 calcium-binding protein A8 (S100A8), S100A9, triggering receptor expressed on myeloid cells 1 (TREM1), toll-like receptor 2 (TLR2), IL1B, and formyl peptide receptor 1 (FPR1) were identified as the hub genes. We found that the immune cell composition in the intestinal tissues of UC patients with primary nonresponse included naïve CD4+ T cells, memory resting CD4+ T cells, resting natural killer cells, resting dendritic cells, activating dendritic cells, eosinophils, and neutrophils. Among these, neutrophils showed the most significant differences. In addition, all six potential predictors were significantly associated with the neutrophil count. Our study identified six potential biomarkers, namely S100A8, S100A9, TREM1, TLR2, IL1B, and FPR1, and one type of immune cell, neutrophils, between UC patients with response and primary nonresponse to infliximab. We speculated that changes in the expression of these six potential biomarkers combined with changes in the activity or local quantity of neutrophils might help predict primary nonresponse to infliximab in patients with UC."
"In response to the COVID-19 pandemic, the CDC issued guidance advising patients and providers to adopt social distancing practices such as home-based infusions (H-BI).
We performed a mixed methods evaluation to summarize perceptions, concerns, and experiences with H-BI among all inflammatory bowel disease patients 18-90 years of age who transitioned to home-based infliximab or vedolizumab infusions between March to July 2020 at a tertiary care center. Semi-structured interviews were conducted and analyzed using an iterative, inductive thematic approach. Baseline characteristics and outcome on safety, COVID-19 transmission, delays in infusions, and H-BI persistence were collected.
Of the 57 participants who transitioned to H-BI, 20 (33%) responded. Four major categories and six major themes related to expectations, experience, perceived safety, and logistical factors were identified. Initial perceptions were mixed, however these resolved. One patient developed COVID-19, one patient experienced an adverse event, 12 (21%) patients experienced an infusion delay, and 6 (11%) patients transitioned from H-BI.
Despite mixed initial perceptions, respondents had a positive experience with most respondents planning to continue H-BI after the pandemic resolves. Several real-world actionable barriers were identified related to scheduling, communication between stakeholders, and nursing quality. No major safety concerns were identified."
"Kawasaki disease (KD) is a medium and small vessel vasculitis which usually has a good response to immunoglobulin therapy (IVIG). We present a case of incomplete KD with IVIG resistance associated with an unusual combination of vesicular guttate-psoriasiform rash, hypertension and late onset small joint arthritis.
A four-month-old male infant from Sri Lanka presented with high fever, conjunctival redness, pedal oedema and skin rash. He was found to have hypertension since admission with a high white cell count and high inflammatory markers. There was poor response to intravenous antibiotics and subsequent 2D echocardiogram revealed coronary artery aneurysms suggestive of KD. In the third week of illness he developed a vesiculo-papular rash involving face, trunk and limbs - which on biopsy revealed features of guttate psoriasis. Fever spikes continued and the coronary arteries showed progressive dilatation despite timely intravenous immunoglobulin administered on day 6 and methylprednisolone administered on day 10-13. Therapeutic response by means of reduction of fever was seen only after initiation of intravenous infliximab on day 28 of illness for which the fever responded within 24 hours. He developed a small joint arthritis of hands and feet on day 40 of illness which responded only after initiating methotrexate therapy. The hypertension persisted for 4 months after the onset of the illness before complete resolution.
This case report depicts an unusual presentation of KD with a vesicular guttate-psoriasiform eruption, hypertension and late onset small joint arthritis. It highlights that clinicians should be aware of the fact that KD could present with such atypical manifestations and could develop unusual complications."
"Cronkhite-Canada syndrome (CCS) is a non-hereditary disorder characterized by non-neoplastic gastrointestinal polyposis and ectodermal changes. While corticosteroids are considered effective, some cases are refractory. A 48-year-old woman presented with diarrhea, anorexia, and epigastralgia lasting for 3 months. She suffered from alopecia and nail dystrophy. Gastrointestinal endoscopy with histological examination confirmed non-neoplastic polyposis from the stomach to the rectum, confirming the diagnosis of CCS. Linked color imaging (LCI) with magnified endoscopy revealed a ribbon-like proliferation of capillaries surrounding the pits in the colonic mucosa. Histologically, the polyps had dilated glands, edematous stroma with inflammatory cell infiltrates and increased capillaries just beneath the epithelium. Immunohistochemical examination confirmed the expression of vascular endothelial growth factor (VEGF), mainly in the superficial epithelial and crypt cells. Steroid therapy was ineffective, and concomitant infliximab therapy provided symptomatic relief. Although symptoms rapidly improved with combination therapy, capillary hyperplasia and slight inflammation persisted in the colon mucosa after polyp resolution. Withdrawal of steroid treatment resulted in flare-ups of symptoms and polyps. Repeated magnified observations at LCI during post-relapse retreatment clearly captured the resolution process of both neovascularization and inflammation. Once the capillary hyperplasia and inflammation subsided, the steroid could be tapered off without relapse. To our knowledge, this is the first report describing the involvement of VEGF-induced angiogenesis and LCI findings in CCS; LCI observations are useful not only in the active phase of CCS, but also in determining subtle capillary hyperplasia and residual inflammation in remission, which may be an indicator of continued treatment."
"Background Damage to the coronary arteries during the acute phase of Kawasaki disease (KD) is linked to inflammatory cell infiltration, myointimal proliferation, and endothelial cell (EC) dysfunction. To understand the response of ECs to KD treatment, we studied the genome-wide transcriptional changes in cultured ECs incubated with KD sera before and after treatment with or without atorvastatin. Methods and Results RNA sequencing of human umbilical vein ECs incubated with pooled sera from patients with acute KD before or after treatment with intravenous immunoglobulin and infliximab revealed differentially expressed genes in interleukin-1, tumor necrosis factor-α, and inflammatory cell recruitment pathways. Subacute sera pooled from patients treated with intravenous immunoglobulin, infliximab, and atorvastatin uniquely induced expression of "
"Few data exist regarding the immunogenicity of the third dose of BNT162b2 relative to the second dose in patients with inflammatory bowel disease (IBD) on different immunosuppressive therapies. We investigated the immunogenicity of BNT162b2 vaccine booster dose in patients with IBD on infliximab combination therapy.
This is a prospective single-center observational study conducted from January 1, 2022 to February 28, 2022. Patients were recruited at the time of attendance at the infusion center. Eligibility criteria included patients with a confirmed diagnosis of IBD who are receiving infliximab with azathioprine or 6-mercaptopurine. Patients who received two doses of BNT162b2 vaccine (second dose group) were compared to patients who had received three doses of BNT162b2 vaccine [third dose (booster) group]. Patients were excluded if they were infected or had symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) previously since the start of the pandemic or received other vaccines than the BNT162b2. Our primary outcome was the concentrations of SARS-CoV-2 antibodies Immunoglobulin G (IgG) and neutralizing antibodies 40-45 weeks from the first dose of BNT162b2 vaccine in patients with IBD receiving infliximab combination therapy. Medians with interquartile range (IQR) were calculated.
In total, 162 patients with IBD and receiving infliximab combination therapy were recruited, and the number of patients in both the second dose group and third dose (booster) group was 81. Mean age was 35 years old in both groups. Median (IQR) SARS-CoV-2 IgG levels were significantly lower after the second dose [125 BAU/ml (43, 192)] compared to patients who received the third booster dose [207 BAU/ml (181, 234)] (
Most patients with IBD on infliximab combination therapy had positive SARS-CoV-2 IgG and neutralizing antibody concentrations 40-45 weeks post BNT162b2 vaccination. However, SARS-CoV-2 IgG and neutralizing antibody concentrations were lower in patients who received two doses only compared to patients who received a third dose. A longer follow-up study is needed to evaluate decay in antibodies over time."
"An association between tumor necrosis factor (TNF)-α inhibitors and hypoglycemia has been detected in a few case reports and small case series; however, no relevant pharmacovigilance data have been published yet.
The objective of this study was to detect and characterize relevant safety signals between hypoglycemia and TNF-α inhibitor use.
Indication-focused disproportionality analysis was conducted to detect increased reporting of TNF-α-associated hypoglycemia compared with all other reports with the same indication during the same time period. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated to determine disproportionality. To reduce potential confounding factors, adjusted RORs were further calculated by logistic regression to control for age, sex, diabetes status, and concomitant drugs that potentially affect blood glucose levels.
In all, 1086 adverse drug reactions related to TNF-α inhibitors were reported as 'hypoglycemia'. There were no disproportionality signals of hypoglycemia in TNF-α inhibitor users with indication of inflammatory bowel disease. When TNF-α inhibitors were considered as a class, disproportion for hypoglycemia only emerged in indication of psoriasis (n = 267, ROR 1.20, 95% CI 1.02-1.41). In further analyses of specific TNF-α inhibitor type, significant RORs for hypoglycemia were found in indication of rheumatic disease, including adalimumab in ankylosing spondylitis (n = 37, ROR 1.97, 95% CI 1.28-3.04), psoriasis (n = 160, ROR 1.64, 95% CI 1.37-1.97), and rheumatoid arthritis (n = 230, ROR 1.35, 95% CI 1.16-1.56) and infliximab in psoriasis (n = 18, ROR 2.14, 95% CI 1.33-3.42). After adjusting for confounding factors, only the signals of adalimumab were stable.
Our study identified some potential pharmacovigilance signals between hypoglycemia and TNF-α inhibitors, which warrants further validation."
"Mucosal healing (MH) is currently the gold standard in Crohn's disease (CD) management. Noninvasive assessment of MH in CD patients is increasingly a concern of clinicians.
This retrospective study included 106 patients with confirmed CD who were divided into a training cohort (n = 73) and a testing cohort (n = 33). Patient demographics were evaluated to establish a clinical model. Radiomics features were extracted from computed tomography enterography (CTE) images. A radiomics signature was constructed, and a radiomics score (Rad-score) was calculated by using the radiomics signature-based formula. A clinical radiomics nomogram was then built by incorporating the Rad-score and significant clinical features. The diagnostic performance of the three models was evaluated using receiver operating characteristic (ROC) curve analysis.
Of the 106 patients with CD, 37 exhibited MH after 26 weeks of infliximab (IFX) treatment. The area under the ROC curve (AUC) of the clinical radiomics nomogram for distinguishing MH from non-MH, which was based on the disease duration and Rad-score, was 0.880 (95% confidence interval [CI]: 0.809-0.943) in the training cohort and 0.877 (95% CI: 0.745-0.983) in the testing cohort. Decision curve analysis (DCA) confirmed the clinical utility of the clinical radiomics nomogram.
This is a preliminary study suggesting that this CTE-based radiomics model has potential value for predicting MH in CD patients. A nomogram constructed by combining radiomics signatures and clinical features can help clinicians select appropriate therapeutic strategies for CD patients.
• The disease duration (odds ratio (OR) = 0.969, 95% confidence interval (CI) = 0.943-0.995, p = 0.021) was an independent predictor of MH in the clinical model. • The AUC of the radiomics model constructed by the five radiomics features was 0.846 (95% CI: 0.759-0.921) in the training cohort and 0.817 (95% CI: 0.665-0.945) in the testing cohort for differentiating MH from non-MH. • The AUC of the clinical radiomics nomogram was 0.880 (95% CI: 0.809-0.943) in the training cohort and 0.877 (95% CI: 0.745-0.983) in the testing cohort for distinguishing MH from non-MH."
"This study explores the potential of gene polymorphisms in the canonical and noncanonical NF-kB signaling pathway as a prediction biomarker of anti-tumor necrosis factor (TNF)α response in Crohn's patients.
A total of 109 Greek patients with Crohn's disease (CD) were recruited, and the genotype of TLR2 rs3804099, LTA rs909253, TLR4 rs5030728, and MAP3K14/NIK rs7222094 single nucleotide polymorphisms was investigated for association with response to anti-TNFα therapy. Patient's response to therapy was based on the Crohn's Disease Activity Index, depicting the maximum response within 24 months after initiation of treatment.
Seventy-three patients (66.7%) were classified as responders while 36 as nonresponders (33.3%). Comparing allelic frequencies between responders and nonresponders, the presence of TLR2 rs3804099 T allele was associated with nonresponse (P = 0.003), even after stratification by anti-TNFα drugs (infliximab: P = 0.032, adalimumab: P = 0.026). No other association was identified for the rest of the polymorphisms under study. Haplotype analysis further enhanced the association of rs3804099 T allele with loss of response, even though the results were NS (P = 0.073).
Our results suggest that polymorphisms in the canonical NF-kB pathway genes could potentially act as a predictive biomarker of anti-TNFα response in CD."
"Ankylosing spondylitis (AS) is a common immune-related systemic chronic inflammatory osteoarthropathy. Previous studies have proven that biologic agents, including IL-17A inhibitors (IL17Ai), TNF-
PubMed, Scopus, Embase, CNKI, and the Cochrane Library were systematically searched. A frequentist framework network meta-analysis with a random-effects model was performed. Ranking effects were calculated by surface under the cumulative ranking analysis (SUCRA) and cluster-rank analysis.
IL17AFi reported both the highest ASAS40 (SUCRA = 91.4%) and ASAS20 (SUCRA = 92.5%) response, while IL6i and IL23i reported the lowest responses (SUCRA = 6.6% and 19.9%, respectively). With the exceptions of IL6i (RR 0.60, 95% CI (0.22 to 1.67) for ASAS40 and 1.36 (0.71 to 2.58) for ASAS20) and IL23i (0.98 (0.68 to 1.40) for ASAS40 and 0.91 (0.70 to 1.19) for ASAS20), all biological drugs demonstrated statistically superior ASAS responses than placebo. TNFiFMA performed best in the suppression of disease activity (SUCRA = 77.4%, SMD 2.35, and 95% CI (1.11 to 3.59)) and functional improvement (SUCRA = 68.8%, SMD 1.67, and 95% CI (0.59 to 2.74)). There were no significant differences in tolerability or safety between biologic drugs and placebo.
The novel IL-17 A/F dual variable domain inhibitor, bimekizumab, may be an ideal future treatment choice for AS, while IL-23 and IL-6 inhibitors demonstrate little potential in the treatment of AS. For patients with rapid disease progression and severe functional limitation, TNF-"
"Infliximab is a chimeric monoclonal antibody against tumour necrosis factor (TNF)-α, with a wide variety of uses. Monoclonal antibody therapies specifically targeting TNF-α, have emerged as a novel treatment option for patients with refractory sarcoidosis, with infliximab being the most widely used. This is not true of other TNF-α inhibitors, for example etanercept, which have a different mechanism of action, and are not effective in sarcoidosis. It is well documented that infliximab therapy can result in the production of autoantibodies, however clinical symptoms or disease is rare. In this report, we describe a 37-year-old male with a history of sarcoidosis requiring infliximab therapy, who presented during the course of his treatment with the onset of new migratory joint pain, increasing fatigue and positive serum autoantibodies, heralding the development of infliximab-induced lupus."
"Depression is a chronic and prevalent neuropsychiatric disorder; clinical symptoms include excessive sad mood, anhedonia, increased anxiety, disturbed sleep, and cognitive deficits. The exact etiopathogenesis of depression is not well understood. Studies have suggested that tumor necrosis factor-alpha (TNF-α) and interleukins (ILs) perform vital roles in the pathogenesis and treatment of depression. Increasing evidence suggests the upregulation of TNF-α and ILs expression in patients with depression. Therefore, biologics like TNF inhibitors (etanercept, infliximab, adalimumab) and IL inhibitors (ustekinumab) have become key compounds in the treatment of depression. Interestingly, treatment with an antidepressant has been found to decrease the TNF-α level and improve depression-like behaviors in several preclinical and clinical studies. In the current article, we have reviewed the recent findings linking TNF-α and the pathogenesis of depression proving TNF-α inhibitors as potential new therapeutic agents. Animal models and clinical studies further support that TNF-α inhibitors are effective in ameliorating depression-like behaviors. Moreover, studies showed that peripheral injection of TNF-α exhibits depressive symptoms. These symptoms have been improved by treatment with TNF-α inhibitors. Hence suggesting TNF-α inhibitors as potential new antidepressants for the management of depressive disorder."
"Despite introduction of biological disease modifying anti-rheumatic drugs (DMARDs) for Rheumatoid arthritis (RA) treatment, therapeutic strategies do not always lead to disease control and remission. Hence, a more efficient patient stratification and monitoring biomarkers and tools are needed to enable a more personalized medicine. We used a whole blood based functional flow cytometry assay to characterize immune cells from RA patients (treated or not), healthy donors and psoriatic arthritis (PsA) patients according to their responses to LPS and/or anti-TNFα (infliximab, IFX). Activation marker expression was measured using a 10-color flow cytometry panel following a no-wash protocol. Naïve-to-treatment RA patients had a stronger inflammatory profile in comparison to healthy donors at basal level. Higher expression of activation markers (CD69 and/or CD11b) on NK, B cells and granulocytes and lower expression of the adhesion molecule CD62L were measured on monocytes, granulocytes and B cells. After LPS, naïve RA patients' cells were less capable of regulating CD69, CD11b, CD16 or CD62L showing impaired activation capabilities. Upon LPS and IFX co-incubation, hierarchical clustering analysis showed different profiles between cohorts. We believe that this whole blood-based approach should further be assessed for RA patient characterization as it provides new perspectives for stratification and/or monitoring."
"There is no consensus on the management of immune checkpoint inhibitor (ICI) for treating cancer in patients with pre-existing inflammatory bowel disease (IBD). The Groupe d'Étude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) aimed to provide recommendations on this topic.
A dedicated working group performed a comprehensive expert-based review of the literature, generated clinical key question and shaped recommendations that were further voted for approval by the educational and scientific committees of the GETAID. Using consensus methods, treatment modalities were defined by vote.
Majority of patients with IBD in clinical remission can be treated with ICI after cancer diagnosis. The rate of relapse or immune-related diarrhoea or colitis upon ICI treatment is up to 39.8% and is maximal with ICI combination therapy compared to monotherapies. When starting ICI in a patient with IBD, it is recommended to assess disease activity and pursue ongoing maintenance therapy. In case of relapse or immune-related diarrhoea or colitis upon ICI treatment, treatment depends on grading of diarrhoea or colitis and may include corticosteroid therapy, infliximab and/or vedolizumab.
In the present publication, we provided recommendations, which may assist gastroenterologists, haematologists, and oncologists for a better management of patients with pre-existing IBD before and during cancer treatment with ICI."
"Recently, the European Respiratory Society (ERS) developed new international guidelines for the treatment of sarcoidosis. This manuscript attempts to distill the ERS Sarcoidosis Treatment Guidelines to a manageable format that can be easily used by practitioners.
The ERS Sarcoidosis Treatment Guidelines addressed the treatment of pulmonary, skin, cardiac, neurologic, and sarcoidosis-associated fatigue. Therapeutic drug dosing and treatment algorithms for these conditions were also addressed. Glucocorticoids were the initial recommended treatment for these conditions except for sarcoidosis-associated fatigue where a pulmonary exercise program or a neurostimulant was initially suggested. Because of the risk of glucocorticoid side-effects, the Guidelines recommended early consideration of glucocorticoid-sparing therapy including certain antimetabolites and two specific tumor necrosis alpha antagonists: infliximab and adalimumab.
The ERS Sarcoidosis Treatment Guidelines used a rigorous GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology to update treatment recommendations for this condition. This manuscript summarizes the Guideline findings in practical terms for clinicians. Suggested algorithms and treatment dosing recommendations are provided."
"Infliximab is a mouse/human chimeric IgG1 monoclonal antibody which recognizes the proinflammatory cytokine, tumor necrosis factor α (TNFα), and inhibits receptor interactions, thereby decreasing inflammation and autoimmune response in patients. This monoclonal antibody has been successfully used to treat rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the high treatment cost limits patient access to this biotherapy. One alternative to this problem is the use of biosimilars. In this work, we describe the stable expression and physicochemical characterization of an anti-TNFα antibody. While infliximab is produced in recombinant murine SP2/0 cells, our anti-TNFα IgG antibody was expressed in recombinant murine NS0 myeloma cells. The best anti-TNFα antibody-expressing clone was selected from three clone candidates based on the stability of IgG expression levels, specific productivity as well as TNFα-binding activity compared to commercial infliximab. Our results indicate that the selected cell clone, culture medium, and fermentation mode allowed for the production of an anti-TNFα antibody with similar characteristics to the reference commercially available product. An optimization of the selected culture medium by metabolomics may increase the volumetric productivity of the process to satisfy the demand for this product. Further experiments should be performed to evaluate the biological properties of this anti-TNFα antibody. KEY POINTS: • An anti-TNFα antibody was produced in NS0 cells using perfusion culture. • A proprietary chemically defined culture medium was used to replace commercially available protein-free medium. • The purified anti-TNFα antibody was comparable to the reference marketed product."
"Project NORTH compared real-world clinical and economic outcomes in Swedish patients with inflammatory bowel disease (IBD) who switched from originator infliximab to its biosimilar.
Data from electronic medical records and Swedish national registries were linked. Switchers (patients switching from originator infliximab to its biosimilar between 1 April 2014, and 31 December 2017) and non-switchers (patients who received originator infliximab and did not switch to a biosimilar by 31 December 2017) were followed up until 31 October 2019.
Baseline concomitant medication use, disease duration, and inflammatory markers were lower among switchers than non-switchers. At 6 months, the proportion of patients with stable disease was higher among switchers than non-switchers (71/109 [65%] vs 54/107 [50%]; 
No substantial differences in clinical outcomes or healthcare resource utilization were observed between switchers and non-switchers. Several analyses indicate that non-switchers might have more poorly controlled/severe disease than switchers at baseline. Overall, numerous difficulties might arise when executing a high-quality, real-world study, including possible selection bias for patients with better disease control for NMS, limiting the generalizability of the results."
"The treatment for Kawasaki disease (KD) patients refractory to intravenous immunoglobulin (IVIG) therapy is still controversial, and the efficacy of plasma exchange (PE) and infliximab (IFX) therapy for infantile KD is unknown.
A total of 22 infantile KD patients refractory to initial and additional IVIG, who received either PE or IFX as third-line therapy from October 2008 to February 2020 were examined retrospectively. The patients' sex, age, days of first IVIG, days of PE or IFX therapy, laboratory data preceding PE or IFX therapy, coronary artery lesions (CALs), and adverse effects were investigated.
Thirteen patients received PE and nine patients received IFX as the third-line therapy. For the median age at onset, the median days of first IVIG and PE or IFX, and pre-PE or IFX therapy blood test results, there were no significant between-group differences. At admission, and before and after the third-line therapy, there were also no significant differences in occurrence of CALs. The frequency of serious adverse events was significantly higher in the PE group than in the IFX group.
Although there were no significant differences in patient background, blood test results, or frequency of CALs, the frequency of adverse events was significantly higher in the PE group. With the trend of expansion of IFX therapy for KD patients refractory to IVIG, the role of PE as the additional therapy may become more limited."
"Immune-related adverse events (irAEs) often require treatment with high-dose systemic steroids (SS) and other immunosuppressive agents (ISAs). NCCN Guidelines recommend prophylactic antibiotics for Pneumocystis jirovecii pneumonia (PJP) for patients receiving prolonged SS/ISAs. However, there is a paucity of evidence regarding the incidence of opportunistic infections (OIs) and non-OIs and the role of prophylactic antibiotics in patients on SS/ISAs for irAEs.
A retrospective analysis was conducted of patients treated using immune checkpoint inhibitor (ICI) therapy at 5 MedStar Health hospitals from January 2011 to April 2018. OIs were defined per the Infectious Diseases Society of America guidelines for the prevention and treatment of OIs in patients with HIV. The study cohort included patients who received ≥20 mg daily of a prednisone equivalent for ≥4 weeks to manage irAEs.
The study cohort identified 112 (15%) of 758 total patients treated using ICIs. Baseline characteristics included the following: median age was 64 years, 74% (n=82) of patients were White, 89% (n=100) had an ECOG performance status ≤1, 61% (n=68) had melanoma, 19% (n=21) had non-small cell lung cancer, 45% (n=50) were treated using an anti-PD-(L)1 ICI, and 33% (n=37) were treated using an anti-PD-1/anti-CTLA-4 combination. The median starting SS dose was 100 mg of a prednisone equivalent, and 25% of patients required additional ISAs, with infliximab (n=15) and mycophenolate mofetil (n=9) being the most common. We found that 20% (n=22) of patients developed any infection, including 7% (n=8) with OIs (oral candidiasis [n=4], nondisseminated varicella zoster infection [n=2], PJP [n=1], and Listeria monocytogenes endophthalmitis [n=1]) and 13% (n=14) with non-OIs (most common: Clostridium difficile and pneumonia [n=5 each]). PJP prophylaxis with sulfamethoxazole/trimethoprim was given to 13% (n=14) patients, of whom 43% (n=6) developed OIs/non-OIs.
Our study highlights the fundamental issues for patients on ICI therapy who require SS/ISAs for irAEs: the degree of immunosuppression and the relative risk of OI. We noted a low incidence of OIs overall and breakthrough infections despite PJP prophylaxis. We question whether PJP prophylaxis is efficacious or necessary. Prospective trials are required to answer these questions."
"Ulcerative colitis is a chronic and progressive inflammatory disorder. The regulator of the G-protein signaling (RGS) is involved in the pathogenesis of several immune system disorders. RGS16, a member of the RGS protein superfamily, has been shown to play critical roles in several immune system-related diseases. However, the roles of RGS16 in ulcerative colitis remain to be elucidated.
We analyzed the expression of RGS16 in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa of ulcerative colitis patients using quantitative reverse transcription-PCR, western blotting and immunohistochemistry. We performed Spearman's correlation to analyze the correlation between RGS16 expression and the ulcerative colitis endoscopic index of severity (UCEIS), Mayo index, erythrocyte sedimentation rate (ESR) and serum tumor necrosis factor alpha (TNF-a) and IL-17A levels. Further, PBMCs were stimulated with inflammatory cytokines in vitro .
RGS16 expression significantly increased in the colonic mucosa and PBMCs from patients with ulcerative colitis and significantly correlated with the Mayo index, UCEIS, ESR and serum TNF-α and IL-17A levels. TNF-α upregulated RGS16 expression in PBMCs in a dose- and time-dependent manner via the nuclear factor kappa beta (NF-kB) signaling pathway. Moreover, anti-TNF treatment with infliximab significantly decreased RGS16 expression in PBMCs and intestinal mucosa of patients with ulcerative colitis.
Our study revealed a novel mechanism by which RGS16 expression in ulcerative colitis is positively correlated with disease activity. Thus, RGS16 might serve as a potential therapeutic marker for the treatment of ulcerative colitis."
"To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD).
A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes.
Eighty-seven patients [Crohn's disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations ( P = 0.018) and in those who were nonnaïve to anti-TNF-α ( P = 0.027).
This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events."
"To describe the management and outcome of two extremely rare and painful cases of Mooren's ulcer, an idiopathic peripheral autoimmune-associated ulcerative corneal disease.
Case report with literature review on the management of ocular inflammation in Mooren's ulcer.
A 47-year-old female and a 76-year-old female presented with progressive bilateral Mooren's ulcer that were refractory to conventional immunosuppressive therapy. Following treatment with infliximab, an anti-tumor necrosis factor alpha, a significant improvement in disease progression was observed, with no corneal thinning or perforation at follow-ups.
This case report highlights how infliximab can be effective in cases with Mooren's ulcer refractory to conventional therapies."
"Patients with inflammatory bowel disease (IBD) requiring infliximab frequently spend hours to attend treatment. Through quality improvement (QI) methodology, we aimed to shorten the time spent in the biologics infusion center using the accelerated infusion protocol and describe patient outcomes, safety, and associated cost savings.
From September 2018 through December 2019, eligible IBD patients receiving infliximab were recruited. We implemented interventions including the accelerated infusion protocol, and modifying collection location of infliximab. Statistical process control charts were created. Patients' clinical outcome and cost savings data were analyzed using descriptive statistics and Pearson's chi-square.
During the study period, a total of 60 patients with IBD receiving infliximab were recruited. A total of 315 infusions were administered-152 were under accelerated infusion protocol and 163 under standard protocol. The mean infliximab infusion time was reduced by 47%, from 2.4 h (142 ± 14 min) to 1.2 h (75 ± 10 min) (142 min 
Our QI project shortened the infliximab infusion time and total time spent in the infusion center, without compromising patient safety. Estimated cost savings were substantial. The protocol helps reduce work productivity loss."
"Limited data are currently available regarding anti-tumor necrosis factor (TNF) use and outcomes in very early onset inflammatory bowel disease (VEOIBD) patients. We aimed to assess the long-term outcomes and time to progression to anti-TNF treatment in VEOIBD patients.
We retrospectively reviewed IBD patients diagnosed under 6 years of age, between January 2005 and December 2019, from the British-Columbia (BC) Pediatric IBD database. Demographic data, disease characteristics, disease location and severity were documented. Data on anti-TNF treatment at initiation and during follow up including type of biologic, dosing, and response were collected. Kaplan-Meier curves were used to assess the number of years to progression to anti-TNF treatment and the parameters influencing commencement.
Eighty-nine patients with VEOIBD were diagnosed during the study period. Median age at diagnosis was 3.8 years [interquartile range (IQR) 2.6-5.1], 45.3% had Crohn disease (CD) and 62.8% were males. Median duration of follow up was 6.39 years (IQR 3.71-10.55). Anti-TNF treatment was started on 39.5% of patients and 7.0% underwent surgery. Rapid progression to biologic treatment was associated with Perianal fistulizing disease or stricturing disease in CD patients ( P = 0.026, P = 0.033, respectively), and disease severity ( P = 0.017) in ulcerative colitis(UC) patients. The median dose of infliximab at 1 year was 10 mg/kg (IQR 7.5-11) and a median dose interval of 4.5 weeks (IQR 4-6). Clinical remission was reported in 61.8% of patients on their first biologic agent.
The response rate was higher than previously reported and might be due to higher infliximab dosing with shorter infusion intervals than standard dosing."
"To explore the effect and mechanism of pirfenidone in inhibiting pulmonary fibrosis in connective tissue disease-associated interstitial lung disease (CTD-ILD).
From 2018 to 2020, 50 CTD-ILD patients were enrolled in the clinical study. Based on whether pirfenidone was used during treatment, patients were enrolled into the pirfenidone group and the control group. Pulmonary function tests were compared before and after treatment. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression of tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), and Krebs Von den Lungen-6 (KL-6) in venous blood before and after treatment. Rat type II (RLE-6TN) lung epithelial cells were cultivated for 
In the clinical study, the pulmonary function indices including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF) and partial pressure (PaO
Pirfenidone improved pulmonary function 1 and decreased TNF-α, STAT3, and KL-6 expression in CTD-ILD patients. Moreover, pirfenidone inhibits cell fibrosis through the TNF-α/STAT3/Mucin 1(MUC1) pathway."
"Pulmonary manifestation (PM) of inflammatory bowel disease (IBD) in children is a rare condition. The exact pathogenesis is still unclear, but several explanatory concepts were postulated and several case reports in children were published. We performed a systematic Medline search between April 1976 and April 2022. Different pathophysiological concepts were identified, including the shared embryological origin, ""miss-homing"" of intestinal based neutrophils and T lymphocytes, inflammatory triggering via certain molecules (tripeptide proline-glycine-proline, interleukin 25), genetic factors and alterations in the microbiome. Most pediatric IBD patients with PM are asymptomatic, but can show alterations in pulmonary function tests and breathing tests. In children, the pulmonary parenchyma is more affected than the airways, leading histologically mainly to organizing pneumonia. Medication-associated lung injury has to be considered in pulmonary symptomatic pediatric IBD patients treated with certain agents (i.e., mesalamine, sulfasalazine or infliximab). Furthermore, the risk of pulmonary embolism is generally increased in pediatric IBD patients. The initial treatment of PM is based on corticosteroids, either inhaled for the larger airways or systemic for smaller airways and parenchymal disease. In summary, this review article summarizes the current knowledge about PM in pediatric IBD patients, focusing on pathophysiological and clinical aspects."
"To investigate the clinical response to infliximab in ocular inflammation patients who develop anti-infliximab antibodies (AIA) vs. those patients who do not develop AIA.
A retrospective review was performed of patients treated with infliximab for noninfectious uveitis (NIU) or scleritis. Clinical response was determined as a composite clinical endpoint and classified as complete, partial, or absent. Nine of 32 infliximab-treated patients (28%) were found to develop AIA. Among the AIA-positive patients, clinical response was complete in 7 patients (78%) and partial in 2 patients (22%). Among the AIA-negative patients, clinical response was complete in 15 patients (65%), partial in 6 patients (26%) and absent in 2 patients (9%). Serum infliximab levels tended to decrease with appearance of AIA but rarely became undetectable.
In this pilot study, AIA-positive patients did not have diminished clinical response to infliximab when compared with AIA-negative patients. There was a high rate of complete clinical response to infliximab in this group of NIU and scleritis patients. Approximately a quarter of patients developed AIA. AIA-positive patients did not have diminished rates of clinical response when compared with AIA-negative patients. This suggests that routine AIA monitoring may not be clinically useful, although validation of this finding in larger cohorts is necessary."
"Juvenile idiopathic arthritis (JIA) is one of the most common pediatric inflammatory rheumatic diseases (PiRDs). Uncontrolled disease activity is associated with decreased quality of life and chronic morbidity. Biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) have considerably improved clinical outcomes. For optimized patient care, understanding the efficacy-safety profile of biologics in subgroups of JIA is crucial. This systematic review based on published randomized controlled trials (RCTs) aims to assess efficacy and safety data for bDMARDs and JAKi with various JIA subgroups after 3 months of treatment.
Data for American College of Rheumatology (ACR) pediatric (Pedi) 30, 50, and/or 70 responses after 3 months of treatment were selected from RCTs investigating bDMARDs or JAKi in JIA according to predefined inclusion/exclusion criteria. Treatment and control arms were compared by calculating risk ratios (RRs) with 95% confidence intervals (CIs), and proportions of overall, serious adverse events (AEs) and infections were analyzed. Forest plots were generated to summarize efficacy and safety endpoints across studies, JIA subgroups, and type of biologics.
Twenty-eight out of 41 PiRD RCTs investigated bDMARD or JAKi treatments in JIA. 9 parallel RCTs reported ACR Pedi 30, 50, and/or 70 responses 3 months after treatment initiation. All treatment arms showed improved ACR Pedi responses over controls. RRs ranged from 1.05 to 3.73 in ACR Pedi 30, from 1.20 to 7.90 in ACR Pedi 50, and from 1.19 to 8.73 in ACR Pedi 70. An enhanced effect for ACR Pedi 70 was observed with infliximab combined with methotrexate in PJIA vs. methotrexate monotherapy. A slightly higher risk of gastrointestinal AEs and infections was observed with treatment arms compared to placebo or methotrexate monotherapy.
Investigated bDMARDs and JAKi showed superior treatment responses compared to controls after 3 months of treatment, which were more pronounced in ACR Pedi 50 and 70 than in ACR Pedi 30. Higher susceptibility to infections associated with bDMARDs or JAKi vs. control arms must be weighed against efficacious treatment of the underlying disease and prevention of disease-related damage. Additional RCTs are warranted to further inform development and utilization of biologics in JIA."
"Based on extrapolation of similar clinical outcomes in rheumatoid arthritis to the originator infliximab (IFX) in randomized clinical trials, the first biosimilar antibody CT-P13 was approved for the treatment of psoriasis. To evaluate the safety, efficacy, and drug survival of CT-P13 for psoriasis in real-world clinical practice, prospective post-marketing surveillance was conducted in 165 Japanese psoriasis patients. During a 1-year follow-up period, adverse drug reactions (ADRs) occurred in 29 patients (17.6%). Infusion reaction was the most frequent ADR (6.7%), and mild pneumonia was reported as the only case of infection. Serious ADRs were reported in two patients (1.2%): acute cholecystitis and interstitial pneumonia. The interstitial pneumonia developed after a single infusion of CT-P13 and the patient died of respiratory failure. In naive patients to biologic therapy (n = 44), the Psoriasis Area Severity Index (PASI) decreased rapidly after the start of CT-P13 treatment, and response rate achieving an absolute PASI score <1 was 55% at 30 weeks. The response rate was high (78%) in patients with psoriatic arthritis, and 40% and 20% in those in plaque psoriasis and pustular psoriasis, respectively. Of patients switched from IFX to CT-P13 mainly for nonmedical reasons (n = 105), 57% had already reached PASI <1 by pretreatment with IFX and CT-P13 maintained this status. The incidence of ADRs in this patient group was low and the drug survival rate was as high as 74%, even at 1 year, which was significantly higher than that in the naïve patient group (47%). Patients switched from other biologics for medical reasons (n = 16) responded similarly to biologic-naïve patients, but drug survival was lower (24%). In conclusion, CT-P13 showed excellent effectiveness as a first-line therapy, no clinical difficulties in switching from IFX, and usefulness in patients who failed other biologics. CT-P13 could be a cost-effective alternative to IFX for the treatment of psoriasis."
"Budesonide remains the backbone therapy for microscopic colitis [MC]; however, relapses are frequent, and some patients are intolerant or dependent. Anti-TNF therapy is increasingly used to treat these patients, but available evidence is still limited. The aim of this study was to evaluate the effectiveness and safety of anti-TNF therapy in MC patients failing budesonide.
In a multicentre retrospective cohort study, budesonide-refractory, -dependent, or -intolerant MC patients treated with anti-TNF agents were included. Clinical remission was defined as fewer than three bowel movements per day, and clinical response was defined as an improvement in stool frequency of at least 50%.
Fourteen patients were included. Median age was 58.5 years, median disease duration was 25 months, and median follow-up was 29.5 months. Seven patients were treated with infliximab [IFX], and seven with adalimumab. Clinical remission without steroids at 12 weeks was reached in 5/14 [35.7%] patients; all of these received IFX. Clinical response at 12 and 52 weeks, was obtained in 9/14 [64.3%] and 7/14 [50%] patients, respectively. Five patients switched to another anti-TNF agent. When considering both first- and second-line anti-TNF therapies, 7 [50%] patients were in clinical remission at Week 52. Mild to moderate adverse events were reported in six ptients. Two patients were treated with vedolizumab, of whom one had clinical response; one patient treated with ustekinumab had no response.
This is the first multicentre cohort study showing that half of patients treated with anti-TNF therapy for MC achieved clinical remission in case of budesonide failure."
"Metastasic Crohn disease (MCD) is the most uncommon cutaneous manifestation of Crohn disease. The actual incidence is not clear. There are fewer than 200 cases described in the literature. We report a case of 21 years-old girl that came to our emergency care with large exudative ulcers in the inguinal folds, the vulva, the perianal region and the popliteal fossae. Histopathological examination of the ulcers revealed a non-caseating granulomatous inflammation with abundant multinucleated giant cells and intense lymphocytic infiltrate. Colonoscopy, contrast study of the small bowel and video capsule endoscopy were carried out without evidence of digestive disease. High potency topical steroids (betamethasone 0,5mg/gr twice daily) and 300mg intravenous Infliximab were initiated as the initial line therapy and the ulcers began to heal. We report this case to highlight the presence of cutaneous ulcers without intestinal disease in a young non-pediatric woman as the unique manifestation of the disease."
"Hidradenitis suppurativa (HS) is a chronic inflammatory often recalcitrant to treatment. There is a lack of an updated systematic data review for infliximab use in HS. We conducted a systematic review and meta-analysis of literature on infliximab in HS. This study was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was pre-registered on PROSPERO (CRD42021283596). In 9/2021, MEDLINE and EMBASE were systematically searched for articles on infliximab in HS. Non-English, duplicate, and studies with <5 HS patients were excluded. Study quality was assessed utilizing Cochrane Risk of Bias for prospective trials and Newcastle-Ottawa Scale for cohort studies. Random effects meta-analytical model, Cochran's Q statistic, and I squared index were performed. Nineteen articles (314 patients) met inclusion criteria (six prospective, 13 retrospective studies). All patients with HS severity data available (n = 299) had moderate-to-severe disease. Outcome measures used for meta-analysis of the pooled response rate were largely based on clinician reported outcomes (16 studies). One utilized both clinician and patient assessment. Two utilized patient-reported response alone. The pooled response rate of HS patients to infliximab was 83% (95% CI, 0.71-0.91). The most common adverse events (AEs) included non-serious infections (13.2%) and infusion reaction (2.9%). The rate of serious AEs was 2.9%. Study limitations include the small number of prospective studies and heterogeneity between studies. Overall, infliximab is an effective treatment for moderate-to-severe HS. Efficacy of infliximab in HS should be compared to other biologics in larger, randomized controlled trials."
"With an increasing number of therapeutic options available for the management of ulcerative colitis (UC), the variability in treatment and prescribing patterns is not well known. While recent guidelines have provided updates on how these therapeutic options should be used, patterns of long-term use of these drugs over the past 2 decades remain unclear.
We analyzed a retrospective, nationwide cohort of more than 1.7 million prescriptions for trends in prescribing behaviors and to evaluate practices suggested in guidelines relating to ordering biologics, step-up therapy, and combination therapy. The primary outcome was 30-day steroid-free remission and secondary outcomes included hospitalization, cost, and additional steroid usage. A pipeline was created to identify cohorts of patients under active UC medical management grouped by prescribing strategies to evaluate comparative outcomes between strategies. Cox proportional hazards and multivariate regression models were utilized to assess postexposure outcomes and adjust for confounders.
Among 6 major drug categories, we noted major baseline differences in patient characteristics at first exposure corresponding to disease activity. We noted earlier use of biologics in patient trajectories (762 days earlier relative to UC diagnosis, 2018 vs 2008; P < .001) and greater overall use of biologics over time (2.53× more in 2018 vs 2008; P < .00001) . Among biologic-naive patients, adalimumab was associated with slightly lower rates of remission compared with infliximab or vedolizumab (odds ratio, 0.92; P < .005). Comparisons of patients with early biologic initiation to patients who transitioned to biologics from 5-aminosalicylic acid suggest lower steroid consumption for early biologic initiation (-761 mg prednisone; P < .001). Combination thiopurine-biologic therapy was associated with higher odds of remission compared with biologic monotherapy (odds ratio, 1.36; P = .01).
As biologic drugs have become increasingly available for UC management, they have increasingly been used at earlier stages of disease management. Large-scale analyses of prescribing behaviors provide evidence supporting early use of biologics compared with step-up therapy and use of thiopurine and biologic combination therapy.
Population-scale analysis reveals patterns in prescribing trends for ulcerative colitis management. Findings include (1) earlier use of biologics in patient trajectories, (2) associations of step-up therapy with higher corticosteroid exposure, and (3) association of combination therapy with positive patient outcomes."
"Cyclosporine is a rescue treatment alternative to avoid colectomy in corticosteroid refractory acute severe ulcerative colitis. In this study, we aimed to evaluate the long-term efficacy and safety of cyclosporine therapy in acute severe ulcerative colitis patients.
Acute severe ulcerative colitis (basal Lichtiger score > 10) patients who did not respond to 40 mg intravenous methylpredniso- lone therapy after 3-5 days were included in the study. The presence of clinical response and remission was assessed at 1st week, 1st, 6th, and 12th month according to the Lichtiger index.
In this study, 40 patients, whose steroid refractory acute severe ulcerative colitis and basal Lichtiger score > 10 points were enrolled. The median disease duration was 49.3 months (2-204). All patients received cyclosporine for 132 ± 78 days (7-270). Clinical response was obtained on seventh day in 82.5%. The clinical response rates of the first and sixth months were 72.5% and 62.5%, respectively. A total of 17/40 (42.5%) patients underwent colectomy within 1 year. In the patients who underwent colectomy, the basal LS (14.2 ± 1.9 vs 12.3 ± 1.7) (P = .002) was higher and the basal hemoglobin value (11.8 ± 2.3 vs 10.1 ± 1.5) (P = .037) was lower than those who did not undergo colectomy.
Our findings suggest that cyclosporine treatment may be successfully and safely used in steroid refractory acute severe ulcerative colitis patients. Cyclosporine is a drug that has recently started to come up again with the introduction of new maintenance treatments. Especially in patients who develop a loss of response to infliximab therapy, or where infliximab therapy is contraindicated, or who have azathioprine intolerance, or are unresponsive."
"In recent years, many antibody drugs that play an important role in the pharmacotherapy of several diseases have been developed. Antibody drugs exhibit immunogenicity in vivo leading to the development of antibodies against the antibody drug (anti-drug antibody). Nonetheless, other factors also affect the pharmacokinetics of antibody drugs. Recently, therapeutic drug monitoring (TDM) of infliximab was introduced for personalized medicine. However, the usefulness of TDM in antibody therapy remains unclear. In addition to intervention studies, real-world data analysis is important. Unlike small-molecule drugs, antibody drugs do not have a uniform molecular weight; therefore, using the conventional analysis methods, it is impossible to determine the true pharmacokinetic outcomes of these agents. To analyze structural changes of antibody drugs in the body, new technologies are necessary. In the future, along with the development of new drugs, the establishment of novel analytical methods is essential to facilitate the promotion of personalized medicine."
"A 20-year-old woman with Crohn's disease receiving infliximab therapy presented to the emergency department with lower extremity swelling secondary to compression of the common iliac vein. On magnetic resonance imaging, an enlarging pelvic mass was identified. The pathology of the mass was consistent with myelolipoma. We believe this is the first case of myelolipoma in a patient on immunosuppression with infliximab."
"Uveitis is the most frequent extra-articular manifestation of juvenile idiopathic arthritis (JIA). Our study is aimed to evaluate the possible difference in arthritis course depending on uveitis presence in patients with JIA, treated with biologics.
From our database of patients with JIA treated with biologics, we extracted patients to whom the first agent was administrated with or without MTX. The exclusion criteria included treatment with current systemic corticosteroids, infliximab, rituximab, observation period <3 years, and no missing data. After selection, 175 patients were eligible for analysis. We evaluated clinically significant flare with joint involvement (which required change of biologic or non-biologic DMARD) and time to flare. We compared two groups: (i) patients with uveitis (
There was no difference in gender distribution and achievement of arthritis remission between groups. Patients in the non-uveitis group predominantly received etanercept (64.3%). In the uveitis group, the most prescribed biologic agent was adalimumab (71.9%). The presence of uveitis increased the risk of JIA flare, OR = 3.8 (95% CI: 1.7; 8.7), and the cumulative probability of joint flare, RR = 4.5 (95% CI: 1.7; 12.1), 
The presence of uveitis proved to be a risk factor in JIA flare. Methotrexate can decrease the cumulative flare probability. Further trials are required."
"For infants exposed in utero to anti-tumour necrosis factor-α [TNF] medications, it is advised that live-attenuated vaccinations be postponed until the drug is cleared, but little is known about time to clearance. To minimize delays before live-attenuated vaccination can be given, we aimed to develop a pharmacokinetic model to predict time-to-clearance in infants exposed during pregnancy.
We prospectively followed in utero infliximab/adalimumab-exposed infants of mothers with inflammatory bowel disease across four countries between 2011 and 2018. Infants with a detectable anti-TNF umbilical-cord level and at least one other blood sample during the first year of life were included.
Overall, 107 infants were enrolled, including 166 blood samples from 71 infliximab-exposed infants and 77 samples from 36 adalimumab-exposed infants. Anti-TNF was detectable in 23% [n = 25] of infants at 6 months. At 12 months, adalimumab was not detected but 4% [n = 3] had detectable infliximab. A Bayesian forecasting method was developed using a one-compartment pharmacokinetic model. Model validation showed that the predicted clearing time was in accordance with the measured observations. A clinician-friendly online calculator was developed for calculating full anti-TNF clearing time: https://xiaozhu.shinyapps.io/antiTNFcalculator2/.
Almost one-quarter of infants born to mothers receiving anti-TNF during pregnancy have detectable anti-TNF at 6 months. To limit the time to live-attenuated vaccination in infants of mothers receiving anti-TNF during pregnancy, the results of a cord drug level at birth and a second sample ≥ 1 month thereafter can be used to estimate the time for full anti-TNF clearance in these children."
"This study aimed to evaluate the pharmacokinetics (PK), safety, and immunogenicity of the infliximab biosimilar CMAB008 compared to the reference product (Remicade) in healthy Chinese male subjects to provide the basis for the similarity evaluation of the 2 drugs. In this phase I randomized, double-blind, parallel-controlled, single-dose study, a total of 90 subjects were randomized 1:1 to receive CMAB008 or infliximab reference product with single intravenous injections (5 mg/kg). Blood samples were collected at designed time points for PK and immunogenicity assessment. If the 90%CI of the geometric mean ratio of area under the plasma concentration-time curve from 0 to the time of the last observation, maximum observed plasma concentration, area under the plasma concentration-time curve from 0 to infinity was completely within the range of 80% to 125%, the PK bioequivalence was established. Other PK parameters including time to maximum plasma concentration"
"Immunoglobulin A vasculitis (IgAV) is the most common childhood vasculitis affecting small vessels. No clear recommendations are available for severe pediatric cases, and until now, anti-TNF agents have had a limited role in IgAV management. In this report, we describe a pediatric case of severe IgAV, successfully treated with combined therapy including the anti-TNF, infliximab."
"Background and context An increasing number of drugs and blood products need to be delivered by intravenous infusion. In the Canterbury region of New Zealand, these have historically been delivered at a hospital site; however, some infusions could be delivered in a community setting without compromising patient safety. Assessment of problem The Canterbury health system has a key strategic objective of delivering care close to patients' homes. In 2018, Canterbury district health board (DHB) put out a tender for a community infusion service that would deliver blood products and other intravenous drugs with appropriate medical oversight. Strategies for improvement Following an interview and selection process, a fee-for-service contract was developed with a group of general practices with partial common ownership. It was nurse-led with medical oversight available. In July 2018, a Community Infusion Service (CIS) was started in two urban sites in Canterbury. It later expanded to two more sites, one urban and one rural. Results From July 2018 to May 2021, over 3000 infusions and blood transfusions were delivered by the CIS across seven infusion types (blood; immunoglobulin; infliximab; natalizumab; pamidronate; toculizumab; zoledronic acid). Both general practice and hospital services referred patients to the CIS. No major incidents were reported. Patients reported satisfaction with the service. Lessons Infusions and blood products can be delivered safely nearer to patients' homes in primary care in a New Zealand setting. Medical input was rarely required; however, the transition was resource-intensive; it required both overall process and criteria negotiations, as well as individual patient discussions. In its initial stages, the CIS did not have adequate clinical governance and operational support, which affected the speed and scale of its development."
"Interleukin-8 (CXCL8) produced in the tumor microenvironment correlates with poor response to checkpoint inhibitors and is known to chemoattract and activate immunosuppressive myeloid leukocytes. In human cancer, IL8 mRNA levels correlate with IL1B and TNF transcripts. Both cytokines induced IL-8 functional expression from a broad variety of human cancer cell lines, primary colon carcinoma organoids, and fresh human tumor explants. Although IL8 is absent from the mouse genome, a similar murine axis in which TNFα and IL-1β upregulate CXCL1 and CXCL2 in tumor cells was revealed. Furthermore, intratumoral injection of TNFα and IL-1β induced IL-8 release from human malignant cells xenografted in immunodeficient mice. In all these cases, the clinically used TNFα blockers infliximab and etanercept or the IL-1β inhibitor anakinra was able to interfere with this pathogenic cytokine loop. Finally, in paired plasma samples of patients with cancer undergoing TNFα blockade with infliximab in a clinical trial, reductions of circulating IL-8 were substantiated.
IL-8 attracts immunosuppressive protumor myeloid cells to the tumor microenvironment, and IL-8 levels correlate with poor response to checkpoint inhibitors. TNFα and IL-1β are identified as major inducers of IL-8 expression on malignant cells across cancer types and models in a manner that is druggable with clinically available neutralizing agents. This article is highlighted in the In This Issue feature, p. 2007."
"During illness, adaptations of the hypothalamic-pituitary-thyroid axis reduce energy expenditure, protein catabolism and modulate immune responses to promote survival. Lower serum free triiodothyronine-to-thyroxine (fT3/fT4) ratio has been linked to non-response to treatment in a range of diseases, including in biologic-treated patients with inflammatory bowel disease.
To assess whether baseline serum fT3/fT4 ratio predicted primary non-response (PNR) and non-remission to infliximab and adalimumab in patients with Crohn's disease METHODS: Thyroid function tests were undertaken in stored serum from biologic-naïve adult patients with active luminal Crohn's disease immediately prior to treatment with infliximab (427 originator; 122 biosimilar) or adalimumab (448) in the Personalised Anti-TNF Therapy in Crohn's Disease study (PANTS).
Baseline median [IQR] fT3/fT4 ratios were lower in women than men (0.30 [0.27-0.34] vs 0.32 [0.28-0.36], p < 0.001), in patients with more severe inflammatory disease, and in patients receiving corticosteroids (0.28 [0.25-0.33] vs. 0.32 [0.29-0.36], p < 0.001). Multivariable logistic regression analysis demonstrated that fT3/fT4 ratio was independently associated with PNR at week 14 (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.31-0.85, p = 0.009), but not non-remission or changes in faecal calprotectin concentrations at week 54. The optimal threshold to determine PNR was 0.31 (area under the curve 0.57 [95% CI 0.54-0.61], sensitivity 0.62 [95% CI 0.41-0.74], and specificity 0.53 [95% CI 0.42-0.73]).
Lower baseline serum fT3/fT4 ratio was associated with female sex, corticosteroid use and disease activity. It predicted PNR to anti-TNF treatment at week 14, but not non-remission at week 54."
"Despite an effective vaccine, hepatitis B remains a major global health problem due to its significant morbidity and mortality. Vaccination in immunosuppressed patients such as those treated for an inflammatory bowel disease (IBD) can be less effective. This case describes an uncommon original diagnosis of an acute hepatitis B infection occurring in a vaccinated but immunocompromised IBD patient under long-term infliximab treatment. A low anti-HBs titer and the presence of HBsAg escape mutations are possible hypotheses to explain this unexpected infection.
A 28-year-old Caucasian male, regularly followed-up for a Crohn's disease treated by infliximab, was regularly screened for sexually transmissible infections because of at-risk behaviors. Despite a correct immunization scheme against hepatitis B virus (HBV), an active HBV infection was diagnosed during one of those screenings. Retrospective testing of a sample collected 6 months earlier was in favor of an evolution from an acute hepatitis B toward a chronic hepatitis B. The patient has always had a low anti-HBs antibody levels (near the threshold of 10 IU/L) possibly explaining his infection. In addition, HBV sequencing revealed a genotype A2 HBV strain, carrying the sD144A substitution on the S protein, known as a potential immune escape variant. Dual therapy combining tenofovir disoproxil fumarate and emtricitabine, active against HBV but also efficient as an HIV pre-exposure prophylaxis, was initiated. Ten months after treatment initiation, all surrogate biochemical and virological endpoints for HBV functional cure were achieved. Treatment and periodical monitoring are being maintained.
Emphasis should be placed on HBV screening, vaccination and regular monitoring of patients under long-term immunosuppressive therapy, particularly those with at-risk behaviors."
"Nearly one-third of patients with inflammatory bowel disease (IBD) do not achieve remission despite our best therapies. When this happens, it is critical to understand the reason for treatment failure. Once nonresponse is confirmed, these patients should be referred to an IBD centre for multidisciplinary care. This review will discuss the remaining treatment options, including escalation of biologics to unlicensed doses, combination biologics, nonvalidated therapies and surgical options. It will additionally provide updates in the management of acute severe ulcerative colitis (ASUC).
There is an increasing interest in combination biologics to treat refractory IBD, although data supporting its safety and effectiveness are limited. The use of hyperbaric oxygen, mesenchymal stem cell therapy and dietary interventions also show early promise in this area. Studies have additionally focused on personalized therapy to identify aggressive phenotypes and predict treatment response in these challenging patients. In ASUC, infliximab and cyclosporine remain mainstays of treatment, and tofacitinib shows promise as a salvage therapy.
Refractory IBD is common, yet large knowledge gaps remain. Recent and ongoing studies have focused on medical, surgical and dietary approaches with mixed success. Larger prospective studies are desperately needed to address this complex issue."
"Over the last decade, there has been rapid expansion of the therapeutic armamentarium, and evolution of treatment strategies, for the management of inflammatory bowel diseases (IBDs). Consequently, there is an increasing need for head-to-head or comparative efficacy trials to inform optimal positioning of therapies, and pragmatic trials comparing treatment strategies to inform treatment approach. In this review, we will discuss the current status and future of comparative efficacy clinical trials in IBD.
Pivotal phase IIIB superiority clinical trials have demonstrated superiority of vedolizumab over adalimumab for achieving clinical remission in patients with moderate-to-severe ulcerative colitis (VARSITY) and failed to demonstrate superiority of ustekinumab over adalimumab in patients with moderate-to-severe Crohn's disease (SEAVUE). Noninferiority clinical trials of biosimilars have confirmed absence of meaningful differences in safety and efficacy of biosimilar infliximab over originator infliximab, as initial therapy or switching stable patients during maintenance. Network meta-analyses, indirect treatment comparison using patient-level data from placebo-controlled trials and real-world observational studies have inform comparative effectiveness and safety of different therapies for management of IBD.
Head-to-head clinical trials are critically important to advance the field of IBD. Comparative efficacy trials are slow and expensive to conduct, may not be broadly generalizable, and are not powered for safety events or other relevant outcomes. Alternative approaches to comparative effectiveness such as network meta-analysis and well designed real-world observational studies are able to bridge gaps in clinical practice."
"Tumor necrosis factor-alpha inhibitors (TNF-ai) are becoming increasingly common to use among patients with skin disease. To safely take these medications, it is recommended to monitor laboratory values routinely; however, the utility of this practice and the risk-benefit of frequent laboratory monitoring has not been explored fully in patients with skin disease. The purpose of this study was to evaluate the necessity of routine laboratory monitoring in patients taking a TNF-ai with a dermatological disease.
Retrospective chart review evaluated laboratory abnormalities (complete blood counts and liver function tests) in adult patients who took a TNF-ai for a dermatologic disease at The University of Kansas Hospital.
There were 27 patients included for a total of 45 entries. The most common skin disease was hidradenitis suppurativa (23/45) and infliximab (22/45) was most the commonly used medication. Of the 45 entries, there were only seven patients that developed abnormal monitoring laboratory values related to initiation of TNF-ai. These abnormalities were transient and most frequently occurred after 12 months, with 2 of the 45 resulting in no discontinuation or dose reduction of TNF-ai. One patient discontinued medication due to anemia that did not improve after medication withdrawal.
Laboratory abnormalities due to TNF-ai were infrequent and when they did occur were transient and mild. The study was limited by the small sample size of patients, and larger prospective studies are needed to evaluate these findings fully. However, dermatologists may be able to employ less frequent laboratory monitoring safely for patients on TNF-ai."
"Tumor necrosis factor (TNF) inhibitors increase the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA). This study compared the incidence of TB after treatment with TNF inhibitors and tocilizumab in patients with RA, separately in those who were treated for latent tuberculosis infection (LTBI) and those without evidence of LTBI.
This study included patients with RA who initiated TNF inhibitors and tocilizumab between December 2013 and August 2018. Patient data were collected from the nationwide database of the Health Insurance Review and Assessment service in South Korea. The incidence of TB was compared among different biologic drugs in patients with or without LTBI treatment.
Of 4736 patients, 1168 were treated for LTBI and 48 developed TB (554.9 per 100,000 person-years). When compared based on etanercept, infliximab showed a higher risk of TB (adjusted incidence rate ratio 2.71, 95% confidence interval 1.05-7.01), especially in patients without evidence of LTBI. Other TNF inhibitors and tocilizumab showed a comparable incidence of TB, regardless of treatment for LTBI. There was no significant difference in TB incidence after biologic therapy between patients with and without LTBI treatment (627.9/100,000 vs. 529.5/100,000 person-years). In patients treated for LTBI, no differential risk of TB was observed among biologic drugs.
The incidence of TB was not significantly different among biologic drugs in the current era, except for infliximab in patients who were not treated for LTBI. Treatment of LTBI might alleviate the drug-specific risk of TB in patients with RA."
"Anti-tumour necrosis factor alpha (anti-TNF) agents are a highly effective treatment for inflammatory bowel disease (IBD). Skin lesions, including psoriasiform, eczematous and lupoid eruptions, may paradoxically result from anti-TNF use and cause significant morbidity leading to discontinuation of therapy. There are no consensus guidelines on the management of these lesions.
This systematic review considers the existing evidence regarding cutaneous complications of anti-TNF therapy in IBD and the development of an algorithm for management.
A systematic review was performed by searching Medline (Pubmed) and Embase for articles published from inception to January 2021. The following search terms were used 'anti-tumour necrosis factor alpha', 'infliximab', 'adalimumab', 'certolizumab', 'golimumab', 'inflammatory bowel disease', 'Crohn disease', 'Ulcerative colitis', 'psoriasis', 'psoriasiform', 'dermatitis', 'lupus', 'skin lesion' and 'skin rash'. Reference lists of relevant studies were reviewed to identify additional suitable studies.
Thirty-four studies were included in the review. Eczema can generally be managed with topical agents and the anti-TNF can be continued, while the development of lupus requires immediate cessation of the anti-TNF and consideration of alternative immunomodulators. Management of psoriasis and psoriasiform lesions may follow a step-wise algorithm where topical treatments will be trialled in less severe cases, with recourse to an alternative anti-TNF or a switch to an alternative class of biological agent.
Assessment of anti-TNF skin lesions should be performed in conjunction with a dermatologist and rheumatologist in complex cases. High-quality prospective studies are needed to clarify the validity of these algorithms in the future."
"The aim of this study was to analyze the therapeutic results of rheumatoid arthritis (RA) therapy with different biologic disease-modifying antirheumatic drugs (bDMARDs) and the first Janus-activated kinase (JAK) inhibitor in real-life clinical settings. This is a prospective, observational, longitudinal study at the largest rheumatology clinic in Bulgaria conducted during the period 2012-2020. One hundred seventy-four patients were followed up for a period of one year. Patients naïve to biological therapy were consecutively assigned on the available at the time bDMARDs (infliximab, etanercept, adalimumab, rituximab, golimumab, cetrolizumab, tocilizumab) or tofacitinib. We evaluated the disease activity score (DAS28-CRP), Health assessment questionnaires (HAQ) and short form 36 (SF-36) were applied at the initiation of biological therapy, after 6, and 12 months of follow-up. We analyze the changes in the two major subgroups of SF36-physical (MCS) and mental health (PCS). The age and gender distribution were similar between the groups on bDMARDs and tsDMARD. All observed indicators for disease control and QoL improve after the initiation of the biological or JAK inhibitor therapy. We also analyze the effect of therapies on DAS28-CRP, HAQ, SF-36 (PCS, MCS). Dispersion analysis for the effect of therapy measured through DAS28 between 1st and 3rd measurement shows a statically significant difference in between the average effect of therapies (p = 0.005). According to the average change in DAS28 between the first and third measurement the most effective is the golimumab (Median difference = 2.745), followed by rituximab (median = 2.305) and etanercept (median = 2.070). According to the average change in HAQ between first and third the most effective is tofacitinib (median 0.563), followed rituximab and infliximab (median 0.500 for both). Less effective in term of HAQ changes between the first and third measurement appears to be etanercept (median difference 0.250). All differences are statistically significant (p < 0.05). Regarding the changes in the QoL measured with SF-36 MCS and PCS there is no statistically significant differences in the average effect of different therapeutic agents. Tofacitinib is non-inferior in comparison to bDMARDs and improve both-disease activity and QoL in patients with RA."
"Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and co-morbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups."
"Few countries integrate patient-reported outcome measures (PROMs) in routine performance assessment and those that do focus on elective surgery. This study addresses the challenges of using PROMs to evaluate care in chronic conditions. We set out a modeling strategy to assess the extent to which changes over time in self-reported health status by patients with inflammatory chronic rheumatic disease are related to their biological drug therapy and rheumatology center primarily responsible for their care.
Using data from the Portuguese Register of Rheumatic Diseases, we assess health status using the Health Assessment Questionnaire-Disability Index for rheumatic patients receiving biological drugs between 2000 and 2017. We specify a fixed-effects model using the least squares dummy variables estimator.
Patients receiving infliximab or rituximab report lower health status than those on etanercept (the most common therapy) and patients in 4 of the 26 rheumatology centers report higher health status than those at other centers.
PROMs can be used for those with chronic conditions to provide the patient's perspective about the impact on their health status of the choice of drug therapy and care provider. Care for chronic patients might be improved if healthcare organizations monitor PROMs and engage in performance assessment initiatives on a routine basis."
"COVID-19 related multisystem inflammatory syndrome in children (MIS-C) can present with cardiovascular complications like shock, arrhythmias, pericardial effusion, and coronary artery dilatation. The majority of MIS-C associated coronary artery abnormalities are dilation or small aneurysms which are transient and resolve in a few weeks. We present here a case of a 3-month-old child who was noted to have giant aneurysms of her coronary arteries (LAD and RCA) 26 days after testing positive for COVID-19. She was treated with IVIG, infliximab, and glucocorticoids along with aspirin, clopidogrel, and enoxaparin. She did not show any signs of coronary ischemia or cardiac dysfunction but continued to have persistent giant coronary artery aneurysms involving the LAD (z-score ∼35) and RCA (z-score ∼30). This study emphasizes the importance of early detection and aggressive management of MIS-C to prevent potentially life-threatening consequences."
"Due to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD. Before evidence-based dosing can be proposed, insight into the PK has to be gained to optimize drug therapy for both mother and fetus. This systematic review aimed to describe the effect of pregnancy and IBD on the PK of drugs used for IBD. One aminosalicylate study, two thiopurine studies and twelve studies with biologicals were included. Most drugs within these groups presented data over multiple moments before, during and after pregnancy, except for mesalazine, ustekinumab and golimumab. The studies for mesalazine, ustekinumab and golimumab did not provide enough data to demonstrate an effect of pregnancy on concentration and PK parameters. Therefore, no evidence-based dosing advice was given. The 6-thioguanine nucleotide levels decreased during pregnancy to 61% compared to pre-pregnancy levels. The potentially toxic metabolite 6-methylmercaptopurine (6-MMP) increased to maximal 209% of the pre-pregnancy levels. Although the PK of the thiopurines changed throughout pregnancy, no evidence-based dosing advice was provided. One study suggested that caution should be exercised when the thiopurine dose is adjusted, due to shunting 6-MMP levels. For the biologicals, infliximab levels increased, adalimumab stayed relatively stable and vedolizumab levels tended to decrease during pregnancy. Although the PK of the biologicals changed throughout pregnancy, no evidence-based dosing advice for biologicals was provided. Other drugs retrieved from the literature search were mesalazine, ustekinumab and golimumab. We conclude that limited studies have been performed on PK parameters during pregnancy for drugs used in IBD. Therefore, more extensive research to determine the values of PK parameters is warranted. After gathering the PK data, evidence-based dosing regimens can be developed."
"The use of infliximab has completely changed the therapeutic landscape in inflammatory bowel disease. However, despite its proven efficacy to induce and maintain clinical remission, increasing evidence suggests that treatment failure may be associated with inadequate drug blood concentrations. The introduction of biosensors based on different nanostructured materials for the rapid quantification of drugs has been proposed for therapeutic drug monitoring. This study aimed to apply atomic force microscopy (AFM)-based nanoassay for the measurement of infliximab concentration in serum samples of healthy donors and pediatric IBD patients. This assay measured the height signal variation of a nanostructured gold surface covered with a self-assembled monolayer of alkanethiols. Inside this monolayer, we embedded the DNA conjugated with a tumor necrosis factor able to recognize the drug. The system was initially fine-tuned by testing known infliximab concentrations (0, 20, 30, 40, and 50 nM) in buffer and then spiking the same concentrations of infliximab into the sera of healthy donors, followed by testing pediatric IBD patients. A good correlation between height variation and drug concentration was found in the buffer in both healthy donors and pediatric IBD patients ("
"Substantial inter-and intra-individual variability of Infliximab (IFX) pharmacokinetics necessitates tailored dosing approaches. Here, we evaluated the performances of a Model Informed Precision Dosing (MIPD) Tool in forecasting trough Infliximab (IFX) levels in association with disease status and circulating TNF-α in patients with Inflammatory Bowel Diseases (IBD).
Consented patients undergoing every 8-week maintenance therapy with IFX were enrolled. Midcycle specimens were collected, IFX, antibodies to IFX, albumin were determined and analyzed with weight using nonlinear mixed effect models coupled with Bayesian data assimilation to forecast trough levels. Accuracy of forecasted as compared to observed trough IFX levels were evaluated using Demings's regression. Association between IFX levels, CRP-based clinical remission and TNF-α levels were analyzed using logistic regression and linear mixed effect models.
In 41 patients receiving IFX (median dose = 5.3 mg/Kg), median IFX levels decreased from 13.0 to 3.9 µg/mL from mid to end of cycle time points, respectively. Midcycle IFX levels forecasted trough with Deming's slope = 0.90 and R2 = 0.87. Observed end cycle and forecasted trough levels above 5 µg/mL associated with CRP-based clinical remission (OR = 7.2 CI95%: 1.7-30.2; OR = 21.0 CI95%: 3.4-127.9, respectively) (
These data establish the value of our MIPD tool in forecasting trough IFX levels in patients with IBD. Serum TNF-α and CRP are reflective of inflammatory burden which impacts exposure."
"The safety of bevacizumab in combination with chemotherapy in patients with inflammatory bowel disease (IBD) and digestive and nondigestive cancers is poorly documented.
We retrospectively evaluated patient records of all adult cancer patients with IBD at our institution from April 2007 to May 2016 with an update in November 2019.
Twenty-seven patients with a history of IBD (Crohn's disease, 
Bevacizumab combined with chemotherapy is safe in cancer patients with moderately active or quiescent IBD."
"Immune checkpoint inhibitor treatment has shown revolutionary therapeutic effects in various carcinomas. However, immune-related adverse events (irAE) following this treatment can sometimes lead to treatment discontinuation. One such frequently encountered adverse event is immune-related colitis (irAE colitis). Corticosteroids (CS) are the first-line treatment for irAE colitis, but we often encounter CS-refractory or -resistant cases. The application of multiple biologics has been proposed as a therapy to be administered after CS treatment; however, the efficacy and safety of biologics for patients with irAE colitis who do not respond to CS have not been established. This review summarizes the treatment regimens available for irAE colitis, focusing on the mechanism of action of corticosteroids, infliximab, vedolizumab, and other drugs."
"The treatment guidelines for hidradenitis suppurativa (HS) vary among different countries, and several biologics and small molecule inhibitors have been tested for treating moderate-to-severe HS over the past few years. However, treatment guidelines for HS vary among different countries.
A systematic review and meta-analysis was performed to exam the efficacy and serious adverse events (SAEs) of biologics and small-molecule inhibitors in treating moderate-to-severe HS. Binary outcomes were presented as risk ratio (RR) with 95% confidence interval (CI).
We included 16 RCTs with a total of 2076 participants on nine biologics and three small-molecule inhibitors for treating moderate-to-severe HS, including adalimumab, anakinra, apremilast, avacopan, bimekizumab, CJM112, etanercept, guselkumab, IFX-1, INCB054707, infliximab, and MABp1. The meta-analysis revealed only adalimumab (RR 1.77, 95% CI, 1.44-2.17) and bimekizumab (RR 2.25, 95% CI, 1.03-4.92) achieved significant improvement on hidradenitis suppurativa clinical response (HiSCR), and adalimumab was superior to placebo in achieving dermatology life quality index (DLQI) 0/1 (RR 3.97; 95% CI, 1.70-9.28). No increase in SAEs was found for all included active treatments when compared with placebo.
Adalimumab and bimekizumab are the only two biologics effective in achieving HiSCR with acceptable safety profile, whereas adalimumab is the only biologic effective in achieving DLQI 0/1."
"To examine the prevalence rates of biosimilar discontinuation and switchback to the originator tumor necrosis factor alpha (TNF) inhibitors following non-medical switch (NMS) in patients.
Real-world studies reporting biosimilar discontinuation and switchback rates following NMS published between January 2012 and August 2018 were identified through a systematic literature review. A meta-analysis estimated the annualized discontinuation and switchback rates. A subsequent meta-analysis assessed annualized incremental discontinuation rate among studies reporting both discontinuation rates in patients who underwent an NMS (switchers) and patients who remained on originators (non-switchers).
A total of 66 publications were identified: 31 in gastroenterology, 32 in rheumatology, and 3 in both. Half of the studies reported switchback rates; only 9 studies reported discontinuation rates for both switchers and non-switchers. Across studies, the mean/range sample size of the NMS patient population was 136/9-1641; mean/range follow-up was 10/3-24 months. Annualized biosimilar discontinuation rate was 21% (95% confidence interval [CI] 18%, 25%). Switchback rate was 14% (95% CI 10%, 17%) among all NMS patients and 62% (95% CI 44%, 80%) among discontinuers. The mean/range sample size of switchers and non-switchers was 344/89-1621 and 768/19-2870, respectively; mean/range follow-up was 11/6-18 and 12/6-8 months, respectively. Annualized incremental biosimilar discontinuation rate was 18% (95% CI 4%, 31%).
Biosimilar discontinuation was found to be prevalent among patients who underwent an NMS from an originator TNF inhibitor to its biosimilar(s) in the real world. In addition, switchback to the originator TNF inhibitors was common following biosimilar discontinuation. Careful consideration is necessary when switching patients already on an originator TNF inhibitor to its biosimilar(s). Main limitations included the heterogeneity of the studies and the limited comparability of the data."
"Patients enrolled in randomised controlled trials (RCTs) may differ from the target population due to restricted eligibility criteria.
To compare treatment response to biologics in routine practice for children with inflammatory bowel diseases (IBD) who would and would not have been eligible for enrolment in the regulatory RCT of the same drug.
We enrolled children with IBD who initiated adalimumab, infliximab, vedolizumab or ustekinumab. The eligibility criteria as defined in the RCT of the corresponding biologic were applied to each patient. The primary outcome was 12-month steroid-free remission (SFR) without switching biologics or undergoing surgery.
We screened 289 children (198 [68%] with Crohn's disease [CD], 91 [32%] with ulcerative colitis [UC]) with 326 initiations of biologics. Only 62 of 164 (38%) children with moderate-to-severe disease would have been eligible for inclusion in the original RCTs. The SFR rate was higher in the eligible children (51%) than in the ineligible children (31%; OR 2.3 [95%CI 1.2-4.5]; p = 0.01). The main exclusion criterion was prohibited previous therapies (47%). Ineligible CD patients were older, more often had a family history of IBD and had higher levels of CRP than eligible children; in UC there were no differences between the groups.
Most children with IBD who initiate biologics would not have been eligible to be included in the corresponding regulatory RCTs. The outcomes of ineligible patients were worse than for eligible patients. Results from RCTs should be interpreted with caution when applied to clinical practice."
"Objectives This study aims to describe the clinical, etiological, and treatment features of noninfectious uveitis in Jordanian children in a single center. Methods A retrospective, observational analysis of medical records of pediatric patients who were diagnosed with noninfectious uveitis from 2015 to 2020 at pediatric rheumatology and ophthalmology clinics at Queen Rania Children's Hospital, Amman, Jordan, was conducted. All patients were below 14 years of age at diagnosis. The collected data included age at diagnosis, anatomical location of uveitis, laterality, associated systemic disease, and used medications. Results Overall, 96 patients were included in this cohort (41 males and 55 females), with a mean age at diagnosis of 8.4±2.4 years. Anterior uveitis (44.8%) was the commonest anatomical location. Based on laterality, bilateral uveitis was reported in 59.3% of all patients. Idiopathic uveitis (46.9%) and juvenile idiopathic arthritis-associated uveitis (JIAU) (35.5%) were the most common diagnoses. Of the children with idiopathic uveitis, 47% had panuveitis, while 61.7% of the children with JIAU had chronic anterior uveitis. Posterior synechiae were the most common complication (12.5%). Patients with refractory uveitis received infliximab (29.1%) and adalimumab (4.1%). Conclusion To the best of our knowledge, this is the first report on noninfectious uveitis in Jordanian children. Compared with other regional and international published reports, JIAU and idiopathic uveitis were the most common diagnoses. To obtain more details on noninfectious uveitis characteristics, a population-based rather than a single-center study is needed in Jordan."
"Dose-intensified rescue therapy with infliximab for hospitalized patients with ulcerative colitis has become increasingly popular in recent years. However, there is ongoing debate about both the efficacy of these regimens to reduce the rate of colectomy and the associated risks of increased infliximab exposure.
The purpose of this study was to compare the colectomy and postoperative complication rates in hospitalized patients with severe ulcerative colitis receiving standard infliximab induction therapy (3 doses of 5 mg/kg at weeks 0, 2, and 6) and dose-intensified regimens including a higher weight-based dosing or more rapid interval.
This was a retrospective cohort study.
This study was conducted at an academic tertiary care hospital.
A total of 145 adult patients received inpatient rescue infliximab therapy for the treatment of ulcerative colitis between 2008 and 2020.
The primary outcome was colectomy rate within 3 months of rescue therapy. Secondary outcomes include mid-term colectomy rates, as well as perioperative complications in patients receiving colectomy within 3 months of rescue infliximab initiation.
The proportion of dose-intensified regimens increased over time. Unadjusted 3-month colectomy rates were 14% in patients who received standard rescue infliximab dosing, 16% in patients given a single dose-escalated dose, and 24% in patients given multiple inpatient dose-escalated doses. These rates were not statistically significantly different. Of the patients requiring colectomy within 3 months of infliximab rescue, those who received multiple inpatient doses of dose-escalated therapy had a higher percentage of colectomy during the initial hospitalization but a lower rate of perioperative complications.
This study was limited by the use of retrospective data and the limited power to account for the heterogeneity of disease.
No significant difference was found in colectomy rates between patients receiving standard or dose-intensified regimens. However, dose-intensified regimens, including multiple inpatient doses given to patients with more severe disease, were not associated with a greater risk of perioperative complications. See Video Abstract at http://links.lww.com/DCR/B864 .
ANTECEDENTES:La terapia de rescate de dosis intensificada con infliximab para pacientes hospitalizados con colitis ulcerosa se ha vuelto cada vez más popular en los últimos años. Sin embargo, existe un debate en curso sobre la eficacia de estos regímenes para reducir la tasa de colectomía y los riesgos asociados a una mayor exposición al infliximab.OBJETIVO:El propósito de este estudio fue comparar las tasas de colectomía y complicaciones posoperatorias en pacientes hospitalizados con colitis ulcerosa grave que recibieron terapia estándar de inducción de infliximab (3 dosis de 5 mg/kg en las semanas 0, 2, 6) y regímenes de dosis intensificada que incluyen una dosificación más alta basada en el peso o intervalo más rápido.DISEÑO:Fue un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un hospital académico de tercer nivel.PACIENTES:Un total de 145 pacientes adultos que recibieron terapia de rescate con infliximab para el tratamiento de la colitis ulcerosa entre 2008 y 2020.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado principal fue la tasa de colectomía dentro de los 3 meses posteriores a la terapia de rescate. Los resultados secundarios incluyen tasas de colectomía a mediano plazo, así como las complicaciones perioperatorias en pacientes que reciben colectomía dentro de los 3 meses posteriores al inicio de infliximab de rescate.RESULTADOS:La proporción de regímenes de dosis intensificada aumentó con el tiempo. Las tasas de colectomía de 3 meses no ajustadas fueron del 14% en los pacientes que recibieron dosis estándar de infliximab de rescate, del 16% en los pacientes que recibieron una dosis única escalonada y del 24% en los pacientes que recibieron múltiples dosis hospitalarias escalonadas. Estas tasas no fueron estadísticamente significativas. De los pacientes que requirieron colectomía dentro de los 3 meses posteriores al rescate de infliximab, aquellos que recibieron terapia de múltiples dosis hospitalarias escalonadas tuvieron un mayor porcentaje de colectomía durante la hospitalización inicial pero una menor tasa de complicaciones perioperatorias.LIMITACIONES:Datos retrospectivos y poder limitado para explicar la heterogeneidad de la enfermedad.CONCLUSIONES:No se encontraron diferencias significativas en las tasas de colectomía entre los pacientes que recibieron regímenes estándar o de dosis intensificada. Sin embargo, los regímenes de dosis intensificadas, incluidas múltiples dosis hospitalarias administradas a pacientes con enfermedad más grave, no se asociaron con un mayor riesgo de complicaciones perioperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B864 . (Traducción-Dr. Ingrid Melo )."
"Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, primarily drug-induced reactions of skin and mucosa. Since they differ in the extent of skin detachment but not in etiology, they are grouped together as epidermal necrolysis (EN). Due to nationwide registration, representative data are available at the German Center for the Documentation of Severe Skin Reactions (dZh). Here, an increasing number of case notifications in the context with new immuno-oncologic drugs, kinase inhibitors and biologics have been observed.
Of 4,150 cases notifications between January 2003 and February 2019, 102 cases with exposure to these drug groups underwent systematic analysis, validation and causality assessment.
Two cases of EN to vemurafenib were confirmed and one case to afatinib and pembrolizumab, respectively. In 14 EN cases other drugs - predominantly allopurinol or cotrimoxazole - were the causative agent. Fourteen cases were EN-like reactions: six bullous lichenoid drug eruptions (DE) to pembrolizumab (2), obinutuzumab, nivolumab, rituximab, infliximab/nivolumab, and eight multiforme-like DE to rituximab (2), adalimumab, ramucirumab, bevacizumab, vemurafenib, sorafenib (2). Lichenoid DE were differentiated from EN through histopathology and by the protracted course of EN, multiforme-like DE by variable skin manifestations with only sparse epidermolysis or mucosal involvement.
A correct diagnosis is highly relevant in terms of prognosis and use of these drugs in malignoma treatment. Re-exposure is contraindicated in EN, but possible in other DE after rigorous risk-benefit evaluation."
"Infliximab dosage de-escalation without prior knowledge of drug concentrations may put patients at risk for underexposure and trigger the loss of response. A single-model approach for model-informed precision dosing during infliximab maintenance therapy has proven its clinical benefit in patients with inflammatory bowel diseases. We evaluated the predictive performances of two multi-model approaches, a model selection algorithm and a model averaging algorithm, using 18 published population pharmacokinetic models of infliximab for guiding dosage de-escalation. Data of 54 patients with Crohn's disease and ulcerative colitis who underwent infliximab dosage de-escalation after an earlier escalation were used. A priori prediction (based solely on covariate data) and maximum a posteriori prediction (based on covariate data and trough concentrations) were compared using accuracy and precision metrics and the classification accuracy at the trough concentration target of 5.0 mg/L. A priori prediction was inaccurate and imprecise, with the lowest classification accuracies irrespective of the approach (median 59%, interquartile range 59%-63%). Using the maximum a posteriori prediction, the model averaging algorithm had systematically better predictive performance than the model selection algorithm or the single-model approach with any model, regardless of the number of concentration data. Only a single trough concentration (preferably at the point of care) sufficed for accurate and precise prediction. Predictive performance of both single- and multi-model approaches was robust to the lack of covariate data. Model averaging using four models demonstrated similar predictive performance with a five-fold shorter computation time. This model averaging algorithm was implemented in the TDMx software tool to guide infliximab dosage de-escalation in the forthcoming prospective MODIFI study (NCT04982172)."
The infliximab biosimilar CT-P13 is used for the treatment of ulcerative colitis. We report for the first time the serum drug levels and long-term health status of the child of a patient treated with CT-P13 throughout her pregnancy.
"Inflammatory bowel disease (IBD) refers to disorders involving chronic inflammation of the gastrointestinal tract. Well-established treatments for IBD have not yet to be suggested. To address this gap, we investigated the effects of co-administration of Lactobacillus gasseri (L. gasseri) KBL697 and infliximab (IFX), the first approved tumor necrosis factor (TNF)-alpha inhibitor, on the dextran sodium sulfate-induced colitis mouse model. 2 × 10"
Pregnancy is a complex biological process. The establishment and maintenance of foetal-maternal interface are pivotal events. Decidual immune cells and inflammatory cytokines play indispensable roles in the foetal-maternal interface. The disfunction of decidual immune cells leads to adverse pregnancy outcome. Tumour necrosis factor (TNF)-
"Fibromyalgia is a clinical condition that affects 1% to 5% of the population. No proper therapy has been currently found. It has been described that inflammation plays a central role in the nerve sensitizations that characterize the pathology.
This paper aimed to evaluate the efficacy of etanercept and infliximab in the management of pain sensitization. Fibromyalgia was induced by three injections once a day of reserpine at the dose of 1 mg/kg. Etanercept (3 mg/kg) and infliximab (10 mg/kg) were administered the day after the last reserpine injection and then 5 days after that. Behavioral analyses were conducted once a week, and molecular investigations were performed at the end of the experiment.
Our data confirmed the major effect of infliximab administration as compared to etanercept: infliximab administration strongly reduced pain sensitization in thermal hyperalgesia and mechanical allodynia. From the molecular point of view, infliximab reduced the activation of microglia and astrocytes and the expression of the purinergic P2X7 receptor ubiquitously expressed on glia and neurons. Downstream of the P2X7 receptor, infliximab also reduced p38-MAPK overexpression induced by the reserpine administration.
Etanercept and infliximab treatment caused a significant reduction in pain. In particular, rats that received infliximab showed less pain sensitization. Moreover, infliximab reduced the activation of microglia and astrocytes, reducing the expression of the purinergic receptor P2X7 and p38-MAPK pathway."
"Our study aims at providing evidence on patterns of use of biologic drugs for psoriasis in Tuscany, Italy. We conducted a drug-utilization study based on administrative databanks of Tuscany (EUPAS45365) from 2011 to 2019. We selected new users of etanercept, infliximab, adalimumab, ustekinumab, or secukinumab between 1 January 2011 and 31 December 2016. We considered subjects with psoriasis and followed subjects until the end of the study period (three years after the first dispensation of biologic drug for psoriasis) or the patient's death, whichever came first. We censored subjects for pregnancy or neoplasia. For each subject, we defined the state as the weekly coverage of one of the biologic drugs of interest. We then defined the switch as the change from a state to another one. A total of 7062 subjects with a first dispensation of a PSObio drug in the inclusion period was identified, and 1839 (52.9% female, 51.6 mean age) patients were included in the analysis. Among new users of adalimumab (N = 770, 41.9%), one third showed a continuous behaviour whereas the others moved to etanercept and ustekinumab. New users of etanercept (N = 758, 41.2%), had the highest proportion of switchers, with adalimumab most often being the second choice. New users of infliximab (N = 159, 8.6%) experienced the highest proportion of treatment discontinuation. The present study suggests that the majority of patients treated with PSObio drugs do not switch from one active ingredient to another. However, patients who started biological therapy with etanercept had the highest frequency of switching to other PSObio drugs, whereas those who started with secukinumab or ustekinumab had the lowest."
"Sarcoidosis is a systemic autoimmune disease that is associated with the development of non-caseating granulomas. The disease especially affects the lymph nodes, lungs, skin and eyes. It is an infrequent but not rare disease, especially in northern Europe, the United States and India. Sarcoidosis affects more women and is diagnosed between the ages of 30 and 50. Etiopathogenically, it is closely linked to environmental factors, especially occupational exposures. Clinically, it stands out for a wide variety of presentation phenotypes (casual diagnosis, involvement of a single organ or systemic presentation). The diagnosis of sarcoidosis is complex and requires the integration of clinical, analytical, radiological, and histolopathogical data carried out by multidisciplinary clinical units. The evolution of the disease is variable, as is the indication for systemic treatment, based on the use of corticosteroids as first-line option, the use of immunosuppressants as second-line therapy, and anti-TNF agents in severe and/or refractory cases."
"Paediatric inflammatory bowel disease [IBD] is characterized by altered immunological and metabolic pathways. Metabolomics may therefore increase pathophysiological understanding and could develop into characterization of biomarkers for diagnosis and IBD treatment response. However, no uniform metabolomic profiles have been identified to date. This systematic review aimed to identify faecal metabolomic signatures in paediatric IBD vs controls, and to describe metabolites associated with disease activity and treatment response.
A literature search was performed in Embase, Medline, Web of Science and Cochrane Library. Studies assessing faecal metabolomics in paediatric patients < 18 years with IBD [de novo, active, inactive] with comparative groups [IBD vs non-IBD; responders vs non-responders] were included. The quality of included studies was assessed according to the Newcastle-Ottawa Scale.
Nineteen studies were included [540 patients with IBD, 386 controls], assessing faecal short-chain fatty acids [SCFA] [five studies], amino acids [AA] [ten studies], bile acids [BA] [eight studies] and other metabolites [nine studies] using various methodologies. Significantly increased levels of AA [particularly phenylalanine], primary BA and lower levels of secondary BA were described in paediatric IBD compared to controls. Faecal SCFA results varied across studies. Additionally, responders and non-responders to exclusive enteral nutrition and infliximab showed differences in baseline faecal metabolites [based on BA, AA].
This systematic review provides evidence for distinct faecal metabolomic profiles in paediatric IBD. However, results varied across studies, possibly due to differences in study design and applied analytical techniques. Faecal metabolomics could provide more insight into host-microbial interactions in IBD, but further studies with standardized methodologies and reporting are needed."
"There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients.
We conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis.
We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications.
Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab."
"To highlight the safety and efficacy of Tumor Necrosis Factor inhibitors (anti-TNF) in inflammatory choroidal neovascularization (CNV) in the pediatric population.
Retrospective case series.
Three patients, < 16 years old with uveitic inflammatory CNV.
Patients received systemic steroids, methotrexate (MTX), intravitreal (IVT) injections of bevacizumab, and anti-TNF (infliximab or adalimumab) in case of refractory leakage.
Five eyes of three pediatric patients (mean age 6 years old) presenting with CNV and put on anti-TNF were followed up for a minimum of 32 months. Four out of five eyes had improved vision, reduced fluid on clinical exam and macular spectral-domain optical coherence tomography (SD-OCT), and cessation of leakage on fundus fluorescein angiography (FFA) after introduction of anti-TNF agents. Two patients developed minor psoriasis treated topically.
Anti-TNF agents showed efficacy and safety in a sustainable leakage control of inflammatory pediatric CNV along with improvement in vision."
"The first subcutaneous (SC) formulation of infliximab CT-P13 has been authorized for the treatment of rheumatoid arthritis (RA) in Europe in 2019. Later, in 2020, approved indications were extended also to ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn's disease (CD) and ulcerative colitis (UC). The present review provides summary of the key features of SC infliximab, with particular focus on pharmacokinetic profile, clinical development program in comparison with the intravenous (IV) formulation, and the latest evidence in the literature. We conclude that SC infliximab represents a new and promising approach in the treatment of patients with RA, offering an optimized clinical profile and a more practical option in comparison to the IV formulation. Nevertheless, SC formulation can improve the use of national health systems resources (e.g., through the time of healthcare workers not having to supervise infusions) and facilitate social distancing measures during the COVID-19 pandemic, as the patient can self-inject the medicine at home without going to the hospital. The limitations of the SC infliximab are mainly due to the limited experience of use in clinical practice and the absence of long-term drug retention data."
"To explore the predictors of mucosal healing (MH) for short- and long-term after exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD) patients.
A retrospective analysis was performed for newly diagnosed active CD patients admitted to our center from January 2017 to 30 December 2020, who were treated with EEN for induction therapy with a minimum of 12 months of follow-up post-EEN. According to the simple endoscopic score for CD (SES-CD), at 1-year post-EEN, 17 patients with an SES-CD < 3 were classified into the sustained MH group (sMH), and 33 patients with an SES-CD ≥ 3 were classified into the sustained non-MH group (sNMH). Statistical methods were used to compare the differences between the two groups and explore the predictors of MH at the end of EEN and 1-year post-EEN.
The SES-CD in the sMH group was lower than that in the sNMH group both at baseline and the end of EEN [sMH vs. sNMH: 8.7 ± 1.2 vs. 16.2 ± 1.0, respectively, 
The SES-CD could predict both short- and long-term MH for EEN. Patients with an SES-CD < 11.5 had a high probability of reaching MH by EEN-inducing therapy and maintaining sustained MH at 1-year post-EEN. Patients with an SES-CD greater than 11.5 at baseline should be treated more aggressively with biologics."
"The increasing incidence of inflammatory bowel disease (IBD) globally has redirected the healthcare system's focus towards safe and affordable pharmacological interventions. The inception of anti-tumor necrosis factor-α (TNF-α) had resulted in a trend shift from surgical interventions. However, as the patents of approved anti-TNF-α drugs expire, biological copies of the many approved products are in the pipeline. The most commonly used biosimilar for IBD has been infliximab, followed by Adalimumab biosimilars which have been approved in major countries across the world. Although biosimilars are approved on the basis of similarity of their reference product, the lack of real-world evidence of its safety in ulcerative colitis and Crohn's disease patients has contributed to physicians' hesitancy. However, biosimilars are expected to reduce treatment costs and provide economic benefits."
"Exposure to immunosuppressive medication in utero is an important cause of secondary T cell lymphopenia in infancy, which can be detected via T cell receptor excision circle (TREC) quantification on severe combined immunodeficiency (SCID) newborn screening (NBS). At present, there is a paucity of literature surrounding management of these infants. A protocol including recommendations for vaccinations and follow-up is needed to augment care. Patients referred to immunology for abnormal TREC results on NBS were identified as having in utero exposure to immunosuppressive medications and were followed until lymphopenia improved. The natural history of these patients' lymphopenia was used to develop general management guidelines. Four infants with low TRECs secondary to in utero immunosuppressive exposure were evaluated. Medication exposures included azathioprine, infliximab, hydroxychloroquine, and fingolimod. All infants were born full term. TRECs ranged from 101-206 (normal value in IL ≥ 250 at time of testing, B-actin control). T cell lymphopenia (CD3 &lt; 1500) was present in 50% of cases. Undetectably low effector CD4 naïve T cell population was present in 100% of cases. Mitogen proliferation was uniformly normal. Severity of TREC abnormality did not correlate with presence of T cell lymphopenia. Immune abnormalities normalized in 75% patients by age 4 months. All age-appropriate vaccinations, including live vaccines, were administered to all patients by age 4 months. It is critical to assess for in utero immunosuppressive exposure in infants with abnormal TREC results on NBS. In the infants evaluated, secondary T cell lymphopenia associated with maternal immunosuppressive use resolved or significantly improved by age 4 months. Once abnormal TREC count is deemed to be secondary to in utero immunosuppression and there are no other contraindications, infants may safely receive live vaccination, are able to drink breast milk, and do not require prophylactic anti-microbials."
"To analyse and compare drug-survival of adalimumab and etanercept (and their biosimilars) in biologic-naïve patients with ERA (Enthesitis-Related Arthritis).
In this retrospective observational study, conventional statistics and machine-learning were applied to compare drug-survival (adalimumab, etanercept and their biosimilars initiated: 2009-2019) in ERA and identify determinants. The primary outcome was discontinuation of treatment due to primary- or secondary-failure and adverse drug-reactions.
During the observation period, 99 of 188 patients with ERA on first-line TNF inhibitors (etanercept-n=108, adalimumab-n=80) discontinued their treatment (median survival-time 3.9years, 95%CI 2.6-4.9years). Adalimumab was associated with longer drug-survival compared to etanercept especially after an initial positive response, with the median time to treatment discontinuation 4.9years (95% CI 3.9-5.7) for adalimumab, compared to 2years (95%CI 1.4-4.0) for etanercept (HR of treatment-discontinuation-0.49, 95%CI 0.32--0.75, p=0.001). Adjusted by propensity-score, adalimumab-methotrexate combination was associated with longer drug survival, compared to adalimumab-monotherapy (HR-0.41, 95%CI 0.20-0.85), etanercept-monotherapy (HR-0.28, 95%CI 0.15-0.53), and etanercept-methotrexate combination (HR-0.39, 95%CI 0.21-0.73). The presence of HLA-B27 was associated with longer drug-survival (HR-0.50, 95%CI 0.29-0.87) following an initial positive response. Higher-CRP at baseline was associated with higher rate of primary-failure (HR-1.68, 95%CI 1.08-2.62). Axial-ERA (sacroiliitis±spinal-involvement) was associated with poorer drug-survival for both primary- and secondary-failure (overall HR-2.03, 95%CI 1.22-3.40). Adjusted by propensity-score, shorter drug-survival was observed in patients with baseline-CRP≥12.15 mg/L, but only in the context of axial-ERA, not in peripheral-ERA (no sacroiliitis/spinal-involvement) (HR-2.28, 95%CI 1.13--3.64).
Following an initial positive primary response, continuing methotrexate with adalimumab was associated with the longest drug-survival compared to adalimumab-monotherapy or etanercept-based regimens. Axial-ERA was associated with a poorer drug-survival. A CRP >12.15 in patients with axial-ERA was associated with a higher rate of primary-failure. Further prospective studies are required to confirm these findings."
"The incidence of ulcerative colitis (UC) is increasing, but there are few reports comparing elderly UC patients undergoing colectomy for elderly-onset UC (EO) and nonelderly-onset UC (NEO). The aim of this study was to analyze the differences between EO and NEO patients who underwent UC-related surgery.
We identified 1973 patients with UC who underwent colectomy at Hyogo College of Medicine between January 1, 1984, and December 31, 2018. Only patients aged 65 years old and older who underwent colectomy were enrolled in this study (n = 221, 11.2%), and their clinical records were retrospectively reviewed. Patients were divided into two groups according to their age at disease onset: those with onset at younger than 60 years old (NEO) and at 60 years old or older (EO).
In the 221 UC patients who underwent colectomy at 65 years old or older, there were 155 cases of EO and 66 cases of NEO. The main surgical indication in NEO patients was colitis-associated cancer/dysplasia (32/66, 47%). In contrast, refractory to medical treatment was the leading cause of surgery in EO patients (80/155, 52%). The distributions of surgical indications were different between the two groups (p < 0.01). The preoperative daily dose of steroids was significantly higher in the EO group than in the NEOgroup (0 mg vs. 10 mg, p < 0.01). The rates of immunosuppressant, infliximab (IFX) and adalimumab use did not differ significantly between the groups. Significantly more patients underwent emergency surgery in the EO group than in the NEO group (14% vs. 35%, p < 0.01). The proportions of patients with postoperative morbidity (Clavien-Dindo grade III or higher) were 17.4% (27/155) in the EO group and 13.6% (9/66) in the NEO group. There was no significant difference between the two groups (p = 0.48). The prognosis of the EO patients who underwent UC-related emergency surgery was worse than that of the NEO patients (p < 0.01). In the EO group, 8 (14.8%) of 54 patients died within 30 postoperative days, while there were no deaths in the NEO group.
Among elderly UC patients undergoing UC-related surgery, EO patients undergoing emergency surgery had very poor outcomes, and the mortality rate was 14.8%. In such cases, it is important for physicians and surgeons to begin communication at an early stage so that the optimal surgical timeframe is not missed."
"Subcutaneous infliximab recently received approval for the treatment of various immune-mediated inflammatory diseases in Europe, following pivotal clinical trials in patients with rheumatoid arthritis and inflammatory bowel disease. Subcutaneous infliximab demonstrated an improved pharmacokinetic profile compared with intravenous infliximab: the more stable exposure and increased systemic drug concentrations mean it has been cited as a biobetter. Alongside the pharmacokinetic advantages, potential benefits for efficacy, immunogenicity, and health-related quality-of-life outcomes have been suggested with subcutaneous infliximab. During the coronavirus disease 2019 pandemic, the benefits of subcutaneous over intravenous therapies became apparent: switching from intravenous to subcutaneous infliximab reduced the hospital visit-related healthcare resource burden and potential viral transmission. Clinical advantages observed in pivotal trials are also being seen in the real world. Accumulating experience from four European countries (the UK, Spain, France, and Germany) in patients with rheumatic diseases and inflammatory bowel disease supports clinical trial findings that subcutaneous infliximab is well tolerated, increases serum drug concentrations, and offers maintained or improved efficacy outcomes for patients switching from intravenous infliximab. Initial evidence is emerging with subcutaneous infliximab treatment after intravenous infliximab failure. High patient satisfaction and pharmacoeconomic benefits have also been reported with subcutaneous infliximab. Treatments aligned with patient preferences for the flexibility and convenience of at-home subcutaneous administration could boost adherence and treatment outcomes. Altogether, findings suggest that switching from intravenous to subcutaneous infliximab could be advantageous, and healthcare professionals should be prepared to discuss supporting data as part of shared decision making during patient consultations.
The tumor necrosis factor inhibitor infliximab is one treatment option that may be appropriate for patients with immune-mediated inflammatory diseases. Patients may prefer tumor necrosis factor inhibitors administered via the subcutaneous (SC) or intravenous (IV) route, with preferences influencing treatment satisfaction and outcomes. In 2019, CT-P13 SC became the first SC infliximab product to receive regulatory approval in Europe, based on pivotal clinical studies that compared SC infliximab to IV infliximab in patients with rheumatoid arthritis and inflammatory bowel disease. Subcutaneous infliximab is now approved in Europe for the treatment of adults with rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. Patients began to switch from IV to SC infliximab outside clinical trials in March 2020, during the coronavirus disease 2019 pandemic. Switching from IV to SC infliximab allowed patients to self-administer treatment at home rather than attend hospital for infusions, reducing potential hospital-acquired infections and lessening the strain on healthcare systems during the pandemic. Clinical trial evidence and growing real-world experience demonstrate that SC infliximab offers clinical advantages in terms of an improved pharmacokinetic profile and potential efficacy, immunogenicity, and health-related quality-of-life benefits compared with IV infliximab. Patients have also reported increased satisfaction with SC infliximab after switching from IV infliximab. Together with the long-standing flexibility and convenience benefits of SC administration, the clinical advantages of SC infliximab make it a valid therapeutic option for rheumatoid arthritis and inflammatory bowel disease. This warrants discussion with appropriate patients as part of shared treatment decision making."
"Immune checkpoint inhibitors (ICIs) cause inflammatory immune-related adverse events (irAEs), which are often effectively managed with steroids. Less is known about the best management of irAEs refractory to steroid treatment.
We aimed to assess the efficacy of second-line medications used to treat gastrointestinal (GI) irAEs.
This study was a single-center, retrospective medical record review of patients who received steroids for an ICI GI irAE and at least one dose of infliximab, vedolizumab, or adalimumab for irAE treatment from March 25, 2011 to September 20, 2019, approved by Yale University's Institutional Review Board. Our primary objective was to assess the efficacy of second-line treatment, measured by the change in the Common Terminology Criteria for Adverse Events Version 5.0 grading system.
A total of 39 patients met inclusion criteria. Treatment for steroid-refractory GI irAEs demonstrated a high response rate, with irAE resolution seen in 89.7% of patients. Patients who were specifically initiated on infliximab within 14 days of starting steroids had a higher percent resolution seen in 94.4% of patients. The average time to response, defined as the average days from second-line therapy to reported symptom resolution, was 17 days.
Steroid-refractory GI irAEs can be managed effectively in most patients with immunosuppressive therapy, such as infliximab. Furthermore, initiating second-line immunosuppressive therapy within 14 days of steroid failure resulted in a higher rate of symptom resolution."
"Inflammation is associated with symptoms of anhedonia, a core feature of major depression (MD). We have shown that MD patients with high inflammation as measured by plasma C-reactive protein (CRP) and anhedonia display gene signatures of metabolic reprograming (e.g., shift to glycolysis) necessary to sustain cellular immune activation. To gain preliminary insight into the immune cell subsets and transcriptomic signatures that underlie increased inflammation and its relationship with behavior in MD at the single-cell (sc) level, herein we conducted scRNA-Seq on peripheral blood mononuclear cells from a subset of medically-stable, unmedicated MD outpatients. Three MD patients with high CRP (>3 mg/L) before and two weeks after anti-inflammatory challenge with the tumor necrosis factor antagonist infliximab and three patients with low CRP (≤3 mg/L) were studied. Cell clusters were identified using a Single Cell Wizard pipeline, followed by pathway analysis. CD14"
"We evaluated the clinical features and treatment response of patients with muscular sarcoidosis. A retrospective cohort of 12 patients showed muscle weakness in 11 and myalgia in seven. One had focal myositis. Four had a negative medical history for sarcoidosis. Muscle imaging showed muscle edema in all and replacement of muscle tissue by fat in half of patients. Muscle biopsy showed non-caseating granulomas in six of nine patients and inflammation without granulomas in three. None of the muscle biopsies showed features of inclusion body myositis. Imaging in three patients without muscle biopsy showed focal intramuscular masses or a 'tiger man' appearance typical for muscular sarcoidosis. Treatment consisted of glucocorticoids in 11, additional methotrexate or azathioprine in seven and infliximab in two patients. Half of the patients had symptoms leading to substantial disability (modified Rankin scale score >1) at last follow-up. A literature review of articles describing more than one muscular sarcoidosis patient published in the last 25 years identified 153 additional patients. We found muscular sarcoidosis to be a rare and often disabling disease which may be recognized by typical muscle imaging characteristics and add focal myositis to the muscular phenotypes of sarcoidosis."
"Observational studies are often considered unreliable for evaluating relative treatment effectiveness, but it has been suggested that following target trial protocols could reduce bias. Using observational data from patients with rheumatoid arthritis (RA) in the Swedish Rheumatology Quality Register (SRQ), between 2006 and 2020, we emulated the protocol of the Swedish Farmacotherapy trial (SWEFOT) and compared the results. SWEFOT was a pragmatic trial nested in SRQ, between 2002 and 2005, where methotrexate (MTX) insufficient responders were randomized to receive additional infliximab or sulfasalazine (SSZ) + hydroxychloroquine (HCQ). Patients with RA initiating infliximab (N = 313) or SSZ + HCQ (N = 196) after MTX were identified in SRQ and the Prescribed Drugs Register, mimicking the SWEFOT eligibility criteria. The primary outcome was the proportion of European Alliance of Associations for Rheumatology (EULAR) good responders at 9 months, classifying patients who discontinued treatment as ""nonresponders."" Through sensitivity analyses, we assessed the impact of relaxing eligibility criteria. The observed proportions reaching EULAR good response were close to those reported in SWEFOT: 39% (vs. 39% in SWEFOT) for infliximab and 28% (vs. 25%) for SSZ + HCQ. The crude observed response ratio was 1.39 (95% confidence interval (CI) 1.04-1.86), increasing to 1.48 (95% CI 0.98-2.24) after confounding adjustment, compared to 1.59 (95% CI 1.10-2.30) in SWEFOT. Results remained close to SWEFOT when relaxing eligibility criteria until allowing prior disease-modifying anti-rheumatic drug (DMARD) use which reduced the observed difference between treatments. By applying a prespecified trial emulation protocol to observational clinical registry data, we could replicate the results of SWEFOT, favoring infliximab over SSZ + HCQ combination therapy at 9 months."
"Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Atherosclerosis leads to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression.
Patients with active TAK arteritis were compared with age- and sex-matched atherosclerotic patients (Controls). In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical changes of the vessel wall were evaluated as well.
TAK patients have increased aortic valve dysfunction and diastolic dysfunction. The degree of dysfunction appears associated with uric acid levels. A significant increase in aortic stiffness was also observed and associated with levels of peripheral T lymphocytes. CD3
Our data suggest that different pathogenic mechanisms underlie vessel damage, including atherosclerosis, in TAK patients compared with Controls. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants."
"A 43-year-old Japanese woman with rheumatoid arthritis treated by infliximab and methotrexate for 11 years was admitted for proteinuria and purpura. A kidney biopsy revealed endothelial damage-dominant nephritis with IgA deposition. Infliximab and methotrexate were discontinued, and tocilizumab was started; however, proteinuria persisted. Therefore, tocilizumab was discontinued, and oral prednisolone and methylprednisolone pulse therapy were administered. After 6 months, urinary protein was less than 0.1 g/day, and purpura subsided. To our knowledge, this is the first case of endothelial damage-dominant nephritis related to IgA vasculitis involving the skin and kidney after long-term use of infliximab and methotrexate."
"Inflammatory bowel diseases (IBDs) are chronic immune disorders of unclear etiology. Tumor necrosis factor (TNF) inhibitors are effective for IBD treatment and are cost-effective because they reduce hospital admissions and are associated with fewer surgery requirements and a better quality of life in IBD patients. A large number of clinical trials of infliximab biosimilar (CT-P13) have suggested that the administration of biosimilars provides high efficacy and safety similar to that of the originators, with a lower cost, so switching from the original to a biosimilar is considered an acceptable treatment. While several abnormalities of blood examination have been observed in patients with CT-P13 administration, no cases of drug-induced liver injury (DILI) caused by CT-P13 has been reported. A 23-year-old woman had been diagnosed with Crohn's disease and was treated with original infliximab (O-IFX) for 9 years. She developed severe jaundice 1 month after switching from O-IFX to CT-P13. Serologic tests of autoimmune and hepatitis viruses were negative, and ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography revealed no abnormalities. A liver biopsy showed prominent pericentral canalicular cholestasis, without features of steatosis or sclerosing cholangitis, which was consistent with drug-induced cholestasis. The cholestasis improved 10 weeks after the discontinuation of CT-P13, and no DILI redeveloped even after re-switching from CT-P13 to O-IFX. This is the first report of DILI due to switching from O-IFX to CT-P13. While the efficacy and safety of CT-P13 are considered equal to those of O-IFX, clinicians need to be alert for certain severe DILIs when switching from O-IFX to CT-P13 with careful monitoring and appropriate treatment."
"Higher infliximab trough levels (TLs) correlate with better clinical, inflammatory, and endoscopic outcomes among inflammatory bowel disease (IBD) patients. Although standard scheduled infliximab therapy regimen consists of infusions at pre-defined time-points (weeks 0, 2, 6, and every 8 weeks), short-period deviations from therapeutic schedule are common in 'real life', but the pharmacokinetic impact of these deviations has not been explored. In this study, we aim to determine whether short-period deviations from infusion schedule affect infliximab-TL.
A retrospective analysis of all IBD patients receiving infliximab maintenance therapy every 8 weeks was conducted in a tertiary medical center. Patients with anti-drug antibodies, deliberate interval shortening and <3 sequential maintenance sera available were excluded. Associations between time since last infusion and TL were studied. Statistical analysis was performed using generalized estimating equations.
Out of over 10,000 sera, 2088 sera of 302 maintenance period stable infliximab-therapy-patients met inclusion criteria (median TL 4.1 μg/mL, interquartile range (IQR) 2.3-6.5 μg/mL). A delay beyond 3 days in infusion schedule (n > 59 days since last infusion) was found to significantly affect TL (mean difference in TL 0.9 μg/mL, 95% confidence interval (CI): 0.03-1.9 μg/mL, 
Real-life delays of ⩽3 days from infusion protocol can probably be allowed. Delays >3 days culminate in measurable decrease of TL, although effect on clinical outcome is unclear. This needs to be taken into account when interpreting drug-level test results.
A total of 2088 sera of 302 maintenance period inflammatory bowel disease (IBD) patients treated with infliximab were analyzed, to assess effect of small deviations from infusion schedule on TLs. A significant decline in patients' trough level (TL) was noted as early as 3 days after scheduled infusion."
"Anti-TNF therapy represented a landmark in medical treatment of ulcerative colitis (UC). There is lack of data on the efficacy and safety of these agents in Brazilian patients. The present study aimed to analyze rates of clinical and endoscopic remission comparatively, between adalimumab (ADA) and infliximab (IFX), in Brazilian patients with UC, and evaluate factors associated with clinical and endoscopic remission after 1 year of treatment.
A national retrospective multicenter study (24 centers) was performed including patients with UC treated with anti-TNF therapy. Outcomes as clinical response and remission, endoscopic remission and secondary loss of response were measured in different time points of the follow-up. Baseline predictive factors of clinical and endoscopic remission at week 52 were evaluated using logistic regression model. Indirect comparisons among groups (ADA and IFX) were performed using Student's t, Pearson χ
Overall, 393 patients were included (ADA, n = 111; IFX, n = 282). The mean age was 41.86 ± 13.60 years, 61.58% were female, most patients had extensive colitis (62.40%) and 19.39% had previous exposure to a biological agent. Overall, clinical remission rate was 66.78%, 71.62% and 82.82% at weeks 8, 26 and 52, respectively. Remission rates were higher in the IFX group at weeks 26 (75.12% vs. 62.65%, p < 0.0001) and 52 (65.24% vs. 51.35%, p < 0.0001) when compared to ADA. According to Kaplan-Meier survival curve loss of response was less frequent in the Infliximab compared to Adalimumab group (p = 0.001). Overall, endoscopic remission was observed in 50% of patients at week 26 and in 65.98% at week 52, with no difference between the groups (p = 0.114). Colectomy was performed in 23 patients (5.99%). Age, non-prior exposure to biological therapy, use of IFX and endoscopic remission at week 26 were associated with clinical remission after 52 weeks. Variables associated with endoscopic remission were non-prior exposure to biological therapy, and clinical and endoscopic remission at week 26.
IFX was associated with higher rates of clinical remission after 1 year in comparison to ADA. Non-prior exposure to biological therapy and early response to anti-TNF treatment were associated with higher rates of clinical and endoscopic remission."
"The pharmacokinetics of drugs, such as immunosuppressants, justify the need of measuring their blood concentrations in order to adjust their dosage. Therapeutic Drug Monitoring (TDM) of ciclosporin, tacrolimus and mycophenolate mofetil has shown its benefit particularly in the management of renal transplantees, in order to prevent graft rejection. When prescribed in autoimmune diseases, their pharmacokinetic variability and the variability of clinical response would justify TDM in practice. TDM may be useful in systemic lupus, for hydroxychloroquine, in order to monitor patient compliance. Despite insufficient data in the literature, for mycophenolate mofetil, TDM would permit to maintain clinical remission in adults and children with lupus nephritis, as well as in mucosal pemphigoid and idiopathic nephrotic syndrome in children. Studies are still necessary to validate the thresholds and TDM conditions. For azathioprine, TPMT phenotyping is recommended before prescription. For methotrexate, tacrolimus and ciclosporin, data are still sparse on the benefit of TDM, although it may improve tolerance to tacrolimus in lupus. Finally, for infliximab, in case of loss of response in maintenance, TDM may be proposed in parallel with detection of anti-drug antibodies."
"The quality of life in psoriatic patients is significantly impaired. Since this century, there have been biologics as a treatment for psoriasis. These biologics reduce symptoms, but more knowledge is needed about potential improvements in quality of life. As a result, biological therapy may be more valuable for patients who experience a lot of burden from their chronic skin condition in daily life. The aim of this systematic review was to investigate the possible improvement of the Dermatology Life Quality Index (DLQI) in psoriatic patients using biologics.
An online search was performed in the PubMed database to identify relevant articles. Inclusion criteria for studies were psoriatic patients, a measurement of DLQI with biologics and without biologics. Exclusion criteria for studies were abstracts not written in English, publications before 2012, full text unavailable, quality of life measurements other than DLQI. Results from the studies with different biologics were combined into the outcome measure: ≥5 points of improvement in the DLQI score. Results of the studies in which biologics were compared with (conventional) systemic therapy were combined in the outcome measure: improvement of the DLQI score is better with biologics than with systemic therapy.
There were nine included articles with a total of 19.926 patients. Adalimumab, alefacept, etanercept, infliximab, ustekinumab and secukinumab were included biologics. Six studies measured the change in DLQI of different biologics in number of points. Of these six studies, 22 sub-analyses were performed and 20 of them showed a DLQI improvement of ≥5 points. The improvement in DLQI was better with biologics than with systemic therapy in two of the three measured studies.
Quality of life of psoriatic patients will be improved by the studied biologics. In the future, more research is needed into biologics on patient and quality of life characteristics."
"Despite the pervasive vaccination program against coronavirus disease 2019 (COVID-19), fully vaccinated people are still being infected by severe acute respiratory syndrome coronavirus 2, making an effective and safe therapeutic intervention a crucial need for the patients' survival. The purpose of the present study is to seek available evidence for the efficacy and safety of three promising medications artesunate, imatinib, and infliximab against COVID-19.
A literature search was conducted in PubMed, Cochrane Library, medRxive, and Google Scholar up to January 2022. Furthermore, the clinical trial databases were screened to find more citations. The Cochrane Collaboration tool and Newcastle-Ottawa scale were used to assess the included studies. Meta-analysis was performed using RevMan 5.4.1.
Five published studies were identified as eligible. Meta-analysis showed that there was no significant difference between the infliximab and control groups in terms of mortality rate (risk ratio [RR]: 0.65; 95% confidence interval [CI]: 0.40-1.07; p = 0.09). However, a significant difference was observed between the two groups for the hospital discharge (RR: 1.37; 95% CI: 1.04-1.80; p = 0.03). No remarkable clinical benefit was observed in favor of using imatinib for COVID-19 patients. Artesunate showed significant improvement in patients with COVID-19.
In the present, limited evidence exists for the efficacy and safety of artesunate, imatinib, and infliximab in patients with COVID-19. The findings of WHO's Solidarity international trial will provide further information regarding these therapeutic interventions."
"Infliximab and adalimumab are monoclonal antibodies against tumor necrosis factor (anti-TNF) used to manage inflammatory bowel disease (IBD). Therapeutic Drug Monitoring (TDM) has been proven to prevent immunogenicity, to achieve better long-term clinical results and to save costs in IBD treatment. The aim of this study was to conduct a systematic review on cost-effectiveness analyses of studies that apply TDM of anti-TNF in IBD and to provide a critical analysis of the best scientific knowledge available in the literature. The quality of the included studies was assessed using Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Cost-effectiveness of the TDM strategies was presented as total costs, cost savings, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Thirteen studies that examined the health economics of TDM of anti-TNF in IBD from 2013 to 2021 were included. Eight of them (61.5%) achieved a score between 17 and 23 on the CHEERS checklist. The comparison between the TDM strategy and an empirical strategy was cost saving. The ICER between reactive TDM and an empirical strategy was dominated (favorable) by reactive TDM, whereas the ICER value for proactive TDM compared to an empirical strategy ranged from EUR 56,845 to 3,901,554. This systematic review demonstrated that a TDM strategy is cost-effective or cost-saving in IBD."
"The Coronavirus Disease 2019 (COVID-19) pandemic has been caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The most important approach to prevent severe disease progression and to contain the pandemic is the use of COVID-19 vaccines. The aim of this study was to investigate the humoral and cellular response in immunosuppressed patients with inflammatory bowel disease (IBD) on treatment with anti-TNF (infliximab, adalimumab) and anti-α4ß7-Integrin (vedolizumab) 6 months after mRNA vaccination against SARS-CoV-2 compared to healthy subjects.
In this prospective study, 20 IBD patients and 9 healthy controls were included 6 months after the second BNT162b2 vaccination. In addition to quantitative determination of IgG antibody levels against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein subunit S1, a SARS-CoV-2 surrogate neutralization test (sVNT) was used to assess potential neutralization capacity. SARS-CoV-2-specific T-cell responses were measured using an interferon-γ (IFN-γ) release assay (IGRA; Euroimmun Medical Laboratory Diagnostics, Lübeck, Germany).
S-IgG could still be detected in the majority of IBD patients 6 months after second vaccination. Compared to healthy controls, IBD patients treated with anti-TNF agents showed both lower neutralizing activity in sVNT (percent inhibition of ACE2 receptor binding by RBD protein) and lower IgG-S (AU/mL) antibody levels (AB) (sVNT: 79% vs. 2%, 
Six months after BNT162b2 vaccination, this study found significantly decreased antibody levels in patients under anti-TNF therapy. IBD patients under anti-TNF and vedolizumab therapy had no impairment of T-cellular reactivity compared to healthy controls at this time point. Further studies with larger collectives for confirmation should follow."
"The long-term use of anti-TNF-α agents can lead to adverse effects, such as infections and immune-mediated cutaneous reactions. Whether de-escalation by dose reduction or interval lengthening reduces these adverse effects is uncertain. This systematic review aims to compare the incidence of infections and skin manifestations after anti-TNF-α dose de-escalation with standard dosing.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to 14 January 2022. Randomized controlled trials (RCTs) and observational studies comparing anti-TNF-α de-escalation strategies with standard dosing among patients with inflammatory conditions, that report on infections, skin manifestations, or both, were included. The risk of bias was assessed with the revised Cochrane risk-of bias tool (RCTs) or the Newcastle-Ottawa scale (non-RCTs).
Fourteen RCTs and six observational studies (or 2706 patients) were included. Eight RCTs had low risk of bias or some concerns. Four non-RCTs were of good methodological quality. The studies described patients with axial spondyloarthritis (8 studies, 780 patients), rheumatoid arthritis (7 studies, 1458 patients), psoriasis (3 studies, 332 patients), or inflammatory bowel disease (2 studies, 136 patients). De-escalation strategies included interval lengthening (12 studies, 1317 patients), dose reduction (6 studies, 1130 patients), or both (2 studies, 259 patients). Overall, the occurrence of infections and skin manifestations did not differ between standard treatment and de-escalation. The disappearance of infections or skin manifestations after de-escalation was only reported in two studies. The majority of studies focused on etanercept and adalimumab. Heterogeneity in reporting of infections and skin manifestations precluded meta-analysis.
We found that anti-TNF-α de-escalation does not reduce infections or skin reactions. A de-escalation strategy should not be recommended for the sole purpose of reducing drug-related adverse effects. The meticulous documentation of adverse effects is recommended to further address this question.
PROSPERO CRD42021252977."
"Orbital myositis is a rare sporadic eye disease associated with extraocular eye muscle inflammation. To date, there have been two reports of familial orbital myositis (FOM), which demonstrate partially penetrant autosomal dominant inheritance.
We report six new Australian cases of FOM, four of whom extend one of the reported pedigrees, as well as a separate mother and daughter manifesting orbital myositis, which constitutes a third report of familial occurrence. We can confirm that the disease has onset in childhood, appearing to go into remission in adult life, and that the inflammation is corticosteroid-responsive. However, one patient went on to develop permanent diplopia in upgaze. We also report two children suffering chronic pain and diplopia who demonstrated complete resolution of symptoms with the anti-TNF-α monoclonal infliximab.
Uncontrolled FOM in childhood may result in permanent extraocular eye muscle damage, while TNF-α blockade provides an excellent steroid-sparing effect."
"Research on the utilization and effectiveness of antitumor necrosis factor (TNF) biologics in children with very early onset inflammatory bowel disease (VEOIBD) is urgently needed. Here we describe anti-TNF use and durability in a multicenter cohort.
We performed a retrospective cohort study of patients diagnosed with VEOIBD (<6 years) between 2008 and 2013 at 25 North American centers. We performed chart abstraction at diagnosis and 1, 3, and 5 years after diagnosis. We examined the rate of initiation and durability of infliximab and adalimumab and evaluated associations between treatment durability and the following covariates with multivariate Cox proportional hazard regression: age at diagnosis, sex, disease duration, disease classification, and presence of combined immunomodulatory treatment versus monotherapy.
Of 294 children with VEOIBD, 120 initiated treatment with anti-TNF therapy and 101 had follow-up data recorded [50% Crohn disease (CD), 31% ulcerative colitis (UC), and 19% IBD unclassified (IBD-U)]. The cumulative probability of anti-TNF treatment was 15% at 1 year, 30% at 3 years, and 45% at 5 years from diagnosis; 56 (55%) were treated between 0 and 6 years old. Anti-TNF durability was 90% at 1 year, 75% at 3 years, and 55% at 5 years. The most common reason for discontinuation of anti-TNF were loss of response in 24 (57%) children. Children with UC/IBD-U had lower durability than those with CD (hazard ratio [HR] 0.17; 95% confidence interval [CI], 0.06-0.51; P = 0.001).
Utilization and durability of anti-TNF in VEOIBD is relatively high and comparable with older children. Having Crohn disease (compared with UC/IBD-U) is associated with greater durability."
"Immune-related hepatitis is an adverse effect following treatment with immune-checkpoint inhibitors, such as ipilimumab, nivolumab and pembrolizumab. International guidelines advise on the use of corticosteroids as first-line treatment, although guidance on how to treat cases resistant to corticosteroids is limited. We aimed to evaluate the presentation and management of patients with grade 3-4 immune-related hepatitis, following treatment with immune-checkpoint inhibitors for stage 4 or unresectable or stage 3 melanoma, with a particular focus on steroid-refractory cases.
A retrospective observational review of patients developing immune-related hepatitis whilst undergoing treatment with immune checkpoint inhibitors for advanced melanoma from July 2014 to February 2020 at a tertiary oncology centre.
Forty-one patients developed immune-related hepatitis, of which 83% had been treated with the combination of ipilimumab and nivolumab. The median time to onset of IR-hepatitis was 47 days (range: 4-476), and the median time to peak alanine aminotransferase was 71 days (range: 4-478). Four patients had resolution of grade 3 immune-related hepatitis without the introduction of corticosteroids. A total of 37 patients were treated with corticosteroids. A total of 12 required oral treatment only and 13 were successfully managed as outpatients. Six patients had steroid-refractory immune-related hepatitis; and all received tacrolimus, with one also receiving mycophenolate mofetil and infliximab.
This study describes the largest UK series of immune-related hepatitis patients in the literature. We present two important deviations from current guidelines. Firstly, there is some evidence that withholding steroids is possible in grade 3-4 immune-related hepatitis. Secondly, tacrolimus can be used successfully to manage patients resistant to corticosteroids, with the early introduction most beneficial to reduce time on steroids."
"Chronic immune-mediated diseases, including inflammatory bowel disease (IBD), present an increased risk of developing early atherosclerosis and cardiovascular events (CVE) at early age.
To describe the baseline and 1-year cardiovascular profile of patients with IBD according to the biologic treatment received, taking into account the inflammatory activity.
It is a retrospective, observational study that included 374 patients. Cardiovascular risk factors (CVRF) and CVE were collected at the baseline visit and at one-year follow-up to describe the cardiovascular risk according to the biological treatment received, also assessing clinical and biological remission.
A total of 374 patients were included: 146 (38.73%) were treated with Infliximab, 128 (33.95%) with adalimumab, 61 (16.18%) with ustekinumab and 42 (11.14%) with vedolizumab. The changes in blood glucose levels are [86.31mg/dL (84.57-88.06) vs. 89.25mg/dL (87.54-90.96), P=.001] for those treated with antiTNFα and [86.52mg/dL (83.48-89.55) vs. 89.44mg/dL (85.77-93.11), P=.11] in the other group. In the group treated with antiTNFα total cholesterol values at baseline visit are [169.40mg/dL (164.97-173.83) vs. 177.40mg/dL (172.75-182.05) at one year of treatment, P=<.001], those of HDL [50.22mg/dL (48.39-52.04) vs. 54.26mg/dL (52.46-56.07), P=<.001] and those of triglycerides [114.77mg/dL (106.36-123.18) vs. 121.83mg/dL (112.11-131.54), P=.054]. Regarding weight, an increase was observed, both in those patients treated with antiTNFα [71.39kg (69.53-73.25) vs. 72.87kg (71.05-74.70), P<.001], and in the group treated with ustekinumab and vedolizumab [67.59kg (64.10-71.08) vs. 69.43kg (65.65-73.04), P=.003]. Concerning CVE, no significant differences were observed neither according to the drug used (p=0.36), nor according to personal history of CVE (P=.23) nor according to inflammatory activity (P=.46).
Our results on a real cohort of patients with IBD treated with biologic drugs show a better control of certain cardiovascular parameters such as CRP or HDL, but a worsening of others such as total cholesterol or triglycerides, regardless of the treatment. Therefore, it is possibly the disease control and not the therapeutic target used, the one that affect the cardiovascular risk of these patients."
"An anal fistula (anorectal fistula) is one of the most common colorectal issues in the U.S. An anal or anorectal fistula is an inflammatory tract or connection between the anal canal and the perianal skin. Classic anal fistulas are the result of a perineal infection and abscess formation. These infections arise from the anal glands, which form a cryptoglandular abscess at the dentate line and then communicate outward to the perianal skin. The abscess or infections can spontaneously drain externally or be drained by a surgical incision and drainage procedure. After the drainage, a chronic tract can form that will intermittently drain or become infected again. Hidradenitis suppurativa, trauma, malignancy, tuberculosis, and Crohn disease can all express as fistulas as well, although these present as atypical fistulas. Initial treatment for all perianal pain and presumed perineal infections is an exam under anesthesia and drainage of the abscess. Over time the abscess should heal, and if there is continued drainage from a punctum or nodule at the perianal skin, then a fistula is presumed. There are multiple types of fistula tracts related to the anatomy through which the fistula courses. The fistula tract can either be deep or superficial to the external anal sphincter. The superficial tracts can simply be opened or unroofed with a fistulotomy to the anal gland, and the tract will heal by secondary intention. The deeper fistulas encompass more of the external anal sphincter and cannot be unroofed as that leads to fecal incontinence. Instead, these tracts should have a Seton (elastic band or heavy suture) placed through the tract, and this allows a slow process to cut through the tract as the deeper parts heal so that incontinence is less likely. A final option for chronic fistulas is a flap closure of the tract with advancement flaps. Patients with complex fistulas pose a challenge to the surgeon. Malignant fistulas will need an interprofessional team approach to rectal and anal cancers, which will involve chemotherapy and radiation therapy. Setons may be used as an adjunct to allow drainage so that abscess formation would not compromise patient care plans. Patients with Crohn disease who have fistula are a challenge. Setons would be the first line of therapy to make sure no abscess or perineal sepsis develops, then adjunct medication like steroids and Infliximab may be used chronically to assist remission of the disease and healing of the fistula tract(s). Hidradenitis suppurative and tuberculosis should be treated with antibiotics, and Setons are adjuncts to make sure the fistulas do not form abscesses during treatment. In some cases, the perineal fistula disease is so severe that fecal diversion with a colostomy assists healing and control of continued perineal infections."
"Modern-day medicine has been revolutionized to be personalized and specific based on individualized specific disease characteristics. Monoclonal antibodies (mAbs) are a prime example of personalized therapeutics enabled by advances in our knowledge of immunology, molecular biology, and biochemistry. As an example, a disease such as cancer can be evaluated for the presence of certain properties (i.e., hormone receptors in breast cancers), which can, in turn, be targeted by mAbs to provide a ""tailored"" therapy. The earliest documented use of (indirect) antibody therapy was by Dr. Edward Jenner in 1796, when he inoculated pustular fluid from smallpox lesions to elicit immunity in the recipient. It was not until 1975 when the generation of mAbs for use in humans was established by Drs Kohler and Milstein. The concept of mAbs as therapeutic options is modeled after the immune system, particularly the humoral immunity (i.e., antibodies) generated by the immune system in response to foreign antigen exposure. The antibodies generated by this immune response are proteins that have high specificity and affinity for the antigen/ molecule they were generated against. Kohler and Milstein utilized these principles to conceive what came to be called a ""hybridoma"" (a fusion cell composed of myeloma cells and splenic B lymphocytes, both murine in origin). These hybrid cells allowed Kohler and Milstein to reliably produce a single antibody clone in large volumes and with a pre-selected specificity, which became known as mAbs. The initial biotechnology of primitive mAbs became quickly problematic when the murine origin of such proteins caused them to become immunogenic and non-sustainable for long-term therapy due to the development of human anti-murine antibodies (HAMA). The increased clearance due to HAMA generation was also accompanied by eventual Immunoglobulin E (IgE) development and anaphylactic reactions on subsequent administrations. Despite the initial challenges associated with murine methodologies of mAb development, research continued, and the development of alternative methods overcame these limitations. Chimeric clones were the next developments, whereby human crystallizable fragment (Fc) regions were attached in place of murine ones. Examples of chimeric mAbs include infliximab and rituximab. Chimeric clones were followed by developing ""humanization,"" a process where murine protein loops (which served as ligand binding sites) were implanted within human immunoglobulins. Examples of humanized mAbs include Daclizumab and trastuzumab. The culmination of all methodologies has led to present-day mAbs production capable of producing fully human mAbs and minimizing the risks originally associated with their predecessors. An example of mAbs generated by recombinant DNA methodologies includes adalimumab. The nomenclature of mAbs depends on the origin of each respective mAb. Common suffixes include -omab, -ximab, -zumab, and -umab, representing murine, chimeric, humanized, and human agents, respectively."
"Tumor necrosis factor (TNF)-alpha inhibitors, including etanercept (E), infliximab (I), adalimumab (A), certolizumab pegol (C), and golimumab (G), are biologic agents which are FDA-approved to treat ankylosing spondylitis (E, I, A, C, and G), Crohn disease (I, A and C), hidradenitis suppurativa (A), juvenile idiopathic arthritis (A), plaque psoriasis (E, I and A), polyarticular juvenile idiopathic arthritis (E), psoriatic arthritis (E, I, A, C, and G), rheumatoid arthritis (E, I, A, C, and G), ulcerative colitis (I, A and G), and uveitis (A). There are also several off-label indications. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, toxicity, and monitoring, of tumor necrosis factors, so providers can direct patient therapy where they are indicated as part of the interprofessional team."
"Infliximab (IFX) is a biologic agent that specifically targets an immune mediator, tumor necrosis factor alpha (TNFa), involved in a pathological process. Anti TNFa agents have enjoyed use as therapeutic modalities since 1998; however, their first use in dermatology dates back to 2002 when they first saw use in the treatment of psoriasis. FDA-Approved indications include Crohn disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and juvenile idiopathic arthritis. This activity describes the mode of action of infliximab-abda, including adverse event profiles, and other key factors e.g. dosing, pharmacodynamics, pharmacokinetics, monitoring, and highlights the role of the interprofessional team in the management of these patients."
"Leurieus quinquestriatus (LQ) is a type of Egyptian scorpions. Prior studies have established the potential use of scorpion venoms in treating several autoimmune diseases. Therefore, the current study investigates the possible pharmacological effect of LQ venom in CFA-induced arthritis - through different mechanisms - by assessing different serum and tissue parameters. This study was divided into two phases: phase I was conducted to determine the lowest therapeutic dose of LQ scorpion venom, whereas phase II investigated the potential therapeutic effect of the chosen dose of LQ venom on induced arthritis through different mechanisms. The Wistar albino rats were divided equally and randomly into normal control group, LQ control group, arthritis control group, infliximab-treated group, and LQ-treated group. On day 20, blood and tissue samples were collected for further analysis of serum and tissue biomarkers as well as histopathological examination. The results revealed a potential therapeutic effect of LQ venom on arthritic-induced rats through a significant decrease in Rheumatoid Factor, Janus Kinase, Signal transducers and activators of transcription, Receptor activator of nuclear factor Kappa-B ligand, Tumor Necrosis Factor-alpha, Interleukin-6, Nuclear factor kappa-light-chain-enhancer of activated B cells and Malondialdehyde by 57%, 66%, 64%, 62%, 75%, 59%, 38%, and 69%, respectively as well as a significant increase in reduced glutathione, and Nuclear factor erythroid 2-related factor 2 by 102% and 360%, respectively. Histopathological examination of knee joint and spleen also revealed a substantial improvement, indicating the possible utilization of LQ venom in the treatment of rheumatoid arthritis."
"Therapeutic monoclonal antibodies (mAbs) represent a very important class of the current biopharmaceutics. The great complexity of their structure made necessary the use of different analytical approaches for assessing different physico-chemical properties. In this work, weak cation exchange (WCX) high performance liquid chromatography with diode array detection ((WCX)HPLC/DAD) is used to assess the charge variant profile. The method here developed combined the effect of ionic strength and controlled pH gradient and allows for the charge variants analysis of the five mAbs studied, namely bevacizumab (BVZ), cetuximab (CTX) infliximab (INF), rituximab (RTX) and trastuzumab (TTZ), which are among the most used mAbs worldwide. The differences in the charge variants in the natural isoforms of the mAbs promoted characteristic WCX chromatograms for each of mAbs that can be also useful for identification purposes. These chromatograms have provided to be suitable for tracking changes in the charge variants of each mAb analyzed both in controlled degraded and in stabilities study along time of in-use samples solutions at 2 mg/mL in 0.9% NaCl stored refrigerated (at 4 °C) and frozen (-20 °C) for two months. The results obtained indicated different stabilities of these mAbs, all IgG1, against degradation by different stressed environmental conditions and in-use stability along two months."
"The medical treatment of fistulizing Crohn's disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD.
We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI).
In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55).
Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.
Despite the era of biologic therapies, the management of fistulizing Crohn’s disease remains challenging. This is the first systematic review and network meta-analysis to compare the efficacy of biologic therapies in inducing response and remission in patients with fistulizing Crohn’s disease. We found that anti-tumor necrosis factor agents are effective in inducing response and remission. Infliximab was superior to adalimumab for inducing response but not for inducing remission."
"Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.
To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety.
For this update of the living systematic review, we updated our searches of the following databases monthly to October 2021: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase.
Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation).
We conducted duplicate study selection, data extraction, risk of bias assessment and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).
This update includes an additional 19 studies, taking the total number of included studies to 167, and randomised participants to 58,912, 67.2% men, mainly recruited from hospitals. Average age was 44.5 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (57%). We assessed a total of 20 treatments. Most (140) trials were multicentric (two to 231 centres). One-third of the studies (57/167) had high risk of bias; 23 unclear risk, and most (87) low risk. Most studies (127/167) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions, except anti-IL23. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23 and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 50.19, 95% CI 20.92 to 120.45), bimekizumab (RR 30.27, 95% CI 25.45 to 36.01), ixekizumab (RR 30.19, 95% CI 25.38 to 35.93), risankizumab (RR 28.75, 95% CI 24.03 to 34.39). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab, ixekizumab and risankizumab showed a higher proportion of patients reaching PASI 90 than other anti-IL17 drugs (secukinumab and brodalumab) and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab and brodalumab) and anti-IL23 drugs (risankizumab and guselkumab) except tildrakizumab showed a higher proportion of patients reaching PASI 90 than ustekinumab and three anti-TNF alpha agents (adalimumab, certolizumab and etanercept). Ustekinumab was superior to certolizumab; adalimumab and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with low- to moderate-certainty for all the comparisons (except methotrexate versus placebo, which was high-certainty). The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.
Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.5 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies and postmarketing reports from regulatory agencies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review."
"Systemic immunosuppressants and biologicals have been a valuable tool in the treatment of inflammatory diseases and malignancies. The safety profile of these drugs has been debatable, especially in localized systems, such as the eye. This has led to the search for fairly local approaches, such as intravitreal, subconjunctival, and topical route of administration. Immunosuppressants have been used as a second-line drug in patients intolerable to corticosteroids or those who develop multiple recurrences on weaning corticosteroids. Similarly, biologicals have also been used as the next line of therapy, when adequate control of inflammation could not be attained or immunosuppressants were contraindicated to patients. Intravitreal immunosuppressants, such as methotrexate and sirolimus, have been extensively studied in noninfectious posterior uveitis, whereas limited studies have established the efficacy of intravitreal biologicals, such as infliximab and adalimumab. Most of these drugs have shown good safety profile and tolerability in animal studies alone and have not been studied further in human subjects. However, most of the studies in literature are single-case reports or case series which limits the level of evidence. In this comprehensive review, we discuss the mechanism of action, pharmacodynamics, pharmacokinetics, indications, efficacy, and side effects of different intravitreal immunosuppressants and biologicals that have been studied in literature."
"To investigate effects of anti-TNF biologic drugs on uveitis severity (comparing visual acuity logMAR levels) in Behçet patients.
Three databases PubMed, Scopus, and the Web of Science were searched for qualified papers focusing on the anti-TNF-α factors treatment in Behçet's disease (BD)-associated uveitis. Studies that were designed pre and post anti-TNF drug treatment, were selected. After determining the search strategy for this study, the relevant data were extracted.
The initial search was performed in the target databases and a total of about 1458 articles were found. Fifteen articles were selected for systematic review and only 12 of them had inclusion criteria for Meta-analysis (with visual acuity data). The mean dose of prednisolone before and after biological treatments was reported in 5 studies (28.56 and 7.56 mg/kg, respectively). Also, the preliminary results indicate a significant reduction in visual acuity logMAR levels (MD=-1.5 IU/L, 95%CI: -2.1, -0.01).
Biological drugs significantly reduce the dose of prednisolone and affect visual acuity values."
"Current evidence suggests vedolizumab (VDZ) may be as effective as Infliximab (IFX) in inflammatory bowel disease. It is unknown if proactive therapeutic drug monitoring (PTDM) of IFX may improve these results.
Case-control study including consecutive patients with primary response to conventional IFX (
Proactive IFX was superior to conventional IFX and VDZ in inducing Fc remission at 1-year (69.4% vs 47.1% vs 37.9%, 
Proactive IFX was superior to VDZ in inducing Fc remission at 1-year, which was associated with improved clinical outcomes.SUMMARYCurrent evidence suggests that vedolizumab may be as effective as Infliximab in the treatment of patients with inflammatory bowel disease.There have been no studies comparing vedolizumab with proactively optimized Infliximab based on trough levels.We confirm that conventional IFX is as effective as vedolizumab but proactive IFX appears superior to vedolizumab in inducing fecal calprotectin remission.Fecal calprotectin remission associates with better clinical outcomes."
"A 24-year-old woman was admitted to our hospital due to abdominal pain and a high fever. She was diagnosed with ileocolonic Crohn's disease (CD), complicated with a gastro-colic fistula and splenomegaly. After initial treatment with an infliximab-biosimilar, all blood cell line counts markedly decreased. Three-dimensional reconstructed computed tomography revealed splenic vein narrowing. Thus, her pancytopenia was deemed to have likely been caused by hypersplenism. Surgery was performed, and clinical remission was maintained without pancytopenia. This is the first report of a CD patient with pancytopenia caused by hypersplenism that was triggered by gastro-colic fistula-associated splenic vein obstruction."
"Nitrofurantoin, minocycline, methyldopa and infliximab, have been found to induce autoimmune-like hepatitis (DI-AILH). Evidence for other drugs and herbal and dietary supplements (HDS) is unclear. The aims of the study were to establish criteria to define and review the published evidence of suspected DI-AILH. Search was undertaken in Pubmed using search terms ""drug-induced liver injury,"" ""autoimmune hepatitis,"" and ""drug-induced autoimmune hepatitis."" DI-AILH was defined as (1) drug as a potential trigger of liver injury with autoimmune features and histological findings compatible with AIH; (2) no or incomplete recovery or worsening of liver tests after discontinuation of the drug; (3) corticosteroids requirement or spontaneous recovery; (4) follow-up without immunosuppression (IS) and no relapse of AIH at least 6 months after discontinuation of IS; and (5) drugs potentially inducing AILH with a chronic course. Cases fulfilling the first four criteria were considered probable DI-AILH with three possible DI-AILH. A total of 186 case reports were identified for conventional drugs (n = 148; females 79%; latency 2.6 months) and HDS (n = 38; females 50%). The most commonly reported agents of DI-AILH were interferons (n = 37), statins (n = 24), methylprednisolone (MPS) (n = 16), adalimumab (n = 10), imatinib (n = 8), and diclofenac (n = 7). Tinospora cordifolia and Khat were the only HDS with probable DI-AILH cases. No relapses of AIH were observed when IS was stopped after interferons, imatinib, diclofenac, and methylprednisolone. Conclusion: Beyond well-recognized nitrofurantoin, methyldopa, hydralazine, minocycline, and infliximab as causes of DI-AILH, interferons, imatinib, adalimumab, and MPS were the best-documented agents leading to probable DI-AILH. Khat and Tinospora cordifolia were the only HDS found to be able to induce DI-AILH. Long-term immunosuppression appears to be rarely required in patients with DI-AILH due to these drugs."
"We aimed to compare demographics and clinical characteristics between patients with inflammatory arthritis (IA) with vs. without neutralizing anti-drug antibodies (nADAb) against tumor necrosis factor inhibitors (TNFi). A secondary aim of the study was to explore if current smokers were more frequently nADAb-positive.
TNFi-treated outpatients with IA were recruited and a broad range of disease activity measures were assessed. nADAb were assessed using a reporter gene assay. Comparisons between nADAb-positive and -negative patients were done in unadjusted analyses as well as in adjusted logistic regression and general linear models.
A total of 282 patients with IA currently under treatment with TNFi were included. nADAb were identified in 11 patients (nine treated with infliximab, one with etanercept and one with certolizumab pegol). Patients with nADAb reported significantly worse joint pain, patient's global assessment, Health Assessment Questionnaire, Bath Ankylosing Spondylitis Disease Activity/Functional Index and Short-Form-36 physical functioning scale score than patients without nADAb (p < 0.04, adjusted analyses). 28-joint Disease Activity Score, Simplified Disease Activity Index and Maastricht Ankylosing Spondylitis Enthesitis score were also significantly worse in the nADAb-positive patients (p < 0.04, adjusted analyses), as were serum calprotectin, C-reactive protein and numbers of circulating peripheral leukocytes (p ≤ 0.001). A significantly higher proportion of nADAb-positive patients were current smokers (46 vs. 15%), in unadjusted as well as adjusted analyses (p ≤ 0.008).
nADAb-positive patients were more frequently smokers and had significantly worse disease activity, physical function, and inflammatory markers, than patients without nADAb. The association between smoking and nADAb positivity warrants further examination."
"CT-P13 is an infliximab biosimilar that was granted market authorization in Switzerland in 2016. Despite the growing literature supporting the equivalence of CT-P13 compared with originator infliximab regarding the efficacy, safety, and immunogenicity and the undeniable cost-saving opportunities, CT-P13 remains widely underused in Switzerland.
Leaving aside the phenomenon of a low initiation rate, this study aimed to explore the reasons behind the high discontinuation rate observed among the patients taking CT-P13 in a large tertiary hospital in Western Switzerland.
We performed a retrospective cohort study using routinely collected data. Patients were eligible if they received originator infliximab or CT-P13 between September 2017 and December 2020. They were included if they had received at least two CT-P13 infusions during the same period. Patients were excluded if the follow-up was incomplete prior to or 6 months after their first CT-P13 infusion and if they had an oncological main diagnosis. Primary outcomes were the reasons for treatment discontinuation.
One hundred and fifty-six patients were included and classified into two groups: switchers who were treated with originator infliximab and were switched to CT-P13 (n = 85, 54%) and initiators who did not receive originator infliximab prior to CT-P13 treatment (n = 71, 46%). Included patients belonged to three different groups of diagnosis: gastroenterological (67, 43%), rheumatological (61, 39%), and immunological (28, 18%). Twenty-three (27%) switchers and 35 (49%) initiators discontinued CT-P13 after 12 months. Main reasons for CT-P13 discontinuation were lack of efficacy (n = 21, 36%) and secondary loss of response (n = 16, 28%); however, objective assessments were not available. Initiators' probability to discontinue CT-P13 at 12 months was significantly higher than switchers' (p < 0.01).
Lack of efficacy and secondary loss of response were the main reasons for the high CT-P13 discontinuation rate observed in a large tertiary hospital in Western Switzerland. Lack of active training and coordination among healthcare professionals and little education in patients may have exacerbated patients' subjective complaints and increased the CT-P13 discontinuation rate."
"To assess the efficacy of tumor necrosis factor-alpha inhibitors (TNFi) on uveitic macular edema (ME) unresponsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).
This multicenter retrospective study included patients with uveitic ME persisting despite csDMARDs. The effect of an additional TNFi on central retinal thickness (CRT), best corrected visual acuity (BCVA) and corticosteroid need was evaluated.
Thirty-five eyes (26 patients, mean age 42.9 ± 15.2 years) were included. CRT decreased from 425 ± 137 µm to 294 ± 66 µm (
The addition of a TNFi resulted in an improvement of CRT and BCVA for up to 4 years in uveitic ME but rescue treatments were needed for some patients."
"Peripheral nerve disorders in sarcoidosis consist of granulomatous neuropathy and non-granulomatous small fiber neuropathy (SFN), which differ in their underlying pathology, diagnostic methods and treatment. While granulomatous nerve involvement is rare in sarcoidosis, SFN is reported in over 40% of systemic cases. Distal symmetric polyneuropathy and asymmetric polyradiculoneuropathy are the most common presentations of granulomatous neuropathy, which typically responds to corticosteroids. In contrast, SFN is often manifested as non-length dependent pain and paresthesias that may improve with intravenous immune globulin or infliximab. Early recognition and treatment of sarcoidosis neuropathy can lead to improved outcomes and patient quality of life."
Large Vessel Vasculitides: Giant Cell Arteritis and Takayasu Arteritis - Similarities and Differences 
"A 53-year-old man was admitted for respiratory failure due to severe acute respiratory syndrome caused by a severe acute respiratory syndrome coronavirus 2 infection. The patient required prolonged artificial ventilation and extracorporeal membrane oxygenation (ECMO) for respiratory support. Despite successful discontinuation of ECMO, the patient experienced profuse watery diarrhea (5-10 L/day). A colonoscopy revealed an inflamed surface without undulation that uniformly extended throughout the colon. Biopsy specimens revealed complete disappearance of existing crypts and replacement with squamous or transitional epithelium normally observed in the anal transitional zone mucosa, with granulation tissue proliferation in the lamina propria. Watery diarrhea persisted despite corticosteroid and infliximab administration. Although diarrhea due to atrophy of the surface and cryptic epithelium as an intestinal manifestation of coronavirus disease 2019 usually responds to corticosteroids, refractory diarrhea can be attributed to squamous metaplasia with complete disappearance of the surface and cryptic epithelium."
"Ulcerative colitis (UC) is characterized by refractory and recurrent mucosal inflammation, leading to a substantial healthcare burden. Diagnostic biomarkers predicting disease activity and treatment response remain elusive. To evaluate the application value of a novel neutrophil-based index (the neutrophil-to-albumin ratio, NAR) as a novel diagnostic biomarker in patients with UC and a predictive marker for disease activity and response to infliximab (IFX) therapy.
Clinical characteristics and laboratory parameters of enrolled subjects (patients with UC and healthy controls) were retrieved from the electronic medical record database of our hospital. Serum cytokine and fecal calprotectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosal expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR).
We found that NAR, which had not yet been explored in UC, was significantly increased in patients with UC (
Our study provides evidences to utilize NAR in the diagnosis, activity monitoring, and IFX response prediction in patients with UC."
"The number of available biological therapies have doubled over the last 10 years and the arrival of novel molecules (interleukin 23p19 inhibitors) is ongoing alongside the development of small molecules. As a result of this vast landscape of treatment, positioning advanced therapies (according to clinical situation, efficacy and safety) is of paramount importance to providing personalized, appropriate IBD treatment. In this publication the recent available literature is summarized for practical integration into clinical practice including comparative efficacy data, patient and disease demographics. We refer to recent publications and expert opinion in order to facilitate the decision making process of positioning biologicals IBD treatment."
"Previous studies reported that transnasal ileus tube was a new and useful method for rapid relief of small intestinal obstruction. However, no study reported the impacts of the transnasal ileus tube for Crohn's disease combined with intestinal obstruction. We aimed to describe the strategy to the small intestine obstruction caused by Crohn's disease on the basis of transnasal ileus tube insertion.
From November 2019 to November 2021, the data of 6 hospitalized patients with CD, diagnosed and conservatively treated in The Second Hospital of Nanjing, were not relived and retrospectively collected. After the insertion of transnasal ileus tube, demographic information, clinical features and treatment data were extracted from medical records.
Six Crohn's disease patients with intestinal obstruction were included. Half of them were male. The patients aged from 29 to 70 years. Five patients had chronic intestinal obstruction more than one year. Three patients had intestinal surgery history. One patient had colonic abdominal fistula and anastomotic fistula, when she took intermittent usage of sulfsalazine and steroid. On admission, all the patients had abdominal pain, distention and mass. Five patients had anemia, low albumin and cholinesterase. All CDAI scores were more than 400. Compared to 19 patients with incomplete intestinal obstruction improved by nasogastric decompression tube, 6 patients with intestinal obstruction catheter had significant difference in time for relieving abdominal pain and distension (p = 0.003), time for alleviating abnormal mass (p ≤ 0.01), drainage volume (p = 0.004), and preoperative CDAI score (p = 0.001). Compared with X-ray image before insertion, complete remission of obstruction of 5 patients were observed in intestinal cavity after insertion. After 1-2 months nutrition, all the patients had small intestine resection and ileostomy, half of them underwent colectomy and fistula repair, and 4 patients were performed enterolysis at the same time, the residual small intestine length ranging from 250 to 400 cm. 1 patient had permanent ileostomy;1 patient had abdominal infection after operation. The typical manifestations of acute and chronic inflammation, transmural inflammation, pseudopolyps and serous fiber hyperplasia could be seen in pathological findings of patients 1 to 5. All the patients continued enteral nutrition after surgery. Four patients were treated with infliximab or vedolizumab.
The current intestinal obstruction catheter which is used to treat patients with Crohn's combined obstruction can afford quick clinical remission, longer nutrition time, and suitable preoperative CDAI score for operation, which is worthy of wildly being used."
"Vaccines against SARS-CoV-2 are believed to play a key role in the suppression of the COVID-19 pandemic. However, patients suffering from inflammatory bowel diseases (IBD) were excluded from SARS-CoV-2 vaccines trials. Therefore, concerns regarding vaccination efficacy and safety among those patients were raised. Overall, vaccination is well tolerated in the IBD population, and different gastroenterological societies recommend vaccinating patients with IBD at the earliest opportunity to do so. Nevertheless, very little is known about the safety of COVID-19 vaccines in special IBD populations such as pregnant and breastfeeding women or pediatric patients, and further research on this matter is crucial. The available data on vaccine efficacy are promising and show high seroconversion rates in IBD patients on different immune-modifying therapies. However, patients treated with high doses of systemic corticosteroids, infliximab or infliximab and immunomodulators may have a blunted response to the vaccination. The data on COVID-19 vaccination willingness among patients with IBD are conflicting. Nevertheless, vaccine effectiveness and safety are reported to be the most common reasons for hesitancy. This review examines the effectiveness and safety of COVID-19 vaccines and describes vaccination willingness and the reasons for potential hesitancy among patients with IBD."
"Biologics are effective, though costly, medications for the treatment of rheumatoid arthritis (RA). Biosimilars are medications that have no clinically meaningful differences when compared with their corresponding reference biologics but cost significantly less. The U.S. Food and Drug Administration and the European Medication Agency have approved biosimilars for adalimumab, etanercept, infliximab, and rituximab for the treatment of RA. Streamlined approval processes are expected to expedite biosimilar development while maintaining strict safety and efficacy standards. Encouragingly, many analyses have demonstrated the potential for massive healthcare savings if biosimilars are used over biologics. Challenges to biosimilar uptake, including patient and provider hesitancy, can likely be overcome with the education of all stakeholders within healthcare systems."
"This study aims to examine the efficacy and safety of the antitumor necrosis factor (TNF) drugs in ankylosing spondylitis (AS) patients with chronic kidney disease.
In this study, 24 male patients with a glomerular filtration rate (GFR) of <60 mL min􏰁1 1.73 m􏰁2 were included among 863 patients who were followed-up once in 3 months regularly from 2010 to 2018years. Twenty-four patients were chosen for the control group among 420 male patients whose renal functions were normal using random sampling. We examined C-reactive protein, erythro- cyte sedimentation rate, serum creatinine, and GFR values, and also the measurements of Bath Anky- losing Spondylitis Disease Activity Index (BASDAI) were recorded at the beginning of the treatment with anti-TNF agents and in the 3rd, 6th, 9th, 12th, and final visit months.
Eleven (45.9%) of the patients included in the study were in the routine dialysis program. The initial anti-TNF treatments were etanercept (62.5%), infliximab (16.7%), adalimumab (16.7%), and goli- mumab (4.1%). Treatment was effective in 22 (91.7%) of the patients. When the values of the two groups' patients were compared at the beginning of the treatment, there was a substantial reduction regarding BASDAI (P < .001). Pleural effusion, infective endocarditis, septic arthritis, and prosthesis infection were major side effects (n 1⁄4 4). The mortality rate of the 24 patients was 29.2% (n 1⁄4 7).
This study demonstrated that anti-TNF drug treatment is effective and safe in patients with AS who have chronic kidney disease."
"In ulcerative colitis (UC), the molecular mechanisms that drive disease development and patient response to therapy are not well understood. A significant proportion of patients with UC fail to respond adequately to biologic therapy. Therefore, there is an unmet need for biomarkers that can predict patients' responsiveness to the available UC therapies as well as ascertain the most effective individualised therapy. Our study focused on identifying predictive signalling pathways that predict anti-integrin therapy response in patients with UC.
We retrieved and pre-processed two publicly accessible gene expression datasets (GSE73661 and GSE72819) of UC patients treated with anti-integrin therapies: (1) 12 non-IBD controls and 41 UC patients treated with Vedolizumab therapy, and (2) 70 samples with 58 non-responder and 12 responder UC patient samples treated with Etrolizumab therapy without non-IBD controls. We used a diffusion-based signalling model which is mainly focused on the T-cell receptor signalling network. The diffusion model uses network connectivity between receptors and transcription factors.
The network diffusion scores were able to separate VDZ responder and non-responder patients before treatment better than the original gene expression. On both anti-integrin treatment datasets, the diffusion model demonstrated high predictive performance for discriminating responders from non-responders in comparison with 'nnet'. We have found 48 receptor-TF pairs identified as the best predictors for VDZ therapy response with AUC ≥ 0.76. Among these receptor-TF predictors pairs, FFAR2-NRF1, FFAR2-RELB, FFAR2-EGR1, and FFAR2-NFKB1 are the top best predictors. For Etrolizumab, we have identified 40 best receptor-TF pairs and CD40-NFKB2 as the best predictor receptor-TF pair (AUC = 0.72). We also identified subnetworks that highlight the network interactions, connecting receptors and transcription factors involved in cytokine and fatty acid signalling. The findings suggest that anti-integrin therapy responses in cytokine and fatty acid signalling can stratify UC patient subgroups.
We identified signalling pathways that may predict the efficacy of anti-integrin therapy in UC patients and personalised therapy alternatives. Our results may lead to the advancement of a promising clinical decision-making tool for the stratification of UC patients."
"Mutations or polymorphisms of genes that are associated with inflammasome functions are known to predispose individuals to Crohn's disease and likely affect clinical presentations and responses to therapeutic agents in patients with Crohn's disease. The presence of additional gene mutations/polymorphisms that can modify immune responses may further affect clinical features, making diagnosis and management of Crohn's disease even more challenging. Whole-exome sequencing is expected to be instrumental in understanding atypical presentations of Crohn's disease and the selection of therapeutic measures, especially when multiple gene mutations/polymorphisms affect patients with Crohn's disease. We report the case of a non-Hispanic Caucasian female patient with Crohn's disease who was initially diagnosed with pediatric acute-onset neuropsychiatric syndrome with fluctuating anxiety symptoms at 9 years of age. This patient was initially managed with pulse oral corticosteroid treatment and then intravenous immunoglobulin due to her immunoglobulin G1 deficiency. At 15 years of age, she was diagnosed with Crohn's disease, following onset of acute abdomen. Treatment with oral corticosteroid and then tumor necrosis factor-α blockers (adalimumab and infliximab) led to remission of Crohn's disease. However, she continued to suffer from chronic abdominal pain, persistent headache, general fatigue, and joint ache involving multiple joints. Extensive gastrointestinal workup was unrevealing, but whole-exome sequencing identified two autosomal dominant gene variants: NLRP12 (loss of function) and IRF2BP2 (gain of function). Based on whole-exome sequencing findings, infliximab was discontinued and anakinra, an interleukin-1β blocker, was started, rendering marked improvement of her clinical symptoms. However, Crohn's disease lesions recurred following Yersinia enterocolitis. The patient was successfully treated with a blocker of interleukin-12p40 (ustekinumab), and anakinra was discontinued following remission of her Crohn's disease lesions.
Loss-of-function mutation of NRLRP12 gene augments production of interleukin-1β and tumor necrosis factor-α, while gain-of-function mutation of IRF2BP2 impairs cytokine production and B cell differentiation. We propose that the presence of these two autosomal dominant variants caused an atypical clinical presentation of Crohn's disease."
"Mucosal healing (MH) has become the treatment goal of patients with Crohn's disease (CD). This study aims to develop a noninvasive and reliable clinical tool for individual evaluation of mucosal healing in patients with Crohn's disease.
A multicenter retrospective cohort was established. Clinical and serological variables were collected. Separate risk factors were incorporated into a binary logistic regression model. A primary model and a simple model were established, respectively. The model performance was evaluated with C-index, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. Internal validation was performed in patients with small intestinal lesions.
A total of 348 consecutive patients diagnosed with CD who underwent endoscopic examination and review after treatment from January 2010 to June 2021 were composed in the derivation cohort, and 112 patients with small intestinal lesions were included in the validation cohort. The following variables were independently associated with the MH and were subsequently included into the primary prediction model: PLR (platelet to lymphocyte ratio), CAR (C-reactive protein to albumin ratio), ESR (erythrocyte sedimentation rate), HBI (Harvey-Bradshaw Index) score and infliximab treatment. The simple model only included factors of PLR, CAR and ESR. The primary model performed better than the simple one in C-index (87.5% vs. 83.0%, p = 0.004). There was no statistical significance between these two models in sensitivity (70.43% vs. 62.61%, p = 0.467), specificity (87.12% vs. 80.69%, p = 0.448), PPV (72.97% vs. 61.54%, p = 0.292), NPV (85.65% vs. 81.39%, p = 0.614), and accuracy (81.61% vs. 74.71%, p = 0.303). The primary model had good calibration and high levels of explained variation and discrimination in validation cohort.
This model can be used to predict MH in post-treatment patients with CD. It can also be used as an indication of endoscopic surveillance to evaluate mucosal healing in patients with CD after treatment."
"Anti-tumor necrosis factor (TNF) therapy is widely used to treat Crohn's disease (CD). Unfortunately, 10%-40% of patients have primary non-response to anti-TNF therapy. TNF family genes play crucial roles in inflammation and immune regulation; however, the effects of TNF family genes on CD remain unclear.
CD expression profiles were downloaded from the Gene Expression Omnibus database. Unsupervised clustering was then used to identify the gene subtypes in CD based on the expressions of TNF family genes. The features of the gene subtypes were characterized using functional enrichment and immune infiltration analyses, and biomarkers of the gene subtypes were identified.
Patients with CD were divided on the basis of unsupervised clustering into two gene subtypes: immune and metabolic. Gene subtype A was significantly correlated with leukocyte migration and cytokine interactions, whereas gene subtype B was associated with metabolic pathways. Whereas 89.5% of the patients in gene subtype B responded to infliximab, only 16.7% of patients in gene subtype A responded. In addition, a combination of interleukin 1 beta (IL1β), interleukin 6 (IL6), and Toll-like receptor 4 (TLR4) can effectively distinguish between gene subtypes A and B.
Comprehensive analyses of the TNF family genes may reveal the underlying pathogenesis of CD. The classification of subtypes may provide new ideas for the personalized treatment of patients with CD."
"Acute COVID-19 in pediatric and young adult patients tends to be milder in severity compared to adult infection. Recent studies seem to show that inflammatory bowel disease (IBD) patients are at no greater risk than the general population. We aim to describe our experience in the follow-up of pediatric and young adult patients with IBD followed in our center and determine possible risk factors of said population for severe COVID-19.
We performed a retrospective study of all patients aged under 25 years followed for IBD at the Unit of Pediatric Gastroenterology in a tertiary center between December 2019 and April 2021 evaluating the incidence of COVID-19 and characterization of positive cases.
Of the 268 participants, 24 had COVID-19: the mean age was 19 years old and gender had an equal distribution; 75% (
Our data suggest that pediatric and young adult IBD patients have a low risk for complications and hospitalization, regardless of IBD treatment. We believe that this experience is encouraging and allows for safe counseling regarding treatment options and school attendance in pediatric and young adult IBD patients.
Na população pediátrica e de jovens adultos a gravidade da COVID-19 tende a ser moderada quando comparada com os doentes adultos. Os estudos mais recentes sugerem que os doentes com doença inflamatória intestinal (DII) não têm risco acrescido em relação à população geral. O objetivo do presente estudo é a descrição da nossa experiência no follow-up de crianças e jovens adultos com DII a COVID-19 e determinar a existência de possíveis fatores de risco para doença grave na referida população.
Foi realizado um estudo retrospetivo de todos os doentes com idade inferior a 25 anos, seguidos na Unidade de Gastrenterologia Pediátrico de um centro terciário por DII, com avaliação da incidência de COVID-19 entre dezembro de 2019 e abril de 2021, e caracterização dos casos postivos.
Entre os 268 participantes, 24 tiveram COVID-19. A idade média foi de 19 anos com uma distribuição por género equiparável. Destes, 75% (
Os nossos dados sugerem que doentes pediátricos e jovens adultos com DII apresentam um risco baixo de complicações ou hospitalização associados à COVID-19, independentemente do tratamento em curso para a DII. Este estudo apresenta resultados encorajadores e contribui para o aconselhamento adequado e fundamentado aos doentes e respetivos cuidadores, no que diz respeito às opções terapêuticas e frequência escolar dos doentes pediátricos e jovens adultos com DII."
"Cell division control 42 (CDC42) regulates multiple processes of inflammation and/or immunity in autoimmune diseases and also relates to the treatment efficacy of biologic regimens clinically. This study aimed to explore the longitudinal change in CDC42 during infliximab (IFX) treatment and its correlation with IFX response in ulcerative colitis (UC) patients.
Active UC patients (N = 48) who received IFX were recruited, and their CDC42 expressions in peripheral blood mononuclear cells (PBMCs) were detected before treatment (W0) and at 12 weeks after treatment (W12) using RT-qPCR. Also, CDC42 in PBMCs from UC patients with remission (N = 20) and health controls (HCs) (N = 20) were detected.
CDC42 was reduced in active UC patients compared with UC patients with remission (p = 0.014) and HCs (p < 0.001). Besides, CDC42 was negatively correlated with CRP (p = 0.025), TNF-α (p = 0.024), IL-1β (p = 0.045), IL-17A (p = 0.039), and Mayo score (p = 0.015) in active UC patients, but did not relate to ESR, disease duration, or IL-6 (all p > 0.05), while CDC42 was only negatively related to CRP in UC patients with remission (p = 0.046). Interestingly, CDC42 was increased at W12 after IFX treatment in active UC patients (p < 0.001). Specifically, CDC42 was elevated during treatment in active UC patients with IFX response (p < 0.001), but did not obviously change in those without IFX response (p = 0.061). Furthermore, CDC42 at W12 was higher in active UC patients with IFX response compared with those without IFX response (p = 0.049).
Cell division control 42 serves as a potential biomarker for monitoring disease progression and IFX response in UC patients."
"The current study aimed to elucidate the neurotoxic potential of DOX to induce AD-like pathology paying attention to the role of wingless-integrated/β-catenin (Wnt/β-catenin) signaling pathway. A major aim was to evaluate the efficacy of infliximab (IFX) either individually or in combination with 2-mercaptoethane sulfonate sodium (MESNA) on the DOX-induced neurotoxicity in rats.
AD-like pathology was induced in adult male Wistar rats by intraperitoneal (i.p.) administration of DOX at a dose of 3.5 mg/kg twice a week for 3 weeks. DOX-injected rats were then treated with either INF at a single dose of 5 mg/kg i.p. (IFX group), MESNA at a dose of 160 mg/kg/day i.p. for 4 weeks (MESNA group) or their combination at the same specified doses (INF + MESNA group). At the end of the study period, behavioral assessment was performed and the brain tissue samples were harvested at sacrifice.
DOX-treated rats significantly exhibited AD-like brain injury, increased amyloid burden, enhanced neuroinflammation and apoptosis, and multifocal histological injury in the cerebral cortex with widespread vacuolations. IFX and MESNA significantly reversed all the aforementioned detrimental effects in the DOX-treated rats.
The study has provided sufficient evidence of the potential of IFX and/or MESNA to ameliorate the DOX-induced neurotoxicity, with the best improvement observed with their combined administration. A new insight has been introduced into the critical role of Wnt/β-catenin activation."
"Numerous previous studies have examined risk of herpes zoster (HZ) in psoriatic disease; however, the results of these studies are conflicting and the relative risks associated with different treatments remain largely unknown. In this meta-analysis, we examined the relative risk of HZ associated with systemic treatments for psoriatic disease.
PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched to identify relevant English-language studies published up to April 2021. Data were extracted using a standardized data extraction form. Network meta-analyses (NMA) was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We examined the differences in HZ risk (incidence rate ratio; IRR) between treatments using a random-effects model for direct pairwise comparisons and NMA. The surface under the cumulative ranking area was calculated to rank the HZ risk for each treatment condition.
This study analyzed 13 studies including 19 treatment arms involving a total of 443,104 patients with psoriatic disease. Corticosteroids (CS) [IRR, 2.56; 95% confidence interval (CI), 1.59-4.13], a Janus kinase inhibitor (JAKi; tofacitinib) (IRR, 2.34; 95% CI, 1.03-5.32), infliximab (IRR, 2.32; 95% CI, 1.27-4.21), conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) + CS (IRR, 2.26; 95% CI, 1.23-4.17), anti-tumor necrosis factor-α (anti-TNF-α) + csDMARDs and/or CS (IRR, 2.13; 95% CI, 1.38-3.31), csDMARDs (IRR, 1.62; 95% CI, 1.18-2.22), and anti-TNF-α except infliximab (IRR, 1.61; 95% CI, 1.13-2.30) were all associated with a significantly higher HZ risk compared to controls. CS treatment possessed the highest HZ risk, followed by infliximab and JAKi (tofacitinib). Phosphodiesterase-4 inhibitor, anti-interleukin-17, -23 or -12/23, phototherapy, and acitretin showed a risk similar to controls without significant differences.
The NMA demonstrated CS, infliximab, and JAKi (tofacitinib), and several combination treatments were associated with higher HZ risk in patients with psoriasis and psoriatic arthritis. Differences in HZ risk should be taken into consideration when considering optimal psoriasis treatment."
"In this study, we aimed to evaluate the clinicobiological findings and the biotherapy treatment response of Moroccan patients with juvenile idiopathic arthritis (JIA), and compare our results with those of populations of the same or different ethnicity. This retrospective cross-sectional study included patients aged 1-14 years, diagnosed between 2003 and 2018 with JIA according to the International League of Associations for Rheumatology (ILAR) 2004 revised criteria, who received biologics and who followed up during the year 2018 in the day hospital of our single-center tertiary pediatric rheumatology unit. Among 59 patients, 53% had systemic JIA, 29% seronegative polyarticular JIA, 8% arthritis-related enthesitis, 5% seropositive polyarticular JIA, 3% oligoarthritis and 2% psoriatic arthritis. Tocilizumab was the most prescribed biologic (34 patients), followed by Etanercept (25 patients), Adalimumab (6 patients), Anakinra (3 patients) and biosimilar Infliximab (3 patients). Eleven patients switched biologics. Erythrocyte sedimentation rate, number of active joints and the Juvenile Arthritis Disease Activity Score 27 (JADAS 27) decreased significantly at month three for 56 patients. These results were maintained at the last visit for 31 patients, while there was a slight worsening in 15 of them and no assessment in 13 patients due to lack of data. At the end of the evaluation, 39% of the patients were exclusively on biotherapy, while 61% were still on other disease-modifying antirheumatic drugs (DMARDs). Twenty-eight patients developed lymphopenia, 4 patients had elevated transaminases, 4 patients developed moderate infection, and 2 patients developed macrophage activation syndrome. To the best of our knowledge, this is the first Moroccan study on biotherapy in JIA. Our study population was characterized by a male predominance, a high frequency of the systemic form and a low percentage of positive antinuclear antibodies. We have shown that in the era of biologics, only 67.4% patients are nearly disease-free at the end of the study with a real risk of side effects. Although effective, biotherapy must be closely monitored because of potentially severe side effects, especially with Tocilizumab use."
"Reactive arthritis particularly affects individuals 20 to 40 years old. The most common preceding infections are enteric and urogenital. The association of group C and group G streptococcal infections with reactive arthritis is rare. We present a case of old-onset bilateral sacroiliitis following group C streptococcal infection in an 81-year-old woman, treated successfully with a steroid taper and infliximab."
"The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia.
A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn's & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018.
In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn's disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively.
The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia."
"The introduction of biological agents with strong anti-inflammatory action, such as antitumor necrosis factor (TNF) agents, has changed inflammatory bowel disease (IBD) treatment strategy and goals, and has contributed significantly to improve the long-term prognosis of patients. Moreover, several biological agents are being used or researched in pediatric populations. However, only two biological agents, infliximab (IFX) and adalimumab (ADL), are currently approved for children and adolescents. In pediatric IBD, there are limitations and burdens associated with facilitating mucosal healing (MH) when utilizing these two biological agents. ADL is effective in both naïve patients and those with previous experience with biologics. Beyond clinical remission, this drug is also effective for MH and histological remission. The use of therapeutic drug monitoring to further enhance the effectiveness of ADL treatment can be expected to reduce treatment failure of ADL and pave the way for appropriate treatment in the treat-to-target era. This review paper focuses on ADL, examine studies conducted in children, and determine the role this agent plays against pediatric inflammatory bowel disease."
"Complex perianal fistulas (CPFs) in children even in the absence of luminal symptoms prompt evaluation for Crohn's disease (CD). Reports of isolated CPF in children, however, are sparse. In perianal CD, antitumor necrosis factor α (anti TNF) therapy is recommended. We aimed to describe our experience with anti TNF therapy in children with isolated CPF without evidence of luminal CD.
We retrospectively reviewed charts of patients with isolated CPF who were treated with anti TNF agents between 2011 and 2019 in a tertiary center. MRI pelvis findings at baseline versus end of follow up were scored using MAGNIFI-CD. Outcomes included clinical remission, radiological response and radiological remission based on MAGNIFI-CD score at end of follow up.
Overall, 17 patients were identified, [10 males (59%), mean age at anti TNF initiation 13.4 ± 2.9 years]. Median time from perianal disease onset to anti TNF was 16.5 months (IQR 9.4-36.4). None of the patients had luminal inflammation. Prior to anti TNF, all patients had been treated with antibiotics without sufficient improvement, and 9/17 with abscess drainage and or Seton insertion. Nine patients (53%) were treated with infliximab while 8 (47%) received adalimumab. Median duration of follow up was 30.7 months (IQR = 12.7-44.8). At the end of follow up 9 patients (53%) achieved clinical remission. When comparing MRI prior to and after anti TNF, 36% (5/14) had radiologic response, of whom 2 (14%) achieved radiologic resolution.
Anti TNF agents may be an effective treatment option for children with isolated CPF. Whether these patients should be considered part of the CD phenotypic spectrum or a distinct entity is unclear.
Therapeutic."
"Sarcoidosis is a multisystem granulomatous disease affecting the nervous system in 3%-5% of cases. It can affect almost any component of the nervous system. Involvement of the cauda equina is an understudied phenotype, and questions remain regarding its natural history and optimal approach to management. This study aims to study the long-term clinical evolution of neurosarcoidosis affecting the cauda equina, response to treatment, and clinical and radiographic outcomes.
Patients with neurosarcoidosis treated at Emory University between January 1, 2011, and December 8, 2021, were retrospectively evaluated for manifestations of cauda equina disease and included if disease of the cauda equina could be substantiated by MRI or EMG.
Of 216 cases, 14 (6.5%) involved the cauda equina. The median age was 49.5 years, and most were female (85.7%) and African American (64.3%). Chronic (>28 days) presentations were most common (78.6%), but acute (<7 days, 14.3%) and subacute (7-28 days, 7.1%) were also seen. The median modified Rankin Scale (mRS) score at nadir was 3 (range 2-4). Symptoms were asymmetric in 78.6% and included leg numbness (85.7%), leg weakness (64.3%), perineal numbness (35.7%), pain (42.3%), and incontinence (21.4%). On MRI, the cauda equina enhanced in 100%, appeared nodular in 78.6%, and was diffusely involved in 71.4%. Coexisting myelitis was common (cervical 28.6%, thoracic 35.7%, and conus medullaris 28.6%). Intracranial inflammation included leptomeningitis (71.4%) and cranial neuropathies (57.1%). Electrodiagnostic studies were conducted in 3 with only one showing features consistent with a radicular process. Serum and CSF angiotensin-converting enzyme levels were elevated in 38.5% and 0.0%, respectively. CSF white blood cell and protein were elevated in 92.9%. Corticosteroids were tried in all patients with durable stabilization or improvement in only 3 (21.4%). Second-line agents associated with improvement included methotrexate/infliximab (3/4, 75%), methotrexate (3/4, 75.0%), and azathioprine (1/1, 100%). During a median follow-up of 22.5 months, the final median mRS score was 3. Relapses occurred at a median of 6 months in 21.4%. In 9 patients with MRI follow-up, 6 improved (66.7%), 1 stabilized (11.1%), and 2 worsened (22.2%).
Characteristic features of cauda equina involvement by neurosarcoidosis include chronically delayed presentations, nodular enhancement on MRI, poor response to corticosteroids, and substantial resultant neurologic disability."
"The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment.
This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases.
Treatment interruptions were associated with immunisation in patients using infliximab (
Our results suggest that the interruptions of the treatment with TNF-inhibitors expose patients to immunisation and increase the need for drug switching. These findings stress the importance of careful judgement of the need for a short interruption in the biological treatment in clinical work, especially during non-severe infections."
"Crohn's disease (CD) is an inflammatory bowel disease (IBD) with major extraintestinal manifestations. Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that has previously been described to have a strong association with CD. Though the pathophysiology remains uncertain, this case series highlights the different aspects of disease presentation, similarities, severity, current treatment modalities, and the relational conflict between HS as a paradoxical side effect of biologic agents (BA) that is not well established. We identified a total of three patients with CD and HS and described their clinical presentation and management. A systematic search of the literature with PubMed and Ovid MEDLINE was done in 2021. Two patients were initially diagnosed with CD prior to developing skin manifestations. The third patient was diagnosed with HS first, then was found to have gastrointestinal symptoms. All patients had HS requiring surgical intervention. One patient failed a biological agent but responded to another. The second patient was treated with cytotoxic agents with acceptable results. The third patient was managed without the use of biologics. One of three patients' clinical courses may suggest a paradoxical side effect of BA.  The relationship between CD and HS is based on several case reports. A prospective study will help establish the relationship as well as shed light on the treatment of both conditions simultaneously. In addition, further evaluation of the causal relationship between BA, specifically adalimumab and infliximab as treatment for CD and HS are warranted to effectively manage Crohn's disease, evaluate paradoxical HS, and improve outcomes of both HS and CD. CD and HS impact a patient's quality of life and physicians should therefore have a high degree of awareness upon diagnosis."
"To compare the risk of five nonpulmonary infections leading to hospitalization between spondyloarthritis (SpA) and nonspecific back pain (NSBP), and to identify the risk factors.
A total of 3018 patients with SpA and 2527 patients with NSBP were identified. Data from December 1995 to June 2019 was retrieved from a centralized electronic medical record system. The date of onset of five types of nonpulmonary infections including: urinary tract infection (UTI), skin infection, gastroenteritis (GE), septic arthritis, and pancreato-hepatobiliary tract infection were identified. Demographic data, comorbidities, and medications used were also retrieved. Comparative risk of each type of infection between SpA and NSBP was determined using propensity score adjustment method. Cox regression model was used to identified risk factors.
Patients with SpA were younger in age, predominantly male, with fewer comorbid diabetes mellitus (DM), renal impairment, and depression. Compared with NSBP, patients with SpA had higher risk of UTI (hazard ratio [HR] 1.91; p < .001), skin infection (HR 1.79; p < .001), and septic arthritis (HR 4.57; p = .04). Risk of GE (HR 1.42; p = 1.00), and pancreato-hepatobiliary tract infection (HR 1.67; p = .06) were not increased. Infliximab was an independent risk factor for UTI (HR 2.21; p = .04). Duration of steroid therapy >6 months (HR 2.22; p < .001), smoker (HR 1.81; p < .001), and psoriasis (HR 2.47; p < .001) were risk factors for skin infection.
SpA was associated with increased risk of UTI, skin infection, and septic arthritis. Infliximab, prolonged steroid therapy, smoking, and psoriasis were associated risk factors."
"This real-world study evaluated biologic treatment patterns in patients with moderate-to-severe ulcerative colitis (UC).
IQVIA PharMetrics, IBM MarketScan, and Optum Clinformatics were pooled to identify UC patients with ≥1 claim for UC and ≥1 claim for adalimumab (ADA), golimumab (GOL), infliximab (IFX), or vedolizumab (VDZ). The index date for each biologic was the first claim for that biologic. Patients could be included in >1 cohort if they switched biologics during the identification period. Continuous eligibility for medical/pharmacy benefits was required for 12 months before (baseline) and after (follow-up) the index date. Patients lacking claims for any biologic during baseline were categorized as bio-naïve; those with any biologic claim were categorized as bio-experienced. Persistence was defined as the proportion of patients that remained on the index biologic without a gap between claims of >28 days for ADA, >56 days for GOL, and >112 days for IFX and VDZ. Dose titration was assessed among patients with ≥2 maintenance doses during follow-up among ADA, GOL, and VDZ patients.
In total, 6,106 bio-naïve UC patients and 1,027 bio-experienced UC patients were identified. Patients treated with VDZ and IFX had the highest persistence followed by ADA and GOL patients for bio-naïve and bio-experienced, respectively. ADA patients had a numerically higher proportion of patients with 50% dose escalation, followed by VDZ and GOL; 50% dose reduction was observed in ≤1% patients.
In this descriptive study of UC patients without confounder adjustment, VDZ persistence was numerically highest followed by IFX, GOL, and ADA across both populations."
"Ulcerative colitis is highly prevalent in Canada and cost-effective ulcerative colitis therapies are warranted. Vedolizumab subcutaneous (SC) formulation was recently approved for ulcerative colitis maintenance therapy. We assessed vedolizumab SC cost effectiveness vs conventional and advanced therapeutics in patients with moderately to severely active ulcerative colitis from a Canadian public healthcare payer perspective.
A hybrid decision tree/Markov model was developed to evaluate vedolizumab SC costs, quality-adjusted life-years, and cost effectiveness vs conventional therapy, adalimumab SC, infliximab intravenous, golimumab SC, tofacitinib, ustekinumab SC, and vedolizumab intravenous. This model predicts the number of patients achieving clinical response and remission after treatment induction, and sustained benefit during maintenance treatment. To account for statistical uncertainties, the base-case analysis was conducted in a probabilistic manner. Scenario analyses examined the impact of previous treatment with anti-tumor necrosis factor agents, dose escalation, loss of efficacy, and treatment adherence.
In the base-case analysis, conventional therapy was the most cost-effective therapeutic option in the overall population. Vedolizumab SC was cost effective and dominant compared with other advanced therapies (adalimumab, golimumab, infliximab, tofacitinib 5 mg, ustekinumab, and vedolizumab intravenous). The annual vedolizumab SC cost per patient was reduced vs ustekinumab SC, tofacitinib 5 mg, vedolizumab intravenous, and golimumab SC by $47,024, $3251, $2120, and $2004 (Canadian dollars), respectively, and exceeded that of infliximab, adalimumab, and conventional therapy by $582, $3293, and $41,024, respectively. Among the treatments, vedolizumab SC generated the highest quality-adjusted life-years overall (14.21), which translated into the best incremental cost per quality-adjusted life-years gained over conventional therapy in the overall population ($109,374) and in anti-tumor necrosis factor-naïve and anti-tumor necrosis factor-experienced patients ($41,658/$114,287).
Conventional therapy offered the most cost-effective therapeutic option followed by vedolizumab SC. Based on a $50,000/quality-adjusted life-year threshold, vedolizumab was cost effective in anti-tumor necrosis factor-naïve patients but not the overall population also when compared to conventional therapy."
"Optimal outcomes in acute severe ulcerative colitis (ASUC) are related to time-bound management based upon early prediction of response to intravenous (IV) steroids. In an earlier study, we described the All India Institute of Medical Sciences (AIIMS) index (baseline Ulcerative Colitis Endoscopic Index of Severity [UCEIS] ≥ 7 and day 3 fecal calprotectin [FCP] > 1000 μg/g) for predicting failure of IV steroids. The current study is designed to validate this index in a prospective cohort.
IV steroid-naïve patients with ASUC, satisfying Truelove and Witts' criteria, hospitalized from August 2018 to July 2019 were included. Patients' assessment included baseline sigmoidoscopy, day 1 and 3 FCP, hemogram, biochemistry and day 3 C-reactive protein. All patients received IV steroids, and the primary outcome was steroid failure, defined as the need for colectomy or rescue therapy with cyclosporine (CYC)/infliximab (IFX) during admission.
Of the 47 patients, eight were excluded (four received steroids outside, two were directly taken for surgery/infliximab therapy, one had toxic megacolon, and one had infectious colitis), and 39 patients were included (mean age: 36.1 ± 12.6 years, male: 31%). Fifteen patients (38%) failed IV steroid and required rescue therapy (IFX: 9, CYC: 2, Colectomy: 3, IFX followed by colectomy: 1). On univariate analysis, UCEIS ≥ 7 at baseline (p = 0.006), day 1 FCP (p = 0.03), day 3 FCP > 1000 μg/g (p = 0.001), Oxford criteria (p = 0.04) and AIIMS index (p < 0.001) were significantly different between steroid responders and steroid failures. On multivariate analysis, day 3 FCP > 1000 μg/g (odds ratio (odds ratio (OR)= 6.4;(95% CI =2.2-196.1) and baseline UCEIS ≥ 7 (OR) = 10.1;(95% CI = 2.1-80.2) were independent predictors. The AIIMS index predicted steroid failure with a better specificity (100% vs. 83%, p = 0.04) and positive predictive value (100% vs. 64%, p = 0.03) than Oxford criteria.
AIIMS index has been validated in 39 prospective ASUC patients as an effective early predictor of steroid failure (sensitivity = 53%, specificity = 100%)."
"Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder characterized by painful nodules, abscesses, fistulae, and scarring with a predilection for flexural regions. Several biologics and small molecule inhibitors are being evaluated in clinical trials for treatment.
The authors discuss the data available from clinical trials and smaller, high-quality studies for existing and emerging biologic and small molecule inhibitor therapies for treatment of HS. Biologics discussed include TNFα, IL-17, IL-23, IL-12/23, and IL-1 inhibitors. Small molecule inhibitors discussed include PDE4, JAK, TYK, IFX-1, and complement cascade inhibitors. Pharmacokinetics and pharmacodynamics for these drugs are also described.
Trial data and our own experience have shown that about half of HS patients experience improvement with adalimumab. However, there is a significant need for pharmacotherapies with higher efficacy goals as in those used for psoriasis. Many biologics and small molecule inhibitors are being tested in clinical trials. The landscape of upcoming therapies for hidradenitis suppurativa appears promising."
"We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes.
This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation.
A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%,P<0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (μg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7,P<0.001; week 6, 12.5 vs. 8.6,P<0.001; week 14, 3.4 vs. 2.5,P=0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5,P=0.046), week 30 (7.9 vs. 11.8,P=0.007), and week 54 (9.3 vs. 12.3,P=0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15,P=0.026], initial C-reactive protein level (aOR=0.87,P=0.032), and CD over UC (aOR=1.92,P<0.001) were independent predictors of clinical remission at week 54.
Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients."
Tumor necrosis factor-α inhibitor-associated adverse cutaneous reactions are common in patients with inflammatory bowel disease. Infection-related dermatoses and psoriasiform eruptions are seen most frequently. We describe a follicular psoriasiform eruption that appeared during treatment with infliximab in two adolescents with Crohn's disease.
"Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baseline Ruminococcus and calprotectin. Additionally, non-responders had higher abundance of Candida, while responders had higher abundance of Saccharomyces at the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future."
"To assess cost-effectiveness of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in rheumatoid arthritis.
We conducted 3 analyses: a lifetime analysis with a cohort model (study A) and 2 short-term analyses (studies B and C). Study A evaluated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained from costs of standard treatments. Study B evaluated yearly costs per person achieving American College of Rheumatology (ACR) response (ACR20, ACR50, and ACR70), and study C, costs per person achieving previously defined claims-based effectiveness (equivalent to 28-joint Disease Activity Score [DAS28] ≤ 3.2). The proportion of ACR responders to the drugs of interest were determined by mixed treatment comparisons. Studies B and C estimated costs using a claims database.
In study A, ICERs of all b/tsDMARDs were lower than 5.0 million JPY per QALY. In study B, yearly costs per person with ACR50 response were lower for subcutaneous tocilizumab (1.9 million JPY) and subcutaneous abatacept (2.3 million JPY). In study C, costs per person were lower for subcutaneous tocilizumab (1.3 million JPY) and intravenous tocilizumab (1.6 million JPY) and effectiveness rates were higher for intravenous tocilizumab (45.3%) and infliximab (43.0%).
The b/tsDMARDs with lower prices showed higher cost-effectiveness."
"To describe a rare case of pediatric actinomycotic rhinosinusitis with orbital subperiosteal abscess and review the current literature to assess methods of diagnosis, treatment modalities, and outcomes with appropriate treatment.
A case report and a review of the literature.
A 12-year-old patient with Crohn's disease on infliximab presented with rhinosinusitis with orbital subperiosteal abscess formation. Endoscopic sinus surgery was performed and cultures grew actinomyces. A prolonged course of antibiotics was started, resulting in the complete resolution of the infection. In a literature review, all cases of uncomplicated and complicated actinomyces rhinosinusitis managed with appropriate surgery and prolonged antibiotics resulted in a cure. Our case is the first reported in a pediatric patient and the first taking immunosuppressive medication. Overall, only 3 cases of actinomyces rhinosinusitis in immunosuppressed individuals have been reported, each with uncontrolled diabetes and each also responded well to surgery and appropriate antibiotics.
Actinomycosis of the paranasal sinuses poses a diagnostic challenge, with infections varying widely in presentation and extent of disease. A high index of suspicion, appropriate testing, and early aggressive treatment are critical in managing patients with this infection. Our case and prior published studies show that actinomyces rhinosinusitis can be successfully managed with endoscopic sinus surgery, abscess drainage as necessary, and a prolonged course of antibiotics, even in immunocompromised and pediatric populations."
"We present two cases of Nodular Regenerative Hyperplasia (NRH) associated with Juvenile Dermatomyositis (JDM).
Case 1: A nine-year-old Caucasian male with refractory JDM and anti-NXP2 autoantibodies was diagnosed at age two. Over seven years, he developed arthritis, dysphagia, dysphonia, severe calcinosis, and colitis. Complications included recurrent cellulitis, infections, and hepatosplenomegaly. Multiple medications were chronically used, including prednisone, methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, rituximab, tacrolimus, etanercept, abatacept, infliximab, and tocilizumab. Case 2: A 19-year-old Asian female with chronically active JDM and anti-MDA5 autoantibodies was diagnosed at age 15. Symptomatology included ulcerative skin lesions, Raynaud's phenomenon with digital ulcers, arthritis, interstitial lung disease with pulmonary hypertension, and calcinosis. Medications included chronic use of prednisone, methotrexate, abatacept, cyclophosphamide, mycophenolate mofetil, rituximab, tofacitinib, and sildenafil. In both patients, clinical symptomatology was not suggestive of liver disease or portal hypertension, but laboratory studies revealed elevated serum transaminases with progressive thrombocytopenia and no active liver-associated infections. The first patient's liver ultrasound showed coarse hepatic texture with mild echogenicity, splenomegaly, and portal hypertension. The second patient's liver ultrasound was normal, but elastography indicated increased stiffness. Liver biopsy confirmed NRH in both patients.
It is difficult to recognize NRH in JDM, as it often presents with elevated transaminases which may be mistaken for JDM muscle flare, corticosteroid-related fatty liver, or medication-related transaminitis. NRH has been associated with several medications used to treat JDM, including methotrexate, azathioprine, and cyclophosphamide, which should be discontinued if NRH develops. Providers should consider NRH in JDM patients with severe, refractory disease who have persistently elevated transaminases and persistent thrombocytopenia."
"Although the use of anti-tumor necrosis factor-alpha (anti-TNF-α) agents is highly effective in achieving and maintaining remission in patients with moderate-to-severe IBD, they place the patient at increased risk of developing opportunistic infections, including new cases of tuberculosis infection (TBI) and/or reactivation of latent tuberculosis infection (LTBI). Our study aims to determine the incidence of TBI [active tuberculosis (ATBI) and LTBI] among patients with Crohn's disease (CD) receiving anti-TNF-α therapy.
We performed a retrospective analysis of consecutive CD patients undergoing anti-TNF-α (infliximab, adalimumab) treatment for a minimum of 6 months, in the period between June 2010 and December 2019, followed-up at a reference IBD center. All patients were HIV negative, and BCG vaccinated. In all patients, ATBI was excluded and all were tested for LTBI prior to initiating a biological treatment.
Before starting the biological treatment, we established LTBI in 11/109 (10.1%): 8/11 (72.7%) patients were TST positive, 2/11 (18.2%) were IGRA positive and TST negative, 1/11 (9.1%) were both IGRA and TST positive. In patients undergoing biological therapy with previous negative screening test for tuberculosis, a total of 16/74 (21.6%) patients were newly diagnosed with LTBI. The median induration (not erythema) diameter of TST is 8 (IQR 5-17) mm. Active pulmonary tuberculosis infection, developed in 3/74 (4.1%) patients. One patient developed ATBI on the background of chemoprophylaxis with INH for LTBI.
Specialists should thoroughly analyse all patient clinical data, chest X-ray results, epidemiological and BCG status, as well as perform a LTBI screening before initiating immunosuppressive and/or biological treatment. IBD patients have a higher risk of developing TBI in the first 12 months."
"This study aimed to investigate the presence of indoleamine-2,3-dioxygenase and bacterial translocation after the administration of 3-aminobenzamide and infliximab in the TNBS model of rat colitis.
The study group was divided into five categories as follows: group 1: (control), group 2: colitis+saline, group 3: colitis+3-aminobenzamide, group 4: colitis+infliximab, and group 5: colitis+3-aminobenzamide+infliximab. Intestinal mesenteric cultures were incubated on specific agar media plates under aerobic and anaerobic conditions, bacterial translocation was evaluated and assessed as colony-forming units per gram of tissue. Colonic tissue samples were evaluated by Western blotting method to detect the presence of indoleamine-2,3-dioxygenase.
The results obtained were as follows: group 1: normal gut flora; group 2: eight of nine samples had bacterial translocation, of which six of them had positive indoleamine-2,3-dioxygenase protein; group 3: five of nine samples had bacterial translocation, of which seven of them had positive indoleamine-2,3-dioxygenase; group 4: three of nine samples had bacterial translocation, of which seven of them had positive indoleamine-2,3-dioxygenase; and group 5: only one sample had exact indoleamine-2,3-dioxygenase protein.
Altered expression of indoleamine-2,3-dioxygenase results in a lower bacterial translocation via infliximab compared with 3-aminobenzamide treatment. Combined treatments emphasized different approaches for the new molecules related to indoleamine-2,3-dioxygenase."
"Studies assessing adult inflammatory bowel disease (IBD) patient perspectives on biosimilar use revealed that most were unfamiliar with biosimilars and had a negative perception. The objective of this study was to evaluate the perspectives of pediatric patients with IBD and their caregivers regarding biosimilar use and non-medical switches.
A survey was given to a cross section of patients with IBD ages 11-21 years receiving the intravenous anti-tumor necrosis factor originator and caregivers of patients with IBD ages 3-21 years receiving the originator. Recruitment occurred via mail, during clinic visits, and infusions. Fisher exact tests were used to test for statistically significant differences.
Response rate amongst caregivers was 49% (n = 98) and among patients was 35% (n = 67). Sixty-four percent of caregivers and 79% of patients had never heard of biosimilars. There was increased discomfort surrounding the use of biosimilars and switching to a biosimilar amongst caregivers who had previously heard of biosimilars compared to caregivers who had not previously heard of biosimilars ( P < 0.05). Similar concerns were not seen in patient respondents. The length of time on the originator had no effect on patient or caregiver concerns related to biosimilar efficacy, adverse effects, or switches.
The majority of pediatric patients and caregivers had never heard of biosimilars. Caregivers that had heard of biosimilars before the study were more likely to have a negative perception of them. This study highlights the importance of providing thorough and accurate education to pediatric patients and families regarding the safety and efficacy of biosimilars."
"Biologicals represent the cornerstone of treatment for moderate-to-severe inflammatory bowel diseases (IBD). Many patients cycle between biologicals when encountering loss of response or adverse events.
To assess the occurrence of serious infections and malignancies with exposure to several (classes of) biologicals.
We performed a retrospective cohort study in a tertiary referral centre including consecutive IBD patients exposed to adalimumab, infliximab, ustekinumab or vedolizumab between 1996 and 2019. All serious infections and malignancies, as well as potential confounders, were accounted for.
In total, 1575 patients were included with a median (interquartile range) follow-up of 10 (6-16) years and a duration of biological therapy of 71 (39-112) months. Incidence rates of serious infections were 3.4 per 100 patients' years (PY) in the post-biological setting. Serious infections after biological exposure were associated with systemic steroids in monotherapy (hazard ratio 2.96 [95% confidence interval 1.78-4.93], p < 0.0001), combination therapy of systemic steroids and a biological (2.44 [1.37-4.34], p = 0.002), female gender (1.25 [1.04-1.51], p = 0.02), and prior serious infections in the pre-biological setting (1.42 [1.03-1.96], p = 0.03). Malignancy rates were 1.06 per 100PY in the post-biological setting and increased with older age at biological initiation (1.04 [1.02-1.05], p < 0.0001). The risk for serious infections or malignancies was independent of type and number of biologicals to which the patient was exposed.
This study shows that the sequential use of biological therapy in IBD does not seem to convey an overall higher risk of serious infections or malignancies, but that underlying more refractory disease seems to increase this risk."
[This corrects the article DOI: 10.1371/journal.pone.0201956.].
"We compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab on the ability to achieve endoscopic healing (EH) after 1 year of therapy in moderate-severe Crohn's disease (CD).
This was a pooled analysis of patient-level data from 299 patients with CD from 4 clinical trials. Proportions of patients treated with each biologic were compared for achieving 1-year complete EH (Simple Endoscopic Score for CD [SES-CD] <3) and ileal and colonic EH separately (SES-CD = 0). Multivariate logistic regression was used to model the relationship between biologics and 1-year outcomes and adjusted for disease duration, concomitant corticosteroid use, and prior antitumor necrosis factor failure.
Compared with vedolizumab (4/56 [7.1%]), adalimumab (17/61 [27.9%], adjusted odds ratio [OR]: 5.79, 95% confidence interval [CI]: 1.77-18.95, P = 0.004) and infliximab (39/141 [27.7%], aOR: 4.59, 95% CI: 1.48-14.22, P = 0.008) had superior rates of 1-year EH. No significant difference was observed between vedolizumab and ustekinumab. Similar results were observed among biologic-naive patients. Among patients with baseline ileal SES-CD ≥3, no significant differences were observed between biologics for 1-year ileal EH. However, for large (>0.5 cm) ileal ulcers, infliximab (20/49 [40.8%]) had superior rates of no ileal ulcers compared with vedolizumab (2/23 [8.7%], aOR: 5.39, 95% CI: 1.03-28.05, P = 0.045). No other differences were observed. For colonic disease, compared with ustekinumab (9/31 [29.0%]), adalimumab (30/48 [62.5%], aOR: 3.97, 95% CI: 1.45-10.90, P = 0.007) had superior rates of 1-year EH in the colon, with similar trends observed for infliximab (55/105 [52.4%], aOR: 2.08, 95% CI: 0.82-5.27, P = 0.121). No other differences were observed.
In this post hoc analysis, TNF-α antagonists were overall superior to vedolizumab and ustekinumab for achieving 1-year EH in moderate-severe CD patients."
"Association of vulvar Crohn's disease (CD) with pyoderma gangrenosum (PG) has been described, yet due to its low prevalence, data on therapeutic management of this association are still limited. We here present a 22-year-old woman with severe vulvar and perianal CD with a major inguinal and perineal ulceration. In the hypothesis of an associated PG, oral corticosteroids were prescribed at a dose of 40 mg with limited efficacy for a duration of 3 months. Afterward, a combination treatment of cyclosporine and infliximab followed by negative pressure wound therapy and split-thickness skin graft resulted in complete healing."
"Genetic variants affecting the function of dual oxidase 2 (DUOX2), the catalytic subunit of membrane-bound enzymes that produce hydrogen peroxide, are associated with very early-onset inflammatory bowel disease (VEO-IBD). We report the case of a 1-year-old boy diagnosed with VEO-IBD after presenting with bloody diarrhea. He had pancolitis and an extensive small intestinal ulcerative lesion at age 4 years. Infliximab treatment was successful but was discontinued due to delayed reaction. At age 7 years, treatment with ustekinumab was started, and remission has been maintained for more than 2 years. Whole-exome sequencing identified compound heterozygous missense DUOX2 variants of unknown significance (p.[R1212H];[F1490Y]). Protein expression in the whole-cell lysate and plasma membrane was lower in F1490Y-DUOX2 than in wild-type (WT)-DUOX2. Hydrogen peroxide generation upon ionomycin stimulation was lower in cells expressing R1212H-DUOX2 and F1490Y-DUOX2 than in those expressing WT-DUOX2. The novel, inherited, biallelic DUOX2 mutations may be molecular risk factors of VEO-IBD."
"To estimate the differential effect of tumor necrosis factor inhibitor (TNFi) therapies and presence or absence of conventional synthetic disease-modifying antirheumatic drugs (DMARDs) on the incidence of psoriasis (PsO) in children with inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and chronic nonbacterial osteomyelitis (CNO).
This was a retrospective cohort study from 2008 to 2020. TNFi and DMARD exposures were dichotomized as ever/never. The primary outcome was incident PsO. Incidence rates (IRs) of PsO were stratified by underlying diagnosis, TNFi agent, and DMARD use. Poisson regression was used to assess the IR ratios (IRRs) between exposure groups.
There were 5088 children who met the inclusion criteria: 3794 (75%) had IBD, 1189 (23%) had JIA, and 105 (2%) had CNO. Of the 2023 children with TNFi exposure, 613 (30%) and 1410 (70%) were with or without a DMARD, respectively. When controlling for DMARD, sex, and family history of PsO, the IRR of developing PsO in patients exposed to adalimumab (ADA) was 2.70 times higher (95% CI 1.53-4.75; 
IRR of TNFi-induced PsO was not significantly different among ADA, IFX, and ETN. However, for patients with exposure to any of the TNFi evaluated, the IRR was significantly lower in those also exposed to a DMARD."
"Ultrasound is valuable in tight control algorithms for Crohn's disease (CD). However, the correlation between ultrasonographic response and anti-tumor necrosis factor (TNF) drug levels remains unknown. Elucidating this correlation would be helpful in optimizing the use of anti-TNF drugs. Thus, the authors aimed to investigate this correlation.
Between June 2020 and June 2021, all patients with CD who completed anti-TNF induction therapy were retrospectively included. Ultrasound was performed at week 0 and week 14, and proactive therapeutic drug monitoring of anti-TNF drugs was performed at week 14. The receiver operating characteristic (ROC) curve was used in the correlation analysis.
Ninety-two patients (60 treated with infliximab and 32 with adalimumab) were included. At week 14, an ultrasonographic response was detected in 43 patients. Patients with ultrasonographic response had significantly higher median drug levels (5.9 mcg/mL for infliximab; 18.2 mcg/mL for adalimumab) than those without (0.9 mcg/mL for infliximab, P < 0.001; 4.8 mcg/mL for adalimumab, P < 0.001). The ROC curve showed a significant correlation between ultrasonographic response and anti-TNF drug levels (area under the curve = 0.79 for infliximab, P < 0.001; area under the curve = 0.86 for adalimumab, P < 0.001). The optimal cut-off values for infliximab and adalimumab correlated with ultrasonographic response were 5.0 and 10.5 mcg/mL, respectively. An incremental increase was observed in ultrasonographic response with higher anti-TNF drug levels.
Higher anti-TNF drug levels are associated with an increased likelihood of ultrasonographic response in patients with CD."
"To provide an overview of biologics that are used to treat noninfectious uveitis, including their different targets, modes of actions, and indications.
A review of recent and well-established literature was used to present the biochemical and pathophysiological background of biologics and to provide an account of evidence-based decision making for their use, not only in noninfectious uveitis in general, but with special regard to indications for their use in particular types of uveitis.
Extensive clinical data for adalimumab shows that it is currently the only approved biologic for the treatment of uveitis. However, there is sufficient evidence to argue that many other biologics, notably TNF-α inhibitors, certain Interleukin inhibitors, Interferons, and B cell and T cell inhibitors, are also suitable for use in uveitis.
Biologics have revolutionized the treatment of noninfectious uveitis and are now considered indispensable. They are used in cases of insufficient response to or intolerance of conventional immunosuppressive agents. However, they can also be indicated as a first-line therapy for certain types of uveitis (e.g., Behçet's disease). TNF-α inhibitors are the most commonly used biologics in the treatment of uveitis.
Ziel dieser Zusammenfassung ist das Vermitteln einer Übersicht zu den verschiedenen Ansatzpunkten, Wirkmechanismen und Indikationen diverser Biologika, die bei der Therapie der nichtinfektiösen Uveitis zum Einsatz kommen.
Etablierte sowie aktuelle Literatur wurden herangezogen, um die biochemischen und pathophysiologischen Grundlagen sowie eine evidenzbasierte Empfehlung zum Therapieeinsatz verschiedener Biologika bei nichtinfektiöser Uveitis allgemein und bei speziellen Uveitisentitäten darzulegen.
Für viele Biologika, hier nennenswert TNF-α-Inhibitoren, einige Interleukininhibitoren, Interferone sowie B- und T-Zell-Inhibitoren, liegen mittlerweile gute Daten vor, was ihren Einsatz in der Uveitistherapie mehr als rechtfertigt. Dies trifft insbesondere für den TNF-α-Inhibitor Adalimumab zu, welcher der einzig zugelassene Vertreter für diese Indikation unter den vorgestellten Biologika ist.
Die Biologika haben die Behandlung der Uveitis revolutioniert und sind aus der aktuellen Therapie der intraokularen Entzündung nicht mehr wegzudenken. Biologika werden bei Ineffektivität oder Unverträglichkeit konventioneller immunsuppressiver Medikamente empfohlen, aber auch bei der Therapie von schwerwiegenden Uveitisformen (z. B. Morbus Behçet). Die TNF-α-Inhibitoren sind die am häufigsten verwendeten Biologika bei Uveitis."
"The comparative long-term survival of first-line biologics for UC and reasons for drug discontinuation are poorly understood. We sought to compare the long-term drug survival related to non-response (NR) and adverse effects (AEs) for vedolizumab, adalimumab, and infliximab among biologic-naïve patients with UC.
This was a retrospective cohort study of adult biologic-naïve patients with moderate-to-severe UC initiating vedolizumab, adalimumab, or infliximab 6/1/14-12/31/20 at a large academic medical center. The primary outcome was time to biologic discontinuation for primary or secondary NR (including colectomy). The secondary outcome was time to biologic discontinuation due to AEs. Inverse probability of treatment-weighted (IPTW) Cox regression was used to perform three pair-wise comparisons of drug survival.
The cohort included 805 patients with UC who initiated vedolizumab (n = 195), adalimumab (n = 278), or infliximab (n = 332). The adjusted hazard of biologic discontinuation for NR was significantly lower for vedolizumab vs adalimumab (HR 0.51, 95% CI 0.34-0.75), similar for vedolizumab vs infliximab (HR 1.32, 95% CI 0.79-2.18), and greater for adalimumab vs infliximab (HR 2.07, 95% CI 1.51-2.86). The adjusted hazard of discontinuation for AEs was significantly lower for vedolizumab vs adalimumab (HR 0.25, 95% CI 0.09-0.64), lower for vedolizumab vs infliximab (HR 0.21, 95% CI 0.10-0.46), and similar for adalimumab vs infliximab (HR 0.85, 95% CI 0.53-1.35).
There was greater survival of vedolizumab compared to adalimumab for clinical response and greater survival of vedolizumab compared to both adalimumab and infliximab for AEs. These long-term data support the use of vedolizumab as a first-line biologic over adalimumab for biologic-naïve patients with UC."
"Anti-drug antibodies (ADAb) frequently form early in the treatment course of infliximab and other tumour necrosis factor (TNF) inhibitors, leading to treatment failure and adverse events.
To identify risk factors for ADAb in the early phase of infliximab treatment.
Patients (n = 410) with immune-mediated inflammatory diseases who initiated infliximab treatment were included in the 38-week Norwegian Drug Monitoring Trial (NOR-DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy. Serum levels of infliximab and ADAb were measured at each infusion. Possible risk factors for ADAb formation were assessed using logistic regression, adjusting for potential confounders.
ADAb were detected in 78 (19%) patients. A diagnosis of rheumatoid arthritis (RA) (odds ratio [OR], 1.9 [95% confidence interval [CI] 1.0-3.6]) and lifetime smoking (OR, 2.0 [CI 1.1-3.6]) were baseline risk factors, while baseline use of concomitant immunosuppressors (OR, 0.4 [CI 0.2-0.8]) and a diagnosis of spondyloarthritis (SpA) (OR, 0.4 [CI 0.2-0.8]) reduced the risk of ADAb. Higher disease activity during follow-up (OR, 1.1 [CI 1.0-1.1]) and ""drug holidays"" of more than 11 weeks (OR, 4.1 [CI 1.2-13.8]) increased the risk of ADAb, whereas higher infliximab doses (OR, 0.1 [CI 0.0-0.3) and higher serum infliximab concentrations (OR, 0.7 [CI 0.6-0.8]) reduced the risk of immunogenicity.
Several risk factors for ADAb formation during early-phase infliximab treatment were identified. This knowledge provides a basis for treatment strategies to mitigate the formation of ADAb and identify patients in whom these measures are of particular importance."
"Emphysematous cystitis (EC) is characterized by the presence of air within the bladder wall, often a complication of urinary tract infection (UTI) by gas-producing organisms. However, EC has also been reported in the setting of infectious colitis suggesting an alternate etiology. We report a rare case of EC in the setting of severe Crohn's colitis with no clinical evidence of UTI.
A 43-year old female presented with a 2-month history of bloody diarrhea consisting of 8-12 bowel movements a day, weight loss of 10 kg and peripheral edema. She also had multiple ulcerated lesions on her abdominal wall and in the perianal region. Initial CT scan was significant for pancolitis, anasarca and EC. The follow-up CT cystogram, flexible cystoscopy and pelvic MRI confirmed the diagnosis of EC and ruled out any fistulous tracts in the pelvis including enterovesical/colovesical fistula. The patient did not report any urinary symptoms and the urinalysis was within normal limits. An extensive infectious workup was negative. Despite the paucity of infectious findings, the EC was empirically treated with an intravenous third-generation cephalosporin. Colonoscopy was significant for multiple ulcerated and hyperemic areas with pseudopolyps all throughout the right, transverse and left colon. Biopsies confirmed Crohn's colitis with no evidence of granulomata or dysplasia. Immunohistochemistry was negative for CMV. The perianal and abdominal wall lesions were suspected to be pyoderma gangrenosum although biopsies were equivocal. The colitis was initially treated with intravenous steroids followed by biologic therapy with Infliximab. Despite appropriate escalation of therapies, the patient developed colonic perforation requiring subtotal colectomy.
This is a rare case of EC in a patient with severe Crohn's colitis. There was no evidence of urinary tract infection or fistulising disease. According to our review, this is the first reported incident of EC in a patient with inflammatory bowel disease without any prior intra-abdominal surgeries. While active Crohn's disease alone is a critical illness, we conclude that concomitant EC may be a poor prognostic factor."
"pediatric patients with inflammatory bowel diseases (IBD) who qualify for biological therapy represent a group of severely ill patients. They have never been successful with conventional medication. Biologic medications in monotherapy are frequently used in the disease course, however they result in a 1-year remission, which can be maintained in approximately 40% of IBD patients.
the present study aims to summarize the review of literature data on the use of therapy with a combination of two biological and small molecule drugs, anti-TNF (infliximab, adalimumab), vedolizumab and ustekinumab, as well as Janus kinase inhibitors (tofacitinib). The risks associated with the use of dual biological therapy and potential adverse effects are particularly important. The literature data was reviewed using the following terms: ""use of combination biologic in paediatric IBD"", ""combination biologics"", and ""dual biologic for treatment of Inflammatory Bowel Disease"".
the use of dual biological therapy is a new therapeutic option. In pediatric IBD, combining the different mechanisms of action of the two biological drugs seems to be safe and effective. Anti-TNF drugs with vedolizumab or ustekinumab may be a particularly beneficial combination. Nevertheless, the clarification and justification of potential advantages of combined biological therapies in further studies, such as randomized control trials, are needed."
"Perianal fistulas are a common complication of Crohn's disease (CD) that has, historically, been challenging to manage. Despite the strong available evidence that anti-tumor necrosis factor (anti-TNF) agents are useful in the treatment of perianal fistulizing Crohn's disease (PFCD), a significant number of these patients do not respond to therapy. The use of therapeutic drug monitoring (TDM) in patients with CD receiving biologic agents has evolved and is currently positioned as an important tool to optimize and guide biologic treatment. Considering the treatment of PFCD can represent a challenge; identifying novel tools to improve the efficacy of current treatments is an important unmet need. Given its emerging role in other phenotypes of Crohn's disease, the use of TDM could also offer an opportunity to enhance the effectiveness of available therapies and improve outcomes in the subset of patients with PFCD receiving biologics. Overall, there is mounting evidence that higher anti-TNF drug levels are associated with better rates of ""fistula healing"". However, studies have been limited by their use of subjective outcomes and observational designs. Ultimately, further interventional, randomized controlled trials looking into the relationship between drug exposure and fistula outcomes are needed."
Solitary rectal ulcer syndrome (SRUS) is an uncommon condition that presents with non-specific symptoms shared by other disease processes. This case report shares a unique presentation in which a patient was thought to have fistulous perianal Crohn's disease then underwent treatment with infliximab but was ultimately found to have SRUS. The prognosis and treatment of SRUS vary greatly from inflammatory bowel disease. Making the correct diagnosis is imperative when considering Crohn's disease and its mimickers.
"Cancer cachexia is syndrome accompanying weight reduction, fat loss, muscle atrophy in patients with advanced cancer. Since tumor necrosis factor-α (TNF-α) played pivotal role in cancer cachexia, we hypothesized preemptive administration of TNF-α antibody might mitigate cancer cachexia. Detailed molecular mechanisms targeting muscle atrophy, cachexic inflammation, and catabolic catastrophe were explored whether TNF-α antibody can antagonize these cachexic mechanisms. Stimulated with preliminary finding human antibody, infliximab or adalimumab, significantly inhibited TNF-α as well as their signals relevant to cachexia in mice, preemptive administration of 1.5 mg/kg adalimumab was done in C-26-induced cancer cachexia. Adalimumab significantly mitigated cancer cachexia manifested with significantly lesser weight loss, leg muscle preservation, and higher survival compared to cachexia control ("
"Myopericarditis is a rare extraintestinal manifestation of Crohn's disease (CD). Myopericarditis has also been attributed to treatment with mesalamine and heart failure to tumor necrosis factor inhibitor (TNFi) use. When a patient with CD, controlled on these medications, presents with myopericarditis and/or heart failure, it can confound both the differential diagnosis and management of such patients. Our case is acute myopericarditis in a 34-year-old male, with a history of CD controlled with mesalamine and infliximab, who had been off TNFi therapy for over six months due to loss of insurance coverage and had been intermittently using leftover mesalamine. He presented to the ED complaining of a one-day history of abdominal pain with bloody diarrheal stools, chest discomfort, and fever. A colonoscopy performed two days back had demonstrated active colonic CD. Findings included ECG evidence of pericarditis, elevated cardiac biomarkers, and reduced left ventricular function on ventriculography consistent with myopericarditis. We present the differential, diagnostic and management challenges encountered in this situation, review the pertinent literature, and discuss decision making in what appears to be myopericarditis attributed to an extraintestinal manifestation of active GI Crohn's."
"Biological therapies are valuable treatments for severe psoriasis. Children aged under 12 years are underrepresented in therapeutic trials for these drugs. The objective of the 'BiPe Jr' cohort study was to evaluate the drug survival, effectiveness, tolerance and switching patterns of biological therapies in children under 12 years of age with psoriasis.
We conducted a multicentre retrospective study of children with psoriasis who received at least one injection of a biological agent, even off-licence, before the age of 12 years in France and Italy, collecting the data between April and August 2021. The data collected were from March 2012 up to August 2021.
In total, 82 children (mean age: 9.1 years; females: 61.0%) received 106 treatments. The drugs administered were adalimumab (n = 49), etanercept (n = 37), ustekinumab (n = 15), anakinra (n = 2), infliximab (n = 2) and secukinumab (n = 1). The most common form of psoriasis was plaque psoriasis (62.9%). The Physician Global Assessment and the Psoriasis Area Severity Index (PASI) scores decreased significantly from baseline to 3 months after treatment initiation for the three main biological drugs; PASI went from 14.1 ± 9.4 to 4.1 ± 11.3 for adalimumab (p = 0.001), 14.9 ± 9.3 to 5.1 ± 4.0 for etanercept (p = 0.002) and 11.6 ± 8.3 to 2.6 ± 2.2 for ustekinumab (p = 0.007). A trend towards higher 2-year maintenance rates was observed for ustekinumab and adalimumab, compared with etanercept (p = 0.06). 52 children discontinued their biological therapy, most frequently due to inefficacy (n = 28) and remission (n = 14). Seven serious adverse events (SAEs) were reported, including four severe infections.
Our analyses of drug survival and treatment patterns, combined with those of previous studies conducted in older children, indicate that there is a trend towards higher 2-year survival rates of ustekinumab and adalimumab. The SAEs identified were rare, but highlight the need for increased vigilance concerning infections. Overall, the biological therapies showed good effectiveness and safety profiles when used in daily practice for the treatment of young children with psoriasis."
"To report a severe bilateral frosted branch angiitis associated with acute onset of systemic dermatomyositis.
History and clinical examination, laboratory evaluation, fundus' and skin's color pictures, fluorescein angiography (FA), optical coherence tomography (OCT).
A 32-year-old female was referred for a bilateral frosted branch angiitis and vitreitis, with skin rash, muscle pain, weakness, severe headache, compatible with dermatomyositis. After an initial improvement following an aggressive treatment by systemic steroids and mycophenolate mofetil, she was switched to intravenous infliximab (RemicadeTM, Janssen Biotech, Inc. USA) due to lack of efficacy. Nine months later, her visual acuity was improved up to 20/20 in OU, with both retinal vasculitis and vitreitis being solved.
Dermatomyositis is a severe multiorgan disease which might severely involve eye structures. Anti-TNF-Alpha agents, particularly Infliximab, might offer a rapid control and long-term remission."
"Inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and overlap myositis (OM), in short myositis, are rare diseases. All forms of myositis have progressive muscle weakness in common, with each subtype characterized by different autoantibody profiles, histological findings and extramuscular manifestations. Due to better understanding of the pathogenesis of the muscle inflammation in myositis, new molecular pathways for targeted therapy have been discovered. Current therapies aim at different components of the innate or the adaptive immune response. Additionally, non-inflammatory mechanisms in myositis have come into focus as possible treatment targets. The use of therapeutical antibodies in myositis has been examined in various clinical studies, several of them randomized controlled ones: Depletion of B-cells by rituximab has been established as treatment of refractory myositis. IVIG, an antibody therapy in the wider sense, has now been licensed for DM following a recent positive clinical trial. Negative study results were reported in randomized trials with infliximab, sifalimumab and bimagrumab. Studies on basiliximab and eculizumab are currently underway, and are expected to yield results in a couple of years. Despite some promising results of clinical studies with antibody therapy in myositis, further research is crucial to optimize the treatment for this debilitating disease and to find treatment alternatives for treatment-refractory patients."
"Oncostatin M was recently highlighted as a promising biomarker for therapeutic effectiveness in inflammatory bowel diseases (IBD), with particular regard for infliximab. The primary aim was to evaluate the ability of serum oncostatin M to predict endoscopic response to different drugs in IBD.
We selected two different cohorts of patients with IBD, treated with anti-TNF (infliximab and adalimumab) or with vedolizumab. Therapeutic response was evaluated at week 54 in terms of mucosal healing. Serum oncostatin M and C-reactive protein were measured at baseline; fecal calprotectin was measured at baseline and after 14 weeks of treatment. We evaluated the association of these biomarkers with mucosal healing at week 54.
Among 66 patients treated with anti-TNFs and 68 treated with vedolizumab, 35 and 31 attained mucosal healing, respectively. Mucosal healing at 54 weeks was significantly associated with low oncostatin M levels at baseline in the anti-TNF cohort; the diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing was 0.91 (95% CI 0.84 to 0.99) in the anti-TNF cohort and 0.56 (95% CI 0.43 to 0.70, P < 0.001) in the vedolizumab cohort. Mucosal healing was also associated with low fecal calprotectin levels at week 14 in both cohorts.
Our study suggests that serum oncostatin M is a drug-specific biomarker, since it could be used to predict therapeutic effectiveness to anti-TNFs but not to vedolizumab. Moreover, these results emphasize the utility of serum oncostatin M measurement in patients treated with anti-TNF."
"Intravenous [IV] infliximab is a well-established therapy for inflammatory bowel diseases [IBD] patients. A subcutaneous [SC] formulation of infliximab [CT-P13] has recently been shown to be as effective as IV infliximab after two doses of IV induction in a randomised trial, but there are no data to support elective switching of patients on maintenance IV infliximab therapy. We aimed to assess the effectiveness of an elective switching programme to SC CT-P13 in patients treated with IV infliximab.
Patients on established maintenance IV infliximab, who switched to SC CT-P13, were included in this retrospective multicentre cohort study. Disease activity was monitored serially with the Harvey-Bradshaw Index [HBI] for Crohn's disease [CD] and the Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis (UC) for up to 12 months at months 3, 6, and 12. Faecal calprotectin [FC] and C-reactive protein [CRP] were recorded at baseline and follow-up, if available. Infliximab trough levels were measured prior to switch and at months 3, 6, and 12 following switch. The primary outcome measure was treatment persistence at latest follow-up. Secondary outcome measures included infliximab pharmacokinetics [PK], safety, need for corticosteroid rescue therapy, and need for surgery.
We included 181 patients, of whom 115 [63.5%] had CD. The majority [72.4%] were on 8-weekly dosing of intravenous infliximab prior to switching, and more than half [59.1%] were on concomitant immunomodulatory therapy. The majority of patients (CD: 106, 92.2%; UC: 46, 76.7%; and IBD unclassified [IBD-U]: 5, 83.3%) were in clinical remission. Treatment persistence rate was high [n = 167, 92.3%] and only 14 patients [7.7%] stopped treatment during the follow-up period. There was no significant difference between baseline and repeat measurements at 3, 6, or 12 months for HBI, SCCAI, CRP, or FC. Of the total cohort, 25 patients (13.8%) had perianal CD. Of these, only two patients [8%] had worsening of perianal CD and required antibiotic therapy and further examination under anaesthesia [EUA]. Both these patients also switched back to intravenous infliximab. Median infliximab level increased from a baseline of 8.9 µg/dl [range 0.4-16] to 16.0 µg/dl [range 2.3-16, p <0.001] at 3 months. Serum levels stayed stable at 6 months [median 16 µg/dl, range 0.3-17.2] and 12 months [median 16 µg/dl, range 0.3-19.1, both p <0.001 compared with baseline]. Among the variables examined, only antibodies to infliximab [ATI] was associated with infliximab levels (odds ratio [OR] -13.369, 95% CI -15.405, -11.333, p <0.001]. A total of 14 patients [7.7%] developed ATI; of these, nine [64.3%] were on concomitant immunomodulatory therapy. Immunomodulatory therapy was not significantly associated with development of ATI [p = 0.15]. In a subset of patients receiving escalated IV infliximab dosing frequency prior to switching, no difference in treatment persistence was observed in patients receiving weekly versus alternate weekly SC CT-P13. Patient acceptance and satisfaction rates with SC CT-P13 were very high.
Among patients on IV infliximab maintenance therapy switched to SC CT-P13, we observed high treatment persistence rates and low rates of immunogenicity, with no change in clinical disease activity indices or biomarkers. Infliximab levels increased after switch to SC CT-P13, and only ATI was associated with serum infliximab levels. Patient acceptance and satisfaction rates were high with SC CT-P13."
"Anti-tumour necrosis factor [anti-TNF] induced skin reactions are common adverse events in paediatric inflammatory bowel disease [IBD]. We aimed to report on outcomes of children with anti-TNF induced skin reactions who switched to ustekinumab [UST] vs. continued anti-TNF therapy.
Charts were reviewed for paediatric IBD patients with anti-TNF induced skin reactions. Skin reactions, including psoriasiform dermatitis [PD], were classified as mild or severe based on a severity score. Primary outcome was frequency of skin resolution at 6 months. Secondary outcomes were combined clinical remission and skin resolution at 6 months and skin resolution at latest follow-up.
A total of 111/638 [17%] children ([85, 21%] infliximab [IFX]; [26, 11%] adalimumab [ADA]) developed skin reactions. Eighty [72%] had PD, 25 [23%] infections, and four [4%] alopecia areata; 71 [64%] continued anti-TNF; and 40 [36%] switched to UST. In all, 73 [66%] had severe reactions and were more likely to switch to UST than if mild (37 [51%] vs. 3 [8%]; p <0.0001). Switching to UST had a higher rate and odds of resolution (29 [73%] vs. 24 [34%]; p <0.0001; odds ratio [OR] = 19.7, 95% confidence interval [CI]: 5.6, 69.5; p <0.0001) and combined remission (21 [52%] vs. 22 [31%]; p = 0.03; OR = 8.5, 95% CI: 2.5, 28.4; p = 0.0005] vs. continuing anti-TNF at 6 months.
Children who switched to UST after anti-TNF induced skin reactions were more likely to have improved outcomes than those who continued anti-TNF therapy. Future studies are needed to determine immune mechanisms of anti-TNF induced skin reactions and treatment response."
"While infliximab combined to thiopurines is more effective than infliximab monotherapy in patients with Crohn's disease (CD) and UC, the impact of adding thiopurines to vedolizumab remains controversial. We emulated two target trials comparing the effectiveness of combination therapy versus vedolizumab monotherapy in CD and UC.
Based on two US and the French nationwide healthcare databases, patients with CD and UC who initiated vedolizumab were identified. The study methodology, including confounding adjustment and outcome definitions, were previously validated in successful emulations of the SONIC and SUCCESS trials. Risk ratios for treatment failure based on hospitalisation or surgery related to disease activity, treatment switch, or prolonged corticosteroids use, were estimated after 1:1 propensity score (PS) matching.
Among a total of 10 299 vedolizumab users, 804 CD and 1088 UC pairs of combination therapy versus vedolizumab monotherapy users were PS matched. Treatment failure occurred at week 26 in 236 (29.3%) and 376 (34.3%) patients with CD and at week 16 in 236 (21.7%) and 263 (24.2%) patients with UC initiating combination therapy and vedolizumab monotherapy, respectively. The risk of treatment failure was decreased with combination therapy compared with vedolizumab monotherapy in CD (RR 0.85, 95% CI: 0.74 to 0.98) and to a lesser extent in UC (RR 0.90, 95% CI: 0.77 to 1.05). Findings were consistent across databases.
Using validated methodologies, combination therapy with vedolizumab and thiopurines was associated with lower treatment failure compared with vedolizumab monotherapy in CD but not UC across the USA and France."
"Rapid drug desensitization (RDD) allows first-line therapies in patients with immediate drug hypersensitivity reactions (DHR) to chemotherapeutic drugs (ChD) and monoclonal antibodies (mAb). Desensitization in delayed drug reactions has traditionally used slow protocols extending up to several weeks; RDD protocols have been scarcely reported.
We retrospectively analyzed the patients referred to the Allergy Department, who had experienced a delayed DHR (> 6 h) related to a ChD or mAb and underwent an RDD protocol. The rate of successful administration of the offending drug and the presence of adverse reactions were evaluated.
A total of 93 RDDs were performed in 11 patients (including 6 men and 5 women, with a median age of 61 years). The primary DHR were maculopapular exanthema (MPE) (8), generalized delayed urticaria (1), MPE with pustulosis and facial edema (1), and facial edema with desquamative eczema (1). The meantime for the onset of symptoms was 3 days (range 1-16 days). RDD was performed using a protocol involving 8-13 steps, with temozolomide (25), bendamustine (4), rituximab (9), infliximab (24), gemcitabine (23), and docetaxel (8), within 4.6-6.5 h. Sixteen breakthrough reactions were reported during the RDD (17.2 %) in 5 patients; all were mild reactions including 11 delayed and 5 immediate reactions. All patients completed their treatment.
RDD is a potentially safe and effective procedure in patients suffering from delayed reactions to ChD and mAb. It allows them to receive full treatment in a short period, thereby reducing time and hospital visits."
"Eosinophilic fasciitis is a rare connective tissue disease of unknown etiology. Therapeutic options include high-dose corticosteroids and other immunosuppressive drugs. We present a typical eosinophilic fasciitis case, which did not respond to first-line treatment, but improved remarkably after infliximab administration. This report demonstrates that in case of initial treatment failure, infliximab might be a relatively safe and effective way of eosinophilic fasciitis management."
"Pyoderma gangrenosum (PG) has been linked to various underlying systemic diseases; many associations are based on case reports or small case series, including hidradenitis suppurativa. Literature examining systemic therapies according to underlying comorbid condition is limited. The study objective was to investigate comorbid diseases of PG and correlate disease associations with effectiveness of therapeutic interventions. Using Johns Hopkins Medical Institutions medical records, 220 patients had an ICD-9 code of 686.01 for PG between 1 January 2006 and 30 June 2015, of whom 130 patients met rigorous inclusion/exclusion criteria for PG (non-peristomal). The 130 PG patients in our study were 69% female, 58% Caucasian, and 35% African American. Documented comorbid conditions included inflammatory bowel disease (IBD; 35%), rheumatoid arthritis (RA; 12%), hidradenitis suppurativa (HS; 14%), and monoclonal gammopathy (12%). PG patients with HS versus without HS were more likely to be African-American (83% vs. 28%; P < 0.001) and had an earlier mean age of PG onset (38 vs. 48 years; P = 0.02). Strikingly, 53% of female African-American patients with PG onset prior to age 40 had comorbid HS. Comorbid inflammatory bowel disease was observed in 38% of PG patients with RA, 28% of PG patients with HS, and 27% of PG patients with monoclonal gammopathy. Of the 32 patients who received infliximab for active PG, complete ulcer healing was observed in 83% (5/6) of patients with comorbid HS versus 31% (8/26) of patients without HS (Fisher exact P = 0.03). Screening patients for associated systemic disease for multiple related illnesses is essential. Effectiveness of systemic therapy may depend upon the underlying systemic disease; hidradenitis suppurativa may be a specific example."
"Immune checkpoint inhibitor-related colitis is a common complication of immunotherapy use in patients with cancer. Current guidelines recommend treatment with standard dose infliximab (IFX) for corticosteroid-refractory colitis; however, this case series suggests IFX dose escalation may be a viable treatment option for refractory cases."
"The differences in the epidemiology and management of patients with axial spondyloarthritis (axSpA) among regions and countries largely depend on the positivity of human leukocyte antigen (HLA)-B27 and the health care system. This review article focused on axSpA in Japan, where the prevalence of HLA-B27 is extremely low (0.3%) and the universal health insurance system typically provides a 70% or more copayment by the government.
A nationwide survey was conducted in Japan in 2018, which estimated that there were 3200 patients (95% confidence interval [CI]: 2400-3900) with ankylosing spondylitis (AS), a term interchangeable with radiographic axSpA (r-axSpA), and 800 patients (95% CI: 530-1100) had non-radiographic (nr)-axSpA. These data indicate a prevalence of 2.6/100,000 or 0.0026% for AS and 0.6/100,000 or 0.0006% for nr-axSpA. Patients with AS, but not those with nr-axSpA, are designated as suffering from intractable diseases in Japan; thus, their medical expenses are reduced by grant under the Act on Medical Care for Patients with Intractable Diseases. As of February 2022, infliximab, adalimumab, secukinumab, ixekizumab, and brodalumab have been approved for AS, and secukinumab, ixekizumab, and brodalumab have been approved for nr-axSpA. An algorithm for nr-axSpA in Japan has been developed for the proper diagnosis and use of these therapeutic agents. A low prevalence of axSpA, especially that of nr-axSpA, was found in Japan. Early referral and the resultant diagnosis and appropriate treatment of these patients by rheumatologists are crucial issues in Japan, as in other countries."
"The aim of this study was to assess the safety of the most frequently used biologic disease-modifying antirheumatic drugs in  rheumatoid arthritis patients in clinical practice.
A retrospective longitudinal observational study was performed. Clinical information was obtained from the electronic health records of patients diagnosed and treated for rheumatoid arthritis, who had received at least one biologic disease-modifying antirheumatic drug  dispensed between 2001 and 2013 from a third-level Hospital pharmacy. Adverse reactions during biologic disease-modifying antirheumatic  drugs treatments were analysed, as well as the reasons for treatment  discontinuation. A disproportionality analysis (odds ratio with 95% confidence interval) was performed to compare adverse drug reactions related  o different system organ classes, the period between the drug start date and  the reaction start date (latency period), and previous knowledge of the adverse reactions.
In total, 210 patients were included in the analysis (73% women, median age 47 years), with 399 prescriptions for biologic  diseasemodifying antirheumatic drugs and 1,515 adverse reactions potentially  related to them. The increased frequency of adverse reactions for  each system organ class related to each biologic disease-modifying  antirheumatic drug was as follows: general disorders and administration site disturbances with infliximab (2.3 [1.3-4.0]), infections (1.6 [1.3-2.1]) and immune system reactions with etanercept (4.2 [1.2-14.6]), hepatobiliary  disorders with adalimumab (2.1 [1.2-3.6]), ophthalmic adverse  reactions  (1.9 [1.2-3.1]) and cardiac disorders (2.9 [1.0-8.4]) with rituximab,  and blood and lymphatic system disorders with tocilizumab (2.9 [1.8-4.7])  and abatacept (3.0 [1.6-5.8)]. The mean latency period was 5 to 33 months.  Most adverse reactions were related to adalimumab (93.6%; P &lt; 0.01),  whereas the fewest adverse reactions were related to tocilizumab (55.2%; P &lt;  0.01). Most treatment withdrawals related to adverse reactions were identified  during the first year of biologic disease-modifying antirheumatic drugs  treatment.
Tumour necrosis factor α inhibitors were associated with general  disorders and administration site disturbances, infections and immune system reactions, and hepatobiliary abormalities, whereas  ontumour necrosis factor α inhibitors were associated with cardiac disorders as  well as blood and lymphatic system disorders. Treatment  ithdrawals mainly occurred during the first year of treatment. Most of the  adverse reactions have been previously described.
Analizar la seguridad del tratamiento con fármacos biológicos modificadores de la enfermedad prescritos con mayor frecuencia en pacientes con artritis reumatoide en la práctica clínica habitual. Método: Estudio observacional retrospectivo, a partir de la historia clínica digitalizada de pacientes con artritis reumatoide de un hospital de tercer  nivel, sobre la seguridad de los fármacos biológicos modificadores de  la enfermedad, entre los años 2001 y 2013. Además de  analizar las reacciones adversas que motivaron la retirada del tratamiento, se  hizo un análisis de desproporcionalidad comparando los órganos y sistemas  implicados en las reacciones adversas asociadas a los diferentes  fármacos biológicos modificadores de la enfermedad calculando la odds ratio con un intervalo de confianza del 95% [odds ratio (IC95%)], del periodo de latencia entre el inicio del tratamiento y el diagnóstico de los efectos adversos, y de su conocimiento previo.
Se analizaron las historias clínicas de 210 pacientes (73% mujeres; mediana de edad: 47 años), que incluían 399 líneas de  tratamiento con algún fármaco biológico modificado de la enfermedad y 1.545 reacciones adversas potencialmente relacionadas con ellos. Se identificó un incremento significativo de reacciones adversas en los siguientes  órganos y sistemas afectados: trastornos generales y del lugar de  administración [2,3 (1,3-4,0)] para infliximab; infecciones [1,6 (1,3‑2,1)] y  trastornos del sistema inmunológico [4,2 (1,2-14,6)] para etanercept;  trastornos hepatobiliares [2,1 (1,2-3,6)] para adalimumab; trastornos oculares  [1,9 (1,2-3,1)]y cardiacos [2,9 (1,0-8,4)] para rituximab; trastornos  de la sangre y del  sistema linfático [2,9 (1,8-4,7)] para tocilizumab y  abatacept [3,0 (1,6-5,8)]. La latencia media osciló entre 5 y 33 meses. La  mayor y menor proporción de reacciones adversas conocidas correspondieron a  adalimumab (93,6%; p &lt; 0,01) y tocilizumab (55,2%; p &lt; 0,01),  respectivamente. Más de la mitad de las retiradas de fármacos biológicos  modificadores de la enfermedad asociadas a reacciones adversas se produjeron  en el primer año de tratamiento.
Los fármacos biológicos modificadores de la enfermedad inhibidores del factor de necrosis tumoral α se asociaron a la  presentación de trastornos generales, infecciones y trastornos del sistema  inmunológico y a alteraciones hepatobiliares, mientras que los no inhibidores del factor de necrosis tumoral α se relacionaron con un incremento  en los trastornos oculares y cardiacos, trastornos de la sangre y del sistema linfático. La interrupción del tratamiento por reacciones adversas  sucedió durante el primer año. La mayoría de las reacciones adversas  registradas eran conocidas."
"Peristomal pyoderma gangrenosum (PPG) is a rare dermatological condition associated with gastroenterological disease. Most gastrointestinal surgeons find it difficult to suspect and treat PPG, especially at early onset. The patient was an 18-year-old female. The patient underwent three-stage restorative proctocolectomy for refractory ulcerative colitis. On postoperative day (POD) 9, the trocar wound near the ileostomy site dehisced. Because the wound culture was positive, the wound was treated with an antibacterial agent as an infection. However, the wound worsened. The patient was referred to a dermatologist for diagnosis. PPG was diagnosed on POD 37. Wound management was initiated using topical steroids. The wound caused difficulties in pain and dressing management. Although infliximab was administered as a systemic therapy, it was discontinued because of allergic symptoms. Sealing therapy with hydrofiber dressing and adequate stoma pouching with stoma paste provided good exudate absorption and a clean environment by protecting the wound from stoma excretion. Oral prednisone was initiated on POD 82. Improvement in the wound condition was observed with a prednisone dose of 30 mg/day. Complete remission was achieved seven months after onset. Twelve months after the surgery, stoma closure was performed. The local cutaneous condition remained in remission without exacerbation. Suspicion of PPG can be difficult when it develops early after stoma creation. We never forget that PPG should be suspected when a progressive ulcerative lesion is found around the stoma, even early after operation. If PPG is suspected, a multidisciplinary team plays an essential role in its diagnosis and management."
"Information on comparative drug efficacy is of great importance for drug development as well as clinical practice. Up to now, the relative efficacy of biologics and small targeted molecules for Crohn's disease (CD) remains unclear. The objective of this study was to quantify the relative efficacy of investigational and approved biological treatments for CD measured in Crohn's Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), and C-reactive protein (CRP). The analysis dataset was composed of summary-level data from 46 trials, containing 12,846 patients, with treatment of 24 drugs. Six mathematical models with non-parametric placebo estimations were developed to describe the time course and dose-response of six efficacy measures. The effects of covariate were further evaluated. Time-response relationships were found in outcomes measured in CDAI. The patients' age, disease duration, baseline CDAI, and CRP showed an impact on the efficacy. Model simulations were performed to compare the efficacies across different drugs. The most achievement in clinical remission (defined as CDAI less than 150) and clinical response (defined as the reduction in CDAI for 100 or 70) was observed in the simulation for PF-04236921 and infliximab, respectively. The most improvement in IBDQ was shown in tofacitinib. In general, tumor necrosis factor (TNF)-α inhibitors were the most effective biologics, and the highest efficacy of small targeted molecules was observed in janus kinase (JAK) inhibitors. These findings have important implications for clinical practice in CD."
"Biologic therapies are effective at inducing and maintaining remission in people with inflammatory bowel disease (IBD). Previous studies have associated TNF-a inhibitors with weight gain, however, it is unclear if this is a class-specific effect or a manifestation of good disease control. To clarify this issue, a retrospective study was undertaken to examine weight changes over time during therapy with different biologic agents.
Adult patients with IBD who received any biological therapy for at least 12 months, between 2008 and 2020, were identified at two specialised IBD services. Demographic, disease, and therapy-related data were examined. Weight change and patterns thereof were examined for each specific therapy and relationships amongst weight outcomes and various predictive factors explored.
Of 294 patients (156 females), 165 received Infliximab (IFX), 68 Adalimumab (ADA), 36 Vedolizumab (VDZ) and 25 Ustekinumab (UST). There was a statistically significant weight gain over time in the IFX and VDZ groups and more weight gain in the IFX vs ADA and VDZ vs ADA at most time points. Three weight trajectories were identified: around 95% of patients had small weight loss or a modest weight gain but 5% of patients, most of whom were on IFX had marked weight gain (24.3 kg). Having a baseline high BMI, being female, having an initiation CRP ≤ 5 or albumin > 35 reduced the odds of major weight gain.
Weight gain in biologic treated IBD patients appears to be associated with clinical factors (male gender, high CRP, low albumin) and therapy-specific factors."
"Gender-based differences are reported in inflammatory bowel diseases (IBD) pathogenesis, but their impacts on IBD outcomes are not well known. We determined gender-based differences in response to treatment with tumor necrosis factor inhibitor (TNFi) therapies in individuals with ulcerative colitis (UC).
We used the Yale University Open Data Access (YODA) platform to abstract individual participant data from randomized clinical trials to study infliximab and golimumab as induction and maintenance therapies in moderately to severely active UC. Using multivariable logistic regression, we examined associations between gender and the endpoints of clinical remission, mucosal healing, and clinical response for each study individually and in a meta-analysis.
Of 1639 patients included in induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Subcutaneous [PURSUIT-SC], active ulcerative colitis trials [ACT] 1 and 2) and 1280 patients included in maintenance trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Maintenance [PURSUIT-IM], ACT 1 and 2), 696 (42.5%) and 534 (41.7%) were women, respectively. In a meta-analysis of induction trials, the adjusted odds ratios (aORs) of clinical remission (aOR, 0.55; 95% CI, 0.31-0.97), mucosal healing (aOR, 0.47; 95% CI, 0.27-0.83), and clinical response (aOR, 0.51; 95% CI, 0.29-0.90) in the treatment arm and of clinical remission in the placebo arm (aOR, 0.34; 95% CI, 0.15-0.82) were lower in men compared to women. There were no differences in outcomes by gender in the treatment and placebo arms in the meta-analysis of maintenance trials.
Men are less likely to achieve clinical remission, mucosal healing, and clinical response compared to women during induction treatment with TNFi for UC, but not during the maintenance phase. Future studies delineating the mechanisms underlying these observations would be informative.
In our meta-analysis of individual patient data from 4 ulcerative colitis clinical trials, the odds of clinical remission, mucosal healing, and clinical response with tumor necrosis factor inhibitors were lower among men compared to women during induction therapy, but not during maintenance therapy."
"Preliminary data indicates that proactive therapeutic drug monitoring (TDM) is associated with better outcomes compared with empiric dose escalation and/or reactive TDM, and that pharmacokinetic (PK) modelling can improve the precision of individual dosing schedules in Crohn's disease (CD). However, there are no data regarding the utility of a proactive TDM combined PK-dashboard starting early during the induction phase, when disease activity and drug clearance are greatest. The aim of this randomised, controlled, multicentre, open-label trial is to evaluate the efficacy and safety of a proactive TDM combined PK dashboard-driven infliximab dosing compared with standard of care (SOC) dosing in patients with moderately to severely active CD.
Eligible adolescent and adult (aged ≥16-80 years) patients with moderately to severely active CD will be randomised 1:1 to receive either infliximab monotherapy with proactive TDM using a PK dashboard (iDose, Projections Research) or SOC infliximab therapy, with or without a concomitant immunomodulator (IMM) (thiopurine or methotrexate) at the discretion of the investigator. The primary outcome of the study is the proportion of subjects with sustained corticosteroid-free clinical remission and no need for rescue therapy from week 14 throughout week 52. Rescue therapy is defined as any IFX dose escalation other than what is forecasted by iDose either done empirically or based on reactive TDM; addition of an IMM after week 2; reintroduction of corticosteroids after initial tapering; switch to another biologic or need for CD-related surgery. The secondary outcomes will include both efficacy and safety end points, such as endoscopic and biological remission, durability of response and CD-related surgery and hospitalisation.
The protocol has been approved by the Institutional Review Board Committee of the Beth Israel Deaconess Medical Center (IRB#:2021P000391). Results will be disseminated in peer-reviewed journals and presented at scientific meetings.
NCT04835506."
"Two antitumor necrosis factor therapies (infliximab [IFX] and adalimumab [ADA]) have been approved for the treatment of pediatric Crohn's disease (CD) but have not been compared in head-to-head trials. The aim of this study was to compare the efficacy and safety of ADA and IFX by propensity score matching in a prospective cohort of pediatric patients with luminal CD and at least a 24-month follow-up.
Among 100 patients, 75 met the inclusion criteria, and 62 were matched by propensity score. We evaluated time to treatment escalation as the primary outcome and primary nonresponse, predictors of treatment escalation and relapse, serious adverse events, pharmacokinetics, and effect of concomitant immunomodulators as secondary outcomes.
There was no difference between ADA and IFX in time to treatment escalation (HR = 0.63 [95% CI 0.31-1.28] P = 0.20), primary nonresponse (P = 0.95), or serious adverse events. The median (interquartile range) trough levels at the primary outcome were 14.05 (10.88-15.40) and 6.15 (2.08-6.58) µg/mL in the ADA and IFX groups, respectively. On a multivariate analysis, the combination of anti-Saccharomyces cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity was a strong independent predictor of treatment escalation (HR 5.19, [95% CI 2.41-11.18], P < 0.0001). The simple endoscopic score for CD, L3 disease phenotype, and use of concomitant immunomodulators for at least the first 6 months revealed a trend toward significance on a univariate analysis.
Propensity score matching did not reveal substantial differences in efficacy or safety between ADA and IFX. The anti-S. cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity combination is a strong predictor of treatment escalation."
"Ustekinumab is effective in the treatment of adult Crohn disease (CD) and ulcerative colitis (UC). However, data on its efficacy and safety in pediatric CD and UC are limited. To the best of our knowledge, there are no reports of Japanese children with UC treated with ustekinumab in the long-term.
A 14-year-old man with diarrhea and bloody stools was referred to our hospital. Colonoscopy revealed total colitis-type UC. His pediatric UC activity index score was 50, indicating moderately active UC.
Ulcerative colitis.
Infliximab was introduced because of steroid-resistant refractory UC; however, secondary ineffectiveness was observed 17 months later. Therefore, ustekinumab was administered along with prednisolone (16 years of age).
The patient achieved UC remission after ustekinumab treatment, leading to maintained remission without side effects.
To the best of our knowledge, this is the first pediatric case of moderately active UC successfully treated with ustekinumab in Japan. Ustekinumab combined with steroids is an effective and safe induction therapy for UC."
"Granulomatosis with polyangiitis is a granulomatous, necrotizing small-vessel vasculitis affecting both children and adults. However, subglottic tracheal stenosis appears more frequently in the pediatric cohort. To date, granulomatosis with polyangiitis is often treated with steroids, cyclophosphamide, azathioprine, or rituximab, but tumor-necrosis-factor-α-antagonistic drugs are increasingly gaining significance in treatment of refractory cases.
We report the case of a 15-year-old Caucasian male diagnosed with proteinase-3-positive granulomatosis with polyangiitis with acute shortness of breath. X-ray and magnet resonance imaging showed extensive subglottic narrowing. Forced expiratory volume in 1 s was reduced to 50% of age norm, with massively increased effective airway resistance. The patient initially responded very well to high-dose steroids and maintenance therapy with azathioprine. He was subsequently treated with four doses of rituximab, and levels of proteinase 3 antibodies normalized. After 6 months of clinical remission, the patient presented again with acute respiratory symptoms. Again, he was treated with high-dose steroids, but showed poor clinical response this time. Therefore, we decided to commence a tumor-necrosis-factor-α-antagonistic treatment with infliximab, under which our patient achieved clinical remission and normalization of lung function parameters.
The use of tumor-necrosis-factor-α-antagonistic agents might be a promising alternative for the treatment of refractory tracheal stenosis in pediatric patients with granulomatosis with polyangiitis."
"Tumor necrosis factor (TNF)-like cytokine 1A (TL1A), a member of the TNF family, exists in the form of membrane-bound (mTL1A) and soluble protein (sTL1A). TL1A binding its only known functional receptor death domain receptor 3 (DR3) affects the transmission of various signals. This study first proposed that the TL1A/DR3 axis was significantly upregulated in patients and mice with both asthma and high TNF-a expression and in TNF-a-stimulated epithelial Beas-2B cells. Two independent approaches were used to demonstrate that the TL1A/DR3 axis of mice was strongly correlated with TNF-a in terms of exacerbating asthmatic epithelial-mesenchymal transformation (EMT). First, high expression levels of EMT proteins (e.g., collagen I, fibronectin, N-cadherin, and vimentin) and TL1A/DR3 axis were observed when mice airways were stimulated by recombinant mouse TNF-a protein. Moreover, EMT protein and TL1A/DR3 axis expression synchronously decreased after mice with OVA-induced asthma were treated with infliximab by neutralizing TNF-a activity. Furthermore, the OVA-induced EMT of asthmatic mice was remarkably improved upon the deletion of the TL1A/DR3 axis by knocking out the "
"Nowadays, it is difficult to find a more complicated inflammatory disease of the abdominal organs in its pathogenesis than acute pancreatitis (AP). The application of antimediatory drugs and antimetabolites is the most promising direction in the correction of inflammatory pathological processes. The study of possible applications of a new group of drugs (monoclonal antibodies) that may trigger inflammation is also of great interest. The present study aimed to study the effect of infliximab on the lethality, volume, and nature of pancreatic lesions in severe necrotizing ductal pancreatic necrosis. The study was conducted on female Wistar rats (n=30) of similar age in the weight range of 200-250g. All manipulations were performed under general anesthesia by intraperitoneal injection of zoletil at a dose of 60 mg/kg, as well as chloral hydrate at a dose of 125 mg/kg. Model of severe acute necrotizing pancreatitis was performed through the injection of 0.5 ml of a buffer solution containing a bile acid salt-sodium taurocholate introductory. The animals were divided into the following groups: Group A (n=6): normal values; Group B (n=6): the mortality study was conducted in acute destructive pancreatitis in a period of 24 h; Group C (n=6): the simulation of acute severe necrotic pancreatitis was performed in this group along with the study of the volume of pancreatic lesions for a period of 6 h from the moment of modeling; Group D (n=6): in this group, the effect of infliximab (at a dose of 60 mkg/kg) was studied on mortality in severe destructive pancreatitis for a period of 24 h from the moment of modeling; Group E (n=6): in this group, the effect of infliximab (at a dose of 120 mkg/kg) was studied on the volume of pancreatic lesions in severe destructive pancreatitis for a period of 6 h from the moment of modeling. During the assessment of pancreatic damage, the mean±SD volume of pancreatic lesions was determined to be 34.8%±1.2% in a period of 6 h after modeling. Assessment of pancreatic damage in group E and the protective effect of infliximab at a dose of 60 mg/kg showed that the total volume of the necrotic pancreatic lesion was determined to be 21.3%±1.4% after a period of 6 h from the moment of AP modeling. In the course of this study, it was revealed that the application of infliximab at a dose of 60 mcg/kg led to a pronounced positive effect on the pancreatic lesion, manifested by up to 50% decrease in mortality for one day in group D. Infliximab had a definite protective effect in AP, decreasing the volume of the injury, as well as the mortality rate by half for 24 h. Therapy with anti-tumor necrosis factor with infliximab could significantly reduce the volume of pancreatic lesions in severe forms of pancreatic necrosis, which contributed to a pronounced decrease in mortality for 1 day from the moment of pathology reproduction."
"Circulating cytokines are central pathological mediators of inflammatory autoimmune diseases like rheumatoid arthritis. Immunological diversity in patients might contribute to inadequate responses to biological drugs. To address this therapeutic challenge, we developed a mathematical model that simultaneously describes temporal patterns of drug disposition for several biologics and their corresponding targeted cytokines, which were linked to triggering inflammatory responses.
A modelling framework was applied to rheumatoid arthritis-relevant cytokines regulating C-reactive protein (CRP) as an inflammatory marker. Clinical data were extracted from the literature for anakinra, canakinumab, infliximab, secukinumab and tocilizumab, along with their corresponding cytokines, interleukin-1 receptor antagonist, IL-1β, tumour necrosis factor α (TNFα), IL-17A and IL-6 receptor (IL-6R). Based on prior knowledge of regulatory mechanisms, cytokines were integrated with CRP profiles.
The model well captured all serum concentration-time profiles of cytokines and CRP ratios to respective baselines following drug treatment with good precision. On external validation, reasonable model performance on CRP dynamics, including rebound effects, was confirmed with clinical data not used in model development. Model-based simulations demonstrated that serum infliximab concentrations were accurately recapitulated in both a dose- and baseline TNFα-dependent manner. Furthermore, high baseline profiles of both IL-1β and/or targeted cytokines could be predictors of poor responses to biologics targeting TNFα and IL-6R, although the impact of IL-1β must be carefully interpreted.
Our model provides a quantitative platform to guide targeting and dosing strategies, including combination and/or sequential therapy, according to distinct baseline cytokine patterns in rheumatoid arthritis patients."
"Obesity is an emerging phenomenon among patients with inflammatory bowel disease (IBD). This study aims to evaluate whether the response to tumour necrosis factor-α (TNF-α) inhibitors (infliximab and adalimumab) could be influenced by BMI in IBD.
We identified a cohort of 181 IBD patients attending a single-tertiary centre, naive to biologic therapy and stratified them according to their BMI. The primary outcome is the first occurrence of loss of response (LOR).
The median BMI was 26 kg/m2 (15-63 kg/m2). Approximately 68% of patients had LOR on both adalimumab (ADA) (n = 52) and infliximab (IFX) (n = 71). However, 83% on ADA with BMI ≥30 kg/m2 had LOR compared to 61% on IFX with BMI ≥30 kg/m2. For patients on ADA, Cox regression analysis revealed that after accounting for age, sex, disease type, duration of disease, fistulising disease, smoking status, haemoglobin, C-reactive protein, albumin and platelet levels, there were statistically significant associations between BMI (≥30 kg/m2 vs. <30 kg/m2) and LOR [P = 0.010; hazard ratio (HR) 3.2; confidence interval (CI), 1.3-7.6]. However, for patients on IFX, after accounting for the same factors, the only significant factor was the association of lower rate of LOR with higher albumin levels (P = 0.024; HR 0.95; CI, 0.91-0.99). There was an increased accelerated time to LOR for patients on ADA with BMI ≥30 kg/m2 compared to BMI <30 kg/m2 (P = 0.026). However, there was no difference in time to LOR for patients on IFX (P = 0.177).
BMI is important in predicting the LOR among IBD patients on TNF-α inhibitors, especially among patients receiving ADA."
"It is necessary to find reliable and appropriate predictors of primary response to anti-TNFα therapy (infliximab and adalimumab) in inflammatory bowel disease (IBD) so as to avoid treatment failure and select optimal treatment. The aim of this study is to reveal useful predictors of the response to anti-TNFα treatment from baseline to 2 months after initial administration of anti-TNFα for individual IBD patients using our pharmacokinetic and pharmacodynamic (PK/PD) model at the time of second administration.
We retrospectively analyzed 26 IBD patients who received anti-TNFα. In the PK/PD model, inflammation was assumed to be suppressed based on the action of anti-TNFα at the rate constant of Kanti-TNFα (day-1). Kanti-TNFα0 (day-1) is Kanti-TNFα in the absence of anti-TNFα. We expressed inflammation caused by factors not affected by the action of anti-TNFα using the rate constant Kelse (day-1). Using univariate and multivariate linear regressions, we statistically analyzed factors related to the improvement of disease activity index.
The significant correlation between Kanti-TNFα0/Kelse and the improvement of disease activity index was shown in Crohn's disease patients (univariate: estimated value 2.4; P = 0.003; and multivariate: 1.8; P = 0.012) and ulcerative colitis patients (univariate: 0.12; P = 0.011), and no other factors were significant.
This is the first study to present a useful predictor of primary response to anti-TNFα of individual IBD patients at second administration. The Kanti-TNFα0/Kelse ratio may help to select the optimal therapeutic drug and avoid the improper continuous administration of anti-TNFα in the induction phase."
"Kawasaki disease (KD) is one of the common acquired heart diseases in under-5-year-old children and is an acute self-limiting vasculitis. After nearly 60 years of research, intravenous immunoglobulin combined with oral aspirin has become the first-line treatment for preventing coronary artery aneurysm in the acute stage of KD. However, glucocorticoid (GC), infliximab, and other immunosuppressants are options for the treatment of KD patients with a high risk of coronary artery aneurysm, no response to intravenous immunoglobulin and a confirmed diagnosis of coronary artery aneurysm. At present, there are still controversies over the use of GC in the treatment of KD. With reference to the latest research findings of KD treatment in China and overseas, this consensus invited domestic pediatric experts to fully discuss and put forward recommendations on the indications, dosage, and usage of GC in the first-line and second-line treatment of KD.
川崎病（Kawasaki disease，KD）是5岁以下儿童常见后天获得性心脏病之一，是一种急性自限性血管炎。经过近60年的研究，静脉注射免疫球蛋白联合阿司匹林口服成为急性期KD预防冠状动脉瘤的一线治疗。但对于发生冠状动脉瘤高风险、静脉注射免疫球蛋白无反应、确诊冠状动脉瘤等KD患者，糖皮质激素（glucocorticoid，GC）、英夫利昔单抗及其他免疫抑制剂是可以选择的治疗药物。目前GC在KD治疗中的应用存在争议。该共识结合KD治疗的国内外最新的研究成果，邀请国内儿科专家充分讨论，对GC在KD中一线及二线治疗的适应证、剂量、用法等提出了推荐意见。.
Kawasaki disease (KD) is one of the common acquired heart diseases in under-5-year-old children and is an acute self-limiting vasculitis. After nearly 60 years of research, intravenous immunoglobulin combined with oral aspirin has become the first-line treatment for preventing coronary artery aneurysm in the acute stage of KD. However, glucocorticoid (GC), infliximab, and other immunosuppressants are options for the treatment of KD patients with a high risk of coronary artery aneurysm, no response to intravenous immunoglobulin and a confirmed diagnosis of coronary artery aneurysm. At present, there are still controversies over the use of GC in the treatment of KD. With reference to the latest research findings of KD treatment in China and overseas, this consensus invited domestic pediatric experts to fully discuss and put forward recommendations on the indications, dosage, and usage of GC in the first-line and second-line treatment of KD."
"Immune checkpoint inhibitors (ICIs) are important novel agents used in advanced non-small cell lung cancer (NSCLC) standard regimens; however, their use increases the risk of immune-related adverse effects (IRAEs). The incidence of IRAE pneumonitis is well documented in ICI use. Corticosteroids continue to be the mainstay of treatment for IRAEs. Here we report one of the first cases of using infliximab to treat durvalumab-associated pneumonitis."
"Although anti-tumor necrosis factor (TNF)-α agents are important therapeutic drugs for Crohn's disease (CD), data regarding their long-term sustained effects are limited. Herein, we evaluated the long-term loss of response (LOR) to anti-TNF-α agents in patients with CD.
This retrospective study included patients with CD who started treatment with infliximab or adalimumab as a first-line therapeutic approach. The cumulative event-free, retention, and surgery-free rates after the start of biological therapy were analyzed. Secondary LOR was analyzed in patients who achieved corticosteroid-free clinical remission after the start of biological therapy. Cox proportional hazards models were used to analyze the predictive factors of secondary LOR.
The cumulative event-free rates at 1, 2, 5, and 10 years were 83.3%, 75.1%, 37.4%, and 23.3%, respectively. The incidence of LOR was 10.6% per patient-year of follow-up. At 12-14 weeks after the start of biological therapy, the proportion of patients with a C-reactive protein to albumin (CRP/ALB) ratio ≥0.18 was significantly higher in patients with LOR (P<0.001). Multivariate analysis indicates that a CRP/ALB ratio ≥0.18 (hazard ratio [HR], 5.86; 95% confidence interval [CI], 1.56-22.0; P=0.009) and upper gastrointestinal tract inflammation (HR, 3.00; 95% CI, 1.26-7.13; P=0.013) were predictive factors of secondary LOR.
Although anti-TNF-α agents contributed to long-term clinical remission of CD, the annual incidence of secondary LOR was 10.6%. The CRP/ALB ratio at 3 months after the start of biological therapy and upper gastrointestinal tract inflammation were identified as predictive factors of secondary LOR."
"Familial Mediterranean fever (FMF), a hereditary auto-inflammatory disease, mainly affects ethnic groups living in the Mediterranean region. Early studies reported colchicine may potentially prevent FMF attacks. For people who are colchicine-resistant or intolerant, drugs such as anakinra, rilonacept, canakinumab, etanercept, infliximab or adalimumab might be beneficial. This is an update of the review last published in 2018.
To evaluate the efficacy and safety of interventions for reducing inflammation in people with FMF.
We searched CENTRAL, MEDLINE, Embase and four Chinese databases on in August 2021. We searched clinical trials registries and references listed in relevant reports. The last search was 17 August 2021.
We included randomized controlled trials (RCTs) of people with FMF, comparing active interventions (including colchicine, anakinra, rilonacept, canakinumab, etanercept, infliximab, adalimumab, thalidomide, tocilizumab, interferon-α and ImmunoGuard (herbal dietary supplement)) with placebo or no treatment, or comparing active drugs to each other.
We used standard Cochrane methodology. We assessed certainty of the evidence using GRADE.
We included 10 RCTs with 312 participants (aged three to 53 years), including five parallel and five cross-over designed studies. Six studies used oral colchicine, one used oral ImmunoGuard, and the remaining three used rilonacept, anakinra or canakinumab as a subcutaneous injection. The duration of each study arm ranged from one to eight months. There were inadequacies in the design of the four older colchicine studies and the two studies comparing a single to a divided dose of colchicine. However, the four studies of ImmunoGuard, rilonacept, anakinra and canakinumab were generally well-designed.  We aimed to report on the number of participants experiencing an attack, the timing of attacks, the prevention of amyloid A amyloidosis, adverse drug reactions and the response of a number of biochemical markers from the acute phase of an attack; but no study reported on the prevention of amyloid A amyloidosis. Colchicine (oral) versus placebo After three months, colchicine 0.6 mg three times daily may reduce the number of people experiencing attacks (risk ratio (RR) 0.21, 95% confidence interval (CI) 0.05 to 0.95; 1 study, 10 participants; low-certainty evidence). One study (20 participants) of colchicine 0.5 mg twice daily showed there may be no difference in the number of participants experiencing attacks at two months (RR 0.78, 95% CI 0.49 to 1.23; low-certainty evidence). There may be no differences in the duration of attacks (narrative summary; very low-certainty evidence), or in the number of days between attacks: (narrative summary; very low-certainty evidence). Regarding adverse drug reactions, one study reported loose stools and frequent bowel movements and a second reported diarrhea (narrative summary; both very low-certainty evidence). There were no data on acute-phase response. Rilonacept versus placebo There is probably no difference in the number of people experiencing attacks at three months (RR 0.87, 95% CI 0.59 to 1.26; moderate-certainty evidence).  There may be no differences in the duration of attacks (narrative summary; low-certainty evidence) or in the number of days between attacks (narrative summary; low-certainty evidence). Regarding adverse drug reactions, the rilonacept study reported there may be no differences in gastrointestinal symptoms, hypertension, headache, respiratory tract infections, injection site reactions and herpes, compared to placebo (narrative summary; low-certainty evidence). The study narratively reported there may be no differences in acute-phase response indicators after three months (low-certainty evidence). ImmunoGuard versus placebo The ImmunoGuard study observed there are probably no differences in adverse effects (moderate-certainty evidence) or in acute-phase response indicators after one month of treatment (moderate-certainty evidence). No data were reported for the number of people experiencing an attack, duration of attacks or days between attacks. Anakinra versus placebo A study of anakinra given to 25 colchicine-resistant participants found there is probably no difference in the number of participants experiencing an attack at four months (RR 0.76, 95% CI 0.54 to 1.07; moderate-certainty evidence).  There were no data for duration of attacks or days between attacks. There are probably no differences between anakinra and placebo with regards to injection site reaction, headache, presyncope, dyspnea and itching (narrative summary; moderate-certainty evidence). For acute-phase response, anakinra probably reduced C-reactive protein (CRP) after four months (narrative summary; moderate-certainty evidence). Canakinumab versus placebo Canakinumab probably reduces the number of participants experiencing an attack at 16 weeks (RR 0.41, 95% CI 0.26 to 0.65; 1 study, 63 colchicine-resistant participants; moderate-certainty evidence). There were no data for the duration of attacks or days between attacks. The included study reported the number of serious adverse events per 100 patient-years was probably 42.7 with canakinumab versus 97.4 with placebo among people with colchicine-resistant FMF (moderate-certainty evidence). For acute-phase response, canakinumab probably caused a higher proportion of participants to have a CRP level of 10 mg/L or less compared to placebo (68% with canakinumab versus 6% with placebo; 1 study, 63 participants; moderate-certainty evidence). Colchicine single dose versus divided dose There is probably no difference in the duration of attacks at three months (MD -0.04 hours, 95% CI -10.91 to 10.83) or six months (MD 2.80 hours, 95% CI -5.39 to 10.99; moderate-certainty evidence). There were no data for the number of participants experiencing an attack or days between attacks. There is probably no difference in adverse events (including anorexia, nausea, diarrhea, abdominal pain, vomiting and elevated liver enzymes) between groups (narrative summary; moderate-certainty evidence). For acute-phase response, there may be no evidence of a difference between groups (narrative summary; low- to moderate-certainty evidence).
There were limited RCTs assessing interventions for people with FMF. Based on the evidence, three times daily colchicine may reduce the number of people experiencing attacks, colchicine single dose and divided dose may not be different for children with FMF, canakinumab probably reduces the number of people experiencing attacks, and anakinra or canakinumab probably reduce CRP in colchicine-resistant participants; however, only a few RCTs contributed data for analysis. Further RCTs examining active interventions, not only colchicine, are necessary before a comprehensive conclusion regarding the efficacy and safety of interventions for reducing inflammation in FMF can be drawn."
"Patients with MS and IBD were as likely to have stricturing, fistulizing, and extensive IBD as IBD controls. Although MS-IBD patients were less likely to initiate anti-TNF therapy, they did not have worsened risk of progression to surgery on follow-up."
"In this study, we aimed to evaluate the clinical features and treatments, including the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in a large cohort of pediatric and adult immunoglobulin A vasculitis (IgAV). Since data on the use of bDMARDs in IgAV are very limited, we collated the reasons for use of bDMARDs during the disease course. Patients who were enrolled in the Hacettepe University Vasculitis Research Centre (HUVAC) registry were included. In this prospective database dating from 2014, there were 436 IgAV patients classified as IgAV according to Ankara 2008 and/or American College of Rheumatology 1990 criteria. 88 adults and 330 pediatric IgAV patients were included as the main study group. Concomitant spondyloarthritis (SpA) was observed only in adult patients (10% vs 0% in children, p < 0.001). IgAV relapse was more common in adults than in children (p: 0.017). Adult patients were mostly treated with corticosteroid (p < 0.001) and conventional synthetic disease-modifying anti-rheumatic drug treatment (< 0.001), while more than half of the pediatric patients were followed up without immunosuppressive treatment. Ten (11%) adult patients used biologics. Among them, two patients used rituximab due to IgAV disease activity, three used infliximab due to SpA, three used etanercept due to SpA (one patient had a pediatric onset enthesitis-related arthritis), and two used anakinra due to recurrent familial Mediterranean fever attacks. This is the first study evaluating the use of all bDMARDs for any reason in the IgAV cohorts in the literature. None of the pediatric patients used biologics. Our data suggest biologics are mainly used for comorbid inflammatory diseases over refractory vasculitis in adult IgAV."
"Immune-modulating medications for inflammatory bowel diseases (IBDs) have been associated with suboptimal vaccine responses. There are conflicting data with SARS-CoV-2 vaccination. We therefore assessed SARS-CoV-2 vaccine immunogenicity at 2 weeks after second mRNA vaccination in 29 patients with IBD compared with 12 normal healthy donors. We observed reduced humoral immunity in patients with IBD on infliximab. However, we observed no difference in humoral and cell-mediated immunity in patients with IBD on infliximab with a thiopurine or vedolizumab compared with normal healthy donors. This is the first study to demonstrate comparable cell-mediated immunity with SARS-CoV-2 vaccination in patients with IBD treated with different immune-modulating medications."
"Behçet's disease (BD) is a recurrent multisystem inflammatory disease. Anti-tumor necrosis factor (TNF) α agents have been used to treat patients with intestinal BD with severe disease activity or those who are resistant to conventional treatments; however, the long-term efficacy of anti-TNFα agents in intestinal BD remains unclear. In the present study, we investigated the clinical outcomes and predictors of discontinuation of anti-TNFα agents in patients with intestinal BD.
We reviewed the medical records of patients with intestinal BD who received first-line anti-TNFα agents between January 2009 and June 2020. The primary outcome was the percentage of patients who continued anti-TNFα therapy for 48 weeks. Secondary outcomes included the percentage of patients who achieved marked improvement, complete remission, and mucosal healing, as well as predictors of discontinuation of anti-TNFα agents.
A total of 29 patients were included in the study. Twenty-two (75.9%) patients continued anti-TNFα therapy for 48 weeks. The percentage of patients who achieved marked improvement, complete remission, and mucosal healing at week 48 was 48.3%, 37.9%, and 48.3%, respectively. At week 96, 11 (37.9%) patients achieved marked improvement, complete remission, and mucosal healing. A higher C-reactive protein level (CRP; ≥ 1 mg/dL) at baseline was a predictor of discontinuation of anti-TNFα agents.
The 48-week continuation rate of anti-TNFα agents was 75.9% in bio-naïve patients with intestinal BD. However, a higher baseline CRP level (≥ 1 mg/dL) was associated with discontinuation of anti-TNFα agents."
"With the onset of the SARS-CoV-2 pandemic, Kawasaki Disease (KD) has come to the fore with its many atypical manifestations. Atypical clinical neurological, ophthalmological, musculoskeletal, gastrointestinal and pulmonary manifestations in a febrile child with raised markers should prompt the clinician to think of Kawasaki disease. Peripheral gangrene is a rare atypical manifestation of KD reported in infancy. We present a three-and-a-half-year-old boy with extensive gangrene all four limbs and face along with purpura fulminans. He was successfully treated with two doses of intravenous immunoglobulin (IVIG) and infliximab, with no residual gangrene. This case highlights that very severe forms of Kawasaki disease require IVIG, pulse steroids as well as infliximab for adequate control and complete resolution of the disease."
"Therapeutic drug monitoring (TDM) is the measurement of serum drug concentrations and anti-drug-antibodies (ADA) for biologic therapies used to treat inflammatory bowel disease (IBD). The aim of this article is to review the current literature concerning reactive and proactive TDM for both adults and children with IBD. Although optimal trough concentration windows for some of these medications are not well defined, there is mounting evidence to suggest that reactive TDM is associated with favorable therapeutic outcomes, including less immunogenicity, greater drug exposure, and a decreased risk of treatment failure. Moreover, while the exact mechanism of loss of response is not fully elucidated, the vast majority of studies have reported a decreased incidence of nonresponse and secondary loss of response when TDM is implemented. Proactive TDM, while even less understood in the literature, employs a schedule of preemptive analysis of serum trough concentrations to accordingly adjust the patient's biologic dosage. Proactive TDM may decrease the need for IBD-related surgery/hospitalization, and therefore merits future studies of investigation."
"Paradoxically, immunosuppressive therapy for inflammatory bowel disease (IBD) can induce psoriasiform or eczematous eruptions. This case-control study identified infliximab exposure, Crohn's disease, and history of inflammatory skin conditions as significant risk factors for these eruptions in children with IBD. Our results also showed possible trends in age and race."
"Infliximab (IFX) treatment is approved in Japan for health insurance coverage in patients with Kawasaki disease (KD). This study aimed to compare the cost-effectiveness of IFX and other therapeutic strategies for KD refractory to initial treatment, including intravenous immunoglobulin (IVIG), steroids, immunosuppressants, and plasma exchange therapy.
This multicenter, retrospective cohort study utilized data from the public medical insurance system of Japan. The target population included those who received treatment for KD between April 2012 and March 2019. Eligibility criteria were as follows: 1) initial onset of KD, 2) age < 15 years at onset, and 3) administration of 3rd line treatment if the 1st line treatment was IVIG alone or 2nd line treatment if the 1st line treatment was a combination of IVIG and steroids, in accordance with Japanese guidelines (2012). Those with KD-related cardiovascular complications before admission and those with congenital cardiac disease were excluded. The primary outcome was cost-effectiveness, which was calculated based on the number of admission events per annum divided by medical expenses per annum (times/10,000 US dollars). The Wilcoxon test was applied to analyze the difference in cost-effectiveness between patients who had received IFX and those who had not.
Among 1267 patients with KD, 25 received IFX treatment, while 206 received another treatment after the disease was designated refractory to initial treatment. The frequency of steroid use during initial IVIG treatment (a predictor of severity) was higher in the non-IFX group than in the IFX group (70.4% vs. 32.0%, p < 0.001) but became comparable after propensity-score matching. Our analysis indicated that IFX was more cost-effective than other treatments [1.04 (0.86, 1.34) vs. 1.38 (1.03, 1.79) (times/10,000 US dollars), p = 0.006].
IFX treatment may be more cost-effective than non-IFX treatment for patients with KD that is refractory to initial treatment."
"To examine the impact of novel biologic disease-modifying antirheumatic drugs (bDMARDs) with tumor necrosis factor (TNF) inhibitors or Interleukin-17A (IL-17A) antibody agents on health-related quality of life (HRQoL) outcomes in patients with radiographic axial spondyloarthritis (r-axSpA).
A literature search on PubMed, Embase, and Clinicaltrials.gov databases was performed through February 2022 to identify randomized controlled trials (RCTs) reporting HRQoL outcomes of bDMARDs for treatment of r-axSpA. Approved bDMARD therapy for r-axSpA included five TNF-inhibitors (infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol) and two IL-17A antibody agents (secukinumab, and ixekizumab). Heterogeneity (I
Sixteen RCTs, involving 3481 participants, were included. The placebo-controlled and treatment blinded durations ranged from 12 to 24 weeks. Compared with the placebo, bDMARD therapy was associated with significant improvement in HRQoL measures with the 36-item Short Form Survey (SF-36), European Quality of Life-5 Dimensions (EQ-5D), and Ankylosing Spondylitis Quality of Life (ASQoL). The pooled mean differences of changes from baseline for the SF-36 Physical Component Score (PCS), SF-36 Mental Component Score (MCS), EQ-5D, and ASQoL were 4.39 [95% Confidence Interval (CI): 3.24 to 5.54, P < 0.001]; 2.37 (95%-CI: 1.25 to 3.49, P = 0.003); 0.11 (95%-CI: 0.07 to 0.14, P < 0.001); and -2.45 (95%-CI: -3.21 to -1.70, P < 0.001), respectively. Heterogeneity was high (I
Biologic therapy was associated with a significant improvement in quality of life in patients with r-axSpA. The results were consistent among all three measures of HRQoL outcomes."
"Pyoderma gangrenosum is an uncommon neutrophilic dermatosis that usually presents with rapidly growing, painful, undermined, and purulent ulcers that are more likely to develop at areas of trauma. It is associated with underlying systemic diseases in more than half of cases, most commonly with inflammatory bowel disease. Pyoderma gangrenosum has no specific clinical, histologic, or laboratory findings, and so the diagnosis is based on exclusion of all other diagnostic possibilities, especially infectious causes. Misdiagnoses are frequent, with systemic vasculitides representing one of the main imitators. Treatment of pyoderma gangrenosum usually requires a multidisciplinary approach, with infliximab emerging as the best treatment option for cases associated with inflammatory bowel disease. The prognosis of pyoderma gangrenosum remains unpredictable, and recurrences are common. Here, we report a case of mucocutaneous pyoderma gangrenosum as a preceding sign of ulcerative colitis that responded to treatment with methylprednisolone and infliximab."
"Glucocorticoids (GCs) are the cornerstone of polymyalgia rheumatica (PMR) therapy, but their long-term use (as is usually necessary in PMR patients) can induce many adverse events. Alternatives have long been sought. The primary aim of our narrative review is to provide an overview about the use of anti-tumor necrosis factor alpha (TNF-α) drugs in patients with PMR, and discuss advantages and disadvantages.
we performed a non-systematic literature search (PRISMA protocol not followed) on PubMed and Medline (OVID interface).
only two anti TNF-α drugs have been prescribed to PMR patients: infliximab in 62 patients and etanercept in 28 patients. These drugs were normally used in addition to GCs when significant comorbidities and/or relapsing PMR were present; less commonly, they were used as first-line therapy. In general, they have been scarcely successful in patients with PMR. Indeed, randomized controlled trials did not confirm the positive results reported in case reports and/or case series. However, an administration schedule and study design different from those proposed in the past could favour new scenarios in the interest of PMR patients."
"Intravenous corticosteroids (IVCS) and rescue therapy with infliximab (IFX) are useful for managing patients with acute severe ulcerative colitis (ASUC). However, nearly one fifth of responders undergo colectomy. Predictive factors of colectomy in this subset of patients are not fully known. We retrospectively examined the long-term risk and the predictors of colectomy in ASUC patients achieving clinical remission following treatment with IVCS or IFX.
Clinical and demographic characteristics were evaluated in consecutive ASUC patients who were admitted to the ""Tor Vergata University"" hospital between 2010 and 2020 and responded to IVCS or IFX. A multivariate logistic regression model was constructed to identify independent predictors of colectomy.
A total of 116 ASUC patients responding to IVCS (98 patients) or IFX (18 patients) were followed up for a median of 46 months. After discharge, 29 patients (25%) underwent colectomy. Multivariate analysis showed that a serum albumin level &lt;3 g/dL and colonic dilation &gt;5.5 cm on admission were independent predictors of colectomy (OR: 6.9, 95% CI: 2.08-22.8, and OR 8.5, 95% CI: 1.23-58.3, respectively). Patients with both these factors had a risk of colectomy 13 times greater than those with no risk factor.
A low serum albumin level and colonic dilation are risk factors of long-term colectomy in ASUC patients responding to IVCS or IFX."
"BACKGROUND Fournier's gangrene (FG) is a rapidly progressive necrotizing infection of the perineum. Risk factors include male sex and immunosuppression. Inflammatory bowel disease and pregnancy may alter immune response by complex mechanisms but have rarely been associated with necrotizing infections of the perineum. To the best of our knowledge, only 5 cases of FG in association with IBD have been reported in the literature, and none of them occurred during pregnancy. CASE REPORT We report the case of a young woman with long-standing Crohn's disease in clinical remission with Infliximab monotherapy who developed FG in the third trimester of pregnancy. A cesarean section was undertaken at 35 weeks due to fetal distress, followed by debridement, diverting stoma, and vacuum-assisted therapy. The perineal defect was closed following 4 debridements and vacuum-therapy exchanges with a unilateral medial thigh advancement flap, and a draining seton was placed in the suprasphincteric fistula. The patient was discharged after 28 days and her recovery was unremarkable. The neonate also recovered well. CONCLUSIONS The treatment of FG is multidisciplinary and includes early debridement and intestinal diversion. Perianal pain should not be disregarded, as it may be the initial symptom of severe perianal sepsis in the immunosuppressed. To the best of our knowledge, this is the first case report of FG during pregnancy in a patient with Crohn's disease."
"Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head.
To compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis.
A systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure.
The NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors-brodalumab, ixekizumab, secukinumab-were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest.
Despite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype."
"To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator.
Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort.
24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted.
The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs."
"Extra-intestinal manifestations in inflammatory bowel diseases (IBD) are frequent and involve virtually all organs. Conversely, the clinical characteristics and course of inflammatory myopathies in IBD remain poorly described and mostly related to orbital myositis. Moreover, alternative therapeutic strategies in non-responder patients to corticosteroid therapy must still be clarified.
A 33-year-old woman with a history of unclassified colitis presented with acute bilateral calf pain. On admission, her clinical and biological examinations were non-specific. However, magnetic resonance imaging showed bilateral inflammatory changes in gastrocnemius muscles suggestive of myositis. Muscle biopsy confirmed the diagnosis of myositis and demonstrated an inflammatory infiltrate mainly located in the perimysial compartment including lympho-plasmocytic cells with the formation of several granulomatous structures while the endomysium was relatively spared. The combined clinical, biological and histomyopathological findings were concordant with the diagnosis of 'gastrocnemius myalgia syndrome' (GMS), a rare disorder associated with Crohn's disease (CD). Ileocolonoscopy confirmed CD diagnosis and systemic corticosteroids (CS) therapy was started, resulting in a rapid clinical improvement. During CS tapering, however, she experienced a relapse of GMS together with a severe active ileocolitis. Infliximab was started and allowed a sustained remission of both conditions at the latest follow-up (20 mo).
The GMS represent a rare CD-associated inflammatory myopathy for which anti-tumour necrosis factor-α therapy might be considered as an effective therapeutic option."
"Number needed to treat (NNT) estimates are a practical metric to help identify the most effective therapies. Our objective is to compare 11 biologic drugs for moderate-to-severe psoriasis in terms of NNT.
The NNT data were obtained from a Bayesian network meta-analysis of 42 double-blind, randomized, phase 3 clinical trials for 11 biologics (adalimumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab). We determined NNT to achieve Psoriasis Area and Severity Index (PASI) 75/90/100 responses at weeks 4, 8, 12, 16, and 48/52 and Dermatology Life Quality Index (DLQI) response 0, 1 at week 12.
Highest efficacy (lowest NNT) was with brodalumab and ixekizumab for PASI 90 at weeks 4, 8, and 12; ixekizumab for PASI 90/100 at week 16; and brodalumab for PASI 100 at week 12. After 48/52 weeks, risankizumab had the highest efficacy for PASI 90/100 overlapping with guselkumab, brodalumab, and ixekizumab for PASI 90 and with brodalumab and ixekizumab for PASI 100. Ixekizumab had the highest efficacy for DLQI (0,1) at week 12.
Brodalumab and ixekizumab had the lowest NNTs for achieving PASI responses at early time points and were not significantly different than risankizumab and guselkumab after 48/52 weeks."
"Infliximab and golimumab are intravenously (IV) administered tumor necrosis factor inhibitors approved to treat moderate-to-severe rheumatoid arthritis (RA) with concomitant methotrexate. Owing to differences in biologic construct, patients with IV-infliximab treatment failure may benefit from switching to IV-golimumab. Utilizing the ACR's Rheumatology Informatics System for Effectiveness (RISE), a large electronic health records registry based in the USA, we assessed RA disease activity in patients switching from IV-infliximab to IV-golimumab. This retrospective, longitudinal, single-arm study included adults (≥ 18 years) with ≥ 1 RA diagnosis code between 2014 and 2018 and ≥ 1 IV-infliximab prescription within 6 months of a new IV-golimumab order (index date). Longitudinal assessments of disease activity using the Clinical Disease Activity Index (CDAI) were calculated in patients continuing IV-golimumab for 6-9- and 9-12-months post-switch. Paired t-tests evaluated significance of mean improvements during the follow-up periods. Most RA patients with disease activity assessments during the 6-month follow-up (N = 100; mean age: 65.3 years; 81% female; 74% white) demonstrated moderate-to-high disease activity (CDAI: 73% [38/52]) at enrollment. On average, patients showed significant improvement in disease activity within 6-9 months of switching; mean CDAI scores improved from 21.3 to 14.1 (p < 0.0001) and were durable through 9-12 months of treatment. Real-world patients with moderate-to-high disease activity who switched from IV-infliximab to IV-golimumab demonstrated significant and sustained improvements post-switch as measured by the CDAI. Key Points • This study used real-world data from the Rheumatology Informatics System for Effectiveness (RISE) registry to evaluate the efficacy of directly switching from intravenous (IV)-infliximab to IV-golimumab to control rheumatoid arthritis (RA) disease activity. • Most IV-infliximab patients had moderate-to-high disease activity at the time of the switch. • On average, IV-golimumab was effective in improving RA disease activity after switching from IV-infliximab as measured by the Clinical Disease Activity Index. • These data suggest that real-world RA patients with persistent symptoms despite treatment with IV-infliximab may realize improved disease control with a switch to IV-golimumab."
"Tumour necrosis factor (TNF) antagonists are an efficacious therapy used in the management of several immune-mediated inflammatory diseases, including inflammatory bowel disease (IBD) and psoriasis. However, since being prescribed more widely, reports of new-onset psoriatic lesions have began to emerge in the literature and are known as paradoxical psoriasis.
To review the evidence available in both the dermatology and gastroenterology literature pertaining to the entity known as paradoxical psoriasis as it relates to IBD and to create a comprehensive guide to assist clinicians who treat this challenging patient population.
A literature search was conducted in PubMed to identify manuscripts that presented, discussed or summarised data pertaining to paradoxical psoriasis presenting in individuals with IBD.
Paradoxical psoriasis is now thought to be a contradictory effect of TNF antagonist therapy leading to psoriatic lesions often within the first year of treatment. The underlying pathogenesis, although not completely understood, is likely related to an imbalance of inflammatory cytokines. The histological appearance, while similar to classical psoriasis, does have unique features. The clinical presentation can vary among patients but often presents during maintenance therapy for inflammatory bowel disease. Treatment options should be determined based upon the severity of the skin lesion, activity of the underlying inflammatory bowel disease and the patient's unique clinical history.
The approach to paradoxical psoriasis in IBD should be discussed with a multidisciplinary team to optimise and preserve intestinal disease remission and to ensure the resolution of debilitating skin lesions."
"With the increasing incidence and prevalence, Crohn's disease (CD) has become one of the most challenging diseases in both diagnosis and treatment of gastroenterology. Evaluation of the disease activity and mucosal healing guides clinical decisions regarding subsequent therapy for CD. In this study, we enrolled a total of 144 patients with CD and 239 healthy controls were enrolled. Clinical characteristics and laboratory parameters of enrolled subjects were retrieved from the electronic medical record database of our hospital. Serum cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosa expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR). We identified two neutrophil-based indexes, the neutrophil-to-albumin ratio (NAR) and neutrophil-to-bilirubin ratio (NBR), both of which had not yet been explored in CD or UC. NAR and NBR were significantly increased in patients with CD compared to those in healthy controls, and both indexes showed significantly positive correlations with CD activity and inflammatory load. In note, NAR and NBR showed better performance than blood neutrophil percentage, serum albumin, or bilirubin alone in these scenarios. More importantly, both NAR and NBR discriminated CD patients who completely or partially responded to infliximab (IFX) induction therapy from those with primary non-response. Our observations suggest that NAR and NBR may serve as promising biomarkers in the diagnosis and prediction of response to IFX therapy in CD."
"Ulcerative colitis is a chronic inflammatory bowel disease. Approximately 20% of patients experience an acute severe attack during their life. In acute severe ulcerative colitis (ASUC), first-line therapy is intravenous (IV) steroids. In the absence of clinical improvement, 2 medical options can be considered: ciclosporin or infliximab."
"Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of the current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial and refractory stages of KD.
An NMA of randomised controlled trials (RCTs) was conducted using the frequentist model applied after electronic searches in PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, and Web of Science. The main outcomes were reduced fever duration/diminished severity of fever subsided. The initial stage of KD was defined as the first stage to treat patients with KD; the refractory stage of KD represents KD patients who failed to respond to standard KD treatment. The cut-off points for intravenous immunoglobulin (IVIG) were low (100-400 mg), medium (1 g), and high (at least 2 g).
A total of fifty-six RCTs with 6486 participants were included. NMA demonstrated that the medium-dosage IVIG + aspirin + infliximab [mean difference=-1.76 days (95% confidence intervals (95% CIs): -3.65 to 0.13 days) compared to high-dosage IVIG + aspirin] exhibited the shortest fever duration; likewise, the medium-dosage IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95% CIs: 0.18-1.37 compared to high-dosage IVIG + aspirin] exhibited the smallest incidence of coronary artery lesion (CAL) in the initial-stage KD. In the refractory-stage KD, the high-dosage IVIG + pulse steroid therapy (OR=0.04, 95% CIs: 0.00-0.43 compared to the high-dosage IVIG only) had the best rate of decline of fever; likewise, the high-dosage IVIG + ciclosporin [OR=0.05 (95% CIs: 0.00-1.21) compared to the high-dosage IVIG only] exhibited the smallest incidence of CAL. Infliximab significantly improved resolution compared to the high-dosage IVIG only group (OR=0.20, 95%CIs: 0.07-0.62) in refractory-stage KD.
The NMA demonstrated that the combination therapy with the standard therapy of IVIG and aspirin might have an additional effect on shortening the duration of fever and lowering the CAL incidence rate in patients with acute KD. Moreover, the combination therapy with high-dose IVIG and pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the rate of decline of fever and lowering the incidence rate of CAL in children with refractory KD. Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results.
None."
"This cross-cohort study aimed to (1) determine a network-based molecular signature that predicts the likelihood of inadequate response to the tumor necrosis factor-ɑ inhibitor (TNFi) therapy, infliximab, in ulcerative colitis (UC) patients, and (2) address biomarker irreproducibility across different cohort studies. Whole-transcriptome microarray data were derived from biopsies of affected colon tissue from 2 cohorts of infliximab-treated UC patients (training N = 24 and validation N = 22). Response was defined as endoscopic and histologic healing at 4-6 weeks and 8 weeks, respectively. From the training cohort, genes with RNA expression that significantly correlated with clinical response outcomes were mapped onto the Human Interactome network map of protein-protein interactions to identify a largest connected component (LCC) of proteins indicative of infliximab response status in UC. Expression levels of transcripts within the LCC were fed into a probabilistic neural network model to generate a classifier that predicts inadequate response to infliximab. A classifier predictive of inadequate response to infliximab was generated and tested in a cross-cohort, blinded fashion; the AUC was 0.83 and inadequate response was predicted with a 100% positive predictive value and 64% sensitivity. Genes separately identified from the 2 cohorts that correlated with response to infliximab appeared distinct but mapped onto the same network region of the Human Interactome, reflecting a common underlying biology of response among UC patients. Cross-cohort validation of a classifier predictive of infliximab response status in UC patients indicates that a molecular signature of non-response to TNFi therapies is present in patients' baseline gene expression data. The goal is to develop a diagnostic test that predicts which patients will have an inadequate response to targeted therapies and define new targets and pathways for therapeutic development."
"In 2019, more than $34.5 billion was spent on prescription drugs in Canada. However, little is known about the distribution of this spending across medications and settings (outpatient and inpatient) over time. The objective of this paper is to describe the largest expenditures by medication class over time in inpatient and outpatient settings. This information can help to guide policies to control prescription medication expenditures.
IQVIA's Canadian Drugstore and Hospital Purchases Audit data from January 1, 2001, to December 31, 2020, were used. In this dataset, purchasing was stratified by outpatient drugstore and inpatient hospital. Spending trajectories in both settings were compared to total expenditure over time. Total expenditure of the 25 medications with the largest expenditure were compared over time, stratified by setting. Nominal costs were used for all analysis.
In 2001, spending in the outpatient and inpatient settings was greatest on atorvastatin ($467.0 million) and erythropoietin alpha ($91.2 million), respectively. In 2020, spending was greatest on infliximab at $1.2 billion (outpatient) and pembrolizumab at $361.6 million (inpatient). Annual outpatient spending, although increasing, has been growing at a slower rate (5.3%) than inpatient spending (7.0%). In both settings, spending for the top 25 medications has become increasingly concentrated on biologic agents, with a reduction in the diversity of therapeutic classes of agents over time.
Identification of the concentration on spending on biologic agents is a key step in managing costs of prescription medications in Canada. Given the increases in spending on biologic agents over the last 20 years, current cost-control mechanisms may be insufficient. Future research efforts should focus on examining the effectiveness of current cost-control mechanisms and identifying new approaches to cost control for biologic agents."
"Paradoxical psoriasis or psoriasiform lesions induced by anti-tumor necrosis factor (anti-TNF) therapies receive increasing attention worldwide. However, no comprehensive meta-analysis investigating the incidence estimates and risk factors for anti-TNF-induced psoriasis is currently available. We aimed to precisely quantify its incidence as well as risk factors in patients with inflammatory bowel disease (IBD).
This study was registered on PROSPERO database under review registration number CRD42021233695. The electronic databases PubMed, EMBASE, and the Cochrane library were comprehensively searched for observational studies published as full-length papers in English and reporting the incidence and/or predictors for psoriasis or psoriasiform lesions in IBD patients. A random-effects meta-analysis was performed to calculate the pooled incidence. Pooled odds ratio (OR) and 95% confidence interval for potential predictors were combined using a fixed-effects or random-effects model.
In total, 30 articles comprising 24,547 IBD patients treated by anti-TNF were finally included. The overall pooled incidence of psoriasis and/or psoriasiform lesions following anti-TNF therapy was 6.0% (5.0-7.0%; 
The incidence of psoriasis or psoriasiform lesions was not uncommon in IBD patients following anti-TNF therapy. Female, younger age, smoker, ileocolonic Crohn's disease, and the types of anti-TNF were significantly associated with such risk. These findings may help gastroenterologists to make more individualized decisions and understand the mechanisms of this paradoxical phenomenon.
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=233695, identifier CRD42021233695."
"To date, there are limited real-world studies published on the use of infliximab-dyyb, a biosimilar to reference product (RP) infliximab approved for the treatment of moderate to severe inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) in North America. This study examined utilization patterns and the effects of infliximab-dyyb on clinical outcomes, patient-reported outcomes (PROs), and healthcare resource use (HCRU) in IBD patients in a real-world setting.
In this prospective, observational study, adult IBD patients in the US and Canada were recruited to initiate treatment with infliximab-dyyb and followed for 12 months. Patients included biologic-naïve users of infliximab-dyyb and patients switching from RP infliximab or other biologics to infliximab-dyyb. Partial Mayo (pMAYO) and Harvey Bradshaw Index (HBI) scores measured clinical outcomes for the UC and CD cohorts, respectively. Key PRO measures included the SIBDQ, EQ-VAS, and psychological outcomes. In addition, work productivity, HCRU, and adverse events (AEs) were assessed.
A total of 67 CD and 48 UC patients were enrolled (51% female; mean age 44 years; 87% Caucasian; mean BMI 27.9). Thirty-nine patients were biologic-naïve, 57 switched from RP infliximab, and 19 switched from other biologics. Among UC biologic-naïve users, pMAYO decreased from 5.67 to 1.09 (p < 0.0001) and the remission rate increased from 5.6 to 90.9% (p = 0.0015). For UC patients switching from RP infliximab, pMAYO decreased from 1.38 to 0.29 (p = 0.0103). For CD biologic-naïve users, HBI scores and remission rates did not significantly change. The scores on all the PROs significantly improved from baseline to 12 months. A total of 22 AEs occurred consistent with the known AE profile for infliximab.
Clinical outcomes among biologic-naïve users of infliximab-dyyb improved for UC and were maintained for CD patients. Biologic-naïve users of infliximab-dyyb showed significant improvements in PROs. Patients switching from RP infliximab to infliximab-dyyb maintained their clinical outcomes and PROs.
ClinicalTrials.gov Registration Number: NCT03801928 (February 23, 2018)."
"Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients."
"Primary immunodeficiency diseases (PIDs) consist of a heterogeneous group of genetically disorders that affect distinct components of the immune system. They manifest as increased susceptibility to life-threatening infections, as well as autoimmunity and inflammatory disease. Among them, patients with diseases of immune dysregulation and autoinflammatory disorders are more complicated with autoimmunity. On the other hand, tumor necrosis factor alpha (TNF-α) is one of the major players in the pathogenesis of autoimmunity and inflammation in PID patients. Monoclonal antibodies (mAbs) targeting TNF-α would be a potential approach as a therapeutic tool for these diseases. In the current review, we aimed to highlight the characteristics of TNF-α and its important role in the pathogenesis of related complication in PID diseases. Critical evaluation of the mAbs targeting TNF-α (e.g. infliximab, etanercept, and adalimumab) in various immune-mediated complications in PID diseases will be provided, and finally, their clinical efficacy and safety will be reported."
"Tumor necrosis factor antagonists (anti-TNF-
Despite the small number of patients, our series adds to the growing body of evidence supporting a causal link between anti-TNF-"
"Enterocolic lymphocytic phlebitis is phlebitis of unknown etiology in which lymphocytes affect veins without arteries and shows evidence of systemic vasculitis in the intestinal wall and mesentery, mainly in the small intestine and colon. Although patients present with a variety of gastrointestinal symptoms and findings like those of inflammatory bowel disease or ischemic bowel disease, there are no specific findings for enterocolic lymphocytic phlebitis. As a result, a diagnosis tends to be made after surgery. There are few case reports of enterocolic lymphocytic phlebitis, and the impact of chronic courses and immunosuppressive drugs on enterocolic lymphocytic phlebitis is not well known. A 47-year-old man was treated with infliximab and steroids for unexplained ulceration and narrowing of the ileocecal area, which was suspected to be inflammatory bowel disease with atypical findings. Lymphocytic phlebitis was noted in the surgical specimen, and enterocolic lymphocytic phlebitis was diagnosed. No recurrence of enterocolic lymphocytic phlebitis was observed postoperatively. This disease should also be considered among patients with inflammatory bowel disease-like lesions that do not respond to infliximab or steroids."
"Patients with Crohn's disease (CD) and ulcerative colitis (UC) may lose weight during periods of active disease and may gain weight when inflammation heals. Studies have hypothesized an association between antitumor necrosis factor-alpha (anti-TNF-α) and unintended weight gain during maintenance therapy, and this association has not been previously clarified.
In a nationwide observational study based on Danish national health registries, we included patients who initiated therapy with infliximab and followed changes in weight during induction therapy (0-90 days) and maintenance therapy (91-270 days). The association between the use of infliximab and weight gain was analyzed by a multilevel mixed-effects linear regression model.
Among 851 patients with CD and UC who initiated infliximab therapy, long-term weight gain was not observed during maintenance therapy in most of the patients. Women with CD who were underweight at the initiation of therapy had an average weight gain of 7.5 kg. Men and women with CD and UC with normal or increased body mass index had an average weight gain of <2 kg during maintenance therapy. Underweight men with CD and UC gained 2.9 kg (95% confidence interval 2.1-3.6) and 2.9 kg (95% confidence interval 1.9-3.9), respectively, in the first 90 days, although neither group had statistically significant weight gain in the maintenance period. Less than 3% of the patients had weight gain greater than 10% of their baseline body weight during the study period.
Weight gain among patients treated with anti-TNF-α therapies is unlikely to be due to an effect from anti-TNF-α therapy."
"Inflammatory bowel disease is a chronic disorder of the large intestine with the prevalence of approximately 400 cases in 100000, and it is rising day by day. However, several drugs like sulfasalazine (composed of sulfapyridine and 5-aminosalicylic acid or 5-ASA), corticosteroids, and immunosuppressants manage the disease. But there are no absolute treatments for the pain and inflammation of the disease. TNFα is an important target, and drugs like infliximab and adalimumab have pharmacological potency but with pronounced toxicity. So, we choose this major target TNFα for the virtual screening of US-FDA-approved drugs for its repurposing using the "
"Pyoderma gangrenosum (PG) is a rare chronic skin disease characterised by painful skin ulcers. There are no treatment guidelines for PG, but systemic treatments including biologics are often used. Recently, adalimumab (ADA), a fully human monoclonal antibody against tumour necrosis factor, was approved for refractory PG treatment in Japan. Herein, we report a case of rheumatoid arthritis with refractory PG 2 months after orthopaedic surgery of the foot during treatment with low-dose etanercept and methotrexate. Although adding a moderate dose of glucocorticoid did not improve her PG, the patient showed a remarkable response after switching from etanercept to ADA in a higher dose than that used to treat rheumatoid arthritis. This higher dose of ADA may be effective for the treatment of refractory PG after the failure of other tumour necrosis factor inhibitors."
"The number of treatment options in psoriasis has increased considerably, so biomarkers should be searched to assist in the selection of the optimal treatment agent. The most common of these biomarkers is HLA-Cw6.
The aim was to determine whether there is a relationship between HLA-Cw6-positivity (HLA-Cw6-POS) and the response of treatment agents in psoriasis.
Blood samples of 124 patients were subjected to genetic study for HLA-Cw6.
Psoriasis area severity index (PASI) score of more than 75% (PASI75) response was received in 34 (73.9%) of the HLA-Cw6-POS methotrexate-treated patients, 30 (78.9%) of the HLA-Cw6-POS cyclosporine-treated patients, and 8 (37.5%) of the HLA-Cw6-POS acitretin-treated patients. The differences were not statistically significant (
None of the agents were affected by HLA-Cw6. When biological agents were evaluated collectively, the treatment response of HLA-Cw6-POS patients was lower."
"The choice between infliximab (IFX) and vedolizumab (VED) as a first-line biological agent in moderate-to-severe ulcerative colitis (UC) can be difficult. Second-line vedolizumab (VED) efficacy may decline following prior infliximab (IFX) treatment failure in UC patients. However, it is not known whether second-line IFX efficacy declines after failure of first-line VED.
We aimed to compare first-line and second-line persistence of IFX and VED, in particular whether second-line IFX persistence declines after failure of first-line VED.
Persistence of IFX and VED was analysed from the Australian Pharmaceutical Benefits Scheme registry data as either first- or second-line treatment in UC. Propensity score matching (1:1) was conducted in the comparison of first-line treatments. Cox proportional hazard regression analysis was used to identify significant predictors and expressed as a hazard ratio (HR and 95% CI).
There were 420 subjects with moderate-to-severe UC who received either first-line IFX (
VED had a significantly longer persistence than IFX as first-line biological agent but does not disadvantage second-line IFX use in moderate-to-severe UC. VED after IFX is associated with significantly poorer persistence. VED, therefore, should be considered as the first-line biological agent of choice in UC."
[This corrects the article DOI: 10.3389/fphar.2021.740057.].
"Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with the colorectum as its major target organ. Involvement of the upper gastrointestinal tract in UC is rare and presents with nonspecific endoscopic and microscopic characteristics. Recent studies have demonstrated proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) to be a serological marker for differentiating UC from Crohn's disease in children and for detecting disease activity and nonresponse to steroid therapy and antitumor necrotizing factor-α agents. Herein, we report a 13-year-old female patient mainly presenting with recurrent bilious vomiting who was initially diagnosed with acute gastroenteritis. Intestinal pseudo-obstruction was confirmed through observation of a patent but segmentally dilated jejunum in the barium follow-through examination and other imaging; such obstruction can be attributed to backwash ileitis, superior mesenteric artery syndrome, ileus due to hypokalemia, or PR3-associated enteritis. Laboratory data revealed leukocytosis with neutrophil predominance and serum antinuclear antibody and PR3-ANCA positivity. Overlapping syndrome with autoimmune diseases was suspected. Pathology revealed a crypt abscess with aggregates of neutrophils consistent with UC but did not indicate vasculitis. The "
"Perianal fistulizing Crohn's disease (CD) is a phenotype with a poor prognosis. There are no studies in our country. Our objective is to determine the clinical, sociodemographic and treatment characteristics of perianal fistulizing CD in a Colombian multicenter registry.
A retrospective, multicenter observational study was carried out, with prospective data collection, in the main reference centers for inflammatory Bowel disease (IBD) in the country. Continuous variables were expressed as medians and interquartile ranges. The categorical outcome variables were compared by the Chi-square test.
Sixty-five patients with perianal fistulizing CD were documented, with a median age of appearance of perianal fistula of 31.0 years (range: 24-42), predominantly in men (61.5%; H:M ratio: 1.4:1). Complex perianal fistulas were more frequent than simple ones (75.35 vs. 24.6%). Regarding medical treatment, 66.2% of the patients received antibiotics, 64.6% steroids, 78.5% biological therapy, 47.7% non-cutting setons, and 46.2% required surgical management, other than seton placement. Only 29.2% achieved complete remission of the fistula, and 9.2% of the patients ended up in a definitive colostomy. CD patients with complex fistulas received more biological therapy, compared to CD patients with simple fistulas (84.8 vs. 56.3%; P: 0.038).
Perianal fistulizing CD has a poor prognosis in our setting, only 3 out of 10 patients achieve complete remission despite treatment. A multidisciplinary management is essential for the comprehensive management of this difficult pathology."
"Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare, severe cutaneous adverse reactions usually triggered by medications. In addition to tertiary-level supportive care, various systemic therapies have been used including glucocorticoids, intravenous immunoglobulins (IVIGs), cyclosporin, N-acetylcysteine, thalidomide, infliximab, etanercept, and plasmapheresis. There is an unmet need to understand the efficacy of these interventions.
To assess the effects of systemic therapies (medicines delivered orally, intramuscularly, or intravenously) for the treatment of SJS, TEN, and SJS/TEN overlap syndrome.
We searched the following databases up to March 2021: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five clinical trial registers, the reference lists of all included studies and of key review articles, and a number of drug manufacturer websites. We searched for errata or retractions of included studies.
We included only randomised controlled trials (RCTs) and prospective observational comparative studies of participants of any age with a clinical diagnosis of SJS, TEN, or SJS/TEN overlap syndrome. We included all systemic therapies studied to date and permitted comparisons between each therapy, as well as between therapy and placebo.
We used standard methodological procedures as specified by Cochrane. Our primary outcomes were SJS/TEN-specific mortality and adverse effects leading to discontinuation of SJS/TEN therapy. Secondary outcomes included time to complete re-epithelialisation, intensive care unit length of stay, total hospital length of stay, illness sequelae, and other adverse effects attributed to systemic therapy. We rated the certainty of the evidence for each outcome using GRADE.
We included nine studies with a total of 308 participants (131 males and 155 females) from seven countries. We included two studies in the quantitative meta-analysis. We included three RCTs and six prospective, controlled observational studies. Sample sizes ranged from 10 to 91. Most studies did not report study duration or time to follow-up. Two studies reported a mean SCORe of Toxic Epidermal Necrosis (SCORTEN) of 3 and 1.9. Seven studies did not report SCORTEN, although four of these studies reported average or ranges of body surface area (BSA) (means ranging from 44% to 51%). Two studies were set in burns units, two in dermatology wards, one in an intensive care unit, one in a paediatric ward, and three in unspecified inpatient units. Seven studies reported a mean age, which ranged from 29 to 56 years. Two studies included paediatric participants (23 children). We assessed the results from one of three RCTs as low risk of bias in all domains, one as high, and one as some concerns. We judged the results from all six prospective observational comparative studies to be at a high risk of bias. We downgraded the certainty of the evidence because of serious risk of bias concerns and for imprecision due to small numbers of participants. The interventions assessed included systemic corticosteroids, tumour necrosis factor-alpha (TNF-alpha) inhibitors, cyclosporin, thalidomide, N-acetylcysteine, IVIG, and supportive care. No data were available for the main comparisons of interest as specified in the review protocol: etanercept versus cyclosporin, etanercept versus IVIG, IVIG versus supportive care, IVIG versus cyclosporin, and cyclosporin versus corticosteroids. Corticosteroids versus no corticosteroids It is uncertain if there is any difference between corticosteroids (methylprednisolone 4 mg/kg/day for two more days after fever had subsided and no new lesions had developed) and no corticosteroids on disease-specific mortality (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.72 to 9.03; 2 studies; 56 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. IVIG versus no IVIG It is uncertain if there is any difference between IVIG (0.2 to 0.5 g/kg cumulative dose over three days) and no IVIG in risk of disease-specific mortality (RR 0.33, 95% CI 0.04 to 2.91); time to complete re-epithelialisation (mean difference (MD) -2.93 days, 95% CI -4.4 to -1.46); or length of hospital stay (MD -2.00 days, 95% CI -5.81 to 1.81). All results in this comparison were based on one study with 36 participants, and very low-certainty evidence. Adverse effects leading to discontinuation of therapy were not reported. Etanercept (TNF-alpha inhibitor) versus corticosteroids Etanercept (25 mg (50 mg if weight > 65 kg) twice weekly ""until skin lesions healed"") may reduce disease-specific mortality compared to corticosteroids (intravenous prednisolone 1 to 1.5 mg/kg/day ""until skin lesions healed"") (RR 0.51, 95% CI 0.16 to 1.63; 1 study; 91 participants; low-certainty evidence); however, the CIs were consistent with possible benefit and possible harm. Serious adverse events, such as sepsis and respiratory failure, were reported in 5 of 48 participants with etanercept and 9 of 43 participants with corticosteroids, but it was not clear if they led to discontinuation of therapy. Time to complete re-epithelialisation and length of hospital stay were not reported. Cyclosporin versus IVIG  It is uncertain if there is any difference between cyclosporin (3 mg/kg/day or intravenous 1 mg/kg/day until complete re-epithelialisation, then tapered off (10 mg/day reduction every 48 hours)) and IVIG (continuous infusion 0.75 g/kg/day for 4 days (total dose 3 g/kg) in participants with normal renal function) in risk of disease-specific mortality (RR 0.13, 95% CI 0.02 to 0.98, 1 study; 22 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. No studies measured intensive care unit length of stay.
When compared to corticosteroids, etanercept may result in mortality reduction. For the following comparisons, the certainty of the evidence for disease-specific mortality is very low: corticosteroids versus no corticosteroids,  IVIG versus no IVIG and cyclosporin versus IVIG. There is a need for more multicentric studies, focused on the most important clinical comparisons, to provide reliable answers about the best treatments for SJS/TEN."
"Behçet's disease (BD) is often associated with neutrophilic dermatosis. However, BD is rarely associated with aseptic abscesses in the spleen or liver. A 2-year-old girl presented to our hospital with a 2-week history of fever, abdominal pain, and a skin ulcer on her leg. Each time her skin was punctured with a needle for a blood test or spinal fluid test, she developed intractable aseptic abscesses on her skin. She was diagnosed with intestinal BD based on gastrointestinal endoscopy findings and was treated with prednisolone, mesalazine, and elemental diet therapy. Although these were effective for her colon ulcers, low-grade fever and mild abdominal pain persisted. Abdominal computed tomography revealed a low-density area in the spleen. Although it is recommended to check the contents with puncture drainage, it was difficult due to the risk of bleeding and pathergy. The abscess expanded despite antimicrobial therapy. We discontinued antimicrobial therapy and switched to intensified immunosuppressive therapy for BD [intravenous infliximab (IFX)]. After administration of IFX, the splenic abscess gradually disappeared, and all her symptoms improved. In cases of BD with splenic abscesses resistant to antimicrobial therapy, intensifying immunosuppressive therapy can be expected to shrink the abscesses and avoid splenectomy."
"Retrospective studies suggest that for patients with ulcerative colitis (UC) combination therapy with low-dose azathioprine and allopurinol (L-AZA/ALLO) may result in higher remission rates than monotherapy with azathioprine (AZA). We prospectively investigated the effects of these drugs for remission in patients with moderate-to-severe UC.
Open-label, unblinded, randomised, controlled, investigator-initiated, multicentre study conducted at eight hospital sites in Denmark. Adult patients with established UC, who were steroid dependent/refractory, thiopurine naïve, had a normal thiopurine methyltransferase, and achieved remission with steroids or infliximab were eligible for inclusion. Patients were randomly assigned by the investigators (1:1) to 52 weeks of treatment with once daily oral AZA (median dose 50 mg) combined with ALLO 100 mg versus AZA monotherapy (median dose 200 mg), using a computer-generated randomisation list with blocks of six. The trial was open without masking. All randomised patients who received at least one dose of study drug were included in primary and safety analyses (intention to treat population). The primary outcome was steroid and infliximab free remission after 52 weeks, defined as a Mayo Score of ≤1 and no rectal bleeding. The trial is completed and is registered in ClinicalTrials.gov (ClinicalTrials.gov NCT03101800).
Between January 9, 2017 and February 10, 2021, 47 patients were randomised to l-AZA/ALLO and 42 to AZA and received at least one dose of the study drug. After 52 weeks, 20 of 47 (43%) patients in the l-AZA/ALLO group and nine of 42 (21%) patients in the AZA group achieved remission (odds ratio 2·54 [95% CI 1·00 to 6.78, 
This study suggests that after one year l-AZA/ALLO therapy may be associated with a beneficial effect on steroid- and infliximab-free clinical remission in patients with moderate-to-severe UC and should be considered as first line therapy.
Funding for AAUC was provided by The Capital Region of Denmark ("
"Drug-induced liver injury (DILI) is a spectrum of pathology that can be classified by mechanism of injury or by type of observed hepatotoxicity. Vanishing bile duct syndrome (VBDS) is a group of acquired and genetic disorders that cause the destruction and disappearance of intrahepatic bile ducts, and cholestasis. VBDS typically presents with severe cholestatic hepatitis and can have immunoallergic features. Infliximab has been reported to rarely cause a cholestatic pattern of liver injury due to ductopenia characteristic of VBDS. Herein we present a clinical case of infliximab-induced DILI resulting in VBDS."
"Rheumatoid factor (RF) binds to the fragment crystallizable (Fc) portion of immunoglobulin. It could bind to the Fc portion of anti-TNF inhibitors (TNFi) and attenuate the clinical efficacy. We tried to determine whether the therapeutic efficacy of TNFi with Fc might be lower than that of TNFi without Fc in rheumatoid arthritis (RA) patients with high titres of RF. The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. RA patients treated with TNFi were included and divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, and etanercept) and TNFi without Fc (certolizumab pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was compared by Mann-Whitney U test between TNFi with and without Fc in each RF titre group. Multiple linear regression analysis was used to analyze the effect of TNFi without Fc for the change of DAS28-ESR adjusted after potential confounders. A total of 705 RA patients were classified into four groups (RF"
"Psoriasis and psoriatic arthritis, together known as psoriatic disease, is highly prevalent chronic relapsing inflammatory disease affecting skin, joints or both and is associated with several comorbidities such as cardiovascular, metabolic, psychiatric, renal disease etc. The etiopathogenesis of psoriasis is complex and mainly driven by aberrant immune response owing to the genetic susceptibility and various environmental factors such as trauma, infections and drugs. Recent advances in understanding molecular and cellular pathways have identified tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-23, IL-22 as major contributors in psoriasis pathogenesis. Advances in the knowledge of pathophysiology, the interaction of autoinflammation and clinical phenotypes have led to the development of highly effective targeted therapeutic agents which include TNF-α, IL-17, IL-23, IL-1 α/β or IL-36 inhibitors or receptor blockers, small molecule drugs like phosphodiesterase-4 inhibitors (apremilast), Janus kinase (JAK) inhibitors, retinoic acid receptor-related orphan receptor γt (RORγt) inhibitors. These novel drugs have promised the potential of improved disease control. In recent years, the transition from biologics to biosimilars especially with TNF-α inhibitors had significant impact on decreasing health care cost and increasing therapeutic options to the patients. However, selection of right treatment for an individual patient still remains challenging. Moreover, interplay between different epigenetic mechanisms such as the DNA methylation, chromatin modifications and noncoding RNA regulation has recently been started to be deciphered. Enzymes inhibitors involved in epigenetic pathways such as DNA methyltransferases and histone deacetylases demonstrated to restore normal epigenetic patterns in clinical settings and have provided the potential as novel therapeutic targets for psoriasis. In this review, we will discuss novel biologic agents and newer therapeutic approaches in treatment of psoriatic disease."
"Infliximab is a monoclonal antibody that binds and neutralizes circulating tumor necrosis factor-alpha, a key inflammatory cytokine in the pathophysiology of sarcoidosis. Despite the paucity of randomized clinical trials, infliximab is often considered a therapeutic option for refractory disease. Our study aimed to investigate the effectiveness of infliximab in patients with refractory sarcoidosis.
Sarcoidosis patients from three tertiary centres were retrospectively identified by pharmacy records based on treatment with infliximab. Treatment with Infliximab was initiated in patients who failed first and second line immunomodulators as determined by a multidisciplinary team of Respirologists, Dermatologists, ENT specialists, Rheumatologists, and Neurologists. Participants were characterized by the primary organ for which infliximab was initiated and the total number of organs involved. Clinical outcomes were categorized as treatment success versus failure. We defined treatment success as (A) improvement of cutaneous, upper airway, lymph node, gastrointestinal, eye, or joint manifestations; or (B) improvement or no change in central nervous system (CNS) or pulmonary manifestations.
33 patients with refractory sarcoidosis were identified. The proportion of treatment success was 100% (95% CI 54.1-100) in CNS, 91.7% (95% CI 61.5-99.8) in cutaneous, 78.6% (95% CI 49.2-95.3) in pulmonary and 71.5% (95% CI 29.0-96.3) in upper airway disease. The use of infliximab was associated with a reduction prednisone dose by 50%.
Infliximab is possibly an effective therapy for refractory sarcoidosis, with the greatest value in neurologic and cutaneous manifestations. Across all disease presentations, infliximab facilitated a clinically relevant reduction in corticosteroid dose. Relapse is common after discontinuation of infliximab."
"Anti-tumor necrosis factor (TNF)α antibody (ATA) and biologics/molecular targeted agents with other mechanisms (non-ATA) are currently available for refractory ulcerative colitis (UC). However, the knowledge about optimal drug selection after the initial treatment with ATA failure is lacking. This study assessed whether the response to the initial ATA could be a basis for selecting subsequent agents in UC patients.
Ulcerative colitis patients treated with ATA or non-ATA as the subsequent biologic after the failure of initial ATA were retrospectively analyzed. The efficacy at 14 weeks was examined according to the response to initial ATA.
Of 163 patients treated with the first ATA, the efficacy of subsequent ATA and non-ATA was evaluated in 63 and 36, respectively. Remission and response to subsequent-line therapy, regardless of ATA or non-ATA, were lower in patients with primary nonresponse (PNR) to initial ATA than in patients with efficacy to initial ATA (33.3% vs 69.2%, P < 0.01). In patients with PNR to initial ATA, the remission rate with subsequent ATA was significantly lower than with subsequent non-ATA (4.3% vs 26.3%, P = 0.04). In patients who showed efficacy to initial ATA, the remission rate with subsequent ATA was also lower than that with subsequent non-ATA (30.6% vs 56.3%, P = 0.08). PNR with initial ATA was the predictor of PNR to subsequent ATA (odds ratio: 5.62, 95% confidence interval: 1.50-21.7).
Non-ATA may be suitable in UC patients as the subsequent biologics regardless of the outcome of the first ATA."
"SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided."
"Iatrogenic immunodeficiency-associated lymphoproliferative disorders (IA-LPD) may arise in patients treated with immunosuppressive drugs for autoimmune disease or other conditions. Polymorphic EBV-positive B-lymphoproliferations often have features mimicking Hodgkin lymphoma and typically a self-limited, indolent course. We present an unusual case with isolated, intracerebral manifestation of polymorphic B-LPD with features of classic Hodgkin-lymphoma in an immunosuppressed patient treated with methotrexate and infliximab, including clinical-radiological features and a detailed description of morphological findings, together with a literature review on reported cases  of primary CNS manifestation of cHL and IA-LPD with Hodgkin-like morphology. The patient achieved complete remission following neurosurgery with gross total tumor resection and drug withdrawal without any additional treatment. Post-operative staging revealed no evidence for focal relapse or systemic disease during the 18 months follow-up period. Among the previously reported 24 cases of primary, isolated Hodgkin lymphoma in the central nervous system, three similar cases of iatrogenic, IA-LPDs were identified and are discussed here. Polymorphic B-LPD are destructive lesions with a range of morphologic features and disease manifestations. It is clinically important to recognize the spectrum of proliferations with features of classic Hodgkin lymphoma in immunodeficiency, iatrogenic settings, because they are likely to impact the choice of treatment strategies.
The online version contains supplementary material available at 10.1007/s12308-021-00478-0."
"Transplacental passage of certain biologic and targeted synthetic DMARDs leads to detectable levels in the neonate, which may impact on the safety of live vaccines. Guidelines advise delaying live vaccine administration in biologic-exposed infants until they are 7 months old.
A systematic review of Embase, Medline and Cochrane identified live vaccine outcomes in infants exposed to biologic or targeted synthetic DMARDs in utero.
Studies included 276 in utero exposures to adalimumab, certolizumab, etanercept, infliximab, golimumab, tocilizumab and ustekinumab. Live vaccine exposures at <12 months of age included Bacille Calmette-Guérin (BCG) (n = 215), rotavirus (n = 46), and measles, mumps and rubella (MMR) (n = 12). We identified no reactions following MMR, seven mild reactions to rotavirus vaccination and eight reactions to BCG, including one death. All infants with an adverse reaction to BCG had been exposed to infliximab in utero, and six had received BCG in the first month of life. A freedom of information request to the Medicines and Healthcare products Regulatory Agency revealed four fatal disseminated BCG infections in infants exposed to TNF inhibitors in utero, including infliximab, adalimumab and one unspecified TNF inhibitor.
Most evidence for a clinically harmful effect was for early administration of the BCG vaccine to infants exposed in utero to TNF inhibitors with high transplacental transfer rates."
"The aim of this retrospective cohort study was to investigate the prevalence of apical periodontitis (AP) in patients affected by autoimmune diseases (ADs) taking biologic medications (BMs).
Ninety-nine patients (2440 teeth) with ADs referred to the university clinic for dental evaluation were investigated. The controls included 99 patients (2655 teeth) with no systemic diseases and taking no medications. The patients underwent a complete oral, dental, and radiographic examination for the presence of AP. The periapical index and the status of endodontic and restorative treatments were obtained. Statistics were based on descriptive analysis and continuous variables for the total sample and by subgroups. Adjusted odds ratios and 95% confidence intervals were calculated.
The prevalence of AP was 65.7% in the autoimmune diseases group (AI) and 46.5% in the controls (P ≤ .05). The association between smoking and AP was significant (P ≤ .05). Among the AI subgroups, rheumatoid arthritis patients at the tooth level had a lower probability of developing AP than patients with inflammatory bowel disease (P ≤ .05). Furthermore, each additional year of age implied a +1% risk of AP; women had a lower periapical index than men in both groups (P ≤ .05), and tocilizumab was associated with a reduced risk of AP compared with infliximab (P ≤ .05).
Patients with ADs taking BMs had a higher prevalence of AP. These results indicate that the status of the patients' immune system may have an effect on the development and prevalence of AP."
This cross-sectional study examines utilization trends for filgrastim and infliximab products and their biosimilars to understand whether biosimilars are associated with reduced spending in Medicare Part D.
"To evaluate the safety of each anti-TNF therapy for patients with rheumatoid arthritis (RA) and then make the best choice in clinical practice.
We searched PUBMED, EMBASE, and the Cochrane Library. The deadline for retrieval is August 2021. The ORs, Confidence Intervals (CIs), and p values were calculated by STATA.16.0 software for assessment.
72 RCTs involving 28332 subjects were included. AEs were more common with adalimumab combined disease-modifying anti-rheumatic drugs (DMARDs) compared with placebo (OR = 1.60, 95% CI: 1.06, 2.42), DMARDs (1.28, 95% CI: 1.08, 1.52), etanercept combined DMARDs (1.32, 95% CI: 1.03, 1.67); certolizumab combined DMARDs compared with placebo (1.63, 95% CI: 1.07, 2.46), DMARDs (1.30, 95% CI: 1.10, 1.54), etanercept combined DMARDs (1.34, 95% CI: 1.05, 1.70). In SAEs, comparisons between treatments showed adalimumab (0.20, 95% CI: 0.07, 0.59), etanercept combined DMARDs (0.39, 95% CI: 0.15, 0.96), golimumab (0.19, 95% CI: 0.05, 0.77), infliximab (0.15, 95% CI: 0.03,0.71) decreased the risk of SAEs compared with golimumab combined DMARDs. In infections, comparisons between treatments showed adalimumab combined DMARDs (0.59, 95% CI: 0.37, 0.95), etanercept (0.49, 95% CI: 0.28, 0.88), etanercept combined DMARDs (0.56, 95% CI: 0.35, 0.91), golimumab combined DMARDs (0.51, 95% CI: 0.31, 0.83) decreased the risk of infections compared with infliximab combined DMARDs. No evidence indicated that the use of TNF-α inhibitors influenced the risk of serious infections, malignant tumors.
In conclusion, we regard etanercept monotherapy as the optimal choice for RA patients in clinical practice when the efficacy is similar. Conversely, certolizumab + DMARDs therapy is not recommended.
identifier PROSPERO CRD42021276176."
"Biologic agents have revolutionized treatment of immune mediated inflammatory diseases (IMIDs). However, despite the benefits of treatment, there is limited data on its use during pregnancy leading to significant variation in practices. We evaluated maternal, neonatal, and disease-related outcomes in pregnant women with IMIDs, comparing those with biologic exposure during pregnancy to those without exposure. Our hypothesis was that there would be no difference in outcomes between the two groups.
This is a retrospective cohort study conducted at a single tertiary care center including women with Crohn's disease (CD), ulcerative colitis (UC), ankylosing spondylitis (AS), rheumatoid arthritis (RA), or psoriasis/psoriatic arthritis (PS/PsA) who delivered between 2010 and 2018 at The Ohio State University Wexner Medical Center. Conditions were identified by ICD-9/ICD-10 code and confirmed by chart review. Demographic data, pregnancy outcomes and disease-related data were collected.
There were 338 pregnancies including 100 with CD, 74 with UC, 15 with AS, 61 with RA, and 90 with PS/PsA. 23% of IMID patients had biologic exposure (biologic use within 3 months of conception) and 18% continued therapy during pregnancy. Those with biologic exposure had increased risk of post-partum disease flare (OR 3.44; 95% CI 1.29, 9.15) and were less likely to breastfeed (OR 0.44; 95% CI 0.23, 0.87). In subgroup analysis of patients with IBD, those with biologic exposure also had increased risk of post-partum flare (OR 4.55; 95% CI 1.27, 16.35). Maternal and neonatal pregnancy outcomes were similar.
Among pregnant women with IMIDs, those that continued biologics during pregnancy had increased rates of major infection, disease related hospital admission, glucocorticoid use, and disease flare within 6 months post-partum, without any significant change in maternal or neonatal outcomes."
"Treatment options for acute severe ulcerative colitis (ASUC) are limited. Tofacitinib, an approved treatment for moderate to severe ulcerative colitis, could be a potential rescue therapy for ASUC given its rapid onset of action.
To evaluate the effectiveness of tofacitinib in hospitalized patients with ASUC refractory to standard therapy in a real-world setting.
Retrospective observational study of hospitalized adult patients with ASUC treated with tofacitinib between January 2019 and September 2020 at five Canadian centers. We extracted patient demographics, clinical status, biomarkers (C-reactive protein and fecal calprotectin), endoscopic findings, and colectomy-free rate at admission, 30 days, 90 days, and 6 months after tofacitinib initiation.
Eight patients with symptoms refractory to standard rescue therapy (corticosteroids ± infliximab if infliximab-naïve prior to admission) were treated with tofacitinib. During index hospitalization, clinical response was observed in 5/8 patients. The median time to discharge post-tofacitinib initiation was 5 days (IQR 5.0-6). At 30 and 90 days, all five responders were in clinical remission. At 6 months, only 3/5 responders remained in clinical remission. The colectomy-free rate was 37.5% during the follow-up period (two colectomies occurred within 30 days; one occurred within 90 days). No drug-related adverse reaction occurred.
In this small case-series, tofacitinib was an effective rescue therapy in patients with refractory ASUC. These findings need to be evaluated in a randomized controlled trial."
"To describe the unusual case of inflammatory CRB1-associated retinal dystrophy that initially presented with self-resolving opsoclonus.
We report the case of a now 2-year-old female who developed opsoclonus without myoclonus at the age of 4 months. An extensive workup for neuroblastoma and other systemic diseases was unremarkable, and all unusual eye movements self-resolved at age 10 months. Twenty-one months after initial presentation, she began having reduced visual behaviors, and comprehensive ophthalmic exam at that time revealed recurrent saccadic intrusions as well as severe, chronic retinal inflammation and dystrophic changes. An extensive infectious and inflammatory workup was negative. Genetic sequencing revealed two variants in CRB1: a heterozygous missense mutation and a heterozygous novel deletion involving exon 12. The patient was treated with monthly infliximab and methylprednisolone infusions with improvement in her optic disc and macular capillary leakage. The patient's 8-month-old sister also harbored the same variants in CRB1 and had early signs of retinal dystrophy and peripheral vascular leakage on exam.
Saccadic intrusions may be the first sign of a retinal dystrophy, and infants and children with this presentation should undergo a complete eye exam. We further highlight the link between CRB1-associated retinal dystrophy and inflammation, and how systemic steroids and tumor necrosis factor alpha (TNF-α) inhibitors may be effective therapies. Finally, we report a novel deletion in CRB1 that is likely highly penetrant."
"Relapsing polychondritis (RP) evolves with variable and intermittent involvement of cartilage and proteoglycan-rich structures. Ocular manifestations are present in up to two-thirds of RP patients. Necrotising scleritis (NS) and peripheral ulcerative keratitis (PUK) may be inaugural and may lead to eye perforation and vision loss. We aimed to review NS and PUK in RP, in order to characterise them, to identify successful treatment options and unmet needs.
A systematic review of the currently available evidence in PubMed, EMBASE and Scopus was performed according to PRISMA, including observational studies, single case reports and case series of NS/PUK in RP. Study design, number of patients, age, gender, treatment and outcome, were extracted. Two RP patients also provided their opinion.
Five case reports and two case series were eligible for inclusion. We identified 10 RP patients with eye-threatening complications (NS and/or PUK), 9 adults (2 males, 7 females, aged 35-72, median age 57.6 years) and one paediatric patient (F, 11 years). Apart from glucocorticoids, cyclophosphamide was effective in 4 patients; infliximab, high-dose immunoglobulins, dapsone, or cyclosporine were also successfully employed in a case each. Surgical repair was reported in 2 cases.
Ocular inflammation is often bilateral and recurring in RP; NS/PUK are rare complications. All patients who develop NS/PUK should be specifically questioned for RP signs and symptoms. Early institution of immunosuppressive therapies is mandatory. Increasing awareness, physicians' and patients' education and a multidisciplinary approach may help improve the prognosis of these serious complications of RP."
"Relapsing polychondritis (RP) is a rare systemic inflammatory disease of unknown etiology, primarily affecting cartilaginous tissue and proteoglycan-rich structures. Clinical manifestations vary from mild symptoms to occasional organ or life-threatening complications. Treatment can be challenging and is mostly based on experience or case reports/series.
There is growing literature investigating the role of biologics in the management of RP. TNFα antagonists, abatacept, tocilizumab, rituximab, anakinra and tofacitinib have been prescribed in several RP patients, mainly as second-line treatment, after conventional immunosuppressive agents' failure.
Glucocorticoids represent the gold standard treatment of RP. Conventional immunosuppressants should be administered in refractory patients or when a glucocorticoid-sparing effect is needed. Biologic therapy should be used after failure of conventional treatments or in severe manifestations. TNFα inhibitors are the most prescribed biologic agent, with partial or complete response in several cases, but loss of efficacy may occur over time. Infliximab and adalimumab should be preferred among TNFα antagonists. Abatacept and tocilizumab proved to be effective as second-line biologic agents, but infections are reported with the former. Data on anakinra and rituximab are controversial, therefore they are not recommended as first-line biologic drugs. The use of JAK inhibitors is still anecdotal."
"The new subcutaneous (sc) formulation of the infliximab (IFX) biosimilar CT-P13 results in homogeneous serum trough concentrations of IFX at steady state. The present study aimed to investigate in Crohn's disease (CD) patients the intra-individual variations of IFX drug levels at multiple time-points during 2 consecutive cycles of maintenance therapy with CT-P13 sc.
CD patients in clinico-biological remission under maintenance therapy with intravenous (iv) IFX/CT-P13 were switched to CT-P13 sc 8 weeks (W) after the last infusion. They were treated with CT-P13 sc, 120 mg every 2 W. Assessments were performed from 8 W after starting CT-P13 sc and patients had to attend 6 visits on 2 consecutive cycles of treatment (cycles A and B). Visits were scheduled on days 4-6 (visit 1), days 7-9 (visit 2) and day 14 (visit 3) of each cycle, where days 1 and 14 were the days of sc injection of CT-P13. At each visit, peripheral blood was collected to measure serum IFX levels and anti-drug antibodies.
Twenty patients underwent 120 evaluations. Large intra-individual variations of serum drug levels of IFX were observed. When pooling the 120 evaluations, the mean drug level was 11.3 ± 4.9 μg/ml, and the median drug level was 10.9 μg/ml (IQR 7.5-15.5). During each cycle, the median drug levels were similar between visits 1 and 2 as well as between visits 1 and 3 and between visits 2 and 3. In cycle A, median drug levels were 11.1 μg/ml (7.8-14.5), 12.0 μg/ml (7.2-16.1) and 11.0 μg/ml (7.5-15.1) at V1, V2 and V3, respectively. Similar results were obtained in cycle B, where median drug levels were 11.6 μg/ml (7.9-14.9), 11.4 μg/ml (8.1-15.2) and 10.9 μg/ml (7.9-15.6) at V1, V2 and V3, respectively. In univariate analysis, we failed to identify factors predictive of low drug levels.
IFX drug levels are quite stable within 14-day treatment cycle, without trough levels in CD patients in remission during the maintenance therapy with CT-P13 sc. In patients with inactive CD under maintenance therapy with CT-P13 sc, therapeutic drug monitoring of IFX can be performed at any time between two CT-P13 sc injections."
"Infliximab (IFX) has contributed to the treatment of several chronic inflammatory diseases, including Crohn's disease (CD), ulcerative colitis (UC), psoriasis (Pso), and rheumatoid arthritis (RA). However, the loss of response in some patients with long-term IFX therapy has been a major problem. Randomized controlled trials (RCTs) are limited in their short duration and lack of generalizability to the real-world population. We aimed to describe the persistence rates of IFX therapy to estimate its long-term effectiveness in clinical practice. Claims data from the Japan Medical Data Center database from January 2005 to June 2017 were used. The study population was identified based on the International Classification of Diseases, 10th Revision and the Anatomical Therapeutic Chemical Classification System. The 5-year persistence rates of IFX therapy were estimated using the Kaplan-Meier method. Overall, 281, 235, 41, and 222 patients with CD, UC, Pso, and RA, respectively, were selected. The 5-year persistence rates for IFX claims were 62.9, 38.9, 22.1, and 28.1% in patients with CD, UC, Pso, and RA, respectively. Patients with CD and UC administered IFX beyond the median dose had higher persistence rates. In patients with RA, female sex and no prior use of other biologics were associated with longer persistence. In conclusion, IFX persistence rates differed across chronic inflammatory diseases, which did not correspond to the results of the major RCTs. Factors associated with longer IFX persistence were identified in each disease group. Our findings may provide useful information to facilitate the proper use of IFX."
"Pediatric Crohn disease (CD) treatment goals have evolved. Among children receiving adalimumab (ADA) we examined long-term durability of clinical remission, linear growth, and associations of trough concentration (TC) with biomarker, endoscopic and imaging outcomes.
Single-center retrospective study. Pediatric CD activity index, C-reactive protein, fecal calprotectin, and height measured longitudinally. Discontinuation due to secondary loss of response (LOR) was assessed using Cox proportional hazards model. Associations between TC and clinical and biomarker remission, endoscopic and magnetic resonance imaging (MRI) improvements were assessed using Cox regression with time-dependent covariates.
Between January 2007 and June 2018, 213 children (median age 14.1 years (interquartile range [IQR] 12.5-15.7) 65% males) initiated ADA. One hundred and seventy-four (82%) achieved clinical remission (PCDAI < 10). During 24.8 (IQR 15.6-38.4) months follow-up, 26 (15%) discontinued ADA due to LOR, and 10 (6%) due to adverse events. Being anti-tumor necrosis factor (TNF) naïve and inflammatory behavior associated with increased likelihood of clinical remission (odds ratio [OR] 2.39, P = 0.033, and 3.13, P = 0.013, respectively) and with decreased LOR (hazard ratio [HR] 0.3, P = 0.002, and HR 0.35, P = 0.01, respectively). Cumulative LOR among 135 anti-TNF naïve patients: 0%, 8%, 15% within 1, 2, 3 years, similarly durable with mono- and immunomodulator combination therapy. Among pre-/early pubertal children mean height (-0.82) normalized to -0.07. TC consistently >7.5 ug/mL was associated with durable clinical remission (HR = 17.24, P < 0.001); TC >10 ug/mL with durable biomarker remission (HR = 6.56, P < 0.001) and endoscopic (OR 10.4, P = 0.002) and MRI (OR 7.6, P = 0.001) improvements.
ADA monotherapy maintains durable clinical remission. Biomarker remission, mucosal and transmural improvements were associated with greater ADA exposure."
"The aim of this study was to evaluate response and drug survival of biologic therapy in patients with moderate to severe plaque-type psoriasis who initiated biologic therapy at least 10 years ago, in a real-world setting.
This was an observational retrospective follow-up study that included patients with moderate to severe plaque-type psoriasis who initiated biologic therapy between October 2006 and December 2009. Efficacy was expressed as the percentage of patients achieving a 50, 75 and 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI 50, PASI 75, PASI 90, respectively) every 3 months during the first year of therapy and then every 12 months up to the end of follow-up or withdrawal from the study.
A total of 56 patients were included in the study, representing 140 treatment lines (median 2, range 1-8); of these patients, 53 were still receiving biologic therapy at the end of the study. The mean duration of biologic therapy was 140.4 (range 47.6-175.4) months. Etanercept was used in 98.2% of patients, followed by efalizumab (42.9%), adalimumab (41.1%), ustekinumab (33.9%) and infliximab (16.1%). Treatment lines were switched in 62.1% of treatments: 24.3% due to secondary failure, 20.7% due to primary failure and 3.6% due to side effects. No patient treated with anti-interleukins had to discontinue treatment due to side effects. Ustekinumab had the highest drug survival.
This study in the real-world-setting shows maintenance of long-term efficacy and safety of biologic therapy in patients with moderate to severe plaque psoriasis in daily practice who initiated biologic therapy 10 years ago."
"Crohn's disease may cause a life-long disease burden in many aspects due to its progressive nature. A large proportion of refractory patients have been benefiting from scheduled maintenance anti-TNF treatment; therefore, strategy to stop anti-TNF agents in Crohn's disease is not widely conducted. There have been observational studies demonstrating that approximately half of the patients relapse within a year after discontinuation. Several factors have been suggested as potential predictors for relapse; however, a consensus has not been reached so far. Although most relapse can be rescued by the re-treatment with the same anti-TNF agent, a proportion of patients may result in progressive bowel damage and the need for surgery. Therefore, an attempt to stop anti-TNF is not recommended without careful discussion, even if they are in long-term remission."
"Up to a third of inflammatory bowel disease) patients show primary nonresponse to antitumor necrosis factor (anti-TNF) biological therapy, and of those who respond, up to 40% develop secondary loss of response (LOR). Therapeutic drug monitoring (TDM) plays a crucial role in assessing patients with LOR to guide therapy by giving more of the drug or switching to a different biological agent. Although reactive TDM is suggested or recommended by the majority of gastroenterology associations, proactive TDM seems to be more controversial.
In this article, we discuss the updated guidelines on TDM and will also discuss the available data supporting proactive and reactive TDM in patients with Crohn's disease and those with ulcerative colitis using the different available biological agents.
Therapeutic drug monitoring (TDM) is a valuable tool to aid in inflammatory bowel disease (IBD) therapy optimization. Reactive TDM is widely accepted in IBD patients with suspected loss of response, especially in those receiving antitumor necrosis factor (anti-TNF) agents. Proactive TDM is emerging as a reasonable approach to patients initiated on anti-TNF therapy, specifically infliximab and, to some extent, adalimumab, particularly for patients with severe ulcerative colitis and fistulizing Crohn's disease. Similarly, TDM may play a role in patients considering de-escalation from combination therapy. To date, proactive TDM is not widely applied to ustekinumab and vedolizumab and more data are required before this becomes part of clinical practice."
"Recent advances in the pathophysiologic understanding of coronavirus disease 2019 (COVID-19) suggests that cytokine release syndrome (CRS) has an association with the severity of disease, which is characterized by increased tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-2, IL-7, and IL-10. Hence, managing CRS has been recommended for rescuing severe COVID-19 patients. TNF-α, one of the pro-inflammatory cytokines commonly upregulated in acute lung injury, triggers CRS and facilitates SARS-CoV-2 interaction with angiotensin-converting enzyme 2 (ACE2). TNF-α inhibitors, therefore, may serve as an effective therapeutic strategy for attenuating disease progression in severe SARS-CoV-2 infection. Below, we review the possibilities and challenges of targeting the TNF-α pathway in COVID-19 treatment."
"Tuberculosis (TB) spondylitis, also known as Pott's disease, is a severe form of extrapulmonary TB. Infliximab treatment for Crohn's disease (CD) patients increases the risk of TB, and is likely to increase the risk of TB spondylitis as well.
We report a rare case of TB spondylitis development in a 16-year-old female with CD. She had a close household contact of active pulmonary TB and received contact investigation. She was diagnosed with latent TB 1 month before the diagnosis of CD, and had started a latent TB treatment regimen with isoniazid for 9 months. At 5 months from the start of latent TB treatment, infliximab was started. Approximately 1 year after infliximab treatment, her infusion interval was shortened from every 8 weeks to every 4 weeks owing to secondary loss of response due to nonimmunogenic pharmacokinetic failure. One month later, miliary TB developed and infliximab was stopped. She received a miliary TB treatment regimen for 6 months, curing the disease. Three months later, spinal TB was incidentally detected on abdominal computed tomography. She received a TB treatment regimen for 12 months, curing spinal TB. Currently, she is receiving vedolizumab to treat CD and is in clinical remission. Although this patient has sufficiently been treated at each stage of TB development, particularly for latent TB and miliary TB, TB spondylitis still developed.
Considering that TB spondylitis developed despite sufficient treatment at each stage, pediatric gastroenterologists should stay cautious when using anti-tumor necrosis factor agents in patients with inflammatory bowel disease with a history of latent TB."
"Behçet's disease (BD) is a rare form of systemic vasculitis that affects small to large vessels. It is characterized by mucocutaneous, pulmonary, cardiovascular, gastrointestinal, and neurological manifestations. Large vessel involvement may occur in a third of cases. Veins are usually more affected than arteries. Furthermore aneurysms are the most frequent arterial complication.
A 41-year-old man presented with multiple arterial aneurysms. He had previous medical history of a right popliteal aneurysm treated with a reversed femoro-popliteal venous bypass, long-term steroids and immunosuppressive treatment. On admission, diagnostic computed tomography angiography revealed multiple aneurysms, including an 87 mm aneurysm of the femoro-popliteal bypass and an abdominal aortic and left common iliac artery aneurysm. He received an intensification of medical treatment with methylprednisolone and infliximab intravenous infusion. Aorto iliac artery aneurysms were treated by infrarenal bifurcated stent graft implantation. The aneurysm of the venous femoro-popliteal bypass was treated by explantation and prosthetic repair. One month later, he presented with acute right limb ischemia related to occlusion of the right limb of the stent graft despite anticoagulation which was treated by mechanical thrombectomy.
Vascular BD can worsen the vascular outcome after surgery. Except in an urgent context, BD must be controlled before surgery. This case report illustrates the importance of combined medical and surgical management, with first BD activity control with corticosteroids and immunosuppressive treatment, then surgical or endovascular treatment."
"Optimal management of patients with inflammatory bowel disease [IBD] after anti-tumour necrosis factor [TNF] discontinuation due to severe induced skin lesions is unclear. Our study aimed to describe dermatological and IBD evolution after anti-TNF discontinuation for this side effect.
We conducted a multicentre retrospective study including consecutive IBD patients who discontinued anti-TNF due to severe induced skin lesions. Our objectives were to determine factors associated with dermatological remission [complete disappearance of skin lesions] and with IBD relapse in patients with inactive disease at inclusion, notably the impact of an early switch to another biological agent within 3 months of anti-TNF discontinuation.
Among the 181 patients [134 women, 160 Crohn's disease] included in the 13 participating centres, dermatological remission occurred in 110 [62%] patients with a median [interquartile range, IQR] interval of 8.0 [6.8-11.0] months. Scalp location was independently associated with less remission of skin lesions (hazard ratio [HR] = 0.64 [95% CI 0.43-0.94], p = 0.02) while early switch was independently associated with a higher probability of remission of skin lesions (HR = 1.64 [95% CI 1.1-2.5], p = 0.02). Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 [51%] patients with a median [IQR] interval of 26.0 [23.0-39.1] months. Survival rates without IBD relapse at 1 year were 85.8% [95% CI 77.5-94.9] in the early switch group and 59.3% [95% CI 48.9-71.9] in the other group [p < 0.01].
Early switch to a new biological is associated with a higher probability of healing of anti-TNF-induced skin lesions and significantly reduces the risk of IBD relapse."
"Therapeutic drug monitoring of infliximab (IFX) is important to optimise treatment of inflammatory bowel disease (IBD). A recent IBD consensus statement recommends targeting trough serum concentrations of >3 μg/mL, higher than our local recommendation of >1 μg/mL. We therefore investigated the relationship between IFX trough concentrations and C reactive protein (CRP), faecal calprotectin (FCP), clinical outcomes and anti-IFX antibody (AB) development as well as the influence of concomitant thiopurine treatment.
Observational data, prospectively collected in a cohort of adult patients with IBD newly initiated on IFX at a single centre.
IFX concentrations >3 μg/mL were associated with a greater reduction in CRP (% change from baseline) and lower FCP; mean (SD) 47 (33.8) % vs 102.3 (136.9) % and 233.9 (505.1) μg/g vs 416.3 (613.5) μg/g, respectively. Lower IFX concentrations were observed in patients who developed AB than those who did not, mean (range) 6.2 (1.1-10) μg/mL vs 0.9 (0.4-4.9) μg/mL, respectively, and also in patients who stopped/switched therapy compared with those who continued, 2.4 (2.9) μg/mL vs 6.5 (2.8) μg/mL; p=0.0002. Patients taking a concomitant thiopurine were found to have higher IFX concentrations; mean (range) 6.4 (0.7-10) μg/mL vs 3.9 (0.4-10) μg/mL.
IFX concentrations are correlated with biomarkers, clinical response and AB development in patients with IBD. Concomitant thiopurine therapy appears to be associated with higher IFX concentrations and reduced likelihood of AB development."
"In postoperative Crohn's disease (POCD), data are lacking on relationships between serum biologic concentrations and treatment outcomes. We assessed if established threshold concentrations of infliximab (IFX), adalimumab (ADA), and ustekinumab (UST) impact outcomes in POCD.
Data were extracted from POCD patients with serum biologic concentration measurements using Weill Cornell Medicine biobanks. The primary outcome compared rates of deep remission (achieving both objective [endoscopic or biomarker] and clinical [Harvey-Bradshaw index or Crohn's Disease Patient Reported Outcome-2] remission), using established serum drug level cutoffs of IFX ≥3 µg/mL, ADA ≥7.5 µg/mL, and UST ≥4.5 µg/mL.
In 130 patients, median IFX, ADA, and UST concentrations were 10 (interquartile range [IQR], 2.9-26.9) µg/mL, 10.5 (IQR, 4.9-14.9) µg/mL, and 6.9 (IQR, 5.1-10.2) µg/mL, respectively. In patients with IFX ≥3 µg/mL, higher rates of deep remission (39% vs 0%; P = .02) existed compared with those with IFX <3 µg/mL. Similar differences existed for clinical (44% vs 9%; P = .04) and objective (83% vs 62%; P = .1) remission. In patients with ADA ≥7.5 µg/mL, rates of deep (42% vs 0%; P = .02), clinical (42% vs 0%; P = .02), and objective (88% vs 40%; P = .007) remission were higher than patients with lower concentrations. For UST, rates of deep (28% vs 17%; P = 1.0), clinical (33% vs 33%; P = 1.0), and objective (70% vs 67%; P = 1.0) remission were similar between patients regardless of drug concentration.
In POCD, established anti-tumor necrosis factor concentrations were associated with improved outcomes. No relationship between UST concentrations and postoperative outcomes existed.
Data are lacking on therapeutic drug monitoring in postoperative Crohn’s disease. The current study found that tumor necrosis factor antagonist concentrations above established drug thresholds were associated with improved outcomes. In contrast, for ustekinumab, no relationship between drug thresholds and outcomes existed."
"Multisystem inflammatory syndrome in children (MIS-C) is a type of hyperinflammatory symptoms similar to Kawasaki disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is commonly observed in children aged 8-10 years. Primary therapeutic medications for MIS-C are intravenous immunoglobulins and glucocorticoids. It has been reported that biologics, such as IL-1 receptor antagonist anakinra, IL-6 receptor antagonist tocilizumab, and TNF-α receptor antagonist infliximab, can be used as an option for critically ill patients. This article elaborates on the mechanism of action of the above biologics and discusses the efficacy and safety biologics in the treatment of MIS-C after SARS-CoV-2 infection, in order to provide methods for the treatment of MIS-C with severe symptoms.
儿童多系统炎症综合征（multisystem inflammatory syndrome in children，MIS-C）是儿童感染严重急性呼吸综合征冠状病毒2后出现的类似川崎病的过度炎症症状，多发于8~10岁儿童。首选治疗药物是静脉注射免疫球蛋白和糖皮质激素，文献报道危重症患者可选择生物制剂如白细胞介素1受体拮抗剂阿那白滞素、白细胞介素6受体拮抗剂托珠单抗、肿瘤坏死因子α受体拮抗剂英夫利昔单抗等治疗。该文通过阐述上述生物制剂的作用机制，结合案例具体分析生物制剂在治疗儿童感染严重急性呼吸综合征冠状病毒2后出现MIS-C中的安全性和有效性，以期对具有严重症状的MIS-C治疗提供方案。.
Multisystem inflammatory syndrome in children (MIS-C) is a type of hyperinflammatory symptoms similar to Kawasaki disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is commonly observed in children aged 8-10 years. Primary therapeutic medications for MIS-C are intravenous immunoglobulins and glucocorticoids. It has been reported that biologics, such as IL-1 receptor antagonist anakinra, IL-6 receptor antagonist tocilizumab, and TNF-α receptor antagonist infliximab, can be used as an option for critically ill patients. This article elaborates on the mechanism of action of the above biologics and discusses the efficacy and safety biologics in the treatment of MIS-C after SARS-CoV-2 infection, in order to provide methods for the treatment of MIS-C with severe symptoms."
"Immune checkpoint inhibitors (ICIs), such as nivolumab and ipilimumab, have drastically changed treatments of advanced melanoma. However, ICI-related enterocolitis is often the most common adverse event, and represents the main reason for ICI discontinuation and mortalities. Here, we report the case of a metastatic melanoma treated with vedolizumab for ICI-induced colitis. A 67-year-old man treated with ipilimumab and nivolumab developed ICI-induced colitis and grade 3 diarrhea refractory to methylprednisolone and infliximab. After his third dose of vedolizumab, oral prednisolone ceased, and the colitis had completely resolved with no recurrence. This case report supports vedolizumab use in treating severe colitis which failed to resolve with first- and second-line immunosuppressive therapy."
"Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease usually occurring after puberty with painful, deep-seated, inflammatory lesions in the apocrine gland-bearing areas of the body. Although HS pathogenesis is still unproven, recent major research advantages have increased our knowledge of the mechanisms behind HS lesions. Particularly, follicular occlusion followed by follicular rupture has been shown to be crucial to HS development, leading to immune response activation, and resulting in typical clinical HS lesions. Moreover, an increased and imbalanced cytokine production, such as interleukin (IL) 17 and tumor necrosis factor (TNF) α, may play a role in HS. In recent years, paradoxical adverse events have been described during treatment. Since the recent increased use of biologic treatments in HS, an increased number of paradoxical HS occurrences have been reported. In this review, we analyzed all current data on paradoxical HS triggered by biological drugs."
"Provide an updated review of the clinical management and diagnosis of Kawasaki disease with inclusion of potential diagnostic difficulties with multisystem inflammatory syndrome in children (MIS-C) given the ongoing COVID-19 pandemic.
Adjunctive corticosteroid therapy has been shown to reduce the rate of coronary artery dilation in children at high risk for IVIG resistance in multiple Japanese clinical studies (most notably RAISE study group). Additional adjunctive therapies (etanercept, infliximab, cyclosporin) may also provide limited benefit, but data is limited to single studies and subgroups of patients with cardiac abnormalities. The efficacy of other agents (atorvastatin, doxycycline) is currently being investigated. MIS-C is a clinically distinct entity from KD with broad clinical manifestations and multiorgan involvement (cardiac, GI, hematologic, dermatologic, respiratory, renal). MIS-C with Kawasaki manifestations is more commonly seen in children < 5 years of age.
The 2017 American Heart Association (AHA) treatment guidelines have included changes in aspirin dosing (including both 80-100 mg/kg/day and 30-50 mg/kg/day treatment options), consideration of the use of adjuvant corticosteroid therapy in patients at high risk of IVIG resistance, and the change in steroid regimen for refractory KD to include both pulse-dose IVMP and longer course of prednisolone with an oral taper. A significant proportion of children diagnosed with MIS-C, a post-infectious syndrome of SARS-CoV-2 infection, meet criteria for Kawasaki disease. Further investigation is warranted to further delineate these conditions and optimize treatment of these conditions given the ongoing COVID-19 pandemic."
"In this case series, ustekinumab therapy demonstrated efficacy in some patients with severe hidradenitis suppurativa previously treated with adalimumab and/or infliximab. Larger prospective studies are needed to evaluate ustekinumab as a treatment option for recalcitrant hidradenitis suppurativa."
"The serological responses after severe acute respiratory syndrome coronavirus 2 vaccination may be attenuated in immunocompromised individuals. The study aimed to systematically evaluate the seroconversion rates after complete vaccination for coronavirus disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD).
Electronic databases were searched to identify studies reporting response to COVID-19 vaccination in IBD. Pooled seroconversion rates after complete vaccination were calculated. Subgroup analysis for vaccine types was also performed. Pooled seroconversion rates for various drugs or classes were also estimated. The pooled rates of breakthrough infections in vaccinated IBD patients were estimated. The pooled neutralization rates after complete vaccination were also estimated. The studies reporting durability of titers were systematically assessed.
A total of 46 studies were included. The pooled seroconversion rate for complete vaccination (31 studies, 9447 patients) was 0.96 (95% confidence interval [CI], 0.94-0.97; I
Complete COVID-19 vaccination is associated with seroconversion in most patients with IBD. The decay in titers over time necessitates consideration of additional doses in these patients."
"Neurosarcoidosis can affect all parts of the nervous system of which myelitis is relatively frequent. The aim of this study was to describe clinical characteristics, treatment and prognosis of patients with myelitis attributable to neurosarcoidosis.
We performed a retrospective cohort study and a systematic review and meta-analysis of neurosarcoidosis-associated myelitis.
Myelitis was identified in 41 of 153 (27%) neurosarcoidosis patients seen at our clinic from 2015 to 2020. Classification of neurosarcoidosis was definite in three (7%), probable in 29 (71%) and possible in nine patients (22%). The median (interquartile range) age at onset was 49 (41-53) years and 20 of the patients were female (49%). The presenting symptoms included muscle weakness in 31 of 41 patients (78%), sensory loss in 35 (88%) and micturition abnormalities in 30 (75%). Spinal magnetic resonance imaging showed longitudinally extensive myelitis in 27 of 36 patients (75%) and cerebrospinal fluid examination showed an elevated leukocyte count in 21 patients (81%). Initial treatment consisted of glucocorticoids in 38 of 41 patients (93%), with additional methotrexate or azathioprine in 21 of 41 patients (51%) and infliximab in 10 of 41 patients (24%). Treatment led to remission, improvement or stabilization of disease in 37 of 39 patients (95%). Despite treatment, 18 of 30 patients (60%) could not walk independently at the end of follow-up (median 36 months). A review of the literature published between 2000 and 2020 identified 215 patients with comparable clinical characteristics and results of ancillary investigations.
Sarcoidosis-associated myelitis is observed in 27% of neurosarcoidosis patients. Although treatment often led to a decrease in disease activity, residual neurological deficits leading to loss of ambulation occurred frequently."
"To examine the long-term efficacy and side effects of antitumour necrosis factor alpha (anti-TNF) therapy in patients with Crohn's disease (CD), the need for surgery and the clinical outcome after discontinuing anti-TNF therapy.
Data were collected from the inflammatory bowel disease (IBD)-TNF register at Østfold Hospital Trust. Clinical and sociodemographic data were recorded for patients initiating anti-TNF therapy from January 2000 until December 2011. Follow-up was conducted until December 2017.
Complete remission (CR) was achieved in 40/154 (26%) patients at the last follow-up (median follow-up time 10 years). A total of 40 (26%) patients had to discontinue treatment due to serious side effects, and malignancy was recorded in 10 (6.5%) patients. Surgical resection was performed in 55 (36%) patients during follow-up. Patients with Montreal phenotype B2 before anti-TNF therapy were estimated to have a 2.54-fold greater risk of surgery than patients with phenotype B1 (
Long-term complete remission was achieved in only one in four patients receiving anti-TNF therapy, and one in four patients had to discontinue therapy due to side effects. Despite anti-TNF therapy, one in four patients with a baseline luminal disease phenotype needed subsequent surgical resection."
"To provide in-depth understanding of real-world tumor necrosis factor inhibitor (TNFi) treatment patterns in patients with ankylosing spondylitis (AS) and treatment satisfaction, productivity loss, and associated factors.
This was a multicenter observational hybrid retrospective chart review and cross-sectional survey study. Disease activity and physical functioning were measured using the Bath AS Disease Activity Index and Bath AS Functional Index, respectively. Treatment satisfaction was determined with the Treatment Satisfaction Questionnaire for Medication (TSQM). Productivity loss was evaluated using the Korean version of the World Health Organization-Health and Work Performance Questionnaire.
A total of 497 patients were enrolled (mean age 40.3 years, 85.3% male, mean AS duration 10 years). The mean duration of TNFi treatment was 6.2 years. Among the four TNFi considered, adalimumab (39.6%) and etanercept (23.5%) were most commonly used at study enrollment. The TSQM convenience domain score was lower than scores in the effectiveness, adverse effects, and global satisfaction domains. Subcutaneous syringe-type injection and intravenous injection were associated with lower patient convenience satisfaction than subcutaneous pen-type injection. Increased costs of lost productivity time were associated with female sex, unemployed status, and higher disease activity.
The most frequently prescribed TNFi was adalimumab, followed by etanercept. Etanercept was used for the longest duration. More convenient treatment options may enhance overall treatment satisfaction. Considerable loss in productivity due to AS was observed in this study. To reflect patients' perspectives, further attention should be paid to factors associated with treatment satisfaction and productivity loss when selecting treatment options."
"The management of moderate to severe ulcerative colitis has undergone significant changes over the past 15 years due to the regulatory approval of several new drugs. In particular, following the approval of the first biological, i.e. infliximab, a number of further biological drugs, such as adalimumab, golimumab, vedolizumab and ustekinumab, and small molecules, such as tofacitinib, have been approved, thus enriching the therapeutic armamentarium for ulcerative colitis. Choice of therapy must take into consideration not only the need to induce and maintain disease remission according to the patient's profile, but also age, co-morbidities, and prior treatments. To guide these decisions, the Italian Group for the Study of Inflammatory Bowel Disease has developed clinical guidelines that supersede its earlier document from 2011. These new guidelines were developed following the GRADE methodology for rating the quality of the evidence and for determining the strength of the recommendations. This article presents the methodology and results, in the form of 20 statements with commentary on the use of the five biologics and tofacitinib for managing the intestinal manifestations of active ulcerative colitis and for maintaining remission. A separate technical review reports the analyses of the evidence upon which the present recommendations are based."
"Drug survival is an important proxy measure for effectiveness of treatments for inflammatory diseases such as rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis. The objective of this study was to examine the real-life drug survival of biologics and novel small-molecule therapies across various disease entities such as RA, AxSpA, PsA, and psoriasis.
We performed a nationwide cohort study using the prospective nationwide registries DANBIO and DERMBIO, comprising all patients treated with biologics or novel small-molecule therapies for RA, AxSpA, PsA, and psoriasis between January 2015 through May 2021 (DANBIO) and November 2009 to November 2019 (DERMBIO). Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy.
The study comprised a total of 12,089 patients (17,903 treatment series), including 5,104 RA patients (7,867 series), 2,157 AxSpA patients (3,016 series3), 2,551 PsA patients (3,313 series), and 2,577 psoriasis patients (3,707 series). In confounder-adjusted models drug survival in RA was highest for rituximab followed by baricitinib, etanercept and tocilizumab respectively. For AxSpA, drug survival was high for golimumab compared to all other drugs, followed by secukinumab and etanercept and lowest for infliximab. For PsA, tofacitinib and infliximab had the lowest drug survival compared to all other drugs. All other drugs performed almost equally well with a tendency of a somewhat higher drug survival for golimumab, followed by secukinumab and ixekizumab. For psoriasis, drug survival was generally highest for guselkumab.
Differing treatment responses to drugs with various modes of action across RA, AxSpA, PsA and psoriasis emphasize that although these diseases have many overlaps in their pathogenesis, there is a need for an individualized treatment approach that considers the underlying disease, patient profile, and treatment history.
None."
"The increased knowledge on the biological mechanisms underlying ulcerative colitis (UC) has triggered an advance in drug development, drastically changing the therapeutic landscape. Several biologics and small-molecule drugs have been regulatory approved (i.e., infliximab, adalimumab, golimumab, vedolizumab, ustekinumab and tofacitinib), and frequently pose clinical dilemmas: physicians need to know how these therapies can be used to optimize patient-important outcomes. Adhering to the ""Grading of Recommendations Assessment, Development and Evaluation"" (GRADE) methodology, this technical review systematically searched and identified the evidence, synthesized it using rigorous meta-analytic methodology, appraised its quality, and concisely presented it in a transparent way, forming the basis for developing clinical recommendations on the use of biologics and small-molecule drugs in adult patients with UC."
"Inflammatory bowel disease (IBD) treatment paradigms recommend objective disease activity assessment and reactive therapeutic drug monitoring (TDM) prior to changes in biologic therapy. We aimed to describe objective marker and TDM assessment in routine clinical practice prior to biologic therapeutic changes in adult IBD patients.
TARGET-IBD is a prospective longitudinal cohort of over 2100 IBD patients receiving usual care at 34 US academic or community centers enrolled between June 2017 and October 2019 who received biologic therapy and had a dose change or biologic discontinuation for lack of efficacy. Objective markers of disease activity within 12 weeks prior included fecal calprotectin, C-reactive protein (CRP), endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). TDM data for infliximab or adalimumab was obtained.
525 patients (71.4% Crohn's disease [CD], 28.6% ulcerative colitis [UC]) receiving biologic therapy underwent dose change (55.6%) or discontinuation (44.4%) for lack of efficacy. The majority were Caucasian (85.7%), 18-39 years old (52.2%), privately insured (81.5%), and at academic centers (73.7%). For dose changes, 67.5% had at least one objective disease activity assessment or TDM in the 12 weeks prior (CD 67.9%, UC 66.2%; P = 0.79). The most common objective marker was CRP in both CD (39.1%) and UC (54.5%). CRP and calprotectin were used significantly more in UC (P = 0.02 and P = 0.03). TDM was obtained in 30.7% (28.8% UC, 31.4% CD; P = 0.72) prior to dose change. For biologic discontinuation, 79.4% patients underwent objective assessment or TDM prior. In CD, CRP (46.3%) was most common, and CT (P = 0.03) and MRI (P < 0.001) were significantly more frequent than in UC. TDM was performed in 40.1% of patients (43.5% UC, 38.0% CD, P = 0.49) prior to discontinuation. Among all participants with dose change or discontinuation, endoscopy was performed in 29.3% with CD and 31.3% with UC. Academic care setting was associated with objective assessment before therapy change (OR 1.59, 95% CI 1.01-2.50).
Nearly one-third of patients undergoing a biologic dose change or discontinuation do not undergo objective disease activity assessment or TDM. Assessment choice differs by disease. Future studies assessing the impact of such practices on long-term outcomes are needed."
"Neurosarcoidosis (NS) affects 5-10% of sarcoidosis patients and can involve any part of the nervous system. The prognosis can be serious and relapse is common. The diagnostic work-up is difficult with many differential diagnoses in inflammatory, infective and malignant neurological diseases. There is no specific marker for NS. Recently proposed diagnostic criteria for NS emphasise that biopsy plays an important role. Infliximab appears to be effective when other treatments are inadequate. The review summarises the clinical features, imaging and laboratory findings, treatment and prognosis of NS."
"Ustekinumab is a recently introduced biological agent for the treatment of Crohn's disease. The clinical use of the trough concentration of ustekinumab is not as standardized as that of infliximab. The authors aimed to introduce a measurement method and the results of trough concentrations of ustekinumab in clinical applications.
Thirty-two blood samples from 10 young adult patients diagnosed with Crohn's disease were analyzed. During the maintenance treatment, injection intervals were shortened from 12 weeks to 8 weeks in 4 patients who exhibited a loss of response. Ustekinumab trough concentrations were measured using 2 commercial ELISA kits, kit A and kit B.
The median trough concentrations measured with kits A and B were 0.26 and 0.38 mcg/mL, respectively. In the case of kit A, low trough concentrations were undetected on many occasions and measured as zero, whereas kit B displayed their relative values even at low concentrations. Poor clinical parameters, elevated erythrocyte sedimentation rate, C-reactive protein, and calprotectin levels were significantly correlated with lower trough concentrations ( P < 0.05). The area under the receiver operating characteristics curve of kit B (0.921) was greater than that of kit A (0.744). The optimal cutoff values for prediction clinical responses were 0.17 and 0.41 mcg/mL for kit A and kit B, respectively.
The trough concentration of ustekinumab measured by the 2 ELISA kits correlated with laboratory results that indicated the activity of Crohn's disease. Furthermore, kit B detected even minute changes in trough concentrations."
"To compare the relapse rate of sight-threatening noninfectious uveitis (NIU) in patients treated with infliximab (IFX) or adalimumab (ADA).
Observational retrospective multicenter study.
A total of 330 patients (median age, 36 years; interquartile range, 27-54), 45.2% men) with sight-threatening NIU (ie, retinal vasculitis and/or macular edema) treated with anti-tumor necrosis factor [TNF]-α agents (IFX intravenously at 5 mg/kg at weeks 0, 2, 6, and every 4 to 6 weeks or ADA subcutaneously at 80 mg, then 40 mg every 2 weeks). Data were obtained retrospectively from patients' medical records. Main outcome measures were relapse rate, complete response of NIU, corticosteroid sparing effect, and safety.
Main etiologies of uveitis included Behçet disease (27%), idiopathic juvenile arthritis (5.8%), and sarcoidosis (5.5%). The estimated relapse rate at 6 months after introduction of biological agents was 13% (95% CI = 0.009-0.16). IFX was associated with less relapse risk than ADA (hazard ratio [HR] = 0.52, 95% CI = 0.36- 0.77, P = .001). ADA and IFX were comparable in terms of complete response rate of NIU as well as corticosteroid-sparing effect. Behçet disease was associated with higher odds of complete response (HR = 2.04, 95% CI = 1.16 -3.60, P = .01] and lower relapse rate (HR = 0.53, 95% CI = 0.33-0.85, P = .009) than other causes of NIU with anti-TNF-α agents.
In sight-threatening NIU, IFX seems to be associated with a lower relapse rate than ADA."
"In 2019, British Columbia's public drug plan, PharmaCare, was the first in Canada to implement a nonmedical switching policy from originator infliximab to its biosimilar, for patients with inflammatory arthritis or psoriasis. We aimed to detect signals of impact on health services utilization during the first year of policy implementation and to provide early data to policy-makers.
We constructed cohorts of users of originator infliximab: 3 historical cohorts (2016-2018) and 1 policy cohort (2019). We extracted data from BC Ministry of Health databases from 2015 to 2020, as we followed each cohort for 365 days from May 27 of each cohort's respective year. We excluded patients with gastrointestinal conditions and those not covered by PharmaCare. We examined the cumulative incidence of infliximab prescription refills, switching to other biologic drugs and use of additional health services. A log-likelihood ratio of 1.96 compared with the null hypothesis was used as the threshold for differences between the policy cohort and the historical cohorts.
The study included a total of 572 unique patients: 520 in the 2016 historical cohort, 461 in the 2017 historical cohort, 423 in the 2018 historical cohort and 377 in the policy cohort (with some patients included in multiple cohorts; 335 [58.6%] were included in all 4 cohorts). During months 8 and 9 of follow-up, a transient signal was observed in infliximab refills (7.2% decrease in refilling infliximab for the fourth time for the policy cohort, log-likelihood ratio > 1.96). An anticipated increase in visits to specialists was observed from month 4 forward (15.0%, log-likelihood ratio > 1.96). No signal was observed for increased use of other health services (log-likelihood ratio < 1.96).
Early monitoring did not detect signals of negative impacts on health services use during the first year of the policy. Detailed, longer-term cohort studies and hypothesis-testing methods could provide additional assurance about the safety of the policy."
"To assess efficacy and safety of biologic therapy (BT) in neurobehçet's disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug.
Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters.
We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30-60) mg/day at the initial visit to 5 (3.8-10) mg/day after 6 months (P &lt; 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)-15.3 (11.9) mm/1st h, P = 0.011] and median (IQR) C-reactive protein [1.4 (0.2-12.8) to 0.3 (0.1-3) mg/dl, P = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment.
BT appears to be effective and relatively safe in refractory NBD."
"We evaluated the risk of acute anterior uveitis (AAU) in patients with ankylosing spondylitis (AS) during treatment with tumor necrosis factor-alpha inhibitors (TNFis).
This study was performed on AS patients using the Korean National Health Insurance claims database. We analyzed the first and total occurrence of AAU during the first 2 years of TNFis use according to the type of TNFis. Additionally, the occurrence of AAU was assessed in subgroups with or without prior AAU before TNFis initiation.
In total, 5938 AS patients initiated TNFis use between 2009 and 2017 and used them for more than 2 years. Among them, 1488 (25.1%) patients had a history of AAU before starting TNFis treatment. Compared to adalimumab, the use of etanercept (hazard ratio [HR] 1.77) increased the risk of AAU. The incidence rate ratio (IRR) of AAU with etanercept was significantly higher than that of adalimumab (IRR 1.78). The IRR of AAU was also higher for etanercept than adalimumab use in patients with (IRR 1.86) and without (IRR 2.92) a history of AAU.
These data suggest that compared to anti-TNF-alpha monoclonal antibodies, etanercept has a higher incidence of AAU regardless of a history of AAU."
"Biologic disease-modifying agents (bDMARDs) are highly effective in controlling the symptoms of autoimmune rheumatic diseases. The decision on whether to continue bDMARDs following a cancer diagnosis can be challenging for patients and physicians. Here, we describe a case of a middle-aged male with ankylosing spondylitis who was controlled on infliximab (IFX) and found to have a myeloid neoplasm with Platelet-Derived Growth Factor Receptor Beta rearrangement. The patient was started on a tyrosine kinase inhibitor imatinib. Given its significant positive effect on patient's quality of life, IFX was continued with a favorable outcome. This case highlights the importance of shared decisionmaking in balancing risks and benefits of immunosuppressants in appropriate cases of hematologic malignancy."
"This multicenter study is the first one on Iranian children with very early onset ulcerative colitis (UC) and one of the few studies about the effect of biological therapy in children with UC under 7 years of age.
Children with very early onset inflammatory bowel disease (IBD) are diagnosed before 6 years of age.
The current study was performed on 14 children under 7 years of age with severe UC. Children with severe UC whose therapy with corticosteroid and azathioprine as conventional treatment had failed were treated with infliximab (IFX) and later with adalimumab (ADA).
Among the total 14 participants, 6 (43%) patients were female. Mean patient age was 4.9 years (range = 3-7 years), mean age at diagnosis was 3.4 years (range = 1.5-6 years), and mean duration of illness was 1.5 years. At the end of 54 weeks of therapy with IFX, 2 (14%) patients were in remission, 2 (14%) patients were mild, and 4 (29%) patients were moderate, with no secondary treatment failure (during the maintenance phase). A total of 6 (43%) patients had primary treatment failure (no response after 14 weeks of therapy). These patients were treated with ADA. At the end of 52 weeks of therapy, 3 (50%) of those 6 (100%) patients were referred for colectomy, 1 (17%) was in remission, and 2 (33%) patients had mild severity.
The current study has shown that IFX is a safe and effective therapy for children with very early onset UC. ADA may be effective in the treatment of children with UC who are refractory to IFX."
"Compare prevalence of infusion reaction (IR) between infliximab (IFX) and infliximab biosimilar (IFX-abda) at standard and rapid rates and measure the impact on health care cost in children with inflammatory bowel disease (IBD).
Records of subjects receiving IFX and IFX-abda were reviewed over a 21-month period. Demographics and IRs were recorded. Cost analysis utilized average wholesale pricing, infusion duration, nursing time, and infusion center throughput.
Fifty-six subjects received 498 infusions. Sixteen subjects received both IFX and IFX-abda. Thirteen IRs occurred for an overall prevalence of 2.6%. One outlier subject accounted for 8 of 13 (62%) of IRs. Data were analyzed with and without the outlier. Standard rate infusion of both IFX and IFX-abda was associated with increased risk of IR compared with rapid rate but only reached significance for IFX when calculated with the outlier removed. Risk of IR was not statistically significant between IFX and IFX-abda for both standard and rapid rates. IFX-abda saved an average of $2,611 per infusion. Rapid infusion saved 70 minutes of infusion time, 20 minutes of estimated nursing time per infusion, and decreased infusion center appointment length by as much as 2 hours per infusion.
Rapid IFX-abda appears safe without increased IRs and decreases cost."
"Biologic agents may satisfy an unmet clinical need for treatment of refractory autoimmune hepatitis. The goals of this review are to present the types and results of biologic therapy for refractory autoimmune hepatitis, indicate opportunities to improve and expand biologic treatment, and encourage comparative clinical trials. English abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed. Rituximab (monoclonal antibodies against CD20 on B cells), infliximab (monoclonal antibodies against tumor necrosis factor-alpha), low-dose recombinant interleukin 2 (regulatory T cell promoter), and belimumab (monoclonal antibodies against B cell activating factor) have induced laboratory improvement in small cohorts with refractory autoimmune hepatitis. Ianalumab (monoclonal antibodies against the receptor for B cell activating factor) is in clinical trial. These agents target critical pathogenic pathways, but they may also have serious side effects. Blockade of the B cell activating factor or its receptors may disrupt pivotal B and T cell responses, and recombinant interleukin 2 complexed with certain interleukin 2 antibodies may selectively expand the regulatory T cell population. A proliferation-inducing ligand that enhances T cell proliferation and survival is an unevaluated, potentially pivotal, therapeutic target. Fully human antibodies, expanded target options, improved targeting precision, more effective delivery systems, and biosimilar agents promise to improve efficacy, safety, and accessibility. In conclusion, biologic agents target key pathogenic pathways in autoimmune hepatitis, and early experiences in refractory disease encourage clarification of the preferred target, rigorous clinical trial, and comparative evaluations."
"Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a significant negative impact on the quality of life of patients.
We conducted a systematic review to assess current treatment for HS, with a special focus on therapies approved or used in Brazil. We used the PICO framework to improve the research process. The systematic review was reported in line with the PRISMA statement checklist. The search was conducted with clinical questions on two global databases (PubMed (MEDLINE) and Google Scholar) and three databases especially selected to retrieve Brazilian outcomes (BVS, SCIELO and REDALYC).
Overall, 4640 articles were screened, 182 articles were analysed and 70 were used in a thematic qualitative analysis. Of these, 12 articles were from Brazil. The evidence-based literature was largely limited to case reports, case series, observational studies and expert opinion. Topical therapy, lifestyle interventions and oral antibiotics appeared as effective measures for mild HS. However, moderate-to-severe HS remains refractory to conventional treatments.
Some biologic agents, such as adalimumab, infliximab, ustekinumab and secukinumab, have been shown to be effective in the management of moderate-to-severe HS that failed conventional treatment and demonstrated a good tolerability and safety profile."
"Takayasu arteritis is a rare chronic granulomatous large vessel vasculitis that predominantly affects the aorta and its branches. The purpose of this review is to unite the current knowledge regarding the pathophysiology, cause, and epidemiology as well as diagnosis, prognosis, and treatment of this condition in children.
Although the etiopathogenesis is not fully understood, studies suggest an autoimmune basis for the disease as well as a genetic predisposition. It is a disease primarily affecting young women with up to a third of cases with onset in childhood. There are distinct features of childhood-onset Takayasu arteritis (cTA) that merit this separate review. Diagnostic criteria and clinical manifestations are unique in pediatric patients with renovascular hypertension being the most prevalent presentation. Traditional treatments involving high-dose corticosteroids and cytotoxic agents are being reconsidered for less toxic contemporary biologic agents. Current algorithms for treatment include early introduction of corticosteroid-sparing agents, such as methotrexate or mycophenolate as well as tumor necrosis factor-alpha (TNF-α) inhibitor (infliximab, adalimumab) and/or interleukin-6 (IL-6) receptor inhibitor (tocilizumab).
Early diagnosis of cTA with goals to develop effective and well tolerated treatment paradigms are essential to improve the long-term prognosis of this rare and devastating disease."
"A 55-year-old man presented with recurrent ulcers and an enterocutaneous fistula at the anastomotic site after surgery for an ileovesical fistula and was diagnosed with intestinal Behçet's disease after undergoing surgery for enterocutaneous fistulae twice. The patient was transferred to our hospital because of recurrent enterocutaneous fistulae. He had a history of recurrent oral aphthous ulcers, folliculitis, and epididymitis and met the diagnostic/classification criteria for incomplete Behçet's disease and thus was diagnosed as having intestinal Behçet's disease. Remission induction therapy with steroids was administered for an ileal ulcer and an enterocutaneous fistula, and adalimumab was initiated for maintenance therapy. The fistula was closed, and the clinical course was favorable. Two months after initiating adalimumab, a subcutaneous abscess was detected at the site of the enterocutaneous fistula scar, and relapse of intestinal Behçet's disease was suspected. Steroids were re-administered for remission induction, followed by maintenance therapy, for which adalimumab was switched to infliximab. No relapse was detected after steroid withdrawal. No therapeutic strategies have been established for intestinal Behçet's disease. Moreover, there have been very few reports on therapeutic strategies and postoperative maintenance therapy for enterocutaneous fistulae. We thus consider this case valuable."
"Real-world data regarding response rates in ulcerative colitis treatment are rare, particularly for later lines of therapy. This study aimed to assess continuity of and changes to advanced therapies, as well as costs and specific indicators defining suboptimal therapy.
German claims data were retrospectively analyzed (January 2014 to June 2019). Patients with ulcerative colitis initiating an advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) were included. Inadequate response was indicated by therapy discontinuation, switch, escalation, augmentation, corticosteroid dependency, disease-related hospitalization, or surgery. Health care resource utilization (inpatient, outpatient, sick leaves, medication, aids, and remedies) and related costs were assessed from therapy initiation until discontinuation or loss to follow-up.
Among 574 patients (median age, 39 years; female sex, 53.5%) who initiated advanced therapies, 458 (79.8%) received an antitumor necrosis factor therapy, 113 (19.7%) vedolizumab, and 3 (0.5%) tofacitinib. After 12 months, 75% had ≥1 indicator for suboptimal therapy. The median time to first indicated inadequate response was 4.8 months. Therapy discontinuation (38%), switching (26%), and prolonged use of steroids (36%) were common within the first year of treatment. In an unadjusted comparison, all-cause total costs per person-year were significantly higher in those who switched vs patients remaining on their therapy (€44,570 vs €36,807; P < .001).
Our study indicates a high prevalence of inadequate response to advanced therapies. Only 25% of patients showed adequate response within 12 months after therapy initiation. Frequent dose and treatment changes were observed. The economic impact of suboptimal therapy in ulcerative colitis is substantial, highlighting the ongoing need for improved treatment strategies."
"The arena of uveitis deals with a number of entities, which can be infectious or immune mediated. Noninfectious uveitis (NIU) has been managed with corticosteroids and immunosuppressives. However, their prolonged use has side effects limiting clinical utility in the long run. Improved knowledge regarding pathogenesis of uveitis and associated systemic disease has led to a new epoch in the development of treatment strategies, of which biologics are the recent ones. Biologics revolutionized the management of NIU especially uveitis associated with spondyloarthropathy and refractory uveitis. They target inflammation at a molecular level with less side effects. The most widely used are tumor necrosis factor-alpha inhibitors (infliximab and adalimumab). Other drugs include anti-CD20 inhibitors (rituximab), interleukin-6R-inhibitor (tocilizumab), Interleukin-1R-inhibitor (anakinra), Iinterleukin-2-inhibitor (daclizumab), and the list is further increasing. New advances in biologics are the biosimilar molecules, which are biological products that are highly similar to the reference product, and they include Infimab (biosimilar of infliximab), Exemptia or Adfrar (biosimilar of adalimumab), and Intacept or Etacept (biosimilar of etanercept). Other group of biologics are Janus Associated Kinase inhibitors (JAK-inhibitors), which are long-term oral treatment options of rheumatoid arthritis. They inhibit JAKs, which cause activation of signal transducer and activator of transcription (STAT) proteins, and initiate transcription of inflammatory genes. Many inflammatory cytokines that are implicated in pathogenesis of ocular inflammation are known to utilize the JAK/STAT-signaling pathway, including interleukin-2 (IL-2) and IL-6. Thus, biologics are the future of uveitis treatment with promising results. This article aims to summarize the current knowledge on biologics and their clinical utility in the management of NIU."
"Drug-induced sarcoidosis-like disease is a rare side effect of anti-tumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA) patients. The most commonly involved organs in such condition are the lungs, skin, and lymph nodes. The aim of this study is to report the number of cases and the clinical manifestations of sarcoidosis induced by anti-TNF in our RA UCLouvain Brussels cohort.
All case records of RA patients ever treated with a TNF inhibitor and presenting anti-TNF induced sarcoidosis in our rheumatology centers from 2000 to 2021 were retrospectively reviewed.
Our RA UCLouvain Brussels cohort includes 2492 patients. Among them, 697 patients have been or are exposed to a TNF inhibitor. Only four patients with sarcoidosis induced by anti-TNF were identified and reviewed. Patient 1 was classified as incomplete Heerfordt syndrome. Patient 2 was a case of sarcoid-like granulomatosis manifesting as life-threatening hypercalcemia, acute kidney injury and atypical parenchymal pneumopathy. Patients 3 and 4 developed pulmonary sarcoidosis with hilar adenopathies. The TNF inhibitor was etanercept for the first three patients and infliximab for the last one. The time occurrence of sarcoidosis was highly variable after anti-TNF exposure. All patients recovered after glucocorticoid treatment and the discontinuation of the anti-TNF agent.
This case highlights this rare paradoxical side effect and the variability of the clinical presentation. Further studies should analyze the immunopathology of such conditions."
"There is currently little knowledge on factors associated with the relapse of Crohn's disease (CD) in children. The aims of this study were to describe the risk factors associated with relapse in pediatric CD and the changes in the relapse rate over the past decade.
Patients younger than 18 years and diagnosed between 2009 and 2019 were included in this retrospective cohort study. Clinical, endoscopic, histological, and laboratory data, as well as induction and maintenance treatments, were collected from the medical records. Survival analyses and Cox regression models were used to assess the impact of these risk factors on relapse.
Six hundred thirty-nine patients were included. There was a decrease in the clinical relapse rate over the past decade: 70.9% of the patients diagnosed between 2009 and 2014 relapsed as compared with 49.1% of the patients diagnosed between 2015 and 2019 (P < 0.0001). The following variables were associated with clinical relapse: female sex (adjusted hazard ratio [aHR] = 1.52, P = 0.0007), exposure to oral 5-ASA (aHR = 1.44, P = 0.04), use of immunomodulatory agents compared with tumor necrosis factor-alpha inhibitors (methotrexate aHR = 1.73, P = 0.003; thiopurines aHR = 1.63, P = 0.002), presence of granulomas (aHR = 1.34, P = 0.02) and increased eosinophils on intestinal biopsies (aHR = 1.36, P = 0.02), high levels of C-reactive protein (aHR = 1.01, P < 0.0001) and fecal calprotectin (aHR = 1.08, P < 0.0001), and low serum infliximab levels (aHR = 2.32, P = 0.001).
Relapse of pediatric CD has decreased in the past decade. The risk of relapse is significantly associated with clinical, endoscopic, histological, and laboratory variables and treatment strategies."
"TNF-a inhibitors, which include adalimumab, infliximab, etanercept, certolizumab, and golimumab, and IL-12/23 inhibitor, ustekinumab, have been widely used as a U.S. Food and Drug Administration (FDA) approved for the treatment of psoriasis. Outside of psoriasis, high levels of TNF-a had also been found in several skin diseases including hidradenitis suppurativa. IL-12 and IL-23 play important role in the pathogenesis of SLE, alopecia areata, and vitiligo. This paper reviews the off-label uses of TNF-a inhibitors and IL-12/23 inhibitors in skin disorders."
Few studies have addressed whether proactive therapeutic drug monitoring (TDM) results in improved clinical outcomes in children with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor. The aim of this study was to investigate the impact of using proactive TDM in this patient group.Pilot single-centre observational study to accrue data on patients managed with proactive TDM.More patients in the proactive TDM cohort were managed by escalating the infliximab (IFX) regime (P < 0.001). The need for switching to different biologics was significantly lower in this patient group (P < 0.001).The introduction of proactive TDM resulted in a significant reduction of patients requiring switch of their primary biologic. The results of this study are indicators that proactive TDM offers a better method of managing children with IBD on IFX therapy.
"Palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) are chronic inflammatory skin conditions characterized by eruptions of sterile pustules on the palms and/or soles. Biologic use has been associated with PPP and PPPP development in the literature.
To identify PPP and PPPP associated with biologics and summarize reported treatments and outcomes.
We systematically searched in MEDLINE and Embase for articles that reported PPP or PPPP during biologic treatment. After a full-text review, 53 studies were included for analysis.
We identified 155 patients with PPP/PPPP onset during biologic treatment, with a mean age of 44.1 years and a female preponderance (71.6%). The most frequently reported biologics were adalimumab (43.9%) and infliximab (33.3%). IL-17 inhibitors, secukinumab (7.6%) and brodalumab (1.5%), were reported only in association with PPPP. Overall, 58.8% of patients had complete remission (CR) in 3.6 months and 23.5% had partial remission (PR) in 3.7 months. The most common treatments that led to CR were topical corticosteroids (n = 16) and biologic switching (n = 8).
Clinicians should anticipate PPP or PPPP as potential drug reactions to biologics such as adalimumab and infliximab. Large-scale studies are required to confirm our findings and further explore the pathogenesis for biologic-associated PPP and PPPP."
"Anti-tumor necrosis factor (TNF) dose intensification represents an effective method of overcoming secondary loss of response (LOR); however, a subset of patients may not respond (tertiary non-response), or fail to demonstrate durable response (tertiary LOR) to intensified dosing. This systematic review and meta-analysis aimed to evaluate these outcomes to determine the clinical effectiveness of empiric dose intensification in Crohn's disease.
Multiple databases including MEDLINE and EMBASE were interrogated to identify studies that reported outcomes following anti-TNF dose intensification to address secondary LOR in Crohn's disease. Studies that used anti-TNF levels as the primary basis for dose intensification were excluded. Studies that reported (1) tertiary response and tertiary non-response within 6 months or (2) tertiary response and tertiary LOR beyond 6 months, were pooled using a random effects model with risk ratio (RR) derived, quantifying the effect of each comparison.
Twenty-six studies reported outcomes following anti-TNF dose intensification to address secondary LOR. Short-term response within 12 weeks of any dose-intensification strategy was 33-90%, while sustained response (⩾48 weeks) was achieved in 25-85%. Tertiary non-response occurred in up to 45% of intensified patients within 6 months of anti-TNF dose intensification, while tertiary LOR beyond 6 months occurred in up to 64% of patients. Tertiary response was more likely than tertiary non-response within 6 months (RR 2.58, 95% CI (1.76, 3.79), 
Although anti-TNF dose intensification is clinically effective in patients with Crohn's disease, particularly within the first 6 months, a proportion of patients will fail to demonstrate short-term and/or sustained clinical response. Hence, clinical reassessment following anti-TNF dose intensification, particularly beyond 6 months, remains important to differentiate between effective and ineffective dose-intensification strategies."
"Patients with multisystem inflammatory syndrome in children (MIS-C) can develop clinical features resembling Kawasaki disease (KD). A full picture of MIS-C in East Asia which has higher incidence of KD than other regions remains unclear. We report on a 15-year-old Japanese boy with refractory MIS-C who was successfully treated with infliximab. A Japanese boy who was diagnosed with coronavirus disease 2019 (COVID-19) before a month developed MIS-C with fulfilling six principal symptoms of KD. Laboratory data showed extreme hyperferritinemia (11,404 ng/mL), besides lymphopenia and thrombocytopenia. The patient was refractory to initial therapy with intravenous immunoglobulin (IVIG; 2 g/kg), aspirin, and prednisolone. He was therefore administered a second IVIG (2 g/kg) and infliximab (5 mg/kg) on days 7 and 8 from the onset of fever, respectively, which resulted in an improvement of clinical symptoms. Only four Japanese cases with MIS-C were reported and all of them were responsive to IVIG. The hyperferritinemia in this case was distinctive from previously reported MIS-C cases in Japan and other cohorts and may be associated with refractoriness to IVIG therapy. Marked elevation of circulating ferritin levels is known to be induced by tumor necrosis factor-α, which plays a key role in the pathogenesis of both KD and MIS-C. Thus, for MIS-C patients with hyperferritinemia, early intervention with adjunctive infliximab may induce a more rapid resolution of inflammation and improve outcome. Because MIS-C may be heterogeneous with respect to immunopathology, genetic background, clinical phenotypes and response to therapies, optimized treatment strategies according to immunopathogenesis are required."
"To compare treatment patterns of United States (US) veterans stable on innovator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on innovator IFX (continuers).
US Veterans Healthcare Administration data (01/2012-12/2019) were used to identify adults with rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis (PsO), ankylosing spondylitis (AS), or Crohn's disease and ulcerative colitis (i.e. inflammatory bowel disease [IBD]), treated with innovator or biosimilar IFX. Index date was the first IFX biosimilar administration for switchers or a random innovator IFX administration for continuers. Patients were required to have ≥5 innovator IFX administrations during the 12 months pre-index (prevalent population). Patients with ≥12 months of observation prior to the first innovator IFX administration were analyzed as the primary population (incident population), and data were assessed from start of innovator IFX. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Treatment patterns were evaluated post-index; continuers were censored before switching to IFX biosimilar. Discontinuation was defined as switching to another biologic (including innovator IFX) or having ≥120 days between 2 consecutive index treatment records.
In the incident population, mean [median] duration of follow-up was 737 [796] days among switchers (
Patients switching from innovator to biosimilar IFX were more likely to discontinue treatment and switch to another innovator biologic (notably back to innovator IFX) than those remaining on innovator IFX; however, reasons for discontinuation and switching are unknown."
"The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs.
In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing.
Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·7]; p<0·0001), or tofacitinib (429·5 U/mL [3·1]; p=0·0012) compared with controls (1578·3 U/mL [3·7]). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL [4·3]; p=0·74), ustekinumab (582·4 U/mL [4·6]; p=0·11), or vedolizumab (954·0 U/mL [4·1]; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08-0·17; p<0·0001) and tofacitinib (0·43, 0·23-0·81; p=0·0095), but not with ustekinumab (0·69, 0·41-1·19; p=0·18), thiopurines (0·89, 0·64-1·24; p=0·50), or vedolizumab (1·16, 0·74-1·83; p=0·51). mRNA vaccines (3·68, 2·80-4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72-0·87; p<0·0001) with lower antibody concentrations.
For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual's treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised.
Pfizer."
Approximately 20% of patients with ulcerative colitis (UC) who undergo total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) develop chronic pouch inflammation (CPI).
"Tumor necrosis factor (TNF) inhibitors are part of the therapeutic arsenal for many immune-mediated diseases and, especially in inflammatory bowel disease (IBD), have led to a change in the management of this disease."
"There is limited data in the literature analyzing the efficacy of methotrexate in Crohn's disease used after thiopurine analogs. We aimed in our study to show the efficacy of methotrexate in Crohn's disease patients who failed to respond to thiopurine treatment.
The study included 29 azathioprine refractory patients with Crohn's disease. Intramuscular methotrexate (25 mg/week) in the induction of remission and intramuscular methotrexate (15 mg/week) in 29 CD patients with a median follow-up time of 13 months was performed. In 15 (51.7%) patients, methotrexate was used in combination with anti-Tumour necrosis factor (TNF) (combination group), while it was used in 14 (48.3%) patients in monotherapy (monotherapy group).
The mean Harvey-Bradshaw index score significantly decreased in the follow-up period (Wk0 = 7.6, last visit = 4.5, P < .001). Remission and response rates at week 12 were 75.9% and 79.3%, respectively. Maintenance of remission (77.8% vs 37.5%, respectively, P = .1) and response rates (77.8% vs 50%, respectively, P = .3) due to last visit examination were numerically higher in combination group but they were not statistically significant. The cumulative probability of remission maintenance in patients with methotrexate therapy was 72.7%, 33.1%, and 22.0% at 1, 2 ,and 4 years after starting methotrexate, respectively.
Our results show that parenteral use of methotrexate is efficacious in inducing and maintaining remission as a step-up agent in azathioprine refractory Crohn's disease patients."
"Sweet syndrome, also known as Acute Febrile Neutrophilic Dermatosis, is a rare inflammatory condition. The exact pathogenesis of Sweet syndrome is unclear, however, autoimmune and inflammatory conditions including inflammatory bowel disease have been linked as underlying etiologies. Since its description, in 1964, there have been published less than fifty reports of Crohn's-associated Sweet syndrome. We report a 43-year-old male patient with a medical history of Crohn's disease who subsequently developed Sweet syndrome. Two years after the diagnosis of Crohn's disease the patient was administered a combo therapy with Infliximab and Azathioprine followed by deep remission. A few months later the patient manifested with skin lesions with histopathological findings suggestive of Sweet syndrome. Sweet syndrome, although rare, may occur as an extra-intestinal manifestation of Crohn's disease. This report illustrates the need for a thorough investigation of patients with Crohn's disease presenting with skin lesions. We hope it will add to the current literature and help understand this rare phenomenon in order to achieve a proper diagnosis."
"Central nervous system (CNS) vasculitis is a rare form of vasculitis involving the blood vessels of the brain. It may be primary when it is confined to the CNS or secondary in the context of systemic inflammatory conditions such as systemic lupus erythematosus, rheumatoid arthritis, or infections. However, there is no known association with axial spondyloarthritis. Herein, we present the case of a 37-year-old man, with axial spondyloarthritis treated with infliximab for 9 years, who presented with persistent fevers, elevated inflammation markers, lateral medullary syndrome, and right-sided hemiparesis. Magnetic resonance imaging of the brain demonstrated multiple cerebral infarcts. Examination of cerebrospinal fluid showed mild lymphocytic pleocytosis and protein elevation. Digital subtraction angiography and transcranial ultrasonography of the cerebral blood vessels revealed luminal narrowing of the basilar and the left posterior cerebral artery. The diagnosis of CNS vasculitis was made and intravenous methylprednisolone and cyclophosphamide pulses were administered, leading to fever remission with gradual improvement and resolution of the neurological manifestations."
"The etiopathogenesis of disuse colitis (DC) has not yet been fully elucidated. The main theories consider that the disease may be related to an increase in anaerobic bacteria, the lack of short-chain fatty acid (SCFA) supply, and immunological disorders that develop in the colorectal segments devoid of fecal transit. The aim of this study was to verify whether the application of infliximab modifies the tissue content of E-cadherin and claudin-3 proteins in colonic epithelium of rats devoid of intestinal transit.
A total of 22 rats underwent intestinal transit bypass using Hartmann's procedure. They remained with the shunt for 12 weeks to allow the development of DC. Later, they were divided into three experimental groups: six animals received 2.0 mL saline solution/week, eight received infliximab at a dose of 5 mg/kg/week, and eight received infliximab at a dose of 10 mg/kg/week for 5 consecutive weeks. At the end of this period, the animals were euthanized, and the colonic segments with and without intestinal transit were removed. DC was diagnosed based on the histological changes defined by a previously validated scale. The tissue expression of E-cadherin and claudin-3 was assessed by immunohistochemistry, and the tissue content of both proteins was quantified by computer-aided image analysis.
The colonic segments excluded from fecal transit showed a higher degree of inflammation than those exposed to fecal transit. The degree of inflammation was lower in animals treated with infliximab, regardless of the dose used. The levels of E-cadherin and claudin-3 were reduced in the excluded colon. Treating animals with infliximab increased the levels of both proteins in the colonic segments without intestinal transit, especially in animals receiving a dose of 10 mg/kg/week.
Infliximab therapy reduces inflammation in the colonic segments excluded from intestinal transit and increases the tissue content of E-cadherin and claudin-3 proteins, especially when used at a concentration of 10 mg/kg/week.
A etiopatogenia da colite por desuso (DC) ainda não foi totalmente elucidada. As principais teorias consideram que a doença pode estar relacionada ao aumento de bactérias anaeróbias, falta de suprimento de ácidos graxos de cadeia curta (AGCC) e distúrbios imunológicos que se desenvolvem em segmentos colorretais desprovidos de trânsito fecal. Verificar se a aplicação de infliximabe modifica o conteúdo tecidual das proteínas E-caderina e claudina-3 no epitélio cólico de ratos sem trânsito intestinal.
Vinte dois ratos foram submetidos a derivação do trânsito intestinal pelo procedimento de Hartmann. Eles permaneceram com o ostoma por 12 semanas para permitir o desenvolvimento da colite de exclusão. Em seguida, foram divididos em três grupos experimentais: seis animais receberam 2,0 ml de solução salina/semana, oito infliximabe na dose de 5 mg/Kg/semana e, os demais, infliximabe na dose de 10 mg/Kg/semana por 5 semanas consecutivas. Em seguida, os animais foram eutanasiados e os segmentos cólicos com e sem trânsito intestinal foram removidos. A colite por desuso foi diagnosticada pelas alterações histológicas definidas por uma escala previamente validada. Expressão tecidual de E-caderina e claudina-3 foi avaliada por imuno-histoquímica, e o conteúdo tecidual de ambas as proteínas foi quantificado por análise de imagem assistida por computador.
Segmentos cólicos exclusos de trânsito fecal apresentaram maior grau de inflamação do que os expostos ao trânsito fecal. Inflamação foi menor nos animais tratados com infliximabe, independente da dose utilizada. Níveis de E-caderina e claudina-3 estavam reduzidos no cólon excluso. O tratamento com infliximabe aumentou os níveis das proteínas em segmentos do cólon sem trânsito intestinal, principalmente nos animais que receberam a dose de 10mg/kg/semana.
Infliximabe reduz inflamação nos segmentos do cólon excluso e aumenta o conteúdo tecidual de E-caderina e claudina-3, especialmente na concentração de 10mg/kg/semana.
A etiopatogenia da colite por desuso (DC) ainda não foi totalmente elucidada. As principais teorias consideram que a doença pode estar relacionada ao aumento de bactérias anaeróbias, falta de suprimento de ácidos graxos de cadeia curta (AGCC) e distúrbios imunológicos que se desenvolvem em segmentos colorretais desprovidos de trânsito fecal.
Verificar se a aplicação de infliximabe modifica o conteúdo tecidual das proteínas E-caderina e claudina-3 no epitélio cólico de ratos sem trânsito intestinal.
Vinte dois ratos foram submetidos a derivação do trânsito intestinal pelo procedimento de Hartmann. Eles permaneceram com o ostoma por 12 semanas para permitir o desenvolvimento da colite de exclusão. Em seguida, foram divididos em três grupos experimentais: seis animais receberam 2,0 ml de solução salina/semana, oito infliximabe na dose de 5 mg/Kg/semana e, os demais, infliximabe na dose de 10 mg/Kg/semana por 5 semanas consecutivas. Em seguida, os animais foram eutanasiados e os segmentos cólicos com e sem trânsito intestinal foram removidos. A colite por desuso foi diagnosticada pelas alterações histológicas definidas por uma escala previamente validada. Expressão tecidual de E-caderina e claudina-3 foi avaliada por imuno-histoquímica, e o conteúdo tecidual de ambas as proteínas foi quantificado por análise de imagem assistida por computador.
Segmentos cólicos exclusos de trânsito fecal apresentaram maior grau de inflamação do que os expostos ao trânsito fecal. Inflamação foi menor nos animais tratados com infliximabe, independente da dose utilizada. Níveis de E-caderina e claudina-3 estavam reduzidos no cólon excluso. O tratamento com infliximabe aumentou os níveis das proteínas em segmentos do cólon sem trânsito intestinal, principalmente nos animais que receberam a dose de 10mg/kg/semana.
Infliximabe reduz inflamação nos segmentos do cólon excluso e aumenta o conteúdo tecidual de E-caderina e claudina-3, especialmente na concentração de 10mg/kg/semana."
"Invasive aspergillosis is a rare opportunistic infection mainly occurring in patients with a well-established risk such as neutropenia or conditions that lead to chronically impaired cellular immune responses. Systemic corticosteroids are a well-known risk factor for fungal infections. Recently, reports of invasive aspergillosis in patients treated with monoclonal biologic agents, such as tumor necrosis factor-alpha inhibitors, have been increasing. We present the case of a 47-year-old female patient with seronegative spondyloarthropathy treated with infliximab and corticosteroids. The patient presented classical symptoms of an acute lower respiratory infection, and she was treated with a β-lactam antibiotic. Infliximab administration was deferred until nine days after clinical recovery. Fourteen days after drug administration, she was admitted with a symptomatic subcortical hematoma in the left parietal region. There was a rapid neurological recovery, and there were no risk factors for haemorrhagic stroke detected. The chest X-ray revealed an oval mass with an air crescent sign, and the CT scan was suggestive of aspergilloma. Bronchoalveolar lavage cytology identified "
"The causes of osteoporosis in Crohn's disease (CD) are multifactorial; cytokines, steroids, and vitamin deficiency all have an essential role. It is imperative to distinguish the factors that contribute to bone resorption, potentially increasing the risk of low bone mineral density (BMD), osteoporosis, and fracture. However, the pathogenicity of osteoporosis associated with CD remains unclear. Although osteoporosis treatment may vary between bisphosphonate and corticosteroid, infliximab's efficacy, when combined with immune modulators, suppresses both CD symptoms and osteoporosis progression. In this review, we aim to understand the present pathogenicity of osteoporosis, including the factors pro-inflammatory cytokines, chronic steroid use, and malnutrition, developing osteoporosis in a different pathological way, and to assist the treatment lines implying a positive outcome of osteoporosis in CD patients. Osteoporosis is considered to be one of the early complications of CD where early detection can prevent osteoporosis progression. This can be done by utilizing dual-energy X-ray-absorptiometry (DEXA) to evaluate the Z-score and treat the existing factors that have a role in the progression of osteoporosis in CD patients."
"Infliximab, a tumour necrosis factor-α (TNFα) antagonist, has advanced the management of ulcerative colitis. Although efficacious, considerable percentage of patients are resistant to treatment. Accumulative inflammatory burden in long-term ulcerative colitis patients refractory to therapy increases the risk of developing colorectal cancer (CRC). Our study investigated anti-TNFα-naïve patients with active ulcerative colitis to identify gene biomarkers whose dysregulated expression correlated with resistance to infliximab (IFX) treatment and poor prognosis in CRC.
Differentially expressed genes (DEGs) from two studies (GSE73661 and GSE14580) with colonic mucosal samples were retrieved. Noninflammatory bowel disease controls were compared with those with active ulcerative colitis that either responded or were resistant to IFX before treatment. DEGs from ulcerative colitis samples resistant to IFX were used to construct a protein-protein interaction network, and clustering gene modules were identified. Module DEGs that overlapped with ulcerative colitis samples responsive to IFX were analysed, based on topological closeness and radiality. Hub genes were obtained, and their correlation with CRC progression was evaluated. Their expression in CRC tissues and their tumour microenvironment immune status was estimated.
Three clusters composed of 582 DEGs from ulcerative colitis samples resistant to IFX were retrieved. Comparative analysis identified 305 overlapping DEGs with ulcerative colitis samples responsive to IFX. Topological analysis revealed a hub gene - SPP1 - whose overexpression in CRC tissues and patients correlated with increased infiltration of immune signatures and poor prognosis.
SPP1 may serve as potential gene biomarker and predictor of resistance to IFX therapy in ulcerative colitis and CRC development."
"The benefit of concomitant immunomodulators (thiopurines or methotrexate) in patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor α (anti-TNF) (infliximab or adalimumab) maintenance therapy is debated. We compared outcomes after immunomodulator withdrawal vs continuation of combination therapy.
This was a retrospective cohort study in a general hospital and a tertiary referral center. We included adult IBD patients, receiving anti-TNF therapy for ≥4 months, plus an immunomodulator at baseline, between January 1, 2011, and January 1, 2019. The primary endpoints were loss of response (LOR) (ie, anti-TNF discontinuation because of disease activity) and anti-drug antibodies. Adjusted hazard ratios (aHRs) were calculated by mixed-effects Cox regression analysis.
We included 614 treatment episodes of combination therapy in 543 individuals, yielding 1664 patient-years of follow-up. The immunomodulator was withdrawn in 296 (48.2%) episodes after 0.9 (interquartile range, 0.6-2.1) years, which was not associated with a higher risk of LOR (aHR, 1.08; 95% confidence interval [CI], 0.72-1.61), although anti-drug antibodies were detected more frequently (aHR, 2.14; 95% CI, 1.17-3.94), compared with continuation. Clinical remission at the time of withdrawal reduced the risk of LOR (aHR, 0.48; 95% CI, 0.25-0.93), while longer duration of combination therapy before withdrawal decreased the risk of anti-drug antibodies (HR per year, 0.56; 95% CI, 0.32-0.91). Higher prewithdrawal infliximab trough levels reduced the subsequent risks of anti-drug antibodies and LOR. Infliximab trough levels were lower after immunomodulator withdrawal (P = .01).
Patients who withdrew the immunomodulator in this retrospective cohort were not at increased risk of LOR within the following 1-2 years, but an increase in anti-drug antibodies was observed. Our findings require prospective validation, preferably in adequately powered randomized controlled trials."
"Infliximab dose escalation (DE) can be used in inflammatory bowel disease patient; however, the long-term benefit remains unclear, especially in those with antibodies to infliximab (ATI). The aim was to assess the effect of DE in patients with ATI on drug level, clinical response and ATI status.
All patients undergoing infliximab DE (a reduction in dose interval between infusions <8 weeks ± an increase in dose up to 10 mg/kg) at a referral centre between April 2016 and August 2019 were included.
Ninety-two patients were DE: 51 were men, 50 had CD and 63 were receiving immunosuppression. A total of 87 people received DE for a median of 44 weeks (range 4-176). Five stopped infliximab after 1 dose of DE: 2 for loss of response and 3 for infusion reaction. In patients with ATI ≤10 vs. >10 AU/mL, DE significantly increased drug levels: median infliximab levels of 1.4 and 0.9 at baseline, respectively, to 3.2 and 3.5 at week 24. After DE, 21/35 ATI-positive patients had a fall in ATI ≤10 AU/mL. At week 24 following DE 62/92 patients were in clinical remission. Duration of clinical remission was shorter in those with ATI >10 AU/mL (median 24 weeks, range 0-88) than in those with transient/ATI ≤10 AU/mL (median 36 weeks, range 0-126, P = 0.06).
A strategy of DE for selected patients receiving infliximab is associated with an increase in drug levels and reduced ATI positivity. This is associated with clinical remission in approximately 70% of patients at 6 months."
"Severe lower gastrointestinal bleeding (SLGIB) is a rare complication of Crohn's disease (CD). The treatment of these patients is a clinical challenge. Monoclonal anti-TNFα antibody (IFX) can induce relatively fast mucosal healing. It has been reported for the treatment of SLGIB, but there are few reports on accelerated IFX induction in CD patients with SLGIB.
A 16-year-old boy with a history of recurrent oral ulcers for nearly 1 year presented to the Gastroenterology Department of our hospital complaining of recurrent periumbilical pain for more than 1 mo and having bloody stool 4 times within 2 wk. Colonoscopy showed multiple areas of inflammation of the colon and a sigmoid colon ulcer with active bleeding. Hemostasis was immediately performed under endoscopy. The physical examination of the patient showed scattered small ulcers in the lower lip of the mouth and small cracks in the perianal area. Combined with his medical history, physical examination, laboratory examinations with high C-reactive protein (CRP), platelet count (PLT), erythrocyte sedimentation rate (ESR) and fecal calprotectin levels, imaging examinations and pathology, a diagnosis of CD was taken into consideration. According to the pediatric CD activity index 47.5, methylprednisolone (40 mg QD) was given intravenously. The abdominal pain disappeared, and CRP, PLT, and ESR levels decreased significantly after the treatment. Unfortunately, he had a large amount of bloody stool again after 1 wk of methylprednisolone treatment, and his hemoglobin level decreased quickly. Although infliximab (IFX) (5 mg/kg) was given as a combination therapy regimen, he still had bloody stool with his hemoglobin level decreasing from 112 g/L to 80 g/L in a short time, so-called SLGIB. With informed consent, accelerated IFX (5 mg/kg) induction was given 7 days after initial presentation. The bleeding then stopped. Eight weeks after the treatment, repeat colonoscopy showed mucosal healing; thus far, no recurrent bleeding has occurred, and the patient is symptom-free.
This case highlights the importance of accelerated IFX induction in SLGIB secondary to CD, especially after steroid hormone treatment."
"Baricitinib is a Janus kinase (JAK) inhibitor used to treat refractory rheumatoid arthritis and blocks the subtypes JAK1 and JAK2. A 35-year-old man with seronegative rheumatoid arthritis complicated by bilateral severe non-granulomatous panuveitis was resistant to steroid treatment, multiple conventional disease-modifying antirheumatic drugs (methotrexate and salazosulfapyridine), and TNF-α inhibitors (adalimumab and infliximab). Therefore, the TNF-α inhibitors were switched to baricitinib to decrease the activity of systemic arthritis. Along with the amelioration of inflammatory activity in seronegative rheumatoid arthritis, the inflammatory activity of uveitis was decreased. Vitreous opacity, serous retinal detachment, and anterior chamber cells showed improvement. Baricitinib was effective not only in refractory systemic arthritis but also in uveitis, which may provide a new treatment option for patients with refractory uveitis."
"This study aimed to determine the correlation of disease activity of rheumatoid arthritis (RA) with Th17/regulatory T cell (Treg) and Forkhead box protein 3 (Foxp3) cells ratio in patients under therapy with anti-tumor necrosis factor (TNF)-α. Totally, 84 patients with RA and 13 healthy controls were included in this case-control study. The patients were divided into four groups to receive only methotrexate (MTX) (n=25), monotherapy (anti-TNF) (n=18), and combined therapy (MTX+anti-TNF) (n=26); however, one group received no medications (n=15) and was regarded as a positive control. Other 13 healthy controls that were considered negative controls were also enrolled in this study. Patients with RA were attending Basrah General Hospital, Rheumatology Unit, Biological Therapy Center for receiving anti-TNF therapy. Flow cytometry was used for measuring Treg/Foxp3 and Th17 markers, and the DAS-28 score was utilized to measure RA disease activity. Anti-TNF inhibitors (e.g., infliximab and etanercept), as well as other inflammatory and hematological parameters (e.g., erythrocyte sedimentation rate, total white blood cells, lymphocytes, monocytes, and neutrophil counts), were also measured in this study. DAS-28 as a disease activity score was significantly correlated with Th17/Treg/Foxp3 ratio and the Th17 cells count. Statistically, Th17/Treg/Foxp3 ratio was not correlated with body mass index, morning stiffness, and duration of the disease. Th17/Treg/Foxp3 ratio correlated significantly with DAS-28 as an RA disease activity. The lower Treg/Foxp3 frequency led to the higher DAS score reflecting higher disease activity. In the combined therapy group, disease activity was found lower than that in other patient groups indicating the effect of this combination on the relationship between MTX and anti-TNF. This study demonstrated that the main advantage of this combined therapy in RA patients was the reversion of Th17 cell expansion."
"Chronic kidney disease (CKD) or acute kidney injury (AKI) causes impaired kidney function, leading to cognitive impairment, neuropathy, and cerebrovascular disease. Due to kidney damage, toxins stay in the blood rather than leaving the body through the urine, and brain function is affected by kidney-brain interaction. The present study aimed to investigate the protective effects of erythropoietin mimetic peptide (pHBSP) and infliximab on ischemic renal reperfusion injury. The experiment was performed on 70 white male Wistar laboratory rats which received recombinant erythropoietin, pHBSP, and infliximab. Under anesthesia, traumatic vascular clamps were applied to the left renal pedicle for 40 min, and nephrectomy was performed on the right. Functional tests and laboratory tests were performed 5 min and 24 h after the reperfusion.  Thereafter, 24 h after the surgery, the plasma creatinine and urea levels in the sham-operated animals were obtained at 45.9±0.8 mmol/L and 6.7±0.2 mmol/L, respectively. Plasma creatinine and urea levels in the control group animals were 102.63±3.6 mmol/L and 21.80±1.29 mmol/L, respectively. The administration of pHBSP and infliximab to the animals with ischemia-reperfusion kidney injury has a pronounced nephroprotective effect, as compared to erythropoietin. There was a significant decrease in blood levels of creatinine and urea, improvement of microcirculation in the kidney, normalization of glomerular filtration rate, and fractional sodium excretion. The results of the study demonstrated pointed to the prospects of pHBSP and infliximab administration in ischemia-reperfusion kidney injury and justified the feasibility of further research in this field."
"To determine if scheduled vital signs monitoring is useful in the detection of infusion reactions to infliximab (IFX).
The infusion records of 35,988 IFX infusions completed in 2017 were reviewed for infusion reactions that occurred during the infusion, which were then examined further to determine how those infusion reactions were detected.
Of the 90 complete infusion reaction records reviewed, no infusion reactions (0) were detected by scheduled vital signs assessment.
According to the infusion reaction data reviewed, scheduled vital sign assessment did not detect any infusion reactions and may not be necessary for the purpose of monitoring patients during infusions for early detection of infusion reactions. Previous research into IFX infusion reactions reviewed also concluded that scheduled vital signs assessment may not be helpful in the detection of infusion reactions and, in many cases, vital signs did not vary significantly enough from baseline to signal an infusion reaction."
"We report a case of new-onset bullous pemphigoid manifesting concurrently with cutaneous Crohn disease in a 58-year-old woman. Cutaneous Crohn disease is an extraintestinal manifestation of Crohn disease characterized by non-specific plaques or nodules. Bullous pemphigoid, a sub-epidermal autoimmune blistering disorder, has been observed in the setting of inflammatory bowel disease. The patient presented with recurrent bullae on the abdomen, thighs, and buttocks of 1 year's duration. She was not on any immunosuppressive therapies and had been treated with infliximab and azathioprine for her Crohn disease, which were discontinued 8 years before the blistering commenced. Punch biopsy of lesional skin showed a sub-epidermal blister with eosinophils. Sarcoidal and tuberculoid granulomas were present in the dermis. Direct immunofluorescence revealed linear 2+ IgG and 3+ C3 along the basement membrane. Indirect immunofluorescence was positive for BP180 and BP230 antibodies. These findings support the diagnosis of bullous pemphigoid with concomitant cutaneous Crohn disease. Both bullous pemphigoid and Crohn disease have been associated with an altered T-cell response. The similarities in the pathogenesis of the underlying inflammatory milieu suggest a possible etiopathogenic connection. This is believed to be the first report of cutaneous Crohn disease presenting simultaneously with bullous pemphigoid on histopathological examination."
"The aim of this study was to describe treatment patterns in RA, including the frequency and reasons for switching or stopping biologic and targeted synthetic DMARDs (b/tsDMARDs).
The reasons for switching or stopping b/tsDMARDs were extracted from the Australian Rheumatology Association Database (ARAD) from 2003 to 2018 for RA participants. Switching patterns for each b/tsDMARD and time on first-, second- and third-line b/tsDMARDs were evaluated using Sankey diagrams and survival methods.
A total of 2839 participants were included in the analysis. The first-line b/tsDMARDs were etanercept (n = 1414), adalimumab (n = 1024), infliximab (n = 155), golimumab (n = 98), abatacept (n = 66), certolizumab (n = 38), tocilizumab (n = 21) and tofacitinib (n = 23). Of those starting first-, second- and third-line biologic therapy, 24.0%, 31.8% and 24.4% switched to another b/tsDMARD within 12 months, respectively. Inefficacy or adverse effects were the most common reasons for stopping therapy, irrespective of line of treatment. Compared with first-line etanercept, participants were more likely to stop adalimumab [Hazard ratio (HR) 1.16, 95% CI: 1.04, 1.29] and infliximab (HR 1.77, 95% CI: 1.46, 2.16). No differences were seen for other b/tsDMARDs. For second-line therapies compared with etanercept, the risk of stopping was lower for tocilizumab (HR 0.41, 95% CI: 0.25, 0.70), rituximab (HR 0.51, 95% CI: 0.30, 0.85) and tofacitinib (HR 0.29, 95% CI: 0.15, 0.57). Participants taking rituximab, tocilizumab and tofacitinib were also less likely to stop third-line therapy in comparison with participants taking etanercept.
Switching between b/tsDMARDs was common among ARAD participants with RA, most commonly due to inefficacy or adverse effects. Durability of exposure and reasons for switching varied between b/tsDMARDs."
"Few published data describe how joint involvement, the most prevalent extraintestinal manifestation, affects quality of life (QoL) of children with Crohn's disease (CD). Arthritis and arthralgia rates in pediatric CD patients are reportedly 3-24% and 17-22%, respectively, but studies on pre-emptive and systematic screening of joint involvement with detailed musculoskeletal rheumatological exam are lacking. More detailed data collection on joint involvement improves our understanding of how arthropathy relates to disease activity and QoL measured by the Pediatric CD Activity Index (PCDAI) and IMPACT-III questionnaire. Our study aims were to assess joint involvement in pediatric CD and correlate it with the PCDAI and IMPACT-III.
In this cross-sectional, observational study, a pediatric gastroenterologist assessed consecutively-seen pediatric CD patients at a tertiary care center. Patients were screened for prevalence of current and previous arthropathy, including arthritis, enthesitis and arthralgia. A single experienced pediatric rheumatologist evaluated detailed musculoskeletal history, joint status, and modified Juvenile Arthritis Multidimensional Assessment Reports (JAMAR). PCDAI, IMPACT-III, sacroiliac MRI, and HLA-B27 genetic testing were also completed.
A total of 82 (male:female, 1.2:1; age, 13.7 ± 3.2 years) patients were involved in this study. Mean disease duration at time of study was 21.6 ± 21 months; eight of the patients were newly-diagnosed. Of the 82 patients, 29 (35%) had evidence of arthritis; for 24 of those, this was revealed by physical exam during cross-sectional screening, and by prior documentation for the remaining five patients. Joint examination confirmed active arthritis in 8/24 (33%), active enthesitis in 1/24 (4%), and evidence of previous arthritis in 15/24 (62.5%) patients. Hip (41%) and knee (38%) joints were most commonly affected. Cumulative incidence of arthralgia was 48% (39/82), and 46% (18/39) of those patients had only arthralgia without arthritis, usually affecting the knee. Axial involvement was present in 10/82 (12%) patients. Joint involvement correlated with more severe CD disease activity, specifically higher PCDAI and lower IMPACT-III scores, and increased requirement for infliximab treatment. Sacroiliitis and HLA-B27 positivity were insignificant factors in this cohort.
When a rheumatologist performed the assessment, joint involvement in pediatric CD was more prevalent than previously reported, in this cross-sectional study. Arthritis was associated with more severe CD disease activity and lower QoL."
"To describe and identify factors associated with articular manifestations occurring in patients treated with anti-tumour necrosis factor (TNF) for inflammatory bowel diseases (IBDs).
Retrospective monocentric study, including all patients who received an anti-TNF for an IBD in our hospital. All incident articular manifestations occurring during treatment were analysed. Characteristics of patients with paradoxical articular manifestations were compared with that of patients without inflammatory articular manifestations.
Between February 2013 and May 2017, we identified 442 patients (36.2±15 years, 50.5% men) who had ever received an anti-TNF for an IBD: Crohn's disease (n=277), ulcerative colitis (n=154) and undetermined colitis (n=11). 115 (26%) patients developed new articular manifestations after a mean of 20 (±22) months of treatment. Among them, 59 (13.3%) had inflammatory manifestations: paradoxical in 39%, concomitant of an IBD flare in 27%, linked to an immunisation against anti-TNF in 27% and 7% to another diagnosis. Among paradoxical articular manifestations, 19 (83%) were new articular symptoms, including 8 (35%) de novo spondyloarthritis. There were no predictive factors of paradoxical articular manifestation. Paradoxical manifestations spontaneously resolved in 16 (70%) patients despite continuation of anti-TNF.
Inflammatory articular manifestations occurred in about 13% of patients treated with anti-TNF for IBD. More than a quarter were linked to an immunisation against anti-TNF, which has to be searched in this situation. About 40% were paradoxical. In most of cases, they were transitory and did not require anti-TNFs discontinuation."
"The ongoing coronavirus pandemic has caused severe acute respiratory syndrome, posing a significant challenge for patients receiving immunotherapy for immune-mediated inflammatory diseases. As of January 2022, immunosuppressants such as tumor necrosis factor inhibitors (anti-TNFα) and azathioprine are inadvisable for an infectious disease caused by the SARS-CoV-2 virus (COVID-19). We continued infliximab as a second induction dose nine days after the onset of COVID-19 symptoms in a patient with acute severe ulcerative colitis.
We report the case of a 34-year-old male with 6 to 8 times bloody diarrhea, fever, and cramping abdominal pain. Ulcerative colitis was diagnosed 6 months earlier and treated with mesalamine 80 mg/kg/day and azathioprine 2.5 mg/kg/day. The patient had never undergone surgery before. Sigmoidoscopy revealed multiple ulcerations and spontaneous bleeding, and the colon samples tested negative for cytomegalovirus and Clostridium difficile. However, intravenous corticosteroids did not induce remission. A nasopharyngeal swab tested positive for SARS-CoV-2.
Acute severe ulcerative colitis and SARS-CoV-2 (COVID-19) pneumonia.
The second loading dose of infliximab was administered nine days after the diagnosis of COVID-19.
The patient completed infliximab induction at a dose of 5 mg/kg at weeks 0, 2, and 6, with no complications.
It is unclear whether anti-TNF-α treatment improves or deteriorates COVID-19 patient outcomes, and this case demonstrates that infliximab can be used safely. Current guidelines make a weak recommendation to avoid using anti-TNFα agents in the presence of acute COVID-19 infection. There is an urgent need for research on biologics therapy."
"Genetic defects in interleukin-12/23/17 immunity are associated with an increased risk of Staphylococcus aureus and herpesvirus skin infections. This study analysed spontaneous safety reports from the WHO Pharmacovigilance Center of bacterial skin or herpesvirus infections associated with secukinumab, ustekinumab and tumour necrosis factor-α inhibitors. Associations found in disproportionality analyses were expressed as reporting odds ratios (ROR). For bacterial skin infections, ustekinumab showed the strongest association (ROR 6.09; 95% confidence interval (95% CI) 5.44-6.81), and, among the tumour necrosis factor-α inhibitors, infliximab showed the strongest association (ROR 4.18; 95% CI 3.97-4.40). Risk was comparable between infliximab and secukinumab (ROR 3.51; 95% CI 3.00-4.09). Secukinumab showed the strongest association with herpes simplex infection (ROR 4.80; 95% CI 3.78-6.10). All biologics were equally associated with herpes zoster. Infliximab was the only biologic associated with cytomegalovirus infection (ROR 5.66; 95% CI 5.08-6.31) and had the strongest association with Epstein-Barr virus infection (ROR 6.90; 95% CI 6.03-7.90). All biologics evaluated were positively associated with bacterial skin infections, herpes simplex, and herpes zoster, compared with all other drugs in the WHO database for which individual case safety reports were collected. The possibility of under-reporting, reporting bias and difference in causality assessment between countries and reporters must be taken into account when interpreting the results of disproportionality analyses."
"The aim of the study was to improve understanding of adherence and persistence to biologics, and their association with health-care resource utilization (HCRU), in Japanese patients with moderate to severe ulcerative colitis (UC).
Data were from Medical Data Vision, a secondary care administrative database. A retrospective, longitudinal cohort analysis was conducted of data from UC patients initiating biologic therapy between August 2013 and July 2016. Data collected for 2 years prior (baseline) and 2 years after (follow-up) the index date were evaluated. Patients completing biologic induction were identified, and adherence/persistence to biologic therapy calculated. HCRU, steroid, and immunosuppressant use during baseline and follow-up were assessed. Biologic switching during the follow-up was evaluated. Descriptive statistics (e.g., means and proportions) were obtained and inferential analyses (from Student's 
The analysis included 649 patients (adalimumab: 265; infliximab: 384). Biologic induction was completed by 80% of patients. Adherence to adalimumab was higher than that to infliximab (
Poor biologic persistence was associated with increased non-medication-associated HCRU. Effective treatments with high persistence levels and limited associated HCRU are needed in UC."
"Evidence regarding the risk of immunogenicity in patients with inflammatory bowel disease (IBD) who switched anti-tumor necrosis factor alpha (anti-TNFα) therapies to a subsequent anti-TNFα (either infliximab or adalimumab) is conflicting. We aimed to assess the risk of consecutive immunogenicity to anti-TNFα in a large cohort of patients.
This was a multicenter retrospective study. Medical records of adult and pediatric IBD switchers who had pharmacokinetic data for both agents between 2014 and 2020 were retrieved. Data including age, sex, disease type, duration of therapies, and concomitant use of immunomodulators (IMMs) were recorded.
Overall, 164 patients were included [52% female; 88% Crohn's disease; mean age = 24.4 ± 14.6 years; 108 (66%) switched from infliximab to adalimumab and 56 (34%) vice versa]; 120 (73.1%) patients switched due to an immunogenic failure. Among patients switching therapy from infliximab to adalimumab due to an immunogenic failure immunogenicity to infliximab was significantly associated with consecutive immunogenicity to adalimumab (
Patients with IBD who switch from infliximab to adalimumab following an immunogenic failure are at increased risk for consecutive immunogenicity to adalimumab. IMM use after a switch prolongs drug retention."
"Idiopathic retinal vasculitis, aneurysms and neuroretinitis is a rare vision-threatening condition. If untreated vision loss occurs due to complications of progressive retinal ischaemia including retinal neovascularisation, neovascular glaucoma and retinal exudation. Despite the proposed underlying inflammatory aetiology this condition demonstrates poor response to corticosteroid treatment. The aim was to describe two paediatric cases of idiopathic retinal vasculitis, aneurysms and neuroretinitis treated with infliximab.
Two case reports.
Infliximab treatment led to resolution of aneurysmal dilatations and retinal vasculitis, and reversal of some retinal capillary non-perfusion.
Early infliximab treatment should be considered in cases of idiopathic retinal vasculitis, aneurysms and neuroretinitis."
"The COVID-19 pandemic highlighted the benefits of subcutaneous (SC) administration for healthcare systems. The first SC infliximab, CT-P13 SC, was safe and effective for the treatment of psoriatic arthritis. Observed patient preferences for continuing CT-P13 SC suggest that patients receiving IV infliximab should be offered a switch to CT-P13 SC."
"Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are registered for treating moderate-to-severe inflammatory bowel disease [IBD], many questions on their use remain unanswered. We set up a multi-stakeholder initiative resulting in a position statement.
Based on publicly available data, statements on subcutaneous infliximab and vedolizumab were developed and reviewed by 45 Belgian IBD physicians in a three-round modified Delphi process. During a consensus meeting, input from 16 IBD patients, nine IBD nurses and two clinical pharmacologists was provided and statements were further discussed, modified and scored. Statements achieving agreement by at least 70% of the IBD physicians were accepted.
The Delphi process resulted in 79 agreed statements. In patients initiating intravenous therapy, IBD physicians would only consider switching to subcutaneous formulations in patients achieving both clinical and biological response [for Crohn's disease] or both clinical and endoscopic response [for ulcerative colitis]. For patients under maintenance therapy, switching to subcutaneous formulations was only considered in those achieving both clinical and endoscopic response while receiving standard dosing of infliximab or vedolizumab. While awaiting more scientific data, IBD physicians should consider weekly subcutaneous injections or switching back to an intravenous formulation in case of loss of response. Finally, switching to a subcutaneous formulation should always be a shared decision.
All stakeholders welcomed subcutaneous infliximab and vedolizumab. However, more scientific data are needed to select the right patients and timing for switching to these newer formulations, and to explore the optimal strategy in case of loss of response."
"The interleukin-6 family cytokine, oncostatin-M (OSM) has been associated with response to tumor necrosis factor-α antagonists (anti-TNFs) in small cohorts of patients with inflammatory bowel disease (IBD). We aimed to evaluate the association between plasma OSM concentrations and response to anti-TNFs (infliximab and adalimumab) in both ulcerative colitis (UC) and Crohn's disease (CD). A retrospective cohort study was conducted in patients with IBD with a history of anti-TNF exposure. Blood samples, collected prior to anti-TNF exposure, were analyzed by enzyme-linked immunosorbent assay for the presence and quantity of OSM. Clinical remission was assessed at 1-year post anti-TNF exposure in addition to the occurrence of surgery, hospitalization, corticosteroid use, and adverse drug events. Lastly the threshold OSM plasma concentration associated with anti-TNF non-response was assessed by receiver operator characteristic (ROC) curve analysis. Patients with IBD (CD, n = 82; UC, n = 40) were assessed. In both UC and CD, mean pre-treatment OSM concentrations were significantly lower in those who achieved clinical remission at 1-year (p < 0.0001). A threshold plasma OSM concentration of 168.7 pg/ml and 233.6 pg/ml respectively separated those who achieved clinical remission at 1-year on an anti-TNF from those who did not in CD and UC respectively (CD: area under the receiver operator characteristic curve, AUROC = 0.880, 95% CI 0.79-0.96; UC: AUROC = 0.938, 95% CI 0.87-1.00). High OSM concentrations were associated with anti-TNF discontinuation and use of rescue steroids in CD and UC. High pre-treatment OSM concentrations identify IBD patients at-risk of anti-TNF non-response at 1-year as well as other deleterious clinical outcomes."
"Sarcoidosis is a systemic inflammatory disease, characterised by granuloma formation upon an unknown trigger in genetically predisposed individuals. The inflammation is characterised by an activation of both the innate immune system, with macrophages differentiating into epitheloid cells and dendritic cells, and the adaptive immune system, particularly T helper (Th) 1 and Th17 cells. Since all organs can be affected to varying extents, clinical presentation is often diverse. Most commonly, the lungs, lymph nodes, skin and eyes are involved, whereas cardiac, renal and neurological manifestations are less common but associated with higher morbidity. Depending on the clinical symptoms, a detailed evaluation including thorough clinical examination, imaging and laboratory tests should explore all possible organ involvements. In some patients, fatigue manifests as a para-sarcoidosis symptom impacting quality of life, even if sarcoidosis is in remission. Some acute syndromic presentations, such as Löfgren's syndrome, have a good prognosis and are commonly self-limiting. If possible, a topical treatment, for example for cutaneous sarcoidosis or bronchial involvement, should be applied. Treatment of severe cases with persisting disease activity necessitates long-term immunosuppressive drugs, with glucocorticoids as the first-line option. Steroid-sparing and second-line drugs include methotrexate, azathioprine, mycophenolate mofetil and immunomodulators such hydroxychloroquine, with the latter being first-line therapy in cutaneous sarcoidosis. Tumour necrosis factor-alpha inhibitors (particularly adalimumab and infliximab) are used as third-line agents but are administered earlier in cases of persistent disease activity, severe organ-involvement or intolerance to conventional drugs. Treatment decisions should be based on a multidisciplinary approach, depending on organ involvement and treatment tolerability. Para-sarcoidosis manifestations, particularly fatigue, should also be carefully addressed, where the patient could also be enrolled in multidimensional rehabilitation programmes. With various organ involvement and different phenotypes, larger studies including real-world data from registries are necessary to evaluate different sarcoidosis endotypes and preferential treatment pathways."
"Effective control of severe immune-related adverse events, including cytokine release syndrome (CRS), is essential for the success of immunotherapy. We present a case of a granulocyte colony-stimulating factor-producing pleomorphic lung carcinoma treated with nivolumab plus ipilimumab which developed CRS and severe immune-related pneumonitis. The effect of immunotherapy was heterogeneous; gastric metastasis was eliminated, but the pulmonary lesion had primary resistance. Steroid and tocilizumab were successful in controlling CRS, but additional infliximab was necessary to control pneumonitis. To control immune-related adverse events, it is important to choose immunosuppressive agents to the specific target organ and inflammatory cells."
"Primary sclerosing cholangitis (PSC) is a relatively common complication of ulcerative colitis (UC). Only a few studies have investigated the impact of PSC on the clinical course of UC, and their conclusions are contradictory. Therefore, we aimed to compare the disease activity of UC with and without PSC.
We collected UC patient data using the Diagnosis Procedure Combination database system in Japan and classified eligible admissions into two groups based on their diagnosis of either UC alone or UC associated with PSC. We then compared therapeutic details (medical treatment and surgery) between the two groups. Multivariable logistic regression analysis and propensity score matching was also performed. The rates of systemic steroid injection and infliximab administration in patients with PSC were lower than those in patients without PSC (21% vs. 28%, 
UC patients with PSC might have less UC disease activity than those with UC alone."
"In recent years, biological therapies have revolutionized the management of inflammatory bowel disease (IBD); however, they are expensive. The development of biosimilar products has allowed us to reduce healthcare costs and improve patients' access to these treatments. Although various studies support the similarity between infliximab and its biosimilar CT-P13 in terms of efficacy and safety, there are unmet needs regarding research on these agents in the context of IBD.
To analyze clinical response rates to CT-P13 and adverse events in IBD patients treated in real-life practice.
An observational, prospective, multicenter study of IBD patients treated with CT-P13 in clinical practice who were naïve to biological treatments or failed to respond to other anti-tumor necrosis factor drugs or had switched from infliximab originator was carried out. No diagnostic or follow-up interventions were conducted on patients outside usual clinical practice. The primary endpoints were clinical response rates and number of adverse events. The primary efficacy variable was the proportion of patients who were in clinical remission and/or had a clinical response at 3, 6, 9, and 12 mo.
A total of 220 IBD patients treated with CT-P13 (Remsima
CT-P13 is an effective and safe infliximab biosimilar for the treatment of IBD in real-life practice and may be a valid and attractive alternative for the treatment of IBD."
"Xanthogranulomatous pyelonephritis (XGP) is one of the rare diseases characterized by chronic inflammation and destruction of the renal parenchyma, and it is usually associated with renal infection, and nephrolithiasis. Infliximab is an anti-tumor necrosis factor-alpha (anti-TNF-α) monoclonal antibody, which is widely used for treating inflammatory bowel disease, and it is known to increase the risk of rare and opportunistic infections. In this study, we report a case of XGP presenting after the initiation of infliximab treatment. We highlight one of the possible complications associated with immunosuppression due to infliximab. Furthermore, the importance of increasing the awareness among physicians for early recognition of this rare complication."
"A 34 year-old young man came to our attention after an occasional finding of complete AV block. We made the diagnosis of systemic sarcoidosis with cardiac involvement through an FDG-PET even with a normal CMR. We started corticosteroid therapy and we decided to follow-up the patient through an implantable loop recorder (ILR). Beyond an initial regression of the AV block, after 8 months the ILR revealed AV block and pauses more than 3 s during the day; a new FDG-PET evidenced FDG uptake in new areas of left ventricle. Hence we started infliximab and implanted a dual chamber ICD."
"COVID-19 vaccinations have been shown to be effective in reducing risk of severe infection, hospitalization, and death. They have also been shown to be safe and effective in patients with inflammatory bowel disease (IBD) who are receiving biologic therapies. In this study, we aimed to evaluate the prevalence of vaccination among patients receiving biologic therapies for IBD.
A single-center prospective cross-sectional study conducted at a tertiary care inflammatory bowel disease center in Kuwait. Data from patients with inflammatory bowel disease (IBD) who attended the gastroenterology infusion clinic from 1 June 2021 until 31 October 2021 were retrieved. Patients who received infliximab or vedolizumab at least six weeks before recruitment were included. The primary outcome was prevalence of COVID-19 vaccination. The secondary outcome was to assess whether prevalence of COVID-19 vaccination differed based on sex, age, type of biologic therapy and nationality.
The total number of inflammatory bowel disease (IBD) patients enrolled in the study was 280 (56.0% male and 44.0% female). Of the total, 112 (40.0%) patients were diagnosed with ulcerative colitis and 168 (60.0%) with Crohn's disease. The number of ulcerative colitis patients who were vaccinated was 49 (43.8%) and the number of Crohn's disease patients who were vaccinated was 68 (40.5%). The median age was 33.2 years and BMI was 24.8 kg/m
The overall prevalence of COVID-19 vaccination among patients with inflammatory bowel disease (IBD) on biologic therapies was lower than that of the general population and world health organization (WHO) recom-mendation. Female patients, patients above the age of 50, and expatriates were more likely to receive the vaccine. Physicians should reinforce the safety and efficacy of COVID-19 vaccines among patients, especially IBD patients on biologic therapies, who express hesitancy towards them."
"Ramsay Hunt syndrome is a rare complication of herpes zoster that results from reactivation of varicella-zoster virus in the geniculate ganglion of the VII cranial nerve. Immunosuppression can lead to reactivation of latent varicella-zoster virus, resulting in herpes zoster. Here, we present a case of Ramsay Hunt syndrome in a patient with ulcerative colitis under treatment with infliximab.
Ramsay Hunt syndrome is a rare form of herpes zoster and characterized by the presence of otalgia, facial palsy, vertigo and vesicular rash in the external ear or on the oropharynx.Treatment with TNF inhibitors increases the risk of its development.Although not generally recommended, vaccination may reduce the risk of herpes zoster recurrence during TNF inhibitor therapy."
"The COVID-19 pandemic emphasized the utility of subcutaneous (SC) biologics for pressured healthcare systems. The first SC form of infliximab, CT-P13 SC, provided safe and effective treatment for ankylosing spondylitis in our case series, with increased convenience relative to intravenous treatment benefitting patients both during the pandemic and beyond."
"Antioxidants are privileged candidates for the development of adjuvants able to improve the efficiency of pharmacological therapies, particularly for chronic inflammatory syndromes. During the last 20 years, anti-TNFα (tumor necrosis factor alpha) monoclonal antibodies infusion has been the biological therapy most frequently administered but there is still large space for improvement in disease remission rates and maintenance. In this context, nutritional bioactive compounds contained in dietary patterns or included as supplements, may act as adjuvants for the induction and maintenance of IBD (inflammatory bowel diseases) remission. To verify this possibility, a single-center preliminary study (SI-CURA, Soluzioni Innovative per la gestione del paziente e il follow up terapeutico della Colite UlceRosA) was designed and carried out to evaluate whether a daily administration of purple corn supplement could improve the response to Infliximab (IFX) infusion of IBD patients with both Crohn's disease (CD) and ulcerative colitis (UC). A cohort of 47 patients was enrolled in the study. Biological samples were collected before the first and the third IFX infusion. All patients received nutritional guidelines, 27 of them received commercial red fruit tea with low anthocyanins content, while 20 received a purple corn supplement with a high anthocyanin content. Results show that the administration of an antioxidant-enriched purple corn supplement could improve IFX-mediated disease remission in terms of circulating inflammatory markers. Comparison between CD and UC patients revealed that, at this anthocyanin dosage, the purple corn extract administration improved the IFX response in CD but not in UC patients. Our results may pave the way for a new metacentric study of CD patients, recruiting a wider cohort and followed-up over a longer observational time."
"Up to 50% of patients with Crohn's disease (CD) experience secondary loss of response (SLR) to infliximab. Patients with SLR may show clinical signs of iron deficiency as a result of inflammation despite being iron-replete. The magnetic resonance imaging (MRI)-based radiomic index, R2"
"The goal of this study was to identify potential predictive biomarkers for the therapeutic effect of infliximab (IFX) in Rheumatoid arthritis (RA) and explore the potential molecular mechanism of nonresponse to IFX treatment to achieve individualized treatment of RA.
Differential gene expression between IFX responders and nonresponders in the GSE58795 and GSE78068 datasets was identified. Coexpression analysis was used to identify the modules associated with nonresponse to IFX therapy for RA, and enrichment analysis was conducted on module genes. Least absolute shrink and selection operator (LASSO) regression was used to develop a gene signature for predicting the therapeutic effect of IFX in RA, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive value of the signature. Correlation analysis and single-sample gene set enrichment analysis (ssGSEA) were used to explore the potential role of the hub genes. Experimental validation was conducted in synovial tissue and RA fibroblast-like synoviocytes (RA-FLSs).
A total of 46 common genes were obtained among the two datasets. The yellow-green module was identified as the key module associated with nonresponse to IFX therapy for RA. We identified a 25-gene signature in GSE78068, and the AUC for the signature was 0.831 in the internal validation set and 0.924 in the GSE58795 dataset(external validation set). 
The 25-gene signature may have potential predictive value for the therapeutic effect of IFX in RA at the beginning of IFX treatment, and autophagy may be involved in nonresponse to IFX treatment. In particular, DERL1 may be associated with the regulation of autophagy."
"Vitamin D deficiency is prevalent in patients with inflammatory bowel disease (IBD). The goal of this study was to assess the efficacy and safety of high-dose, interval cholecalciferol administration in patients with IBD receiving infliximab.
This prospective, longitudinal, open-label study enrolled pediatric and young adult patients with IBD and vitamin D deficiency. Subjects received 50,000 IU every 4 to 5 weeks (n = 11) or 100,000 IU every 6 to 8 weeks (n = 32) of oral cholecalciferol for 1 year. Dosing was directly observed and administered in conjunction with infliximab infusions. The primary endpoint was vitamin D sufficiency, defined as a 25-hydroxy-vitamin D (25-OHD) level ≥30 ng/mL.
Forty-three participants constituted the primary analysis population. 25-OHD levels reached steady-state after the third dose, and mean increases in 25-OHD levels were 8 vs. 4.5 ng/mL in the 100,000 IU vs. 50,000 IU treatment groups, respectively. Only 43.8% of patients receiving 100,000 IU and 18.2% of patients receiving 50,000 IU achieved sufficiency. There was no difference in the 25-OHD level responsiveness in patients with Crohn disease versus those with ulcerative colitis (P = 0.72). There was no correlation between 25-OHD levels and clinical disease activity in patients with Crohn disease (P = 0.85) or ulcerative colitis (P = 0.24).
Supplementation with cholecalciferol was well-tolerated and direct observation is a promising paradigm for ensuring compliance with therapy. Patients with IBD, however, appear to require high doses of cholecalciferol, with less than half of patients (37% overall) achieving vitamin D sufficiency. Additional studies are necessary to determine the optimal treatment regimens."
"Therapeutic options for the management of inflammatory bowel disease [IBD] have been expanding in recent decades. New biological and small molecule therapies have been incorporated into the pharmacological arsenal, allowing a more personalized management, and seeking increasingly strict remission goals. However, the fear of developing adverse events represents one of the most important limitations in deciding its use by patients and by a multidisciplinary team. Despite the risk of hepatotoxicity of thiopurines and methotrexate, these drugs are still used either as monotherapy or as combined therapy with anti-tumour necrosis factor [anti-TNF] biological agents. Although drug-induced liver injury [DILI] appears to be less frequent with anti-TNF agents, newer biologics and small molecules, liver tests should be considered in the follow-up of these patients, especially regarding future combined therapy of biologics or of these drugs with small molecules. The objective of this review is to show data on the risk of developing DILI in patients with IBD who are undergoing treatment with traditional therapy or new drugs, whether biological or small molecules."
"Immune checkpoint inhibitors have shown remarkable efficacy as new-generation drugs in anti-tumor therapy. However, the nonspecific activation of the immune system leads to a number of adverse side effects, so-called immune-related adverse events (irAEs), including the occurrence of diarrhea and colitis in about one third of treated patients.Endoscopically and histologically, there is significant overlap of immune-mediated colitis with classic IBD, making differentiation difficult.Therapeutically, high-dose glucocorticoids are used in grade 3 (severe) to grade 4 (life-threatening) colitis, in addition to discontinuation of ICI therapy. Steroid-refractory cases (up to 42%) benefit from the TNF inhibitor infliximab. Vedolizumab, analogous to inflammatory bowel disease, represents second-line therapy for infliximab-refractory cases. Little data exist to date on the efficacy of tofacitinib in refractory cases.We describe the case and therapeutic management of severe and persistent immune-mediated colitis after successful immunochemotherapy with pembrolizumab in an 80-year-old man with metastatic non-small cell carcinoma of the lung and pre-existing colitis unclassified and other comorbidities.
Immuncheckpoint-Inhibitoren haben als neue Generation von Medikamenten in der Anti-Tumortherapie bemerkenswerte Wirksamkeit gezeigt. Die unspezifische Aktivierung des Immunsystems führt jedoch zu einer Reihe von unerwünschten Nebenwirkungen, sog. immune-related adverse events (irAEs), inklusive des Auftretens von Diarrhoe und Kolitis bei etwa einem Drittel der behandelten Patienten.Endoskopisch und histologisch gibt es weitreichende Überlappungen der immunvermittelten Kolitis mit der klassischen CED, was eine Unterscheidung erschwert.Therapeutisch kommen bei Grad-3- (schwere) bis Grad-4-Kolitiden (lebensbedrohlich) neben dem Abbruch der ICI-Therapie hochdosiert Glukokortikoide zum Einsatz. Steroidrefraktäre Fälle (bis 42%) profitieren vom TNF-Hemmer Infliximab. Vedolizumab stellt, analog bei chronisch entzündlichen Darmerkrankungen, die Zweitlinientherapie bei Infliximab-refraktären Fällen dar. Zur Wirksamkeit von Tofacitinib bei therapierefraktären Fällen existieren bislang nur wenige Daten.Wir beschreiben den Fall und das Therapiemanagement einer schweren und andauernden immunvermittelten Kolitis nach erfolgreicher Immunochemotherapie mit Pembrolizumab bei einem 80-jährigen Mann mit einem metastasierten, nicht kleinzelligen Karzinom der Lunge und vorbestehender Colitis indeterminata (colitis unclassified) sowie weiteren Komorbiditäten."
"Carcinogenesis is one of the major complications for patients with inflammatory bowel disease (IBD) and causes poor prognosis. We aimed to describe cancer incidence in the Chinese IBD cohort compared to general population-based cancer registration data and further explore associated risk factors for cancer occurrence in IBD patients. IBD inpatients from January 1998 to January 2018 in Peking Union Medical College Hospital (PUMCH) were included in our study. Patients were followed-up from the date of IBD diagnosis until either the date of first cancer diagnosis or January 2019. Standardized incidence ratios (SIRs) of overall cancer and site-specific cancers were calculated. A total of 869 Ulcerative Colitis (UC) and 516 Crohn's disease (CD) patients were finally included with median follow-up time of 7 and 5 years, respectively. Fifty-three cases developed malignancies. After standardization by age and gender, SIR of total cancer occurrence in IBD patients was 1.77 (95% CI, 1.33-2.32). As for UC, digestive cancers (SIR 3.75; 95% CI, 2.29-5.80), thyroid cancer (SIR 10.34; 95% CI, 4.72-19.64) and hematological malignancies (SIR 6.25; 95% CI, 1.68-16.00) had the highest incidence, which were prominent in young and middle-aged patients. Use of steroids, immunosuppressants or infliximab did not present higher risk of malignancies in UC patients. There was no significant difference in cancer risk between CD patients and general population. In conclusion, the increased risks of multiple cancers are particularly prominent in Chinese UC patients and these findings can provide more targeted guidance for cancer monitoring in Chinese IBD patients."
"Different treatment approaches have been described for the management of COVID-19-related multisystem inflammatory syndrome in children (MIS-C), the pathogenesis of which has not yet been fully elucidated. Here, we comprehensively review and summarize the recommendations and management strategies that have been published to date.
MIS-C patients are treated with different regimens, mostly revolving around the use of immunomodulatory medications, including IVIG and glucocorticoids as first-tier therapy. Refractoriness to IVIG and glucocorticoids warrants a step-up of immunomodulatory therapy to biologic agents such as anakinra, tocilizumab, and infliximab.
We review the current evidence regarding the use of monotherapy versus combination therapy, as well as the current recommendations for assessing thrombotic risk and administering antiplatelet and anticoagulant therapy. We anticipate that future studies will provide evidence for management plans that maximize short- and long-term outcomes.
The online version contains supplementary material available at 10.1007/s40124-021-00259-4."
"Patient under anti-TNF-alpha treatment have an increased risk of mycobacterial infections, particularly tuberculosis. Only four case reports of "
"Less than 50% of patients with inflammatory bowel diseases (IBD) receiving monoclonal antibody (mAb) therapy achieve endoscopic remission. Poor outcomes may indicate a need for dose optimization. During therapeutic drug monitoring (TDM), drug concentrations are measured, and when found too low, dosage regimen escalations are performed. To date, benefits of TDM of mAbs in patients with IBD are uncertain.
This review presents an overview of what clearance monitoring is, how it can be performed, and why and when it may be valuable in treating patients with IBD. Virtual patients were used for illustration. A literature search was performed to summarize current evidence for clearance monitoring in IBD and other disease settings.
During clearance monitoring, mAb clearance is calculated and monitored over time. Higher mAb clearance in patients with IBD has been associated with higher target load (target-mediated drug disposition), protein-losing enteropathy (fecal drug loss), and immunogenicity. Although not prospectively confirmed, clearance monitoring might facilitate identification of (yet) asymptomatic disease flares or presence of (yet) undetectable anti-drug antibodies. Furthermore, clearance monitoring may be used to predict treatment outcomes. Whether dosage regimen adjustments can modify the clearance time course and the treatment outcome is to be determined."
"Therapy regimens used in patients with inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections or viral reactivation. Moreover, it is uncertain whether IBD patients have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or infected patients may have an increased risk for severe coronavirus disease 2019 (Covid-19). Managing severe acute flare in ulcerative colitis during the Covid-19 pandemic is a challenge for clinicians and their patients. The results of the published studies mainly report on the role of the prior medication, but not how to treat severe acute flare of IBD patients with severe Covid-19 pneumonia.
We report the case of a 68-year-old patient with a long history of ulcerative colitis. He was initially admitted to an external hospital because of severe acute flare. The initiation of a high-dose oral cortisone therapy did not improve the clinical symptoms. During the inpatient treatment, he was tested positive for SARS-CoV-2. At admission to our hospital the patient showed severe flare of his ulcerative colitis and increased Covid-19 symptoms. A cortisone-refractory course was noticed. After detailed multidisciplinary risk-benefit assessment, we initiated an intravenous tacrolimus therapy and dose of prednisolone was tapered gradually. After clinical response, the therapy was adjusted to infliximab. Additionally, the Covid-19 pneumonia was kept under control despite immunosuppression and the patient could be discharged in clinical remission.
This case suggest the use of tacrolimus as a bridging therapeutic option for severe acute, cortisone refractory ulcerative colitis in Covid-19 patients. Nevertheless, the best treatment strategy for IBD patients presenting a flare during the outbreak has yet to be defined. Further data for IBD patients under calcineurin inhibitor therapy are urgently needed."
"NUDT15 polymorphisms are associated with leukopenia during treatment with thiopurines. However, data regarding its effect on treatment outcomes are scarce.
To investigate the outcomes between NUDT15 normal and intermediate metabolisers in paediatric patients with Crohn's disease (CD) treated with a combination therapy of infliximab (IFX) and azathioprine (AZA).
In this retrospective observational study, 143 patients categorised into the NUDT15 normal and intermediate metaboliser groups were compared based on clinical remission (CR), biochemical remission (BR), mucosal healing (MH) at 1 year treatment, IFX trough levels (TLs), antibodies to IFX (ATIs), 6-thioguanine nucleotide (6-TGN) levels, loss of response (LOR) and IFX durability.
No significant differences were observed between the groups in CR, BR, MH at 1 year, whereas IFX TLs and ATIs and 6-TGN levels were comparable. However, LOR (6.5% vs 27.7%, P = 0.025) was significantly lower and IFX durability significantly higher (96.8% vs 80.4% P = 0.027) in the intermediate group. Multivariable Cox proportional hazard regression analysis showed that ATI positivity (hazard ratio (HR): 4.76, 95% CI: 2.25-10.07, P < 0.001) and the NUDT15 metaboliser group was associated with LOR (HR: 0.18, 95% CI: 0.04-0.76, P = 0.019). The Kaplan-Meier survival curves showed that the LOR-free survival rate was significantly lower in normal metabolisers (log-rank test P = 0.009).
NUDT15 intermediate metabolisers were associated with lower LOR in paediatric patients with CD treated with IFX and AZA combination therapy. This finding may partially explain the longer durability of IFX in Korean children than their counterparts in Western countries."
"Since the expiry of the patents on originator anti-TNF agents in Europe, France has authorized the sale of biosimilars. The penetration rate of anti-TNF agents and their biosimilars, and the cost savings driven by the introduction of biosimilars appears to vary widely. This study aimed to describe the market share of anti-TNFs and their biosimilars, and the cost savings generated by the introduction of biosimilars in French hospitals 5 years ago.
The pharmaceutical component of the French national uniform hospital discharge data set database (PMSI) was used to study sales of infliximab, etanercept and adalimumab originators and biosimilars, and to estimate cost savings generated by the introduction of biosimilars onto the market, using the historical tariffs of the originators.
The penetration rate of anti-TNF biosimilars in France in 76% for infliximab, 74% for etanercept and 77% for adalimumab. In 2020, Inflectra® (41%) was the Remicade® biosimilar with the highest sales volume, while Erelzi® (57%) and Amgevita® (64%) were the most widely sold biosimilars of Enbrel® and Humira® respectively. In terms of cost savings since the launch of biosimilars, overall, for all biosimilars taken together, over the 5-year period, a total of 824 million Euro was saved, in relation to the historical tariffs of the originators.
This study shows firstly that the penetration rate of anti-TNF biosimilars in France 5 years after their launch is close to 80%. Secondly, we show that the cost savings generated by the use of biosimilars to anti-TNF agents exceed 820 million Euro over 5 years."
"Inflammatory bowel disease (IBD) is a term used to describe disorders that involve chronic inflammation in the gastrointestinal tract, affecting more than 6.8 million people worldwide. Biological therapy is used in the most severe cases of IBD where anti-tumour necrosis factor-alpha (TNF-α) antibodies are the first choice for a biological treatment. When administrated to patients, these antibodies interact with TNF-α, usually overexpressed in these diseases, neutralizing its biological activity. Because of the chronic nature of these diseases, a recurring administration of the therapeutic antibodies is required, thus making therapy monitorization essential for the correct management of these diseases. The aim of this work is the development of an enzyme-linked immunosorbent assay (ELISA) microfluidic biosensor to quantify the therapeutic antibodies in IBD patient plasma samples, where the commercial monoclonal antibody Infliximab (IFX) is used as a model target. By providing a faster and more accurate measurement of IFX, the proposed method leads to improved therapy scheduling and a reduced risk of endogenous anti-drug antibodies (ADAs) reducing the efficacy of the treatment. The time needed between sample insertion and result output for the microfluidic ELISA (mELISA) is 24 minutes, drastically shorter than the time required by the conventional ELISA (cELISA). The mELISA presented in this work has a LoD of 0.026 μg mL"
"Few studies have demonstrated treatment strategies about the duration and cessation of medications in patients with Crohn's disease (CD). We investigated factors affecting clinical relapse after infliximab (IFX) or azathioprine (AZA) withdrawal in pediatric patients with CD on combination therapy. Pediatric patients with moderate-to-severe CD receiving combination therapy were analyzed retrospectively and factors associated with clinical relapse were investigated. Discontinuation of IFX or AZA was performed in patients who sustained clinical remission (CR) for at least two years and achieved deep remission. A total of 75 patients were included. Forty-four patients (58.7%) continued with combination therapy and 31 patients (41.3%) discontinued AZA or IFX (AZA withdrawal 10, IFX withdrawal 15, both withdrawal 6). Cox proportional-hazards regression and statistical internal validation identified three factors associated with clinical relapse: IFX cessation (hazard ratio; HR 2.982, P = 0.0081), IFX TLs during maintenance therapy (HR 0.581, P = 0.003), 6-thioguanine nucleotide (6-TGN) level (HR 0.978, P < 0.001). However, AZA cessation was not associated with clinical relapse (P = 0.9021). Even when applied in pediatric patients who met stringent criteria, IFX cessation increased the relapse risk. However, withdrawal of AZA could be contemplated in pediatric patients with CD who have sustained CR for at least 2 years and achieved deep remission."
"The novel coronavirus pandemic has emerged as one of the significant medical-health challenges of the current century. The World Health Organization has named this new virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first detection of SARS-CoV-2 in November 2019 in Wuhan, China, physicians, researchers, and others have made it their top priority to find drugs and cures that can effectively treat patients and reduce mortality rates. The symptoms of Coronavirus Disease 2019 (COVID-19) include fever, dry cough, body aches, and anosmia. Various therapeutic compounds have been investigated and applied to mitigate the symptoms in COVID-19 patients and cure the disease. Degenerative virus analyses of the infection incidence and COVID-19 have demonstrated that SARS-CoV-2 penetrates the pulmonary alveoli's endothelial cells through Angiotensin-Converting Enzyme 2 (ACE2) receptors on the membrane, stimulates various signaling pathways and causes excessive secretion of cytokines. The continuous triggering of the innate and acquired immune system, as well as the overproduction of pro-inflammatory factors, cause a severe condition in the COVID-19 patients, which is called ""cytokine storm"". It can lead to acute respiratory distress syndrome (ARDS) in critical patients. Severe and critical COVID-19 cases demand oxygen therapy and mechanical ventilator support. Various drugs, including immunomodulatory and immunosuppressive agents (e.g., monoclonal antibodies (mAbs) and interleukin antagonists) have been utilized in clinical trials. However, the studies and clinical trials have documented diverging findings, which seem to be due to the differences in these drugs' possible mechanisms of action. These drugs' mechanism of action generally includes suppressing or modulating the immune system, preventing the development of cytokine storm via various signaling pathways, and enhancing the blood vessels' diameter in the lungs. In this review article, multiple medications from different drug families are discussed, and their possible mechanisms of action are also described."
"The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA.
Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed.
One hundred two IBD patients under maintenance therapy with IFX or ADA were enrolled. Of these, 53 (52%) were ANA positive with 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity was found to be correlated with age (P = 0.008), female gender (P = 0.03), duration of treatment (P = 0.06), arthralgias (P = 0.04) and TLs (P = 0.005). However, in multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P = 0.04 and P =  = 0.006, respectively). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found.
In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs. The clinical significance of this finding remains to be defined in future larger prospective studies."
"We conducted retrospective cohort studies of patients with relapsing polychondritis (RP) twice in 2009 and 2019, using a physician questionnaire. We compared the patients' clinical statuses between the years. Age and gender were comparable between the two surveys. Mean disease duration was longer in 2019 survey (8.3 years) than that in 2009 survey (4.8 years, P < 0.001). The mortality rate declined in 2019 survey compared with those in 2009 survey (from 9.2 to 1.6%, P < 0.001). Incidence of airway involvement decreased in 2019 survey compared with that in 2009 survey (from 49 to 37%, P = 0.012). In 2019 survey, we found more frequent use of biological agents and immunosuppressants in patients with airway involvement. When we focused on RP patients with airway involvement, physicians in 2019 chose methotrexate and calcineurin inhibitors preferentially, compared with azathioprine and cyclophosphamide. Of note is that increased use of infliximab was observed in RP patients with airway involvement, but not in those without. Reduction of airway involvement and mortality in patients with RP was observed in 2019 survey. The reduction may associate with the frequent use of biologics including infliximab in RP patients with airway involvement."
"Recent studies have confirmed that combined surgery and anti-TNF therapy could improve outcomes in patients with perianal fistulising Crohn's disease (PFCD). However, the optimal timing for infliximab infusion after surgical intervention is uncertain. We aimed to determine the long-term efficacy of early initiation of infliximab following surgery among PFCD patients.
We performed a retrospective cohort study of PFCD patients who received combined infliximab and surgical treatment between 2010 and 2018 at a tertiary referral hospital. Patients were grouped according to the time interval between surgery and infliximab infusion, with < 6 weeks into early infliximab induction group and > 6 weeks into delayed infliximab induction group. The primary outcome was to compare surgical re-intervention between early and delayed infliximab induction groups. The secondary outcomes were fistula healing and predictors associated with these outcomes of early infliximab induction approach.
One hundred and seventeen patients were included (73 in early infliximab induction, 44 in delayed infliximab induction). The median interval between surgery and infliximab initiation was 9.0 (IQR 5.5-17.0) days in early infliximab induction group and 188.0 (IQR 102.25-455.75) days in delayed infliximab induction group. After followed-up for a median of 36 months, 61.6% of patients in early infliximab induction group and 65.9% in delayed infliximab induction group attained fistula healing (p = 0.643). The cumulative re-intervention rate was 23%, 32%, 34% in early infliximab induction group and 16%, 25%, 25% in delayed infliximab induction group, at 1, 2, and 3 years respectively (p = 0.235). Presence of abscess at baseline (HR = 5.283; 95% CI, 1.61-17.335; p = 0.006) and infliximab maintenance therapy > 3 infusions (HR = 3.691; 95% CI, 1.233-11.051; p = 0.02) were associated with re-intervention in early infliximab induction group. Presence of abscess at baseline also negatively influenced fistula healing (HR = 3.429, 95% CI, 1.216-9.668; p = 0.02).
Although no clear benefit was shown compared with delayed infliximab induction group, early initiation of infliximab after surgery could achieve promising results for PFCD patients. Before infliximab infusion, durable drainage is required for patients with concomitant abscess or prolonged infliximab maintenance therapy."
"Tumor necrosis factor alpha (TNFA) is an important cytokine that influences multiple biological processes. It is one of the key mediators of acute and chronic systemic inflammatory reactions and plays a central role in several autoimmune diseases. A number of approved monoclonal antibodies (mAbs) are widely used to subside these autoimmune diseases. However, there is a high rate of non-responsiveness to treatments with these mAbs. Therefore, it is important to be able to predict responses of the patients in an individualistic manner to these therapeutic antibodies before administration. In the present study, we used in silico tools to explore the effects of missense variants in the respective epitopes of four therapeutic anti-TNFA mAbs-adalimumab (ADA), certolizumab pegol (CZP), golimumab (GLM), and infliximab (IFX)-on their interactions with TNFA.
The binding affinities of CZP and ADA to corresponding epitopes appear to be reduced by four (TNFA
These variants may contribute to the observed inter-individual variability in response to anti-TNFA mAbs treatments and be used as markers to predict responses, and thus optimize therapeutic benefits to the patients."
"To compare the timing of serum anti-drug antibodies in adult and pediatric age groups, males and females, treated for inflammatory bowel disease or arthritis with adalimumab or infliximab by retrospectively combining data collected during a 2-year therapeutic drug monitoring period.
Four hundred thirty sera were divided in groups collected at 0, 3, 6, 12, and 24 months (T0, T3, T6, T12, and T24) after initiation of therapy and assayed for drug and relative anti-drug antibodies levels. At each time point, the percentage of sera presenting anti-drug antibodies, as well as the drug concentrations, were calculated and correlated with patient age and sex.
Anti-drug antibodies were present in 31.5% of sera and were significantly higher in the pediatric age group than in the adult age group, through all time points. The percentages of sera showing anti-drug antibodies were significantly different as early as 3 months and were sera from pediatric female group. The percentages of sera showing anti-drug antibodies reached the highest value at 6 months in the pediatric age group and at 12 months in the adult age group.
Sera from pediatric had an earlier presence of anti-drug antibodies than adults. In particular, pediatric females sera showed the fastest anti-drug antibodies development."
"Idiopathic multifocal choroiditis (MFC) is part of the group of choriocapillaritis entities. The clinical definition of the disease has evolved with time. The aim of this article was to undertake a review on MFC, on its present-day appraisal and nomenclature and we also report a series of patients with emphasis on the clinical presentation and the importance of vigorous immunosuppressive management.
A review of the literature and a retrospective case series study which was performed in the Centre for Ophthalmic Specialised care (COS), Lausanne, Switzerland. Patients diagnosed from 1994 to 2020 with idiopathic multifocal choroiditis (MFC) treated with multiple immunosuppressants were included. Exclusion criteria were insufficient follow up and cases not treated with vigorous immunosuppressive therapy. Imaging analysis included spectral domain optical coherence tomography (SD-OCT) / enhanced depth imaging OCT (EDI-OCT), OCT angiography (OCT-A). Fluorescein and Indocyanine angiography (FA, ICGA) before and after the instauration of treatment. Best corrected visual acuity (BCVA), intraocular pressure (IOP), routine ocular examination, laser flare photometry (LFP) were performed at presentation and follow-up. Immunosuppression comprised at minimum two among the following agents: prednisone, cyclosporine, azathioprine, mycophenolic acid or infliximab. Mean duration of therapy was calculated.
26 (52 eyes) of 2102 new patients (1.24%) were diagnosed with MFC. 25 (96%) patients were female and 1 (4%) was male. 43/52 (82%) eyes were myopic with a mean dioptre of - 5.87 ± 2.94, six (12%) eyes were hypermetropic with mean dioptres 2.0 ± 2.68 and three (6%) were emmetropic. 14/52 (27%) eyes had at least 1 anti-VEGF injection because of choroidal neovascularisation (CNVs), 1 eye had a phototherapy laser and 37/52 (71%) had no complication of CNVs during the follow-up. 5/26 (19%) fulfilled the inclusion criteria for our study. Mean age was 26.4 ± 9.3 years. Snellen best corrected visual acuity (BCVA) at presentation was 0.955+/-0.26. Mean follow up was 84+/-55 months. LFP at presentation was 6.34 ± 2.94 ph/ms. None of four patients with prolonged treatment and prolonged follow-up showed disease activity. One patient still under therapy after 4 months' follow-up still showed an active neovascular membrane.
Treatment with multiple immunosuppressive agents was shown to stop the progression of the disease."
"Therapeutic antibodies and Fc-conjugates are becoming increasingly popular for disease management and accurate and sensitive pharmacokinetic measurements are critical in lead candidate selection in pre-clinical drug discovery.
Human Fc-specific intact monoclonal antibodies, polyclonal antibodies, Fab fragments, aptamers, affibodies and nanobodies were screened for potential as biotinylated capture moieties in a microfluidic assay. Test compounds were Bevacizumab, Rituximab, Infliximab as well as an in-house IgG1.1 and an IgG1-drug conjugate.
Capture molecules were tested for specificity in plasma matrices from beagle dog, rat, mouse, pig, rhesus monkey and cynomolgus monkey. We find that the llama nanobody provides the best selectivity across across species. The assay usability were verified in cynomolgus monkey pharmacokinetic studies of in-house IgG1.1 and IgG1-fusion molecules.
The presented generic nanobody-based assay may find relevance in preclinical testing of future human Fc-containing drug conjugates devoid of Fab fragments and intact monoclonal antibodies."
"Although most of the progressive multifocal leukoencephalopathy cases in sarcoidosis patients are explained by the treatment with immunosuppressive drugs, it is also reported in treatment-naive sarcoidosis patients, which implies a general predisposition of sarcoidosis patients for progressive multifocal leukoencephalopathy. Indeed, it was shown that active sarcoidosis patients have increased regulatory T cell frequencies which could lead to a subsequent systemic immunosuppression. However, if sarcoidosis with systemic changes of T cell subsets frequencies constitute a risk factor for the development of progressive multifocal leukoencephalopathy, which could then be counteracted by sarcoidosis treatment, is not known. In this cohort study, we included, characterized and followed-up six patients with bioptically confirmed definite progressive multifocal leukoencephalopathy and definite or probable sarcoidosis presenting between April 2013 and January 2019, four of them had no immunosuppressive therapy at the time of developing first progressive multifocal leukoencephalopathy symptoms. Analysis of immune cell subsets in these patients revealed significant imbalances of CD4"
"Infliximab (IFX) is an effective medication for ulcerative colitis (UC) patients. However, one-third of UC patients show primary non-response (PNR) to IFX. Our study analyzed three Gene Expression Omnibus (GEO) datasets and used the RobustRankAggreg (RRA) algorithm to assist in identifying differentially expressed genes (DEGs) between IFX responders and non-responders. Then, an artificial intelligence (AI) technology, artificial neural network (ANN) analysis, was applied to validate the predictive value of the selected genes. The results showed that the combination of "
"Inflammatory bowel diseases (IBDs) are global health problems that are associated with immune regulation, but clinical IBDs treatment is currently inadequate. Effective preventive or therapeutic methods for immune disorders rely on controlling the function of immune cells. Isosteviol sodium (STV-Na) has antioxidant activity, but the therapeutic effect of STV-Na against IBD remain undocumented. Herein, we investigated the therapeutic effect of STV-Na in mice models with IBDs.
Mice received 3.5% DSS for 7 days to establish IBD models. Intraperitoneal STV-Na was given 2 days before DSS and lasted for 9 days. Commercially available drugs used in treating IBDs (5-aminosalicylic acid, dexamethasone, and infliximab) were used as positive controls. Samples were collected 7 days after colitis induction. Histopathological score, biochemical parameters, molecular biology methods, and metabolomics were used for evaluating the therapeutic effect of STV-Na.
Our data revealed that STV-Na could significantly alleviate colon inflammation in mice with colitis. Specifically, STV-Na treatment improved body weight loss, increased colon length, decreased histology scores, and restored the hematological parameters of mice with colitis. The untargeted metabolomics analysis revealed that metabolic profiles were restored by STV-Na treatment. Furthermore, STV-Na therapy suppressed the number of CD68 macrophages and F4/80 cell infiltration. And STV-Na suppressed M1 and M2 macrophage numbers along with the mRNA expressions of proinflammatory cytokines. Moreover, STV-Na administration increased the number of regulatory T (Treg) cells while decreasing Th1/Th2/Th17 cell counts in the spleen. Additionally, STV-Na treatment restored intestinal barrier disruption in DSS-triggered colitis tissues by ameliorating the TJ proteins, increasing goblet cell proportions, and mucin protein production, and decreasing the permeability to FITC-dextran, which was accompanied by decreased plasma LPS and DAO contents.
These results indicate that STV-Na can ameliorate colitis by modulating immune responses along with metabolic reprogramming, and could therefore be a promising therapeutic strategy for IBDs."
"The coronavirus disease 2019 (COVID-19) pandemic has prompted significant changes in patient care in rheumatology and gastroenterology, with clinical guidance issued to manage ongoing therapy while minimising the risk of nosocomial infection for patients and healthcare professionals (HCPs). Subcutaneous (SC) formulations of biologics enable patients to self-administer treatments at home; however, switching between agents may be undesirable. CT-P13 SC is the first SC formulation of infliximab that received regulatory approval and may be termed a biobetter as it offers significant clinical advantages over intravenous (IV) infliximab, including improved pharmacokinetics and a convenient mode of delivery. Potential benefits in terms of reduced immunogenicity have also been suggested. With a new SC formulation, infliximab provides an additional option for dual formulation, which enables patients to transition from IV to SC administration route without changing agent. Before COVID-19, clinical trials supported the efficacy and safety of switching from IV to SC infliximab for patients with rheumatoid arthritis and inflammatory bowel disease (IBD), and SC infliximab may have been selected on the basis of patient and HCP preferences for SC agents. During the pandemic, patients with rheumatic diseases and IBD have successfully switched from IV to SC infliximab, with some clinical benefits and high levels of patient satisfaction. As patients switched to SC therapeutics, the reduction in resource requirements for IV infusion services may have been particularly welcome given the pandemic, facilitating reorganisation and redeployment in overstretched healthcare systems, alongside pharmacoeconomic benefits and a reduction in exposure to nosocomial infection. Telemedicine and contactless healthcare have been pushed to the forefront during the pandemic, and a lasting shift towards remote patient management and community/home-based drug administration is anticipated. SC infliximab supports the implementation of this paradigm for future improvements of healthcare value delivered. The accumulation of real-world data during the pandemic supports the high level of confidence, with patients, physicians, and healthcare systems benefitting from its uptake."
"Proactively monitoring infliximab levels is an emerging area of interest in pediatric Crohn's disease. There are only limited data on therapeutic drug monitoring for children with Crohn's disease. The goal of our study was to determine the utility of therapeutic drug monitoring in achieving clinical remission in a cohort of pediatric Crohn's disease patients receiving infliximab.
This prospective single-center study enrolled 37 patients with Crohn's disease at the start of infliximab infusions and monitored trough levels at 6-month intervals for 18 months. Each participant was matched to a historic control for the modified pediatric Crohn's disease activity index (mPCDAI) at baseline, age and sex. The primary outcome was an mPCDAI score of ≤7.5 at 6, 12 and 18 months. A multivariate logistic regression analysis was performed.
Data were available for all 37 cases at 6 and 12 months and for 34 cases at 18 months. Demographics and disease characteristics were similar between groups. All 34 cases demonstrated clinical remission at 18 months (100% vs. 88%, P=0.114). Univariate and multivariate analyses did not show statistical significance. Dose intensification was seen more often in the cases at 18 months.
All of our moderate-to-severe pediatric Crohn's disease patients who received prospective therapeutic drug monitoring of infliximab were in clinical remission at follow up, but this was not statistically significantly different from the 88% clinical remission rate of the control group."
"To report the efficacy of anti-tumor necrosis factor α (anti-TNFα) on autoimmune-mediated macular cone dysfunction in a Japanese woman with ulcerative colitis (UC).
A 41-year-old woman presented with bilateral visual acuity loss and photophobia. She suffered from UC, and had been treated with prednisolone and 5-aminosalicylate since age 37. Although fundus photographs and optic coherence tomography images were unremarkable, electroretinograms (ERGs) were abnormal. A full-field electroretinogram (full-field ERG) revealed mildly decreased cone responses and oscillatory potential responses bilaterally. Importantly, focal-macular ERG (fmERG) and a multifocal electroretinogram (mfERG) revealed severe macular cone dysfunction in both eyes. Infliximab, a chimeric monoclonal anti-TNFα antibody, was administrated to treat recurrent abdominal symptoms and continued at 8-week intervals. Almost 6 months after infliximab therapy, the mfERG response (especially in the central retina), the fmERG response, and visual acuity recovered bilaterally. Abdominal symptoms also improved after infliximab therapy.
Bilateral cone dysfunction with normal fundus were observed in a UC patient, resulting in loss of visual acuity and photophobia. This retinopathy may have been caused by an autoimmune mechanism, such as an autoimmune retinopathy or acute zonal occult outer retinopathy, which is most identifiable by ERG changes. This is the first report demonstrating the efficacy of infliximab in autoimmune retinal dysfunction."
"The management of patients with acute severe ulcerative colitis and SARS-CoV-2 presents a clinical challenge. We report on the first case of a patient with acute severe ulcerative colitis and mild coronavirus disease 2019 (COVID-19) who received rescue infliximab therapy, followed by a relapse caused by enterohemorrhagic Escherichia coli 0157:H7. The treatment challenges we faced were biologic therapy administration during active COVID-19, about which little was known at the time, and how to treat EHEC due to the risk of hemolytic uremic syndrome. Acute severe ulcerative colitis was treated with rescue infliximab therapy, and enteric infection with an antibiotic, both with satisfactory clinical response. The decision to induce biologic therapy for inflammatory bowel disease relapse in SARS-CoV-2-positive patients should be made on a case-to-case basis and should be driven by the dominant disease. Our patient tested positive for SARS-CoV-2, but actually had mild disease. At the same time, she had acute severe ulcerative colitis, so we started anti-tumor necrosis factor therapy despite serological tests and the recommendation to delay biological therapy administration for two-weeks. Second, due to severity of the first flare, COVID-19, and the patient's general condition, we opted for an antibiotic treatment of Escherichia coli 0157:H7 while monitoring the parameters of potential hemolytic uremic syndrome development."
"Accelerated infliximab (IFX) induction is often based on clinical parameters as opposed to pharmacokinetics (PK). We aimed to investigate the impact of dashboard-guided optimized induction dosing on IFX durability and immunogenicity in a real-world inflammatory bowel disease (IBD) setting.
Pediatric and adult IBD patients were enrolled in a prospective single arm intervention trial. Cumulative data from each infusion (INF), weight, albumin, C-reactive protein, IFX dose, IFX trough level, and antidrug antibody presence were used to inform subsequent INF dosing. Forecasts driven by adaptive Bayesian modeling were generated to maintain trough levels for the third (INF3) and fourth (INF4) infusions of 17 μg/mL and 10 μg/mL, respectively. The primary outcome was proportion of patients prescribed accelerated dosing (AD) intervals by INF3 (<22 days) or INF4 (<49 days). Secondary outcomes included week 52 clinical and PK outcomes. Multivariate analyses and Kaplan-Meier curves compared outcomes based on adherence to dashboard forecasts.
Of the 180 per-protocol population, AD was forecast for 41% (INF3) and 69% (INF4) of patients with median intervals of 17 (INF3) and 39 (INF4) days. Baseline age >18 years, albumin >3.5 g/L, and 10-mg/kg dose were independently associated with lower rates of AD by INF4. Nonadherence with the INF4 forecast (n = 39) was an independent predictor of antidrug antibody (P < .0001) and IFX discontinuation (P = .0006). A total of 119 of 123 patients on IFX at week 52 were in steroid-free remission.
The application of a PK dashboard during induction can optimize dosing early to improve IFX durability and immunogenicity.
We present the first proactive infliximab optimization study during induction guided by a pharmacokinetics dashboard in a real-world inflammatory bowel disease setting. At 1 year, clinical outcomes were impacted significantly by the timing of the first maintenance infusion."
"Disseminated histoplasmosis (DH) is typically seen in patients with organ transplantation or human immunodeficiency virus and rarely presents with acute liver failure. Tumor necrosis factor inhibitors may be immunosuppressive but unlikely to result in DH. A 70-year-old woman with a history of psoriatic arthritis on infliximab presented with altered mental status, fevers, and severe liver injury. She was found to have DH, which resolved on antifungal agents. Because the use of tumor necrosis factor inhibitors has increased, providers should consider this uncommon infection in patients who present with cryptogenic severe liver injury."
"Limited data are available on biological therapy de-escalation after prior escalation in inflammatory bowel disease (IBD) patients. This study aimed to assess the frequency and success rate of de-escalation of biological therapy in IBD patients after prior dose escalation and to evaluate which measures are used to guide de-escalation.
This multicentre retrospective cohort study enrolled IBD patients treated with infliximab (IFX), adalimumab (ADA) or vedolizumab (VEDO) in whom therapy was de-escalated after prior biological escalation. De-escalations were considered pharmacokinetic-driven if based on clinical symptoms combined with therapeutic or supratherapeutic trough levels, and disease activity-driven if based on faecal calprotectin less than or equal to 200 µg/g or resolution of perianal fistula drainage or closure or endoscopic remission. Successful de-escalation was defined as remaining on the same or lower biological dose for greater than or equal to 6 months after de-escalation without the need for corticosteroids.
In total, 206 IFX users, 85 ADA users and 55 VEDO users underwent therapy escalation. Of these patients, 34 (17%) on IFX, 18 (21%) on ADA and 8 (15%) on VEDO underwent therapy de-escalation. De-escalation was successful in 88% of IFX patients, 89% of ADA and 100% of VEDO. The probability of remaining on the de-escalated regimen or further de-escalation after 1 year was 85% for IFX, 62% for ADA and 100% for VEDO. Disease activity-driven de-escalations were more often successful (97%) than pharmacokinetic- and no marker-driven de-escalations (76%); P = 0.017.
De-escalation after biological dose escalation was successful in the majority of carefully selected IBD patients. Objective assessment of remission increased the likelihood of successful de-escalation."
"A 26-year-old woman under immunosuppression with infliximab due to Crohn's disease was referred to the gynaecology emergency room with dispersed and coalescing vesicular lesions on the vulvar region extending to the right lower limb involving S2-S3 dermatome, associated with severe pain. Clinical history, physical examination and serological testing was consistent with herpes zoster infection. The patient was treated with valaciclovir for 14 days and cefradine for 7 days (due to the possibility of secondary bacterial infection). Significant symptomatic improvement was noted after 1 week. The 1-year follow-up was unremarkable. According to our knowledge and review of the literature, this is one of the few cases reported of vulvar herpes zoster, especially related to infliximab."
"Between 20% and 40% of patients with severe ulcerative colitis (UC) are either steroid-refractory UC (SRUC) or steroid-dependent UC (SDUC). Tacrolimus is an oral and relatively inexpensive drug, which has been extensively used in Japan for steroid-refractory and steroid-dependent disease.
Patients diagnosed with SDUC/SRUC were treated with tacrolimus 0.05-0.1 mg/kg in this prospective study. Clinical Mayo score (CMS) and UC Endoscopic Index of Severity (UCEIS) were evaluated prior to starting the drug and subsequently after 8 weeks. 5-Aminosalicylic acid agents (5-ASA) and immunomodulators were continued if the patients were previously on these drugs. Clinical response at 8 weeks was defined as decrease in CMS by at least 3 points. Clinical remission was defined as CMS ≤2 and combined remission as CMS≤2 with UCEIS <3.
Fifty-two patients (29 males) with a mean age of 35.1± 12.8 years with predominantly E3 disease (71%) were prospectively evaluated in this study. SDUC and SRUC were diagnosed in 31 and 21 patients, respectively. Seven failed treatment within 8 weeks, four were subjected to surgery, and 3 were switched to infliximab. Forty-two patients continued tacrolimus for 8 weeks. Mean CMS and UCEIS prior to starting tacrolimus were 6 ± 1.1 and 4.8 ± 1.1, respectively. At 8 weeks, median CMS and UCEIS decreased to 2.6 ± 1.7 and 2.7 ± 1.3, respectively. Clinical response was documented in 29 patients (56%) at week 8 whereas clinical remission was seen in 25 patients (48%). Combined clinical and endoscopic remissions were seen in 18 patients (35%). Except for a single  patient who developed reversible renal dysfunction, no other adverse event was  observed.
Our results show that tacrolimus is effective in inducing a clinical response in 56% of patients with SDUC and SRUC. In view of its low cost and safety profile, it may be considered first-line therapy for SDUC/SRUC."
Acute severe ulcerative colitis (ASUC) is a medical emergency which is associated with significant morbidity and a mortality rate of 1%. ASUC requires prompt recognition and treatment. Optimal management includes admission to a specialist gastrointestinal unit and joint management with colorectal surgeons. Patients need to be screened for concomitant infections and thromboprophylaxis should be administered to mitigate against the elevated risk of thromboembolism. Corticosteroids are still the preferred initial medical therapy but approximately 30%-40% of patients fail steroid therapy and require rescue medical therapy with either infliximab or cyclosporine. Emergency colectomy is required in a timely manner for patients who fail rescue medical therapy to minimise the risk of adverse post-operative outcomes. We discuss current and emerging evidence in the management of ASUC and outline management approaches for clinicians involved in managing ASUC.
"The potential use of pan-enteric capsule endoscopy (pan-CE) to evaluate mucosal changes during treatment has not been evaluated. We aimed to assess the ability of pan-CE to measure changes in mucosal disease activity before and after starting biologic treatment in Crohn's disease patients.
In this two-center prospective study, patients with clinical and biochemical signs of active Crohn's disease underwent pan-CE before and 8 to 12 weeks after treatment initiation with infliximab, adalimumab or vedolizumab. Endoscopic disease activity was assessed using the simple endoscopic score for Crohn's disease (SES-CD) and the Crohn's disease endoscopic index of severity (CDEIS), expanded with two segments (i.e., the jejunum and pre-terminal ileum). Occurrence of endoscopic remission (i.e., absence of ulcers) and endoscopic response (i.e., 50% decrease in SES-CD and CDEIS scores compared to baseline) was assessed and the standardized effect size was calculated.
Twenty-two patients (50% females) completed the study. Endoscopic remission was observed in 6 out of 22 (27%) patients and 13/22 patients (59%) showed an endoscopic response for both the SES-CD and CDEIS score. Median SES-CD and CDEIS scores decreased from 16.0 (IQR 10.0 - 24.0) to 6.0 (IQR 2.8 - 12.0, 
Pan-CE was a useful technique to assess changes in mucosal disease activity in Crohn's disease patients."
"The temporal trends in medical treatment and long-term outcomes of patients with Crohn's disease (CD) have not been well elucidated in China over the past 2 decades. Accordingly, we aimed to evaluate the treatment paradigm and long-term clinical course of Chinese patients with CD in a hospital-based cohort.
All adult patients newly diagnosed with CD (n = 1338) between 1999 and 2019 in the Sir Run Run Shaw Hospital were included in this cohort. Medication utilization, disease outcomes, and risk factors were investigated.
Overall, 48.7%, 35.6%, 67.8%, and 61.6% of patients used 5-aminosalicylates (5-ASA), corticosteroids, thiopurines, and infliximab (IFX), respectively. The cumulative risk of 5-ASA and corticosteroid initiation decreased during follow-up, whereas that of IFX initiation increased. Throughout a median follow-up duration of 26.4 (interquartile range, 12.0-49.2) months, a total of 486 and 300 patients underwent hospitalization and surgery, respectively. Of the 1097 patients with B1/B2 disease behavior at diagnosis, 10.3% experienced phenotype progression. The hospitalization rate decreased after 2015; however, surgery and phenotype progression rates did not significantly change. A Cox regression analysis indicated that IFX use since diagnosis was a contributing factor for lower rates of hospitalization and phenotype progression, whereas thiopurine use was associated with a lower surgery rate.
Infliximab use was observed to increase as 5-ASA and corticosteroid use decreased. Additionally, hospitalization rates decreased following temporal changes in IFX management, yet the surgery and phenotype progression rates remained the same."
"Carbon tetrachloride (CCl
Twenty-four male Sprague-Dawley rats were assigned into control, CCl
The application of CCl
This study shows that Infliximab ameliorates nephrotoxicity by reducing lipid peroxidation, oxidative stress, and apoptosis in acute kidney damage developing in association with CCl"
"Visceral herpes zoster following reactivation of dormant varicella-zoster virus can rarely occur, usually in highly immunosuppressed patients, and may present with abdominal pain without the relevant rash. In the absence of skin manifestations, diagnosis of visceral herpes zoster is extremely difficult, while computed tomography may reveal isolated periarterial fat stranding. We describe a rare case of visceral herpes zoster in a medically immunocompromised adult with psoriatic arthritis, who presented with acute abdomen, was diagnosed based on computed tomography findings and subsequent serum polymerase chain reaction results, and was appropriately treated with an uneventful recovery. This case underlines the significance of considering varicella-zoster virus infection as a cause of severe abdominal pain even in the absence of rash in this setting, and highlights the potential role of appropriately performed computed tomography in such unusual and complex cases, where early diagnosis and initiation of treatment is extremely important for a favorable outcome."
"The first ECCO-ESPGHAN guidelines for the medical management of pediatric Crohn disease (CD) were published in 2014. Whether their implementation, and the consequent increased use of an upfront anti-tumor necrosis factor therapy, have changed the course of the disease has not been investigated yet. We aimed at comparing the evolution of pediatric CD patients diagnosed and treated before and after 2014.
Single-center retrospective study including all children diagnosed with CD from January 2010 to December 2018. Patients diagnosed between 2010 and 2014 (group 1) were compared to those diagnosed after 2014 (group 2). For each patient, at baseline and every 6-month, number of relapses, the occurrence of complication, therapy received and biological parameters were noted, as well as any endoscopic or radiologic evaluation.
One hundred and fifty-four patients were included in the analysis, 78 (51%) diagnosed after 2014. The cumulative probability of a relapse-free and surgery-free course was significantly higher for patients treated according to the guidelines (log rank hazard ratio [HR] = 1,818, P = 0.003 and HR = 3,15, 95% confidence interval, P = 0.04, respectively). Mucosal healing rate was significantly higher among patients of group 2 at 1 and 2 years (P = 0.04 and P = 0.05, respectively), while no significant difference was observed for transmural healing rates, as well as for the risk of complications.
The implementation of the 2014 CD guidelines appears to have a significant impact on disease outcomes, with a significantly lower risk for relapse and surgery, while no effect could be observed on the risk of developing complications."
"Adamantiades-Behçet's disease (ABD) is a chronic, idiopathic, relapsing immune-mediate disease that may involve multiple organs. It is characterized by recurrent oral and genital ulcers, skin lesions, ocular, gastrointestinal, vascular, neurological and joint involvement. It can lead to significant morbidity and mortality. Due to its heterogeneity in clinical findings and physiopathology, its treatment can be various as ABD manifestations in different organs may differently respond to the same drug. The cornerstone of therapy for inducing remission is systemic corticosteroid, whereas immunomodulatory and immunosuppressive agents such as colchicine, azathioprine, cyclosporine-A, interferon-alpha, and cyclophosphamide are used as steroid-sparing agents and to prevent relapses. For aggressive, refractory or frequently relapsing cases, tumor necrosis factor (TNF) alpha inhibitors (infliximab, adalimumab, etanercept) have been reported beneficial. Herein, we describe our experience of 7 patients treated with TNF-alpha inhibitors with recommendations regarding treatment choice during the COVID-19 era."
"Coronavirus disease 2019 (COVID-19) remains a global threat to humanity. Its pathogenesis and different phases of disease progression are being elucidated under the pandemic. Active viral replication activates various immune cells and produces large amounts of inflammatory cytokines, which leads to the cytokine storm, a major cause of patient death. Therefore, viral inhibition is expected to be the most effective early in the course of the disease, while immunosuppressive treatment may be useful in the later stages to prevent disease progression. Based on the pathophysiology of rheumatic diseases, various immunomodulatory and immunosuppressive drugs are used for the diseases. Due to their mechanism of action, the antirheumatic drugs, including hydroxychloroquine, chloroquine, colchicine, calcineurin inhibitors (e.g., cyclosporine A and tacrolimus), glucocorticoids, cytokines inhibitors, such as anti-tumor necrosis factor-α (e.g., infliximab), anti-interleukin (IL)-6 (e.g., tocilizumab, sarilumab, and siltuximab), anti-IL-1 (e.g., anakinra and canakinumab) and Janus kinase inhibitors (e.g., baricitinib and tofacitinib), cytotoxic T lymphocyte-associated antigen 4 blockade agents (e.g., abatacept), and phosphodiesterase 4 inhibitors (e.g., apremilast), have been tried as a treatment for COVID-19. In this review, we discuss the mechanisms of action and clinical impact of these agents in the management of COVID-19."
"Infliximab (IFX) is increasingly being used for the treatment of severe manifestations of Behçet's syndrome (BS). However, emergence of new manifestations has also been occasionally reported during IFX treatment. We aimed to assess the frequency of new manifestations in our BS patients treated with IFX.
A chart review was conducted to identify all BS patients treated with IFX in our clinic between 2004 and 2020. Demographic data, indications for IFX initiation, concomitant treatments and outcomes were recorded. A new manifestation was defined as the emergence of a new organ involvement or mucocutaneous manifestation developing for the first time during IFX treatment or within 12 weeks after the last infusion of IFX.
Among our 282 patients who used IFX, 19 (7%) patients had developed a total of 23 new manifestations during a mean follow-up of 20.0 (15.3) months. Patients with vascular involvement were more likely to develop a new manifestation (12/19, 63%). Initial manifestations that required IFX were in remission at the time of new manifestation in 14/19 patients. IFX treatment was intensified (n = 6) and/or glucocorticoids, immunosuppressives or colchicine was added to IFX (n = 21). IFX was switched to another agent for the remaining manifestations (n = 8). These treatment modifications led to remission in 17/19 patients.
New manifestations developed during IFX treatment in 7% of our patients with BS. They could be managed by intensifying IFX treatment or adding other agents in the majority of these manifestations."
"Approximately 30% of patients with rheumatoid arthritis (RA) respond poorly to combination therapy of multiple drugs. The molecular mechanisms of different responses to methotrexate + leflunomide + infliximab therapy in patients with RA were explored in this study.
Infliximab was administered to patients with RA whose disease activity score was higher than 5.1 after 1 month of combination therapy with methotrexate and leflunomide. After 14 weeks of undergoing triple therapy, patients with RA were classified as responders and non-responders. Protein profiles at baseline and 14th week were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and proteins with significant differences ≥1.2 folds change or ≤0.8 folds change were defined as differentially expressed proteins (DEPs). Overlapping DEPs between responders and non-responders were confirmed by parallel reaction monitoring (PRM). Bioinformatic analyses were performed for DEPs.
The results revealed 5 non-responders (NRs) and 15 responders (Rs). iTRAQ analysis indicated 13 overlapping DEPs and included 6 opposite change DEPs such as testicular tissue protein Li 70, cofilin 1, fibrinogen beta chain, galectin-10, serotransferrin (TF) and albumin. The difference in serotransferrin between responders and non-responders confirmed by PRM was significant. Verification by PRM indicated that TF was elevated in the Rs group and was reduced in the NRs group. Bioinformatic analysis indicated that serotransferrin was involved in the hypoxia-inducible factor-1 pathway and ferroptosis.
Serotransferrin-related molecular mechanism may be a new direction to study refractory RA."
"Up to 60% of inflammatory bowel disease (IBD) patients treated with infliximab develop antibodies to infliximab (ATI), which are associated with low drug levels and loss of response (LOR). Hence, mapping out predictors of immunogenicity toward infliximab is essential for tailoring patient-specific therapy. Jewish Sephardi ethnicity, in addition to monotherapy, has been previously identified as a potential risk factor for ATI formation and infliximab failure.
To explore the association between Jewish sub-group ethnicity among patients with IBD and the risk of infliximab immunogenicity and therapy failure. To confirm findings of a previous cohort that addressed the same question.
This retrospective cohort study included all infliximab-treated patients of Jewish ethnicity with regular prospective measurements of infliximab trough levels and ATI. Drug and ATI levels were prospectively measured, clinical data was retrieved from medical charts.
The study comprised 109 Jewish patients (54 Ashkenazi, 55 Sephardi) treated with infliximab. There was no statistically significant difference in proportion of ATI between Sephardi and Ashkenazi patients with IBD (32% Ashkenazi and 33% Sephardi patients developed ATI, odds ratio [OR] 0.944, P = 0.9). Of all variables explored, monotherapy and older age were the only factors associated with ATI formation (OR 0.336, 95% confidence interval 0.145-0.778, P = 0.01, median 34 vs. 28, interquartile range 28-48, 23-35 years, P = 0.02, respectively).
Contrary to previous findings, Sephardi Jewish ethnicity was not identified as a risk factor for ATI formation compared with Ashkenazi Jewish ethnicity. Other risk factors remained unchanged."
"To determine the safety, pharmacokinetics, and immunomodulatory effects of 2-6 weeks of anakinra therapy in patients with acute Kawasaki disease with a coronary artery aneurysm (CAA).
We performed a Phase I/IIa dose-escalation study of anakinra (2-11 mg/kg/day) in 22 patients with acute Kawasaki disease with CAA. We measured interleukin (IL)-1RA concentrations after the first dose and trough levels up to study week 6. Markers of inflammation and coronary artery z-scores were assessed pretreatment and at 48 hours, 2 weeks, and 6 weeks after initiation of therapy.
Up to 6 weeks of anakinra (up to 11 mg/kg/day) was safe and well tolerated by the 22 participants (median age, 1.1 years), with no serious adverse events attributable to the study drug. All participants were treated with intravenous immunoglobulin (IVIG), and 20 also received infliximab (10 mg/kg) before initiation of anakinra. Serum levels of IL-6, IL-8, and tumor necrosis factor α decreased similarly in patients with Kawasaki disease treated with IVIG, infliximab, and anakinra compared with age- and sex-matched patients with Kawasaki disease treated only with IVIG and infliximab. Anakinra clearance increased with illness day at diagnosis. Simulations demonstrated that more frequent intravenous (IV) dosing may result in more sustained concentrations without significantly increasing the peak concentration compared with subcutaneous (SC) dosing.
Both IV and SC anakinra are safe in infants and children with acute Kawasaki disease and CAA. IV dosing every 8-12 hours during the acute hospitalization of patients with Kawasaki disease may result in a sustained concentration while avoiding frequent SC injections. The efficacy of a short course of IV therapy during hospitalization should be studied. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT02179853."
"Knowledge of the levels of anti-TNFa drugs can modify treatment in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA).
To compare the levels of anti-TNFa in patients with RA vs SpA, in different clinical situations.
A retrospective, observational study was conducted. Levels of anti-TNFa and the presence of anti-drug antibodies were measured in consecutively selected patients, using the ELISA technique.
Fifty-three, 73 and 78 patients treated with infliximab, adalimumab and etanercept were studied, respectively. The median drug levels in patients using standard doses were infliximab 2.2 µg/mL (1.4-5.2), adalimumab 4.9 µg/mL (0.8-8.9) and etanercept 3.1 µg/mL (2.3-4.4). There were no differences in drug levels according to disease activity but we found differences in etanercept and infliximab levels according to DMARD use.
Levels of anti-TNFa drugs will change with DMARD treatment."
"Burn injury remains a serious cause of morbidity and mortality worldwide. Severity of burns is determined by the percentage of burned area compared to the body surface area, age of patient, and by the depth of skin and soft tissue involvement; these factors determine management as well as prospective outcomes. The pathophysiology of partial- to full-thickness burn conversion remains poorly understood and is associated with a worse overall prognosis. Recent studies have demonstrated that an altered inflammatory response may play a significant role in this conversion and therefore a reduction in early inflammation is crucial to ultimately decreasing burn severity and morbidity. We hypothesize that the application of a microcapillary gelatin-alginate hydrogel loaded with anti-TNF-α (infliximab) monoclonal antibodies to a partial-thickness burn will reduce inflammation within partially burned skin and prevent further progression to a full-thickness burn.
Assembly of the microfluidic hydrogels is achieved by embedding microfibers within a hydrogel scaffold composed of a gelatin-alginate blend, which is then soaked in a solution containing anti-TNF-α antibodies for drug loading. 12 young (2-4 months) and 12 old (>16 months) mice were given partial thickness burns. The treatment cohort received the anti-TNF-α infused hydrogel with an occlusive dressing and the control cohort only received an occlusive dressing. Mice were euthanized at post-burn day 3 and skin samples were taken. Burn depth was evaluated using Vimentin immunostaining.
All mice in the treatment cohort demonstrated decreased conversion of burn from partial to full thickness injury (old = p < 0.01, young = p < 0.001) as compared to the control group. Old mice had greater depth of burn than young mice (p < 0.001). There were greater eosinophils in the treatment cohort for both young and old mice, but it did not reach statistical significance.
The application of a novel microcapillary gelatin-alginate hydrogel infused with anti-TNF-α antibody to partial thickness burns in mice showed reduction in partial to full thickness burn secondary progression as compared to controls using this murine model; this promising finding might help decrease the high morbidity and mortality associated with burn injuries."
"Dendritic cells (DC) are heterogeneous cell populations essential for both inducing immunity and maintaining immune tolerance. Chronic inflammatory contexts, such as found in rheumatoid arthritis (RA), severely affect the distribution and the function of DC, contributing to defective tolerance and fueling inflammation. In RA, the synovial fluid of patients is enriched by a subset of DC that derive from monocytes (Mo-DC), which promote deleterious Th17 responses. The characterization of environmental factors in the joint that impact on the development and the fate of human Mo-DC is therefore of great importance in RA. When monocytes leave the blood and infiltrate inflamed synovial tissues, the process of differentiation into Mo-DC can be influenced by interactions with soluble factors such as cytokines, local acidosis and dysregulated synoviocytes. Other molecular factors, such as the citrullination process, can also enhance osteoclast differentiation from Mo-DC, favoring bone damages in RA. Conversely, biotherapies used to control inflammation in RA, modulate also the process of monocyte differentiation into DC. The identification of the environmental mediators that control the differentiation of Mo-DC, as well as the underlying molecular signaling pathways, could constitute a major breakthrough for the development of new therapies in RA."
"A meta-analysis of publicly available transcriptomic datasets was performed to identify metabolic pathways profoundly implicated in the progression and treatment of inflammatory bowel disease (IBD). The analysis revealed that genes involved in tryptophan (Trp) metabolism are upregulated in Crohn's disease (CD) and ulcerative colitis (UC) and return to baseline after successful treatment with infliximab. Microarray and mRNAseq profiles from multiple experiments confirmed that enzymes responsible for Trp degradation via the kynurenine pathway (IDO1, KYNU, IL4I1, KMO, and TDO2), receptor of Trp metabolites (HCAR3), and enzymes catalyzing NAD"
"The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC "
"Inflammatory Bowel Disease (IBD) comprises a group of disorders, in particular Crohn's disease (CD) and ulcerative colitis (UC), characterized by chronic inflammation affecting the gastrointestinal tract. The treatment of these conditions is primarily based on anti-inflammatory drugs, although the use of biological drugs with lower side effects quickly increased in the last decade. However, the presence of certain polymorphisms in the population may determine a different outcome in response to therapy, reflecting the heterogeneity of the efficacy in patients. Considering that several studies showed important correlations between genetic polymorphisms and response to biological treatments in IBD patients, this systematic review aims to summarize the pharmacogenetics of biologicals approved for IBD, thus highlighting a possible association between some polymorphisms and drug response. With this purpose, we reviewed PubMed papers published over the past 21 years (2000-2021), using as the search term ""drug name and IBD or CD or UC and polymorphisms"" to underline the role of pharmacogenetic tests in approaching the disease with a targeted therapy."
"Heightened inflammatory bowel disease (IBD) activity during pregnancy is associated with higher rates of preterm birth, miscarriage, and low birth weight. Therefore, its adequate treatment is essential, considering the risk-benefit of medication use. Although previous literature has described the management of IBD during pregnancy, few studies have assessed the pharmacokinetics of IBD drugs in the newborn. In this case report, we describe the management of ulcerative colitis during pregnancy and discuss the benefits of checking serum levels of infliximab in newborns exposed to the medication during pregnancy.
A 37-year-old patient with ulcerative colitis in clinical and endoscopic remission had been undergoing treated with infliximab since 2008. The patient became pregnant in 2018.
Infliximab medication was discontinued at the 29th week of pregnancy.
The pregnancy was uneventful, and the levels of infliximab in the umbilical cord were >20 μg/dL. Live vaccinations were postponed until the baby was 6 months old, when a new serum drug level proved to be undetectable.
Our case suggests that the use of infliximab is safe in pregnancy, and drug discontinuation could be considered from the 24th week of pregnancy onward to reduce placental transfer to the newborn in patients at low risk of relapse. Vaccines with live attenuated organisms should be delayed for at least 6 months or until the serum level of the medication is undetectable."
"Biological therapies and small molecules continue to be evaluated in moderate to severely active ulcerative colitis, but are often studied in placebo-controlled trials, meaning their relative efficacy and safety is unknown. We examined this in a network meta-analysis.
We searched the literature to October 2021 to identify eligible trials. We judged efficacy using clinical remission, endoscopic improvement, or clinical response, and according to previous exposure or non-exposure to antitumour necrosis factor (TNF)-α therapy. We also assessed safety. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs. Interventions were ranked according to their P-score.
We identified 28 trials (12 504 patients). Based on failure to achieve clinical remission, upadacitinib 45 mg once daily ranked first versus placebo (RR 0.73; 95% CI 0.68 to 0.80, P-score 0.98), with infliximab 5 mg/kg and 10 mg/kg second and third, respectively. Upadacitinib ranked first for clinical remission in both patients naïve to anti-TNF-α drugs (RR 0.69; 95% CI 0.61 to 0.78, P-score 0.99) and previously exposed (RR 0.78; 95% CI 0.72 to 0.85, P-score 0.99). Upadacitinib was superior to almost all other drugs in these analyses. Based on failure to achieve endoscopic improvement infliximab 10 mg/kg ranked first (RR 0.61; 95% CI 0.51 to 0.72, P-score 0.97), with upadacitinib 45 mg once daily, second, and infliximab 5 mg/kg third. Upadacitinib was more likely to lead to adverse events, but serious adverse events were no more frequent, and withdrawals due to adverse events were significantly lower than with placebo. Infections were significantly more likely with tofacitinib than placebo (RR 1.41; 95% CI 1.03 to 1.91).
In a network meta-analysis, upadacitinib 45 mg once daily ranked first for clinical remission in all patients, patients naïve to anti-TNF-α drugs and patients previously exposed. Infliximab 10 mg/kg ranked first for endoscopic improvement. Most drugs were safe and well tolerated."
"Antibodies to infliximab (ATI) are associated with secondary loss of response and increased risk for drug reactions. Limited studies have associated ATI with increased infliximab clearance.
We assessed the impact of ATI on infliximab clearance and loss of response in an inception paediatric Crohn's disease cohort with 1-year follow-up.
This multi-centre prospective cohort study collected peak and trough serum infliximab/ATI concentrations from 660 infusions (78 patients) during the first year of therapy. Clinicians were blinded to these research labs. The primary outcome was the difference in infliximab clearance between ATI-positive (ATI) and ATI-negative (no-ATI) patients. Secondary outcomes included pre-treatment predictors of ATI (including HLA-DQA1 genotyping). Clinical remission, loss of response and infliximab clearance were compared between pre-ATI, during ATI and following ATI resolution with MANOVA. Time to ATI was calculated by Cox proportional Hazards model.
ATI were detected in 68% (53/78) patients with a median concentration of 76 ng/mL (range 23-1828). Maximum ATI concentration was <200 ng/mL in 73.6% (39/53). Median clearance in ATI patients was higher (with higher clearance if loss of response), compared to no-ATI patients (P < 0.001). Neutrophil CD64 ratio >6 and starting dose <7.5 mg/kg independently predicted ATI in multivariable regression, while HLA-DQA1*05 presence did not. Dose adjustment resolved ATI in 37.5% (12/32) patients with concomitant infliximab concentration and clearance recovery. A maximum ATI level of ≤99 ng/mL predicted ATI resolution (area under the receiver operating curve 0.80 [95% CI 0.64-0.96]).
In this real-world cohort, ATI as low as 23 ng/mL impacted drug clearance. Our data suggest that dose optimisation for low-level ATI can improve infliximab clearance and prevent loss of response."
"This retrospective cohort study aimed to find out predictors and early biomarkers of Infliximab (IFX) refractory intestinal Behçet's syndrome (intestinal BS).
We collected the baseline clinical characteristics, laboratory parameters, and concomitant therapies of intestinal BS patients treated by IFX from the Shanghai Behçet's syndrome database. After 1 year IFX therapy, intestinal BS patients with non-mucosal healing (NMH, intestinal ulcers detected by colonoscopy) and/or no clinical remission [NCR, scores of the disease activity index for intestinal Behçet's disease (DAIBD) ≥20] were defined as IFX refractory intestinal BS. Multivariate logistic regression analysis was performed to evaluate the predictors for NMH and NCR in IFX refractory intestinal BS.
In 85 intestinal BS patients, NMH was identified in 29 (34.12%) patients, and NCR was confirmed in 20 (23.53%) patients. Erythrocyte sedimentation rate (ESR; ≥24 mm/h) and free triiodothyronine (fT3; ≤3.3pmol/L) were the independent risk factors of NMH in IFX refractory intestinal BS. Drinking alcohol and the fT3/free thyroxine ratio (fT3/fT4; ≤0.24) were independent risk factors, and thalidomide was an independent protective factor, for NCR in intestinal BS patients treated by IFX.
This study may be applicable for adjusting the therapeutic strategy and sidestepping unnecessary exposure to IFX in intestinal BS patients. Routine assessments of ESR, fT3, and fT3/fT4 ratio are helpful to identify high-risk individuals of IFX refractory intestinal BS. Thalidomide is suggested to be a concomitant therapy with IFX for intestinal BS patients."
"Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy.
To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM.
Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020.
Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230).
The primary outcome was sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period.
Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6% (95% CI, 9.0%-26.2%; P < .001) favoring TDM. Adverse events were reported in 137 patients (60%) and 142 patients (63%) in the TDM and standard therapy groups, respectively.
Among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, proactive TDM was more effective than treatment without TDM in sustaining disease control without disease worsening. Further research is needed to compare proactive TDM with reactive TDM, to assess the effects on long-term disease complications, and to evaluate the cost-effectiveness of this approach.
ClinicalTrials.gov Identifier: NCT03074656."
"The consequences of cytokine-specific immune modulation in the development and course of Kaposi's sarcoma (KS) are poorly understood. A retrospective chart review of patients treated with biologic/small molecule drugs and followed at the dedicated KS outpatient service of our Dermatology Unit was performed. The literature on biologic and small molecule drug use in KS patients was also reviewed. Data concerning 12 KS patients treated with biologic/small molecule drugs were collected. After a median delay of 6 months following biologic or small molecule drug introduction, nine patients experienced either KS onset or reactivation. Drugs associated with KS onset or flaring were: rituximab, infliximab, ruxolitinib apremilast (1), mirikizumab, abatacept (1). After a median follow-up of 25 months, all cases achieved persistent complete response through culprit drug discontinuation or drug withdrawal plus treatment. No effect on KS course was recorded with tocilizumab and vedolizumab. Based on our experience with the largest case series reported to date as well as the available literature, tocilizumab and ustekinumab seem to exert an overall neutral effect on KS. On the other hand, rituximab, infliximab, and ruxolitinib have been associated with the development or worsening of pre-existing KS and should be carefully pondered before use. Due to limited and partly controversial evidence, no definitive conclusions can be drawn on vedolizumab, apremilast, mirikizumab, abatacept."
"Ménétrier's disease (MD) is a rare gastropathy characterised by giant rugal folds which can present with nausea, vomiting, abdominal pain and protein losing gastropathy. We report a 21-year-old woman with comorbid MD and ulcerative colitis (UC). Management was complicated by limited treatment options for MD, significant symptom burden, worsening nutrition and difficulty determining which disease was the predominant cause of symptoms. Since age 18 the patient experienced recurrent UC flares characterised by diarrhoea, persistent vomiting and corticosteroid dependence. Endoscopic assessment demonstrated concurrent MD and active UC. Octreotide and cetuximab were trialled given persistent hypoalbuminaemia and suspicion for MD associated protein-losing gastropathy. UC management comprised dose-optimised infliximab and methotrexate. Repeat endoscopic assessment demonstrated improvement in UC without corresponding improvement in symptoms or hypoalbuminaemia. Nasojejunal feeding and parenteral nutrition failed to significantly improve nutritional status and accordingly the patient proceeded to radical total gastrectomy. Postoperatively, MD-associated symptoms and hypoalbuminemia resolved completely."
"Inflammatory bowel disease (IBD) is a debilitating chronic disorder that is classified into Crohn's disease, ulcerative colitis, and unspecified which are marked by recurrent gastrointestinal inflammatory episodes. Anti-tumor necrosis agents, especially infliximab, are considered the cornerstone in disease management. However, rare but serious adverse effects related to infliximab have been reported. Limited studies reported cardiac adverse effects as a result of using infliximab in IBD especially in the pediatric age group. Here, we report a case of an 11-year-old boy known to have Crohn's disease, who was on a regular infusion of infliximab at a monthly basis which developed dilated cardiomyopathy with severe depression of myocardial function."
"Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials.
In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903.
Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment-time interactions were -0·09 (95% CI -0·19 to 0·00) for namilumab and 0·06 (-0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group.
Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation-as measured by CRP concentration-in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19.
Medical Research Council."
"To compare treatment retention between biosimilars and their originator products among first starters (etanercept, infliximab, adalimumab and rituximab), as well as after non-medical switch.
Patients with rheumatic diseases starting, for the first time, an originator or biosimilar etanercept, infliximab, adalimumab or rituximab were identified in the national Swedish Rheumatology Quality Register. Moreover, patients switching from an originator to its biosimilar were identified and individually matched to patients continuing on the originator. One-year treatment retention was calculated and hazard ratios (HR) for discontinuation with 95% CIs were estimated, adjusting for comorbidities and socio-economic factors.
In total, 21 443 first treatment courses were identified. The proportion of patients still on the drug at 1 year and the HR for discontinuation revealed no differences across adalimumab (Humira, Imraldi, Amgevita and Hyrimoz) nor across rituximab products (Mabthera, Ritemvia/Truxima and Rixathon). The proportions on the drug at 1 year were similar for Benepali (77%) and Enbrel (75%) and the adjusted HR for Benepali compared with Enbrel was 0.91 (95% CI 0.83, 0.99). For infliximab, the proportion still on the drug at 1 year was 67% for Remicade and 66% for Remsima/Inflectra and the HR compared with Remicade was 1.16 (95% CI 1.02, 1.33). Among 2925 patients switching from an originator drug to one of its biosimilars, we noted no statistically significant or clinically relevant differences in drug survival compared with those who remained on originator therapy.
This large observational study supports the equivalence of biologic DMARD biosimilar products and originators when used in routine rheumatology care."
"Linked Article: Maul et al. Br J Dermatol 2021; 185:1160-1168. Psoriasis is a chronic, scaly skin condition affecting about 2·5% of the population. It has a negative impact on people's quality of life, more so in women. It is usually treated with creams but is sometimes severe enough to need strong medicines, which are not always effective. This study examines differences between men and women in their responses to treatment. The 5346 adult patients were identified from Swiss and German patient registries; 60% were male. The men were heavier than women (average 91 kg versus 78 kg). At the start of treatment men had worse psoriasis whereas women had worse quality of life scores. All received systemic medicines, including non-biologics (methotrexate, fumaric acid esters, ciclosporin, acitretin or apremilast) or biologics (adalimumab, etanercept, infliximab, ustekinumab or secukinumab). They were followed up for up to a year after starting treatment and women showed better improvements on two scales called the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) than men. These results might reflect better drug adherence in women, or their lower bodyweight - where the same dose is used for men and women, women will receive a higher dose per kilogram of body tissue. Also, because of hormonal factors, women's bodies contain a higher proportion of fat, which may allow the drug to spread more easily through the body. Finally, women experience their psoriasis more negatively than men and so there was more room for improvement in DLQI. These findings indicate a need for more personalized treatment, taking gender into account."
"The aim of this post-marketing surveillance (PMS) study is to evaluate the real-world safety and efficacy of CT-P13, the first biosimilar of infliximab (IFX).
Japanese patients with rheumatoid arthritis were prospectively registered from November 2014 and followed up for 1 year.
Of 794 patients in the analysis set, 318 patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) showed an immediate decrease in Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) and increased remission rate (DAS28-CRP < 2.6). In patients who switched from IFX to CT-P13 for non-medical reasons (n = 374), the low DAS28-CRP due to previous IFX treatment decreased further with continued CT-P13 therapy. As in naïve patients, patients who switched from other bDMARDs, mainly for medical reasons (n = 102), responded similarly to CT-P13. CT-P13 in this PMS and IFX in a previous PMS had similar adverse reaction profiles, although the incidence rate in naïve patients in this current PMS was lower due to earlier initiation of CT-P13 therapy.
CT-P13 showed excellent effectiveness as first-line therapy, no clinical difficulties in switching from IFX, and clinical improvement in patients who failed other bDMARDs. CT-P13 could be a cost-effective alternative to IFX in the treatment of rheumatoid arthritis."
"It is a well-known fact that disruptions in the immune system and systemic inflammation are associated with accelerated atherosclerosis in rheumatoid arthritis (RA) patients. Elevated levels of tumor necrosis factor α (TNF-α), a major pro-inflammatory cytokine, are involved in endothelial cell activation of medium and large arteries, leading to increased endothelial permeability, generation of superoxide anion radical and hydrogen peroxide, and decreased availability of nitric oxide (NO). The present study aims to determine the influence of anti-TNF therapy and homocysteine (Hcy) levels on the carotid intima-media thickness (IMT) in patients with RA. Assessments were performed on 115 patients diagnosed with RA on biological treatment to determine the evolution of IMT and Hcy levels. Carotid ultrasonography was used to assess the IMT, as a fast and easy tool for the prediction of cardiovascular events in patients with RA. The first measurement of IMT was noted as IMT1, followed by a second measurement after 1 year, noted as IMT2. The group of patients was divided into approximately three equal groups, each being treated with a different biological product, respectively, etanercept, adalimumab, and infliximab. In the 3 groups, after 1 year of anti-TNF-α therapy, IMT2 progression was significantly reduced compared to baseline. No significant differences were found among the three groups of treatment. A strong association was observed between IMT1-IMT2 in the etanercept group (P<0.001, r=0.758), in the adalimumab group (P<0.001, r=0.761) and in the infliximab group (P<0.001, r=0.829). The low level of Hcy2 after 12 months of anti-TNF-α therapy was significantly correlated with a decrease in IMT2 (P<0.001) in patients who had a high level of Hcy and IMT >0.9 mm at baseline. The results from the present study showed that biological treatment and the low level of homocysteinemia reduced the cardiovascular risk in RA, regardless of the treatment chosen (infliximab, adalimumab, or etanercept)."
"In the 1990s, tumour necrosis factor-α inhibitor therapy ushered in the biologic therapy era for inflammatory bowel disease, leading to marked improvements in treatment options and patient outcomes. There are currently four tumour necrosis factor-α inhibitors approved as treatments for ulcerative colitis and/or Crohn's disease: infliximab, adalimumab, golimumab and certolizumab pegol. Despite the clear benefits of tumour necrosis factor-α inhibitors, a subset of patients with inflammatory bowel disease either do not respond, experience a loss of response after initial clinical improvement or report intolerance to anti-tumour necrosis factor-α therapy. Optimizing outcomes of these agents may be achieved through earlier intervention, the use of therapeutic drug monitoring and thoughtful switching within class. To complement these approaches, evolving predictive biomarkers may help inform and optimize clinical decision making by identifying patients who might potentially benefit from an alternative treatment strategy. This review will focus on the current use of tumour necrosis factor-α inhibitors in inflammatory bowel disease and the application of personalized medicine to improve future outcomes for all patients."
"The objective of this study is to identify subgroups of pediatric Crohn disease (CD) who had differential responses to the infliximab treatment through trajectory cluster analysis of disease activity using data from electronic health records.
We conducted a retrospective study of 295 pediatric patients with CD who had been treated with infliximab for a minimum of one year at the Center for Inflammatory Bowel Disease at The Children's Hospital of Philadelphia between January 2010 and December 2017. The evolution of disease was described, and subgroups of patients were identified using trajectory analysis of longitudinal data of C-reactive protein (CRP). We compared patient characteristics, biomarker for disease activity, and long-term surgical outcomes across subgroups. Cox regression models were used to evaluate the added value of the subgroup classification to baseline phenotype and location in prediction of long-term surgical outcomes.
We identified three subgroups of patients with differential relapse-and-remission profiles (n = 33, 65 and 197 from subgroup 1 to 3), which represented patients with a higher risk of infliximab non-response, with infliximab response but with occasional disease flares, and patients with long-term response. Patients with the best treatment response had a significantly lower frequency of complicated disease phenotypes (P = 0.01), including perianal involvement (P = 0.05), lower baseline CRP (P < 0.01) and calprotectin (P = 0.01), and lowest risk of IBD-related gastrointestinal surgery within 10 years of starting treatment (P < 0.01).
Readily available longitudinal data from electronic health records can be leveraged to provide deeper characterization of treatment response in pediatric CD."
"It is uncertain if higher infliximab trough levels (TLs) confer a greater risk of infectious/noninfectious complications (IC/NIC). We aimed to assess the risk of IC and NIC in patients with different TLs.
We retrospectively evaluated a cohort of Crohn's disease (CD) patients treated with infliximab who underwent therapeutic drug monitoring (TDM), at a tertiary inflammatory bowel disease center, between January 1, 2010, and December 1, 2019. TDM was defined as checking of infliximab trough and antibody levels within a 48-hour period before administration. Patients with a minimum of 3-month assessment pre-TDM and post-TDM were included. In the case of multiple TDMs, the highest TL was considered, and patients were distributed across 4 predefined TL groups (A: <5 µg/mL, B: 5 to 10 µg/mL, C: 10 to 15 µg/mL, and D: ≥15 µg/mL). Rates of IC and NIC during the 3-month prior and following TDM were compared across the groups. In addition, duration of exposure, in terms of months up to TDM, was collected to analyze differences in rates of IC and NIC.
Our study included 341 CD patients (median age: 35 y, 58% men). IC and NIC occurred in 52 (15%) and 30 (9%) patients, respectively. Rates of IC and NIC were similar across the 4 TL groups ( P =0.9 and 0.7, respectively for IC and NIC). On multivariable analysis, exposure to infliximab >40 months (as determined by receiver operating characteristic curve analysis) was associated with decreased odds for IC (adjusted odds ratio=0.51, P =0.04), but not NIC (adjusted odds ratio=0.72, P =0.46).
In this large CD cohort, there was no association between infliximab TL and risk of short-term IC or NIC. Interestingly, a shorter duration of exposure predicted higher rates of IC. This supports the safety of targeting higher infliximab TLs when necessary and greater vigilance during the early stages of treatment."
"Juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogeneous group of systemic autoimmune diseases. Juvenile dermatomyositis (JDM) is the predominant form of JIIMs, and is a rare, chronic autoimmune illness characterised by symmetric, proximal muscle damages and involvement of the skin. In the last two decades, the use of monoclonal antibodies has also been expanded to JIIMs; however, there is limited evidence on use of these treatments. We assessed the efficacy/effectiveness and safety of biologic agents in JIIMs.
A systematic literature review was conducted using Embase®, MEDLINE®, MEDLINE®-In Process and Cochrane library to identify studies on biologics agents in JIIMs published in English language as full-text articles (1975 to December 2020) or conference abstracts (2000 to December 2020). Databases were searched with the key words regarding chronic myositis crossed with ""biologic agents OR tocilizumab OR rituximab OR adalimumab OR infliximab OR anti-TNF OR etanercept"". Of note, we did not include children, age, or age limits in the search as medical subject headings terms because we may have been able to extract a sub cohort of children from studies including both children and adults.
Of the 1633 retrieved publications, 18 articles were identified for a total of 165 patients. In real-world studies, definition of complete (CR) or partial response (PR) varied. JIIMs patients were most often treated with anti-TNF (88 pts); patients received etanercept (ETA), 48 patients infliximab (IFX), 4 patients received adalimumab (ADA). In other 15 patients IFX was followed by ADA. Rituximab (RTX) was used in 73 children. A single case series reported the use of abatacept (ABA) in 4 patients. Despite the reduced number of treated patients, complete response on myositis was reported in 29.6% (8/26) patients treated with at least one anti-TNF and in 38% (10/26) treated by RTX. Complete response of skin vasculitis has been reached in 33% (4/12) children on anti-TNF and in 36% on RTX (21/58). Anti-TNF agents might be efficient in treating calcinosis lesions.
Currently, the available evidence regarding the use of biologic treatment in JIIMs results quite limited but suggest a promising the use of anti-TNF agents and RTX in treating active JIIMs. Anti-TNF treatment might have a role in treating calcinosis. However, an overall very low quality of the available studies and multiple confounding factors hamper to suggest a treatment over another. Thus, randomised clinical trials are urgently required to attempt the optimal treatment in real-world setting."
"Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it.
We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation.
We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09-1.46; p = 0.002).
Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more."
"To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy.
Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint.
197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004).
This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients."
"Anti-tumor necrosis factor agents were the first biologic therapy approved for the management of Crohn's disease (CD). Heart failure (HF) is a rare but potential adverse effect of these medications. The objective of this report is to describe a patient with CD who developed HF after the use of infliximab.
A 50-year-old woman with a history of hypertension and diabetes presented with abdominal pain, diarrhea, and weight loss. Colonoscopy and enterotomography showed ulcerations, areas of stenosis and dilation in the terminal ileum, and thickening of the intestinal wall. The patient underwent ileocolectomy and the surgical specimen confirmed the diagnosis of stenosing CD. The patient started infliximab and azathioprine treatment to prevent post-surgical recurrence. At 6 mo after initiating infliximab therapy, the patient complained of dyspnea, orthopnea, and paroxysmal nocturnal dyspnea that gradually worsened. Echocardiography revealed biventricular dysfunction, moderate cardiac insufficiency, an ejection fraction of 36%, and moderate pericardial effusion, consistent with HF. The cardiac disease was considered an infliximab adverse effect and the drug was discontinued. The patient received treatment with diuretics for HF and showed improvement of symptoms and cardiac function. Currently, the patient is using anti-interleukin for CD and is asymptomatic.
This reported case supports the need to investigate risk factors for HF in inflammatory bowel disease patients and to consider the risk-benefit of introducing infliximab therapy in such patients presenting with HF risk factors."
"Pyoderma gangrenosum (PG) is a relatively rare inflammatory skin disease that progressively causes necrotic ulceration mainly on the lower extremities and trunk. Systemic corticosteroid is considered a first-line treatment for PG as it facilitates wound healing; however, several cases where tumor necrosis factor-α inhibitors, adalimumab and infliximab, were administered showed good response. For intractable PG with a large ulcer or problematic epithelization, chemical or mechanical debridement of necrotic tissue in combination with skin grafting may be necessary to promote wound healing. Our report presents a case of intractable ulcerative PG requiring oral prednisolone and skin grafting. Although mechanical debridement was performed, granulation was poor; therefore, after the PG activity became quiescent, we utilized a vacuum-assisted closure (VAC) system to promote granulation and adaptation of the grafted skin. Although more cases are required for a definitive conclusion, the VAC system may be a choice for PG with large ulcers."
"Pembrolizumab is an immunoglobulin G4 isotype antibody that targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It is used in the treatment of advanced non-small cell lung cancer (NSCLC). The safety and efficacy of immunotherapy for autoimmune disease are currently unknown;immune-related adverse events induced by immune checkpoint inhibitors (ICIs) have been reported. We report a case of severe colitis induced by the administration of pembrolizumab for pulmonary adenocarcinoma in a patient with ulcerative colitis. A 72-year-old man with a 3-year history of ulcerative colitis maintained clinical remission with mesalazine. The recurrence of lung adenocarcinoma was diagnosed and treated with pembrolizumab as second-line treatment. Diarrhea and bloody stool recurred 5 months after the first administration of pembrolizumab. The colitis did not respond to corticosteroids and infliximab. Because of the recurrence of ulcerative colitis, treatment of the lung adenocarcinoma was discontinued, and the patient died 1 year after the first administration of pembrolizumab. Few cases of severe colitis induced by the administration of pembrolizumab in patients with ulcerative colitis have been reported. This case suggests that the clinical stratification of autoimmune disease and typical standards of effectiveness of treatment are needed for patients with autoimmune disease who are treated with ICIs."
"Subclinical intestinal inflammation is common in Crohn's disease (CD). We aimed to explore its impact in the disease progression of infliximab-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers.
The registry-based, prospective, observational, multicenter DIRECT (study to investigate the correlation of fecal calprotectin with serum Drug levels and development of an antI-dRug antibodiEs among adult patients with inflammatory bowel disease reCeiving anti-TNF-alfa treatment or vedoluzimab treatment) study followed infliximab-treated CD patients for 2 years in a tertiary care setting. Persistent inflammation definition was based on FC (>150 μg/g, >250 μg/g, or >350 μg/g) or serum CRP (>3 μg/mL) concentrations over 2 consecutive or at least 3 visits. Patients were categorized according to a composite outcome reflecting disease progression that incorporated surgery; hospitalizations; new fistulae, abscess, or stricture; and treatment escalation.
Of 322 DIRECT study patients, 180 asymptomatic, infliximab treated on maintenance regimen were included in the analysis. Patients developing the composite endpoint (n = 96) presented higher median levels of FC (205 [interquartile range, 98-515] μg/g; P = .045) but not of CRP (2.50 [interquartile range, 0.80-6.00] μg/mL; P = .895). Biomarker-defined persistent subclinical inflammation prevalence ranged from 24% to 81%. Considering FC >250 μg/g in 2 consecutive visits, prevalence was 50%, odds of achieving the endpoint were increased 3-fold (odds ratio, 2.996 [95% confidence interval, 1.557-5.776]), and time-to-outcome occurrence was significantly lower among subjects with persistent inflammation (median time: 11 months). Both clinical-related and treatment-related components were significantly associated with persistent inflammation. Definitions based on CRP >3 μg/mL, FC >150 μg/g, FC >350 μg/g, double biomarkers (FC >250 μg/g and/or CRP >3 μg/mL), or more visits did not improve predictive ability.
Persistent inflammation, defined simply and readily by FC >250 μg/g over 2 consecutive visits, was associated with a significantly higher risk and shorter time to occurrence of a composite outcome reflecting disease progression in asymptomatic infliximab-treated CD patients."
"To evaluate effectiveness and safety of infliximab dose escalation in Takayasu arteritis (TAK) patients. To identify factors associated with refractoriness to standard-dose infliximab.
Medical records of infliximab-treated TAK patients from a large single-centre observational cohort were reviewed. Infliximab therapy duration, concomitant therapies, and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained infliximab standard-dose and those who needed dose-escalation was performed. Factors associated with refractoriness to standard dose were analysed.
Forty-one patients were included. Starting infliximab dose was 5 mg/kg 6-weekly and 28 patients (68%) needed dose escalation. Persistence/recurrence of clinical symptoms was the most frequent reason for escalation. Median therapy duration was 39 (IQR, 26-61) months in the standard-dose group and 68 (38-87) months in the intensified-dose group. In the intensified-dose-group, infliximab was suspended in eight patients (29%) after a median of 38 (31-71) months, due to loss of response (n = 7) or patient's request (n = 1). Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient) and received a higher cumulative steroid dose (1.7 [1.6-2.3] vs 1.3 [1-1.6] g/month of prednisone). Three patients from the intensified-dose group had serious infections; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, age at diagnosis and age at infliximab start were associated with infliximab escalation.
In TAK, dose escalation is safe and allows to optimise infliximab durability in refractory patients. Younger patients seem to be more refractory to standard dosages."
"The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.
La precocidad y la eficacia de las vacunas desarrolladas hasta ahora frente al COVID-19, ha sido el avance más significativo y salvador frente a la pandemia. El desarrollo vacunal no ha impedido, durante todo el periodo de la pandemia, la búsqueda constante de remedios terapéuticos, tanto entre los medicamentos ya existentes y con indicaciones diversas, como en el desarrollo de nuevos fármacos. Sobre estos nuevos fármacos, sobre las novedades en la inmunoterapia y sobre lo aprendido de los moduladores de la respuesta inmune ya conocidos y que se han mostrado eficaces frente al virus, el Comité Científico del COVID-19 del Ilustre Colegio de Médicos de Madrid ha querido ofrecer una aproximación precoz, simplificada y critica que pueda ayudar a comprender la situación actual."
"Behcet's disease is a systemic vasculitis that can involve gastrointestinal tract. This is a systematic review and meta-analysis evaluating the efficacy and safety of anti-tumor necrosis factor (TNF) agents in treating patients with intestinal Behcet's disease.
We conducted searches on PubMed, Embase, and Cochrane. Data from eligible studies were used to calculate the pooled estimate of proportions of clinical remission, mucosal healing at Months 3, 6, 12, and 24 as well as the pooled incidence of adverse drug reactions. And subgroup analysis based on the specific type of anti-TNF agents was performed.
Of the 828 studies initially identified, 13 were included finally, all of which were single-arm cohort studies. The pooled proportions of clinical remission at Months 3, 6, 12, and 24 were 0.61 (95%CI 0.48-0.78), 0.51 (95%CI 0.40-0.66), 0.57 (95%CI 0.48-0.67), and 0.38 (95%CI 0.16-0.88), respectively. The pooled proportions of mucosal healing at Months 3, 6, 12, and 24 were 0.66 (95%CI 0.50-0.86), 0.82 (95%CI 0.48-0.98), 0.65 (95%CI 0.51-0.81), and 0.69 (95%CI 0.39-1.00), respectively. The pooled estimate of proportion of overall adverse drug reactions for infliximab was 0.22 (95%CI 0.07-0.69).
Anti-TNF agents, including infliximab and adalimumab, were an efficient therapy for intestinal Behcet's disease. The safety of anti-TNF agents used in the treatment of intestinal Behcet's disease was acceptable."
"Crohn's disease is a debilitating chronic inflammatory disorder of the mammalian gastrointestinal tract. Current interventions using anti-tumour necrosis factor [anti-TNF] biologics show long-term benefit in only half of patients. This study focused on the role of the TNF receptor 1 [TNFR1] in pathogenesis in a TNF-driven model of ileitis.
We studied TNFΔAU-rich element [ARE]/+ [TNFdARE] mice, which develop progressive ileitis similar to Crohn's ileitis. Histopathological analysis and gene expression profiling were used to characterize disease progression from 5 to 16 weeks. Mice with TNFR1 hemizygosity [TNFdARE/R1het] allowed us to assess gene dosage effects. Transcriptional profiling established inflection points in disease progression; inflammatory gene expression increased at 8 weeks with a plateau by 10 weeks, so these were selected as endpoints of treatment using the TNF biologic infliximab and the TNFR1-specific XPro1595. Differences in recruitment of cells in the lamina propria were assessed using flow cytometry.
TNFdARE/R1het mice displayed stable long-term protection from disease, associated with decreased recruitment of CD11bhiF4/80lo monocytes and CD11bhiLy6Ghi neutrophils, suggesting an important role of TNFR1 signalling in pathogenesis, and indicating potential benefit from TNFR1-specific intervention. Treatment with infliximab and XPro1595 both showed a similar impact on disease in TNFdARE mice. Importantly, these beneficial effects were greatly surpassed by hemizygosity at the TNFR1 locus.
Treatment with either infliximab or XPro1595 produced moderate protection from ileitis in TNFdARE mice. However, hemizygosity at the TNFR1 locus in TNFdARE mice showed far better protection, implicating TNFR1 signalling as a key mediator of TNF-driven disease."
"Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still's disease (AOSD). The newly described VEXAS, associated with somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS).
To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome.
A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML.
Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS.
Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation."
"To estimate the seroprevalence of SARS-CoV-2 infection in patients with rheumatic diseases and to specify the proportion of asymptomatic and symptomatic forms of COVID-19.
We screened for SARS-CoV-2 infection among spondyloarthritis (SpA, n=143) or rheumatoid arthritis (RA, n=140) patients in our outpatient clinic at Cochin Hospital in Paris between June and August 2020. We performed a qualitative SARS-CoV-2 serological test which detects IgG directed against the N nucleocapsid protein (anti-N) and, for some patients, against the Spike protein (anti-S). Descriptive analyses were managed.
During June-August 2020, the SARS-CoV-2 seroprevalence rate in our population was 2.83% (8/283 patients) without significant difference between RA and SpA patients (2.14% and 3.5%, respectively). We report 11 out of 283 patients (3.8%) with a diagnosis of SARS-CoV-2 infection. Among these 11 patients, 1 patient was asymptomatic (9%) with a confirmed diagnosis of COVID-19 by anti-S serology. Of the 283 patients, 85% were under bDMARDs, mainly on rituximab (RTX) (n=44) and infliximab (IFX) (n=136).
The seroprevalence of SARS-CoV-2 in patients with rheumatic diseases, mainly under bDMARDs treatments, was 2.83%. Among infected patients, 9% were asymptomatic. Detecting SARS-CoV-2 infections could be based on the strategy using patients' interview and anti-N serology."
"Psoriasis is a common, chronic, immune-mediated inflammatory skin disease with increased epidermal proliferation. The objective of this review was to systematically identify the evidence and perform a network meta-analysis (NMA) to estimate the relative efficacy of secukinumab (SEC) against adalimumab (ADA) and infliximab (INF) for the treatment of moderate-to-severe plaque psoriasis.
A systematic literature review (SLR) was conducted according to a pre-specified protocol to identify relevant studies. Initially, the databases were searched from database inception till June 2013, and the SLR was updated in April 2020. The eligibility criteria included adult patients (≥18 years old) with moderate-to-severe plaque psoriasis, and the SLR included randomized controlled trials (RCTs). The comparators of interest were SEC, ADA, INF, and placebo (PLA), while outcomes of interest were Psoriasis Area and Severity Index (PASI) (50, 75, and 90) at weeks 12, 16, and 24. A Bayesian NMA for PASI was utilized with a framework that evaluated the probability of PASI responses in different categories of PASI thresholds within a single model.
A total of 23 RCTs that assessed the efficacy of SEC, ADA, and INF in patients with moderate-to-severe plaque psoriasis were identified. At 12 weeks, SEC was associated with a significantly better response compared with PLA and ADA for PASI 75 and 90, while response results were comparable against INF. At 12 weeks, risk ratio (95% confidence interval) derived from NMA for SEC vs. ADA and INF for PASI 75 was 1.35 (1.19, 1.57) and 1.01 (0.90, 1.18), respectively. At the 16-week and 24-week time interval, SEC was significantly better than PLA, ADA, and INF for PASI 75 and 90.
Efficacy of SEC in the treatment of patient populations with moderate-to-severe plaque psoriasis is well demonstrated through NMA."
"Therapeutic management of inflammatory bowel diseases (IBD) is rapidly evolving, with an expanding armoury of biological drugs at our disposal. However, real-world findings about treatment persistence and the impact of biologicals on surgery remain inconsistent.
This study aimed to investigate trends in biological use and surgery rates in a nationwide cohort of biological-naïve IBD patients.
Patients with IBD who initiated biological treatment between 2011 and 2018 were identified in the Danish National Patient Registry. Data on use of biologicals, surgeries and healthcare costs were retrieved and analysed for time trends.
Between 2011 and 2018, a total of 6,036 IBD (51% ulcerative colitis (UC), 49% Crohn's disease (CD)) patients received biological treatment for the first time. Cumulative use of biologicals increased from 5.0% to 10.8% among UC and 8.9%-14.5% among CD patients. Infliximab remained the most-prescribed first-line biological for UC and CD. Treatment persistence was 44.3% and 16.9% after 1 and 3 years in UC, compared to 59.9% and 33.6% in CD patients. Overall, 32.8% of patients switched to a second biological. Surgery rates decreased in both UC (P = 0.015) and CD (P = 0.008) patients and remained significant for UC in the Cox regression model (P = 0.002). Outpatient and surgical costs also fell among both UC and CD patients.
Persistence rates for first-line biologicals among IBD patients were low and one-third switched treatment. Surgery rates and direct costs decreased over time, but whether this is related to the use of biologicals has yet to be determined."
"Fecal biomarkers have emerged as one of the most useful tools for clinical management of inflammatory bowel disease (IBD). Oncostatin M (OSM), like fecal calprotectin (FC), is highly expressed in the inflamed intestinal mucosa which may have potential usefulness. We aimed to evaluate the additional utility of these two fecal biomarkers for IBD diagnosis, activity, and prediction of infliximab response over FC alone.
In group 1, 236 IBD patients (145 Crohn's disease, 91 ulcerative colitis), 50 disease controls, and 32 healthy controls were recruited for IBD diagnosis and activity. In group 2, baseline stool samples were collected from 62 patients to predict infliximab response at week 28 and 52. The performance of fecal biomarkers for IBD management was assessed by the area under the receiver operating characteristic curve (AUC).
Fecal OSM and FC levels were increased in IBD patients and were positively correlated with clinical and endoscopic activity. Their combination showed a better ability for disease diagnosis (AUC = 0.93) and slightly improved the capability to identify mucosal healing (AUC = 0.923). Baseline OSM and FC levels were elevated in non-responders at week 28 and 52. The AUCs of OSM, FC, and their combination to predict therapeutic response were 0.763, 0.834, and 0.859 at week 28, 0.638, 0.661, and 0.704 at week 52, respectively. Combined use of fecal and blood biomarkers improved predictive accuracy with an AUC of 0.919 at week 28 and 0.887 at week 52.
In addition to FC, OSM is a novel fecal biomarker, and their combination is more beneficial for disease diagnosis and prediction of infliximab response but not for disease activity in IBD patients. Further larger-scale studies are required to confirm our findings."
"To determine the contribution of clinical and biochemical inflammation to structural progression of patients with psoriatic arthritis (PsA).
We analysed patients from the Infliximab Multinational Psoriatic Arthritis Controlled Trial 2 trial (infliximab vs placebo). We obtained total modified Sharp/van-der-Heijde Scores from baseline and year one images, and swollen joint counts (SJC) and levels of C reactive protein (CRP) throughout the second half of year 1 (5 measurements) from 74 placebo-treated patients. We computed radiographic progression, time-averaged SJC (taSJC) and CRP (taCRP) values and assessed their impact on structural progression by logistic regression analysis. We further categorised patients as 'active' (+) or 'inactive' (-) based on their taSJC (cut-off point: 2/66 joints) and taCRP (cut-off point: 0.5 mg/dL) and compared radiographic progression across three groups (double inactive, single active, double active).
ORs for progression were 1.24 (95 % CI 1.04 to 1.47; p=0.016) for taSJC and 6.08 (95 % CI 1.12 to 33.03; p=0.036) for taCRP. When predictors were dichotomised (+ vs -), differences were maintained between taSJC+ and taSJC- patients (1.05±3.21 and 0.56±2.30, respectively), as well as for taCRP+ vs taCRP- patients (1.14±3.23 and 0.05±2.37, respectively). Progression was intermediate in the presence of abnormalities of one but not the other inflammatory variable, indicating increasing radiographic progression with increasing inflammation (p=0.05).
In patients with PsA, both clinical and biochemical inflammation have an impact on structural progression. Overall, progression is smallest in the absence of both clinical and biochemical inflammation, higher when either clinical or biochemical inflammation is present and highest with both clinical and biochemical inflammation."
"Extracellular vesicles (EVs) are a heterogeneous family of small vesicles released by donor cells and absorbed by recipient cells, which represent important mediators with fundamental roles in both physiological and pathological conditions. EVs are present in a large variety of biological fluids and have a great diagnostic and prognostic value. They have gained the interest of the scientific community due to their extreme versatility. In fact, they allow us to hypothesize new therapeutic strategies since, in addition to being cell signal mediators, they play an important role as biomarkers, drug vehicles, and potential new therapeutic agents. They are also involved in immunoregulation, have the ability to transmit resistance to a drug from one cell to a more sensitive one, and can act as drug delivery systems.
The main reciprocal interactions between EVs and immunosuppressive drugs will be presented.
The known interactions between EVs and immunosuppressive drugs, in particular cyclosporin, glucocorticoids, rapamycin, methotrexate, cyclophosphamide, eculizumab, infliximab, certolizumab, etanercept, glatiramer acetate, and fingolimod are presented.
This review provides relevant information on the links between EVs and immunosuppressive drugs with a focus on EVs' role as tools to assess the effects of immunosuppressants, suggesting innovative properties and new possible therapeutic uses."
"Biologic therapies are often used in patients with ulcerative colitis (UC) who are nonresponsive to conventional treatments. However, nonresponse or loss of response to biologics often occurs, leading to dose escalation, combination therapy, and/or treatment switching. We investigated real-world treatment patterns of biologic therapies among patients with UC in the USA.
This study analyzed data from the IBM® MarketScan® Commercial and Medicare Supplemental Databases (medical/pharmacy claims for >250 million patients in the USA) to identify patients with UC initiating a biologic therapy (adalimumab, infliximab, golimumab, or vedolizumab) with 12 months of follow-up post-initiation. Key measures were patient baseline characteristics, dose escalation (average maintenance dose >20% higher than label), adherence (proportion of days covered), and ulcerative colitis-related healthcare costs in the 12 months following biologic therapy initiation.
Of 2,331 patients included in the study (adalimumab [N = 1,291], infliximab [N = 810], golimumab [N = 127], and vedolizumab [N = 103]), 28.1% used concomitant immunosuppressant therapy within 12 months post-initiation. Overall, 23.6% (adalimumab), 34.8% (infliximab), 9.9% (golimumab), and 39.2% (vedolizumab) of patients dose escalated within 12 months. Patients who dose escalated incurred USD 20,106 higher total UC-related healthcare costs over 12 months than those who did not. Adherence (covariate-adjusted proportion of days covered) ranged from 0.63 to 0.73, and 39.3% of patients discontinued within 12 months (median treatment duration = 112 days).
Dose escalation was common, and incurred higher costs, in patients with UC initiating biologic therapies. Suboptimal adherence and/or discontinuation within 12 months of initiation occurred frequently, highlighting the challenges in managing these patients."
"Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease that causes joint destruction. The condition imposes a significant economic burden on patients and societies. The present study is aimed at evaluating the cost-effectiveness of Infliximab, Adalimumab, and Etanercept in treating rheumatoid arthritis in Iran.
This is a cost-effectiveness study of economic evaluation in which the Markov model was used. The study was carried out on 154 patients with rheumatoid arthritis in Fars province taking Infliximab, Adalimumab, and Etanercept. The patients were selected through sampling. In this study, the cost data were collected from a community perspective, and the outcomes were the mean reductions in DAS-28 and QALY. The cost data collection form and the EQ-5D questionnaire were also used to collect the required data. The results were presented in the form of an incremental cost-effectiveness ratio, and the sensitivity analysis was used to measure the robustness of the study results. The TreeAge Pro and Excel softwares were used to analyze the collected data.
The results showed that the mean costs and the QALY rates in the Infliximab, Adalimumab, and Etanercept arms were $ 79,518.33 and 12.34, $ 91,695.59 and 13.25, and $ 87,440.92 and 11.79, respectively. The one-way sensitivity analysis confirmed the robustness of the results. In addition, the results of the probabilistic sensitivity analysis (PSA) indicated that on the cost-effectiveness acceptability curve, Infliximab was in the acceptance area and below the threshold in 77% of simulations. The scatter plot was in the mentioned area in 81% and 91% of simulations compared with Adalimumab and Etanercept, respectively, implying lower costs and higher effectiveness than the other two alternatives. Therefore, the strategy was more cost-effective.
According to the results of this study, Infliximab was more cost-effective than the other two medications. Therefore, it is recommended that physicians use this medication as the priority in treating rheumatoid arthritis. It is also suggested that health policymakers consider the present study results in preparing treatment guidelines for RA."
"Immune checkpoint inhibitors (ICIs) are targeted cancer therapies regarded to have less toxicity than chemotherapy. Immune-related adverse events (irAEs) of ICIs are well described in the literature but limited data exist on their infectious complications. The objective is to describe the spectrum and risk factors for developing serious infections in patients receiving ICIs.
Retrospective review of patients with melanoma, renal cell carcinoma, or nonsmall-cell lung cancer on nivolumab, pembrolizumab, and/or ipilimumab from January 1, 2017 to November 30, 2017. Exclusion: receipt of less than two ICI doses or history of other malignancy. Characteristics: age, sex, prior chemotherapy, steroid use, and temozolomide or infliximab use. Data identified from microbiology, radiography, serology, or physician note documentation. Serious infection is defined as infections requiring hospitalization and/or IV antibiotics from initiation of ICI until the end of the study period.
One hundred and eleven pts received ICIs. Suspected or confirmed bacterial infections occurred in 24% (27/111) with 8% (9/111) confirmed bacterial cultures. The overall serious infection rate was 14% (16/111) with 25% (4/16) confirmed bacterial cultures. Suspected or confirmed infection sites: genitourinary 20% (22/111), pneumonia 5% (7/111), skin/soft tissue 7% (8/111). Noninfectious pneumonitis (NIP) occurred in 5% (5/111). No association regarding the risk of infection between the type of malignancy and ICI used. Steroid use was the only risk factor significantly associated with serious infection: 12/16 (75%) on steroids versus 27/95 (28.4%) without steroid use (p = 0.0003).
The rate of serious infection with ICI was higher in our study compared with previous reports of pts treated with melanoma. Infectious complications are encountered with ICIs and correlate with steroid use."
"Transitioning patients from an originator to a corresponding biosimilar has been extensively studied in both randomized controlled trials and observational studies. Although transitioning is considered well-tolerated, with no negative impacts on efficacy and/or safety, 2.6-25.8% of patients restart treatment with the originator (retransitioning). Retransitioning to the originator can be considered an indication of biosimilar treatment failure or dissatisfaction with biosimilar treatment. Increasing our knowledge of patients who retransition might help to reduce the number of patients retransitioning.
Our objective was to estimate the cumulative incidence of patients who retransitioned from a tumor necrosis factor (TNF)-α inhibitor biosimilar to originator and to explore potential patient, disease, and treatment and implementation strategy factors associated with retransitioning.
We conducted a systematic literature search in the PubMed, EMBASE, and Cochrane Central Register of controlled trials databases until March 2021. Studies on TNFα inhibitors, biosimilar transitioning, and retransitioning were included. Transitioning was defined as switching from an originator to a biosimilar, and retransitioning was defined as switching from an originator to a biosimilar and back to the originator. Characteristics of the studies were descriptively analyzed. Studies were weighted by the number of patients transitioning, and the primary outcome was the median cumulative incidence of retransitioning. For each of the factors related to patient, disease, and treatment and implementation strategy, studies were stratified according to the categories of that factor. The weighted medians and interquartile ranges (IQRs) of the cumulative incidence of retransitioning in these studies were calculated and compared to explore whether a potential association existed between these factors and the cumulative incidence of retransitioning.
Of 994 screened publications, 37 were included. The weighted median cumulative incidence of retransitioning was 7.6% (IQR 6.8-17.2). Studies that included only patients with inflammatory bowel disease (6.6 vs. 15.1-17.7% for other indications), included only patients with stable disease (7.0 vs. 13.7% for including all patients), and did not offer retransitioning at the introduction of the biosimilar (7.0 vs. 11.1% for studies that offered retransitioning) reported less retransitioning. In addition, the incidence of retransitioning was lower when extra laboratory monitoring was part of the implementation strategy (1.6 vs. 6.1%) and when gainsharing (patients' healthcare directly benefits from financial savings from transitioning) (1.4 vs. 7.2% for studies without gainsharing) was applied.
In studies on transitioning patients from TNFα originator to biosimilar, 8% of patients retransitioned. Retransitioning appeared to be lower in studies that included only patients with stable disease and in studies that did not offer patients the option of retransitioning at the introduction of the biosimilar. In addition, retransitioning appeared to be lower in studies that implemented extra laboratory monitoring as part of the biosimilar implementation strategy. Clinicians should consider implementing these suggestions as they might reduce retransitioning rates and improve the introduction of biosimilars in clinical practice. PROSPERO registration ID: CRD42021226381."
"This study aims to clarify shoulder joint damage in rheumatoid arthritis patients receiving biological disease-modifying antirheumatic drugs (bDMARDs) and the relationship between joint damage and clinical factors.
In this retrospective study conducted between April 2005 and December 2008, 36 shoulders in 19 patients (2 males, 17 females; mean age: 58.9 years; range 42 to 75 years) were evaluated at baseline and two years after the initiation of bDMARD therapy with infliximab (n=14) or etanercept (n=5). Standard anteroposterior radiographs of the shoulder joints were taken at baseline and two years after institution of biological therapy. Structural damage in the shoulder joints was assessed using the Larsen scoring method, the medial displacement index (MDI), and the upward migration index (UMI).
There was a significant correlation between MDI, UMI, and Larsen grade before biological therapy. Univariate analysis revealed that the disease activity score 28-count erythrocyte sedimentation rate (ESR) at baseline (odds ratio [OR]: 4.298) was associated with progression of MDI. But multivariate logistic regression revealed that there was no association with the progression of MDI. Univariate analysis revealed that ESR at baseline (OR: 0.967) and matrix metalloproteinase-3 (MMP-3) at baseline (OR: 0.996) were associated with the progression of UMI. Multivariate logistic regression revealed that MMP-3 at baseline (OR: 0.994) was independently associated with the progression of UMI.
Medial displacement index and UMI correlated with the Larsen grade of the shoulder joint strongly and moderately, respectively. This study suggests that MDI and UMI may help to evaluate radiographic progression of damage in shoulder joints in patients on bDMARDs, which is difficult to detect using the Larsen grade."
"Infliximab is an inhibitory of tumor necrosis factor-alpha which is used successfully for the treatment of inflammatory bowel disease and rheumatic disease. It has various side effects including injection-induced reactions, immunosuppression, demyelinating diseases, and cardiac effects. One of the most serious side effects is tuberculosis. In particular, the immunosuppressant drugs have a high risk of reactivating latent tuberculosis infection. Its activation probably may occur as an extra-pulmonary and, occasionally, may result in an unusual infection. Herein, we report a 30-year-old male case treated with infliximab and suffered from isolated testicular tuberculosis."
"In pediatric patients with Inflammatory Bowel Disease renal parenchymal disease is infrequent. There are only two reports about the association between IgA Nephropathy and Pediatric Crohn Disease. IgA Nephropathy is a rather uncommon complication of Tumor Necrosis Factor-alpha (TNF-α) inhibition. We describe a case of IgA Nephropathy which has arisen in a 11-year-old child 2 years after Crohn disease diagnosis, during therapy with anti-TNF-α. An ileal e jejunal Crohn disease was diagnosed at 9 years old, initially treated with prednisone, followed by biological therapy with anti-TNF-α (Adalimumab) due to severe disease activity, with gradual improvement of clinical conditions until clinical remission is achieved. Two years after the diagnosis, the child suddenly presented macroscopic hematuria. Subsequent laboratory examinations showed acute renal failure. So kidney biopsy was performed and IgA Nephropathy diagnosis was made. Adalimumab was discontinued and the child has been treated with steroids for sixth months associated with angiotensin-converting enzyme inhibitor resulted in clinical improvement over the following year and remission was maintained. To our knowledge the association of IgA Nephropathy and pediatric IBD during therapy with anti-TNF-α has never been reported. Careful monitoring of renal function, proteinuria, and autoantibodies is advised in patients treated with anti-TNF-α agents."
"Immunomediated adverse events [IAEs] are the most frequently reported infliximab [IFX]-related adverse events. Combination therapy may reduce their incidence, although this strategy is not recommended in elderly patients. We aimed to compare the rates of IFX-related IAEs and loss of response [LOR] in elderly and younger patients.
Adult patients in the ENEIDA registry who had received a first course of IFX therapy were identified and grouped into two cohorts regarding age at the beginning of treatment [over 60 years and between 18 and 50 years]. The rates of IAEs and LOR were compared.
In total, 939 patients [12%] who started IFX over 60 years of age and 6844 [88%] below 50 years of age were included. Elderly patients presented a higher proportion of AEs related to IFX [23.2% vs 19%; p = 0.002], infections [7.1% vs 4.3%; p < 0.001] and neoplasms [2.2% vs 0.5%; p < 0.001]. In contrast, the rates of IAEs [14.8% vs 14.8%; p = 0.999], infusion reactions [8.1% vs 8.1%; p = 0.989], late hypersensitivity [1.3% vs 1.2%; p = 0.895], paradoxical psoriasis [1% vs 1.5%; p = 0.187] and drug-induced lupus erythematosus [0.6% vs 0.7%; p = 0.947] were similar in elderly and younger patients. LOR rates were also similar between the two groups [20.5% vs 19.3%; p = 0.438]. In the logistic regression analysis, IFX monotherapy, extraintestinal manifestations and female gender were the only risk factors for IAEs, whereas IFX monotherapy, extraintestinal manifestations and Crohn's disease were risk factors for LOR.
Elderly patients with inflammatory bowel disease have a similar risk of developing IFX-related IAEs and LOR to that of younger patients."
"Generalized pustular psoriasis (GPP) is characterized by acute flare-ups induced by various factors, but few reports have described GPP onset or flare-up induced by vaccination. To our knowledge, only three such cases following coronavirus disease 2019 (COVID-19) vaccination have been reported. We herein report a case of GPP flare-up after COVID-19 mRNA vaccination. A 65-year-old man with GPP controlled by infliximab presented with widespread pustular erythema, fever, and malaise following his second COVID-19 mRNA vaccination. A skin eruption was apparent at the injection site. He also exhibited systemic capillary leak syndrome (SCLS), which responded rapidly to secukinumab and systemic corticosteroids. Two biopsies, one of which was of the injection site, revealed not only findings typical of GPP, but also a dermal mixed-cell infiltration with eosinophils, and microthrombi in the small dermal vessels. The latter findings have been observed in cutaneous lesions induced by both COVID-19 infection and vaccination. This is the first case of a GPP flare-up accompanied by SCLS induced by a COVID-19 mRNA vaccine. Also, this is the first flare-up induced by the second vaccine dose, and the first such report including detailed histological data, including for the injection site."
"To determine whether patients with inflammatory autoimmune diseases treated with rituximab (RTX) have more severe forms of COVID-19 compared with patients treated with anticytokine therapies, such as Tumour Necrosis Factor (TNF) inhibitors.
We included all patients who were on either RTX or infliximab (IFX) in two Swiss cantons during the first wave of the COVID-19 pandemic. We collected self-reported symptoms compatible with COVID-19, PCR-confirmed diagnoses of COVID-19 and the evolution of COVID-19 infections. We computed the raw and propensity score-adjusted incidence of COVID-19 by treatment group.
190 patients were enrolled, of whom 121 (64%) were in the RTX group and 69 (36%) were in the IFX group. Twenty-one patients (11%) reported symptoms compatible with COVID-19 (RTX: 10, IFX: 11, p=0.14). Among patients with COVID-19 symptoms, four developed severe forms of the disease, with life-threatening pulmonary manifestations requiring intensive mechanical ventilation (RTX: 4 of 10, IFX: 0 of 11, Fisher's exact test p=0.04). The incidence rate of COVID-19 symptoms was 0.73 (95% CI 0.39 to 1.37) cases per 1000 patient-days on RTX vs 1.52 (95% CI 0.82 to 2.85) cases per 1000 patient-days on IFX (crude p=0.10, adjusted p=0.07). The incidence rate of severe COVID-19 was 0.28 (95% CI 0.08 to 0.7.2) cases per 1000 patient-days on RTX compared with null on IFX (95% CI 0.0 to 0.44) (p=0.13). A replication in an independent validation cohort confirmed these findings, with consistent results in the Swiss Clinical Quality Management registry.
While the incidence of symptoms compatible with COVID-19 was overall similar in patients receiving RTX or IFX, the incidence of severe COVID-19 tended to be higher in the RTX group."
"Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that is frequently accompanied by systemic complications including peripheral neuropathies. Anti-tumor necrosis factor-alpha agents such as infliximab are an established treatment for immune-mediated diseases. However, they have been associated with adverse effects, including local reactions, infections, congestive heart failure, malignancies, and, rarely, they can cause neurological adverse effects on the central nervous system, as well as peripheral nervous system demyelination. Here, we report the case of an 80-year-old man with CD on infliximab therapy who presented with progressive weakness and numbness. A neurological examination and a nerve conduction study suggested chronic inflammatory demyelinating polyneuropathy (CIDP). The patient was started on oral corticosteroids and experienced transient improvement of his symptoms at the end of this course. Thus, CIDP could be one of the extraintestinal presentations of CD."
"There is a growing armamentarium for the treatment of moderate-to-severe ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics and small molecule drugs for the treatment of patients with moderate-to-severe ulcerative colitis.
In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials without language restrictions for articles published between Jan 1, 1990, and July 1, 2021. Major congresses' databases from Jan 1, 2018, to July 3, 2021, were reviewed manually. Phase 3, placebo-controlled or head-to-head randomised controlled trials (RCTs) assessing the efficacy and safety of biologics or small molecule drugs as induction or maintenance therapies for patients with moderate-to-severe ulcerative colitis were included. Phase 2 RCTs were excluded because of their small sample sizes and inclusion of doses not further explored in phase 3 RCTs. Summary data from intention-to-treat analyses were extracted from included reports by JSL and PAO. The primary outcome was the induction of clinical remission. A network meta-analysis was done under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. The surface under the cumulative ranking (SUCRA) was used to rank the included agents for each outcome. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety. Maintenance data on efficacy for treat-straight-through and randomised responder trials are also presented. This study is registered with PROSPERO, CRD42021225329.
Our search yielded 5904 results, from which 29 studies (four being head-to-head RCTs) fulfilled our inclusion criteria and were included. Of these, 23 studies assessed induction therapy with either a biologic or small molecule drug, comprising 10 061 patients with ulcerative colitis. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib was significantly superior to all other interventions for the induction of clinical remission (infliximab [OR 2·70, 95% CI 1·18-6·20], adalimumab [4·64, 2·47-8·71], golimumab [3·00, 1·32-6·82], vedolizumab [3·56, 1·84-6·91], ustekinumab [2·92, 1·31-6·51], etrolizumab [4·91, 2·59-9·31], tofacitinib [2·84, 1·28-6·31], filgotinib 100 mg [6·15, 2·98-12·72], filgotinib 200 mg [4·49, 2·18-9·24], and ozanimod (2·70, 1·18-6·20), and ranked highest for the induction of clinical remission (SUCRA 0·996). No differences between active interventions were observed when assessing adverse events and serious adverse events. Vedolizumab ranked lowest for both adverse events (SUCRA 0·184) and serious adverse events (0·139), whereas upadacitinib ranked highest for adverse events (0·843) and ozanimod ranked highest for serious adverse events (0·831).
Upadacitinib was the best performing agent for the induction of clinical remission (the primary outcome) but the worst performing agent in terms of adverse events in patients with moderate-to-severe ulcerative colitis. Vedolizumab was the best performing agent for safety outcomes. With the paucity of direct comparisons in the published literature, our results might help clinicians to position drugs in treatment algorithms.
None."
"Inflammatory bowel disease affects many women of childbearing potential. Women who wish to conceive face many uncertainties. Effects of their medications and their disease may interfere with normal pregnancy and development of the child.
A 30 year old woman with Crohn's disease has a wish to conceive. Her disease has been in remission for 2 years with infliximab use. She is concerned about effects of the medication on her pregnancy and child. An individual risk assessment was made and infliximab was continued until week 22 of gestation. Her pregnancy was monitored, a healthy neonate was born at 38 weeks.
For women on chronic medication an individual preconceptional risk assessmentis needed. The influence of the disease on pregnancy and fetushas to be weighed against possible risks of the drug(s). Crohn's disease is preferably in remission well before and during pregnancy."
"Biologics are important in treating patients with hidradenitis suppurativa (HS). However, to our knowledge, data on their real-life performance and treatment patterns in HS are limited.
To examine the drug survival of biologic therapies for HS in a real-world setting.
This cohort study included all patients with HS between January 1, 2005, and December 31, 2018, who were treated with biologics at the 5 academic hospital clinics where all biologic treatment for HS is conducted in Denmark. Biologics included adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, secukinumab, and ustekinumab. Data were analyzed between June 1, 2021, and June 20, 2021.
Drug survival was depicted through Kaplan-Meier curves, and Cox regression models were used to calculate adjusted (age, sex, previous number of biologic treatment series) hazard ratios (aHRs) with 95% CIs for the risk of treatment discontinuation. Switching patterns were visualized through a Sankey diagram.
The study comprised 241 patients (176 women [61.8%]; total of 386 treatment series) with a mean (SD) age of 41.8 (12.6) years at initiation of first biologic therapy. There were a total of 256 (189 [73.8%] biologic naive), 66 (32 [48.5%] biologic naive), 23 (9 [39.1%] biologic naive), and 22 (9 [40.9%] biologic naive) treatment series with adalimumab, infliximab, etanercept, and ustekinumab, respectively. The median time to discontinuation was 36.0 (IQR, 21.9-63.0), 28.7 (IQR, 15.1-62.9), 26.0 (IQR, 16.9-155.9), and 17.9 weeks (IQR, 12.9-41.0) for adalimumab, infliximab, ustekinumab and etanercept, respectively. The risk of drug discontinuation was significantly higher for etanercept compared with adalimumab (aHR, 1.81; 95% CI, 1.16-2.82), infliximab (aHR, 1.77; 95% CI, 1.03-3.05), and ustekinumab (aHR, 2.49; 95% CI, 1.12-5.52), whereas no difference was observed when comparing these 3 therapies with each other. We found no significant differences in drug survival for biologic-naive vs nonnaive treatment series. Increasing C-reactive protein levels (aHR, 1.01; 95% CI, 1.00-1.03) and concomitant antibiotic treatment (aHR, 2.82; 95% CI, 1.36-5.86) were associated with the risk of discontinuing infliximab therapy. Men (aHR, 0.69; 95% CI, 0.51-0.91) had a reduced risk of discontinuing use of adalimumab.
In this cohort study, drug survival was comparable between adalimumab, infliximab, and ustekinumab but significantly lower for etanercept. There were no differences in drug survival among biologic-naive and nonnaive patients."
"Therapeutic drug monitoring is used to guide anti-tumour necrosis factor [TNF] therapy. However, the associations between serum drug levels [SDL], TNF-bound, and free anti-TNF in the target tissue are incompletely defined. We aimed to assess the interactions between these parameters in inflammatory bowel disease [IBD] patients.
assays [ELISA assays] were used to detect free drug and TNF-drug complexes in intestinal tissues. Concurrent SDL, anti-drug antibodies [ADA], pharmacotherapy, clinical response, endoscopic appearance, and histological severity were determined. Comparisons between anti-TNFs and paired inflamed/non-inflamed tissue were performed. Variables were correlated and potential interactions detected using multivariate analysis.
A total of 95 biopsies taken from 49 anti-TNF treated IBD patients [26 receiving infliximab and 23 adalimumab] were studied. Free drug levels were higher in inflamed compared with non-inflamed paired specimens. Tissue free-drug and TNF-drug complexes levels were higher in adalimumab-treated patients. In adalimumab-treated patients, SDL were correlated with free drug, but not TNF-drug complex levels, in both inflamed and non-inflamed segments. In infliximab-treated patients, higher SDL were associated with the presence of tissue free drug in both inflamed and non-inflamed segments, whereas TNF-drug complexes were mostly detected in non-inflamed but not in inflamed tissue. In the presence of ADA, neither free drug nor TNF-infliximab complexes were measured in the tissue. Tissue levels did not correlate well with clinical, endoscopic, or histological scores.
SDL correlated with tissue free drug levels; however, different dynamics were observed for TNF-drug complex levels. Infliximab and adalimumab tissue drug dynamics differ. Better understanding of these interactions may allow future therapeutic optimisation."
"For inflammatory bowel disease (IBD) therapy, systemic exposure of anti-TNF-α antibodies brought by current clinical injection always causes serious adverse effects. Colon-targeted delivery of anti-TNF-α antibodies through the oral route is of great importance but remains a formidable challenge. Here, we reported a biomimetic nanocomposite made of a ginger-derived exosome and an inorganic framework for this purpose. A large mesoporous silicon nanoparticle (LMSN) was uniquely customized for the antibody (infliximab, INF) to load it at high levels up to 61.3 wt% and prevent its aggregation. Exosome-like nanovesicles were isolated from ginger (GE) with a high-level production (17.5 mg kg"
"Crohn's disease (CD) patients included in the Tailored Treatment With Infliximab for Active Crohn's Disease (TAILORIX) trial started infliximab in combination with an immunosuppressant for 1 year. The aim of the present study was to determine the long-term disease course beyond the study period.
We compared the outcomes of patients who did or did not reach the primary end point of the TAILORIX trial, defined as sustained corticosteroid-free clinical remission from weeks 22 through 54, with no ulcers on ileocolonoscopy at week 54. The primary outcome of this follow-up study was the progression-free survival of CD defined by anal or major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment.
The 95 patients (median disease duration, 4.5 mo; interquartile range, 1.0-56.6 mo) analyzed, including 45 (47%) who achieved the primary end point, were followed up for a median duration of 64.2 months (interquartile range, 57.6-69.9 mo) after the end of the study period. There was no significant difference in CD progression-free survival at 1, 3, and 5 years between patients who achieved the TAILORIX primary end point and patients who did not (P = .64). No difference was observed between both groups for each component of CD progression: anal surgery, major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment.
Achieving a sustained clinical remission off steroids with complete endoscopic remission in this cohort of 95 patients with early CD was not associated with less disease progression. Prospective trials to define the therapeutic goals that change the natural history of CD and prevent complications are needed."
"Although endoscopy is the gold standard to assess disease activity and infliximab efficacy in inflammatory bowel disease (IBD), the invasive, costly, and time-consuming procedure limits its routine applications. We aimed to investigate the clinical value of serum oncostatin M (OSM) as a surrogate biomarker.
Fifty healthy controls, 34 non-IBD patients, and 189 IBD patients who were pre-infliximab treatment (n = 122) or in infliximab maintenance (n = 67) were enrolled. A chemiluminescence immunoassay (CLIA) was constructed to quantify serum OSM concentrations. Receiver operator characteristic (ROC) curve analysis was used to evaluate the performance of blood biomarkers for IBD management.
The methodology of CLIA exhibited great analytical performance with a wide linear range of 31.25-25000 pg/mL, a low detection limit of 23.2 pg/mL, acceptable precision, and applicable accuracy. Patients with IBD (121.5 [43.3-249.4] pg/mL, p < 0.001) and non-IBD (72.4 [51.4-129.6] pg/mL, p = 0.005) had higher serum OSM levels than healthy controls (35.8 [23.2-56.4] pg/mL). In the analysis of clinical and endoscopic activity, serum OSM levels were elevated in moderate and severe patients compared to those in remission. IBD patients without mucosal healing had higher serum OSM levels than those with mucosal healing (AUC = 0.843). Besides, serum OSM levels were increased in clinical non-responders (287.3 [127.9-438] pg/mL) compared to responders (24.1 [23.2-53.4] pg/mL, p < 0.001), and showed great recognition ability with an AUC of 0.898.
The newly developed methodology of CLIA had great potential for use in the clinic. Elevated serum OSM expression was a promising biomarker of severe disease and infliximab non-response in IBD patients."
"Management of Rheumatoid Arthritis (RA) has improved following the implementation of early intensive treat to target recommendations and the availability of different biologicals. Most experience is with TNF blockers, but challenges remain in the efficacy/safety balance, immunogenicity, and long-term drug survival as well as availability and affordability despite the introduction of biosimilars.
We provide an overview of the development of CT-P13 SC based on infliximab biosimilar CT-P13 IV. The one-year pivotal phase I/III trial in RA showed CT-P13 120 mg SC fixed dose to have favorable pharmacokinetics compared to CT-P13 IV classical weight adapted dosing, similar to lower anti-drug antibodies, similar safety and non-inferiority for efficacy at 6 months.
CT-P13 SC is an additional option in RA treatment and by extension for other inflammatory diseases as Inflammatory Bowel Disease. This new way of administration has the potential to improve long-term drug survival of infliximab, improve patient outcomes, and patient comfort."
"The efficacy of diet and its influence on gut microbiome composition has been largely demonstrated in inflammatory bowel disease (IBD). Little is known about its potential in the management of extraintestinal manifestations. We report a successful application of Crohn disease exclusion diet (CDED) in association with infliximab and methotrexate, as salvage therapy in a child affected by chronic recurrent multifocal osteomyelitis (CRMO) and Crohn disease (CD) resistant to optimized therapy. Both intestinal and bone symptoms remitted after the application of CDED. Diet may have acted on common microbic inciting agents that trigger both intestinal and bone inflammation, supporting the role of microbiota in the pathogenesis of IBD-associated extraintestinal manifestations. Our experience suggests the potential benefit of CDED in association with combined therapy in resistant patients affected by CD and extraintestinal manifestations."
"Vaccines to prevent the impact of SARS-CoV-2 are now available, including for patients with autoimmune diseases. However, there is no information about how inflammatory bowel disease (IBD) treatment could impact the cellular and humoral immune responses. This study evaluated SARS-CoV-2-specific humoral and cellular responses after vaccination with a two-dose schedule in a Crohn's disease patient treated with Infliximab (10 mg/kg); we included comparisons with a monozygotic twin. The results showed that the Crohn's disease's twin (twin 2) had no antibody detection and reduced activation of CD4+ T cell responses, unlike the twin without the autoimmune disease (twin 1). Twin 2 developed antigen-specific central memory CD8+ T-cells and IFNγ production after the second dose of COVID-19 vaccination, similar to twin 1. These findings elucidated the role of T-cell immunity after COVID-19 immunization on IBD patients despite the lack of antibody production. Finally, our observation supports the consensus recommendation for IBD patients to receive COVID-19 vaccines."
"Patients with psoriatic arthritis (PsA) often develop joint symptoms years after their initial diagnosis of psoriasis disease; therefore, dermatologists should test for and detect PsA early. In this study, we focused on patients with psoriasis with both nail and joint disease being treated with tumor necrosis factor-α inhibitors by dermatologists. We performed a noninterventional, prospective, multicenter, and open-label study to evaluate the effectiveness of adalimumab, etanercept, or infliximab over 24 months of continuous therapy in patients with moderate to severe plaque-type psoriasis (Pso) and PsA. Disease assessments with the Psoriasis Area and Severity Index, Nail Psoriasis Severity Index (NAPSI), joint assessment, Dermatology Life Quality Index (DLQI), and Health Assessment Questionnaire (HAQ) instruments were performed every 3 months for the first year and twice annually thereafter. The cohort included 100 patients with Pso, nail psoriasis, and PsA. A significant reduction of NAPSI was observed 3 months after therapy initiation compared with the baseline (mean ± SD, 22.9 ± 17.8 vs. 33.8 ± 21.4; "
"Infliximab is an anti-TNF-α monoclonal antibody approved in chronic inflammatory bowel diseases (IBD). This study aimed at providing an in-depth description of infliximab target-mediated pharmacokinetics in 133 IBD patients treated with 5 mg/kg infliximab at weeks 0, 2, 14, and 22. A two-compartment model with double target-mediated drug disposition (TMDD) in both central and peripheral compartments was developed, using a rich database of 26 ankylosing spondylitis patients as a reference for linear elimination kinetics. Population approach and quasi-steady-state (QSS) approximation were used. Concentration-time data were satisfactorily described using the double-TMDD model. Target-mediated parameters of central and peripheral compartments were respectively baseline TNF concentrations (R"
"The use of biological drugs has improved outcomes in pediatric inflammatory bowel disease (IBD). Prediction of the response to biological drugs would be extremely useful in IBD, and even more so in children, who are still growing physically and psychologically. Specific clinical, biochemical, and genetic parameters are considered predictive of response to biological drugs, although few studies have been carried out in children with IBD. In this review, we present current evidence on biological treatments used in pediatric IBD and the available biomarkers of response. We examine demographics, clinical characteristics, biomarkers (genetic, genomic, and cellular), and microbiota."
"The identification and accurate quantitation of the various glycoforms contained in therapeutic monoclonal antibodies (mAbs) is one of the main analytical needs in the biopharmaceutical industry, and glycosylation represents a crucial critical quality attribute (CQA) that needs to be addressed. Currently, the reference method for performing such identification/quantitation consists of the release of the "
"The current COVID-19 outbreak has highlighted the need for the development of new vaccines and drugs to combat Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Recently, various drugs have been proposed as potentially effective against COVID-19, such as remdesivir, infliximab and imatinib. Natural plants have been used as an alternative source of drugs for thousands of years, and some of them are effective for the treatment of various viral diseases. Emodin (1,3,8-trihydroxy-6-methylanthracene-9,10-dione) is a biologically active anthraquinone with antiviral activity that is found in various plants. We studied the selectivity of electrophilic aromatic substitution reactions on an emodin core (halogenation, nitration and sulfonation), which resulted in a library of emodin derivatives. The main aim of this work was to carry out an initial evaluation of the potential to improve the activity of emodin against human coronavirus NL63 (HCoV-NL63) and also to generate a set of initial SAR guidelines. We have prepared emodin derivatives which displayed significant anti-HCoV-NL63 activity. We observed that halogenation of emodin can improve its antiviral activity. The most active compound in this study was the iodinated emodin analogue "
"Vaccination is a promising strategy to protect vulnerable groups like inflammatory bowel disease (IBD) patients against COVID-19 and associated severe outcomes. COVID-19 vaccine clinical trials excluded IBD patients taking infliximab with azathioprine or 6-mercaptopurine (infliximab combination). Therefore, we sought to evaluate serologic responses to COVID-19 vaccination with the mRNA vaccine, BNT162b2, in patients with IBD receiving infliximab combination therapy compared with healthy participants.
This was a multicenter prospective study. Patients with IBD were recruited at the time of attendance at infusion center between 1 August 2021, and 15 September 2021. Our primary outcome were the concentrations of SARS-CoV-2 antibodies 4-10 weeks after vaccination with two doses of BNT162b2 vaccine in patients with IBD taking infliximab combination therapy (study group) compared with a healthy participants group (control group). Both study and control groups were matched for age, sex, and time-since-last-vaccine-dose using optimal pair-matching method.
In total, 116 participants were recruited in the study, 58 patients in the study group and 58 in the control group. Median (IQR) IgG concentrations were lower in the study group (99 BAU/mL (40, 177)) than the control group (139 BAU/mL (120, 188)) following vaccination (
In patients with IBD receiving infliximab combination therapy, SARS-CoV2 IgG, IgA, and neutralizing antibody levels after BNT162b2 vaccination were lower compared with healthy participants. However, most patients treated with infliximab combination therapy seroconverted after two doses of the vaccine."
"Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn's disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar infliximab (CT-P13).
A total of 65 patients (32 with CD and 33 with UC) were recruited. The overall response rate in both CD and UC patients exceeded 80%. There were no significant differences in treatment response and CT-P13 levels for patients with CD or UC. We did not find significant differences in the percentage of patients achieving drug levels of 3 μg/mL at week 6, 10, or 12; a significant decrease was observed at week 14. Up to 55.5% of patients with CD and 64.3% of patients with UC with sub-therapeutic CT-P13 levels at week 14 primarily responded to treatment.
Intermediate measurements of drug levels at weeks 10 and 12 did not capture any pronounced decrease in infliximab concentrations below therapeutic levels in either group, thus suggesting no clinical usefulness. A significant percentage of patients primarily responded to treatment despite sub-therapeutic drug levels after the induction phase."
"Cytomegalovirus (CMV) infection is associated with exacerbation of disease activity in patients with ulcerative colitis (UC). However, the risk factors for CMV reactivation in this population remain debatable. This meta-analysis was performed to identify the risk factors for CMV reactivation in UC patients. PubMed, Cochrane Library, EMBASE, Web of Science, and China National Knowledge Infrastructure were searched&nbsp;from the inception of these databases to 31 August 2021, with the aim of identifying studies that investigated the risk factors of CMV reactivation in UC patients. A quality assessment of the included studies was performed with the Newcastle-Ottawa Scale. The publication bias was assessed respectively via a funnel plot and Egger's regression asymmetry test. The robustness and reliability of each outcome were evaluated by sensitivity analysis. Twenty studies were included in the final meta-analysis, comprising a total of 2099 patients with UC. A significantly higher risk of CMV reactivation was observed in patients with severe UC (OR = 1.465, 95% CI: 1.107 to 1.939, "
"Biologic medications are systemic therapeutic options for inflammatory dermatoses. Local forms of administration are less well-studied. To provide a summary of intralesional (IL) administration of biologics for various non-malignant inflammatory dermatologic conditions reported in the literature. A systematic review was performed in the PubMed and Embase databases from 2000 to 2020. Inclusion criteria included the local use of biologic medications for non-malignant cutaneous conditions. Quality was assessed with the modified Oxford Centre for Evidence-Based Medicine ratings. A total of 19 articles describing the use of 5 biologic medications in 9 dermatologic conditions were identified, comprising 172 patients. Conditions successfully treated with intralesional biologics included pemphigus vulgaris (rituximab), granuloma faciale (rituximab), perianal Crohn's disease (infliximab), lichen sclerosus (adalimumab), and necrobiosis lipoidica (etanercept and infliximab). Intralesional etanercept reduced pruritus associated with keloids. A case report of the use of infliximab for pyoderma gangrenosum did not demonstrate any efficacy. There was no consistent effect noted with treatments for sarcoidosis (infliximab) or cutaneous lymphoid hyperplasia (rituximab). Local administration of biologic medications may offer an additional method of treating refractory inflammatory dermatoses, but further study is needed to develop standardized dosing protocols, clarify efficacy rates, and identify optimal treatment candidates."
Relapses in inflammatory bowel disease (IBD) complicated by 
"Pigmented villonodular synovitis (PVNS) is a rare disease that has clinical and histopathological characteristics of both benign proliferative disorder and a chronic inflammatory process of the synovial tissue. The primary mode of treatment is surgery followed by an adjuvant radiotherapy; however, the risk of recurrence is a significant (40-70%). Several publications suggest that the TNF-α inhibitors might be a treatment option. We present a case of a 29-year-old female diagnosed with PVNS of the knee joint, refractory to surgery and 3 radionuclide synovectomies. Because the possibilities of conventional therapy were exhausted, treatment with an intra-articular anti-TNF-α monoclonal antibody (infliximab) was performed. Despite a high safety profile and a good tolerance of that therapy we did not observe significant clinical and radiological improvement. To assess the effectiveness of intra-articular TNF-α inhibitors as an adjuvant treatment in PVNS, prospective studies are needed."
"Biologics are indicated for the treatment of a wide range of conditions and have transformed care in several therapeutic areas; however, they are expensive for both health care systems and patients. The use of biosimilars, which are approved by the US Food and Drug Administration as being ""highly similar"" to the originator biologic, has the potential to change the health care landscape in the biologic space through considerable cost savings for both payors and patients. With the introduction of biosimilars, organizations are increasingly evaluating how to switch patients from originator biologics to biosimilars. While published studies have evaluated the outcomes of patients switched from originator biologics to biosimilars, there are few publications describing the process health care systems have used to adopt and switch patients to biosimilars. Since 2016, Kaiser Permanente Colorado (KPCO) has undertaken several biosimilar switches starting with the first biosimilar introduced to the market, filgrastim, and has been able to successfully switch 91.8% of patients receiving infliximab, 99.8% receiving rituximab, and 100% receiving filgrastim, trastuzumab, and bevacizumab originator biologics to their respective biosimilars. In an effort to support other health care systems and provide a framework for implementing biosimilar switches, the purpose of this paper is to describe the biosimilar switch model and share learnings from the KPCO experience."
"Biologics are a good therapeutic option for severe, chronic plaque psoriasis; however, they come with significant cost to the health care system.
To conduct a cost-utility analysis of outpatient biologics (adalimumab, etanercept, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab) available to adults with severe, chronic plaque psoriasis from the perspective of the Australian health care system.
A Markov cohort model was constructed to estimate the quality-adjusted life years (QALYs) and costs accrued for treatment pathways commencing with different first-line biologics, over a 96-week time horizon. The model adhered to the Australian Pharmaceutical Benefits Scheme eligibility criteria and guidelines.
A biologic treatment pathway commencing on tildrakizumab was the most cost-effective first-line treatment (Australian dollar 39,930; total utility of 1.57 QALYs over 96 weeks). First-line secukinumab and risankizumab had incremental cost-utility ratios of Australian dollar 194,524/QALY and Australian dollar 479,834/QALY, respectively, when compared with first-line tildrakizumab.
The efficacy and utility input parameters were derived from international randomized control trials and patients from the United Kingdom, respectively. Findings from this study cannot be generalized beyond Australia.
Tildrakizumab may be considered as first-line treatment for adult patients with severe, chronic plaque psoriasis embarking on biologic therapy, from the economic perspective of the Australian health care system."
"Several Canadian provinces have introduced reimbursement policies mandating substitution of innovator biologics with lower-cost biosimilars. We estimated the number of patients affected and cost implications if such policy changes were to be implemented in Ontario, Canada.
We conducted a cross-sectional time series analysis of Ontarians dispensed publicly funded biologics indicated for inflammatory diseases (rheumatic conditions, inflammatory bowel disease: infliximab, etanercept, adalimumab) between January 2018 and December 2019, and forecasted trends to Dec. 31, 2020. The primary source of data was pharmacy claims data for all biologics reimbursed by the public drug program. We modelled the number of patients affected and government expenditures (in nominal Canadian dollars) of several biosimilar policy options, including mandatory nonmedical biosimilar substitution, substitution in new users, introduction of a biosimilar for adalimumab, and price negotiations. In a secondary analysis, we included insulin glargine.
In 2018, 14 089 individuals were prescribed a publicly funded biologic for inflammatory diseases. A mandatory nonmedical biosimilar substitution would potentially have affected 7209 patients and saved $238.6 million from 2018 to 2020. A new-user substitution would have affected 757 patients and saved $34.2 million. If an adalimumab biosimilar were to become available, 12 928 patients would be affected by a mandatory nonmedical substitution and the 3-year savings would increase to $645.9 million (all biosimilars priced at 25% of innovator biologics). Finally, an expanded nonmedical substitution policy including insulin glargine would affect 115 895 patients and save $288.7 million (not including adalimumab).
Policies designed to curb rising costs of biologics can have substantially different effects on patients and government expenditures. Such analyses warrant careful consideration of the balance between cost savings and effects on patients."
"Ion mobility-mass spectrometry (IM-MS) and collision-induced unfolding (CIU) assays of monoclonal antibody (mAb)-based biotherapeutics have proven sensitive to disulfide bridge structures, glycosylation patterns, and small molecule conjugation levels. Despite promising prior reports detailing the capabilities of IM-MS and CIU to differentiate biosimilars, generic mAb therapeutics, there remain questions surrounding the sensitivity of CIU to mAb structure changes that occur upon stress, the reproducibility of such measurements across IM-MS platforms, and the correlation between CIU and differential scanning calorimetry (DSC) datasets. In this report, we describe a comprehensive IM-MS and CIU dataset acquired for three Infliximabs: Remicade, Inflectra, and Renflexis. We subject each infliximab sample to forced degradation through heat stress and observe broadly similar yet subtly different stability patterns for these three biotherapeutics. We find that CIU is capable of tracking differences in mAb higher-order structure (HOS) imparted during forced heat stress degradation and that DSC is less sensitive to these alterations in comparison. Furthermore, we collected our comprehensive IM-MS and CIU data across two instrument platforms (Waters G2 and Agilent 6560), with both producing similar abilities to differentiate mAbs while also revealing minor differences between the results obtained on the two instruments. Finally, we demonstrate that CIU-based heatmaps and classification allow for rapid assessment of the most differentiating charge states for the analysis of infliximab, and using multiplexed classification, we conservatively estimate a 30-fold improvement in the time required to perform mAb stability and HOS measurements over standard DSC tools."
"Deep remission (DR) defined by clinical-biomarker remission and mucosal healing (MH) has emerged as a new therapeutic target in inflammatory bowel disease (IBD). The aim of this study was to define an optimal cut-off concentration for IFX and ADA during maintenance therapy associated with DR. The secondary objective, was to evaluate the influence of variables on anti-TNF concentrations and DR.
Retrospective study including 120 and 122 patients IBD diagnosed who received maintenance therapy with IFX and ADA. Biomarker remission was considered by C-reactive protein (CRP)&lt;5 mg/L and fecal calprotectin (CF)&lt;100 mcg/g. Crohn's disease (CD) clinical remission was defined by a Harvey Bradshaw score&lt;5 and MH by a simple endoscopic score for CD (SES-CD)&lt;3.  In ulcerative colitis (UC), it was defined as a Mayo total score&lt;3 and Mayo endoscopic subscore&lt;2. Receiver operating characteristic (ROC) test was performed to determine drug concentration thresholds associated with DR. Anti-TNF concentrations were classified into quartiles. X2 and Kruskal-Wallis test were used to compare discrete and continuous variables between quartile groups. Multivariate logistic regression was performed to identify patient characteristics and serological factors associated with DR.
Anti-TNF concentrations were higher in patients with DR, in IFX (4.4, IQR: 3.3-6.5 vs 2.3, IQR: 1.1-4.2 μg/mL, P&lt;0.005) and ADA (6.3, IQR: 4.2-8.2 vs 3.9, IQR: 2.4-5.5 μg/mL, P&lt;0.005). A ROC identified a concentration threshold of 3.1 μg/mL in IFX (area under the ROC curve [AUROC], 0.72) and 6.3 μg/mL in ADA (AUROC, 0.75) associated with DR. Factors associated with the highest quartiles of serum IFX concentration were: elevated body mass index (BMI), absence of previous IBD-surgery, CRP&lt;5 mg/L, and FC&lt;100 μg/g. In ADA, higher quartiles were related to concomitant immunosuppressants, low BMI, absence of previous IBD-surgery, and CRP&lt;5 mg/L and FC&lt;100 μg/g. Multivariate regression identified FC&lt;100 μg/g, CRP&lt;5mg/L, IFX ≥3.1μg/mL and ADA concentrations ≥6.3μg/mL as factors significantly associated with DR.  CONCLUSIONS: Trough IFX and ADA concentrations, CRP&lt;5mg/L and FC&lt;100 μg/g are associated with DR during maintenance therapy. Cutoff point of 3.1 and 6.3 g/mL for IFX and ADA respectively, were identified as DR predictors.
Objetivo: La remisión profunda, definida como remisión clínico-analítica y  curación de la mucosa, es el objetivo terapéutico en la enfermedad inflamatoria intestinal. En este estudio se define el punto de  corte óptimo de concentración valle de infliximab y adalimumab asociado a  remisión profunda en fase de mantenimiento. El objetivo secundario es  evaluar las covariables relacionadas con las concentraciones de antifactor de necrosis tumoral y la remisión profunda.Método: Estudio retrospectivo que incluyó 120 y 122 pacientes  diagnosticados de enfermedad inflamatoria intestinal tratados con infliximab y adalimumab. La proteína C reactiva &lt; 5 mg/l y la calprotectina  fecal &lt; 100 μg/g se consideró para remisión analítica. En la enfermedad de Crohn, la remisión clínica se definió mediante puntuación Harvey  Bradshaw &lt; 5; la curación de la mucosa por puntuación endoscópica simple para enfermedad de Crohn &lt; 3; en colitis ulcerosa, por índice total de Mayo &lt; 3 e índice subendoscópico de Mayo &lt; 2. Se realizó un análisis por  curva de eficacia diagnóstica para determinar el cutoff asociado  a remisión profunda. Las concentraciones de antifactor de necrosis tumoral se clasificaron en cuartiles. Se utilizó la prueba X2 y Kruskal-Wallis para comparar variables discretas o continuas. Se realizó una  regresión  logística multivariante para identificar las características de  pacientes y serológicas asociadas a remisión profunda.Resultados: Las concentraciones de antifactor de necrosis tumoral fueron  superiores en remisión profunda en comparación con los que no la  alcanzaron en infliximab (4,4; rango intercuartílico: 3,3-6,5 versus 2,3;  rango intercuartílico: 1,1-4,2 μg/ml; P &lt; 0,005) y adalimumab (6,3; rango  intercuartílico: 4,2-8,2 versus 3,9; rango intercuartílico: 2,4-5,5 μg/ml; P &lt;  0,005). Se identificó un cutoff de 3,1 μg/ml en infliximab (área bajo la curva  de eficacia diagnóstica 0,72), y 6,3 μg/ml en adalimumab (área bajo la curva de eficacia diagnóstica 0,75). Los factores asociados a concentraciones  más elevadas de infliximab fueron: elevado índice de masa  corporal, ausencia de cirugía previa de enfermedad inflamatoria intestinal,  proteína C reactiva &lt; 5 mg/l y calprotectina fecal &lt; 100 μg/g. En  adalimumab, concentraciones más altas se relacionaron con  oadministración  de inmunosupresores, bajo índice de masa corporal,  ausencia de cirugía previa, proteína C reactiva &lt; 5 mg/l y calprotectina fecal  &lt; 100 μg/g. Se identificó calprotectina fecal &lt; 100 μg/g, proteína C reactiva  &lt; 5 mg/l, infliximab ≥ 3,1 μg/ml y adalimumab ≥ 6,3 μg/ml como factores  asociados a remisión profunda.logística multivariante para identificar las características de pacientes yserológicas asociadas a remisión profunda.Resultados: Las concentraciones de antifactor de necrosis tumoral fueronsuperiores en remisión profunda en comparación con los que no la alcanzaronen infliximab (4,4; rango intercuartílico: 3,3-6,5 versus 2,3; rango intercuartílico:1,1-4,2 μg/ml; P &lt; 0,005) y adalimumab (6,3; rango intercuartílico:4,2-8,2 versus 3,9; rango intercuartílico: 2,4-5,5 μg/ml; P &lt; 0,005).Se identificó un cutoff de 3,1 μg/ml en infliximab (área bajo la curva deeficacia diagnóstica 0,72), y 6,3 μg/ml en adalimumab (área bajo la curvade eficacia diagnóstica 0,75). Los factores asociados a concentraciones máselevadas de infliximab fueron: elevado índice de masa corporal, ausenciade cirugía previa de enfermedad inflamatoria intestinal, proteína C reactiva&lt; 5 mg/l y calprotectina fecal &lt; 100 μg/g. En adalimumab, concentracionesmás altas se relacionaron con coadministración de inmunosupresores,bajo índice de masa corporal, ausencia de cirugía previa, proteína C reactiva&lt; 5 mg/l y calprotectina fecal &lt; 100 μg/g. Se identificó calprotectinafecal &lt; 100 μg/g, proteína C reactiva &lt; 5 mg/l, infliximab ≥ 3,1 μg/ml yadalimumab ≥ 6,3 μg/ml como factores asociados a remisión profunda.Conclusiones: Las concentraciones valle de infliximab y adalimumab, proteínaC reactiva &lt; 5 mg/l y calprotectina fecal &lt; 100 μg/g se asocian a remisiónprofunda. Se identifican concentraciones cutoff de 3,1 y 6,3 μg/ml en infliximaby adalimumab, respectivamente, como predictoras de remisión profunda."
"This phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade
Patients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity.
A total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62-68.20%) and 56.89% for the INF group (95% CI 50.90-62.74%). The difference between the two groups was 5.65% with a 95% CI of - 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable.
GB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF."
"Home infusions (HIs) for biologic medications are an option for inflammatory bowel disease (IBD) patients in the United States. We aimed to describe the population receiving HIs and report patient experience with HIs.
We conducted a retrospective cohort study in the Quintiles-IMSLegacy PharMetrics Adjudicated Claims Database from 2010 to 2016 to describe the population receiving infliximab (IFX) and vedolizumab (VDZ) HIs and determine predictors for an urgent/emergent visit post-HIs. We then administered a cross-sectional survey to IBD Partners Internet-based cohort participants to assess knowledge and experience with infusions.
We identified claims for 11 892 conventional IFX patients, 1573 home IFX patients, 438 conventional VDZ patients, and 138 home VDZ patients. There were no differences in demographics or median charges with IFX home and conventional infusions. Home VDZ infusions had a greater median charge than conventional VDZ infusion. Less than 4% of patients had an urgent/emergent visit post-HIs. Charlson comorbidity index > 0 (odds ratio [OR]: 1.95; 95% confidence interval [CI], 1.01-3.77) and Medicaid (OR: 3.01; 95% CI, 1.53-5.94) conferred significantly higher odds of urgent/emergent visit post-HIs. In IBD Partners, 644 IBD patients responded; 56 received HIs. The majority chose HIs to save time and preferred HIs to conventional infusions. Only 2 patients reported an urgent/emergent visit for HI-related problems.
HI appears to be safe in IBD patients receiving IFX and VDZ. However, patients with fewer resources and more comorbidities are at increased risk for an urgent/emergent visit post-HIs. The overall patient experience with HI is positive. Expansion of HIs may result in decreased therapy-related logistic burden for carefully selected patients."
"Acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) is associated with decreased aquaporin-5 (AQP5) expression. Lipopolysaccharides (LPS) can decrease AQP5 expression. The effects and mechanisms of lidocaine pretreatment on primary alveolar epithelium type II (AEC II) cells injured by LPS were investigated. Primary AEC II cells were isolated from rats previously injured with LPS as an ALI model. The groups of cells were evaluated: 1) pretreated with lidocaine (2, 20, 200μg/ml) and/or Infliximab, an anti-TNF-α neutralizing antibody, 2) uninjured cells; 3) solvent pretreated injured cells and 4) untreated injured cells as controls. TNF-α levels were evaluated by ELISA. AQP5 expression was determined by mRNA and protein expression (q-PCR and western blot).The release of TNF-α was increased significantly in AEC II cells following LPS injury. The release of TNF-α was decreased by 33%-100% as a result of lidocaine pretreatment in a dose-dependent fashion. This decrease was accompanied by up-regulated AQP5 expression in LPS injured AEC II cells, and Infliximab can greatly block AQP5 expression in LPS injured AEC II cells pretreated with lidocaine. Lidocaine pretreatment (2-200μg/ml) of LPS injured AEC II cells results in a decrease in TNF-α release, then up-regulates AQP5 expression, which maybe involved in the mechanism of its effects on AEC II cells injured by LPS."
"Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis.
We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment.
Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment.
To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint.
F Hoffmann-La Roche."
"Immunogenicity with formation of anti-drug antibodies (ADA) to biologics is an important reason for treatment failure in inflammatory bowel disease (IBD). Our aim was to assess the rate of ADA, the effect of combination therapy with immunomodulators on ADA and the influence of ADA on efficacy and safety of biologics for IBD treatment.
MEDLINE, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to April 2020 for trials of biologics that assessed immunogenicity. The overall certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). The primary outcome was rate of ADA. Secondary outcomes included efficacy and safety outcomes among patients with detectable versus undetectable ADA. For dichotomous outcomes, pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated.
Data from 68 studies were analyzed and 33 studies (5850 patients) were included in the meta-analysis. Pooled ADA rates for biologic monotherapy were 28.0% for infliximab, 7.5% for adalimumab, 3.8% for golimumab, 10.9% for certolizumab, 6.2% for ustekinumab and 16.0% for natalizumab. Pooled ADA rates were 8.4% for vedolizumab and 5.0% for etrolizumab for combo- and monotherapy combined. In all biologics, ADA rates were underestimated by use of drug-sensitive ADA assays and higher dose and/or frequency. ADA rate was significantly reduced in patients treated with combination therapy for infliximab (RR 0.52; 95% CI 0.44-0.62), adalimumab (RR 0.31; 95% CI 0.14-0.69), golimumab (RR 0.29; 95% CI 0.10-0.83), certolizumab pegol (RR 0.30; 95% CI 0.14-0.67) and natalizumab (RR 0.20; 95% CI 0.11-0. 39). ADA to infliximab were associated with lower clinical response rates (RR 0.75; 95% CI 0.61-0.91) and higher rates of infusion reactions (RR 2.36; 95% CI 1.85-3.01).
Differences in analytical methods to detect ADA hamper comparison of true ADA rates across biologics in IBD. Use of combination therapy with immunomodulators appeared to reduce ADA positivity for most biologics. For infliximab, ADA were associated with reduced drug efficacy and increased adverse events."
"Uveitis is an inflammation of the iris, ciliary body, vitreous, retina, or choroid, which has been shown to be the first manifestation of numerous systemic diseases. Studies about the immunopathogenesis and treatment of uveitis are helpful to comprehend systemic autoimmune diseases, and delay the progression of systemic autoimmune diseases, respectively. Tumor necrosis factor-alpha (TNF-α), a pleiotropic cytokine, plays a pivotal role in intraocular inflammation based on experimental and clinical data. Evidence of the feasibility of using anti-TNF-α agents for uveitis management has increased. Although there are numerous studies on TNF-α in various autoimmune diseases, the pathological mechanism and research progress of TNF-α in uveitis have not been reviewed. Therefore, the objective of this review is to provide a background on the role of TNF-α in the immunopathogenesis of uveitis, as well as from bench to clinical research progress, to better guide TNF-α-based therapeutics for uveitis."
"To analyze the factors associated with response (control of ocular inflammation and corticosteroid-sparing effect) to biologics (anti-tumor necrosis factor [TNF]-α agents and tocilizumab) in patients with refractory uveitic macular edema (ME).
Multicenter, retrospective, observational study.
Adult patients with uveitic ME refractory to systemic corticosteroids, disease-modifying antirheumatic drugs, or both.
Patients received anti-TNF-α agents (infliximab 5 mg/kg at week 0, 2, 6, and every 4-6 weeks [n = 69] and adalimumab 40 mg/2 weeks [n = 80]) and tocilizumab (8 mg/kg every 4 weeks intravenously [n = 39] and 162 mg/week subcutaneously [n = 16]).
Analysis of complete and partial response rates, relapse rate, low vision (visual acuity in at least 1 eye of ≥ 1 logarithm of the minimum angle of resolution), corticosteroid-sparing effect, and adverse events at 6 months.
Two hundred four patients (median age, 40 years [interquartile range, 28-58 years]; 42.2% men) were included. Main causes of uveitis included Behçet's disease (17.2%), birdshot chorioretinopathy (11.3%), and sarcoidosis (7.4%). The overall response rate at 6 months was 46.2% (21.8% of complete response) with anti-TNF-α agents and 58.5% (35.8% of complete response) with tocilizumab. In multivariate analysis, treatment with tocilizumab (odds ratio, 2.10; 95% confidence interval [CI], 1.06-4.06; P = 0.03) was associated independently with complete response of uveitic ME compared with anti-TNF-α agents. Anti-TNF-α agents and tocilizumab did not differ significantly in terms of relapse rate (hazard ratio, 1.00; 95% CI, 0.31-3.18; P = 0.99) or occurrence of low vision (odds ratio, 1.02; 95% CI, 0.51-2.07; P = 0.95) or corticosteroid-sparing effect (P = 0.29). Adverse events were reported in 20.6% of patients, including serious adverse events reported in 10.8% of patients.
Tocilizumab seems to improve complete response of uveitic ME compared with anti-TNF-α agents."
"RA patients who fail to respond to MTX can receive biologic dMARDs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and its association with clinical response to bDMARDs.
The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-Ig (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood.
TTV was measured in 95 patients (INF, n = 23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5 × 104 copies/ml [c/ml; interquartile range (IQR) 0-7.5 × 105] after 3 months. TTV levels at month 3 were associated with the Simplified Disease Activity Index (SDAI) (P = 0.03) and the Clinical Disease Activity Index (CDAI) response (P = 0.026) at month 6. A TTV cut-off level of 1.2 × 106 c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of an 85% reduction in SDAI at month 6.
Our data suggest that TTV levels increase upon TNF, CD20 and costimulation blockade and are associated with the clinical response to bDMARDs in RA patients.
ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715."
"Crohn's disease and ulcerative colitis evolve with alternate outbreaks and remissions of variable duration in both cases. Despite the advances, about 10-30% of patients do not respond to the treatment after the induction period. Besides, between 20% to 50% further patients need an optimization of the dose to respond the treatment. Recent studies have pointed gut microbiota can play a role in the anti-TNF treatment response. This study aimed to define a bacterial signature that could be used to predict the response of patients to anti-TNF treatment.
There were obtained 38 stool samples from 38 IBD patients before starting anti-TNF treatments: Adalimumab, Golimumab or Infliximab. Patients were differentiated in 2 groups: responders and non-responders to biological treatment. From each sample, DNA was purified and used in a qPCR for the quantification of the 8 microbial markers.
In this proof of concept, the predictive ability to identify anti-TNF treatment responders was analyzed. An algorithm consisting in the combination of 4 bacterial markers showed a high capacity to discriminate between responders and non- responders. The algorithm proved high sensitivity and specificity reporting values of 93.33% and 100% respectively, with a positive predictive value of 100% and a negative predictive value of 75% for predicting response to biologic treatment.
A specific bacterial signature could beneficiate patients with inflammatory bowel disease predicting the therapeutic effectiveness of an anti-TNF treatment, leading to a personalized therapy, improving the patients' quality of life, saving costs and gaining time in patient improvement.
This study aimed to define a microbial signature that could be used to predict the response of patients to anti-TNF treatment in inflammatory bowel disease. An algorithm consisting in the combination of 4 bacterial markers showed a high capacity to discriminate between responders and nonresponders."
"The risk of thromboembolism (TE) is increased in patients with inflammatory bowel disease (IBD), mainly due to an increased risk of venous TE (VTE). The risk of arterial TE (ATE) is less pronounced, but an increased risk of cardiovascular diseases needs to be addressed in IBD patients. IBD predisposes to arterial and venous thrombosis through similar prothrombotic mechanisms, including triggering activation of coagulation, in part mediated by impairment of the intestinal barrier and released bacterial components. VTE in IBD has clinical specificities, "
"Current treatment guidelines for immune-mediated diarrhea and colitis (IMDC) recommend steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) for refractory cases. We aimed to compare the efficacy of these two SITs and their impact on cancer outcomes.
We performed a two-center, retrospective observational cohort study of patients with IMDC who received SITs following steroids from 2016 to 2020. Patients' demographic, clinical, and overall survival data were collected and analyzed.
A total of 184 patients (62 vedolizumab, 94 infliximab, 28 combined sequentially) were included. The efficacy of achieving clinical remission of IMDC was similar (89% vs 88%, p=0.79) between the two groups. Compared with the infliximab group, the vedolizumab group had a shorter steroid exposure (35 vs 50 days, p<0.001), fewer hospitalizations (16% vs 28%, p=0.005), and a shorter hospital stay (median 10.5 vs 13.5 days, p=0.043), but a longer time to clinical response (17.5 vs 13 days, p=0.012). Longer durations of immune checkpoint inhibitors treatment (OR 1.01, p=0.004) and steroid use (OR 1.02, p=0.043), and infliximab use alone (OR 2.51, p=0.039) were associated with higher IMDC recurrence. Furthermore, ≥3 doses of SIT (p=0.011), and fewer steroid tapering attempts (p=0.012) were associated with favorable overall survival.
Treatment with vedolizumab as compared with infliximab for IMDC led to comparable IMDC response rates, shorter duration of steroid use, fewer hospitalizations, and lower IMDC recurrence, though with slightly longer time to IMDC response. Higher number of SIT doses was associated with better survival outcome, while more steroid exposure resulted in worse patient outcomes."
"An 11-year-old boy presented with 2 weeks of intermittent headache, right orbital pain, and constant diplopia. Brain MRI showed dural thickening and enhancement of the right lateral cavernous sinus, right orbital apex, and tentorium. Initial cerebral spinal fluid analysis showed only mild pleocytosis, and serum diagnostics were unrevealing. The working diagnosis was Tolosa-Hunt syndrome. His pain and sixth nerve palsy resolved with corticosteroids. Five months after initial presentation, he developed new numbness of the right cheek, complete right ophthalmoplegia, and weakness and numbness of his right hand and leg, all of which were responsive to steroids. Fifteen months later, he returned to the emergency department with 2 weeks of left-sided headaches and acute diplopia. On examination, he had a left cranial nerve 6 palsy. Dural biopsy showed diffuse mononuclear inflammatory cell reaction consisting mostly of lymphocytes with no signs of granuloma formation, nor any epithelioid or giant cells. His clinical course was consistent with an autoinflammatory condition of unknown etiology. Genetic testing with an immunodeficiency panel showed a risk allele in NOD2 (nucleotide-binding oligomerization domain 2) c.3019dup (p.Leu1007Prof*2) that is associated with an increased risk for Crohn disease. His clinical condition had similarities to central nervous system sarcoidosis. Because of the similarities between our patient's clinical, imaging, and genetic findings and neurosarcoidosis, he was switched to a more targeted therapy-infliximab. His condition has since been stable for nearly 2 years. In conclusion, genetic testing should be considered in patients with suspected occult autoimmunity."
"Orbital myositis is a common cause of orbital inflammation with localized involvement of the extra ocular muscles. This study aimed to assess the value of infliximab in controlling orbital myositis and reducing its relapse rate.
We conducted a retrospective review of the medical records of all consecutive patients with orbital myositis treated with infliximab between 2007 and 2016. We examined change in corticosteroid and immunomodulatory doses as well as relapse rates following treatment with infliximab.
The study included seven patients with an average follow up of 19 ± 13.4 months. The mean dose of systemic corticosteroid was reduced from 28.57 ± 14.35 mg/day at the time of infliximab initiation to 7.00 ± 6.83 mg/day at final follow-up (
This study supports the role of infliximab in treating refractory orbital myositis and this was associated with clinical improvement, decreasing relapse rate with dose reduction of conventional treatment."
"The prediction of the real-world cost of adverse drug reactions (ADRs) has historically relied on the data from randomized controlled trials (RCT). However, trial conditions do not always reflect the real-world applications of pharmaceutical products; hence, they may not accurately portray the actual risks of ADRs associated with them. The objective of this study is two-fold: (a) demonstrate whether and how post-market and RCT ADR data could lead to different conclusions for a set of drugs of interest, and (b) evaluate the potential economic impact of the post-market ADRs associated with those drugs.
We selected two TNF-α inhibitor biologics, infliximab and adalimumab, and used the Canada Vigilance Adverse Reaction (CVAR) online database as a source of post-market ADR data. Adverse reaction data from RCTs were obtained from ClinicalTrials.gov . Direct healthcare costs associated with adverse reactions were obtained from Canadian Institute for Health Information (CIHI) or Interactive Health Data Application, Alberta. We calculated post-market ADR rates and compared them with those found in the randomized controlled trials of these two drugs. Using the post-market data, we estimated the costs associated with serious ADRs from three perspectives: patient, health system, and societal.
For both drugs, the post-market and RCT data exhibited significantly different adverse reaction rates for several different clinical outcomes. As a general trend, more serious adverse reactions, such as death, appeared to have a higher rate in post-market applications compared to the clinical trials. The estimated average annual economic burden of the severe adverse reaction outcomes ranged from $10 million to $20 million for infliximab and $6 million to $19 million for adalimumab.
The frequency and severity of post-market adverse reactions associated with pharmaceutical products may significantly differ from those detected in the clinical trials. Despite possible methodological differences, this is due to the fact that post-market data reflect the externalities of the real-world that are absent in RCTs. The economic burden of adverse reactions can be substantial, and the cost calculated using post-market data is better reflective of the cost of ADRs in the real-world."
"Therapeutic drug monitoring (TDM) is a useful strategy to optimize biologic medications for inflammatory bowel disease not responsive to standard dosing regimens. TDM is cost effective for anti-tumor necrosis factor agents in the setting of loss of response (reactive TDM). Optimizing drug dosing when patients are in remission (proactive TDM) may be beneficial in certain circumstances. However, frequently the serum drug concentration in isolation becomes the focus TDM. Additionally, the lines of reactive and proactive TDM can quickly blur in many common clinical settings. Physicians employing a TDM based strategy need to place the drug concentration in context with the inflammatory status of the patient, the underlying pharmacokinetics and pharmacodynamics of the drug, the risk of immunogenicity, and the therapeutic goals for the patient. Physicians should understand the limits of TDM and feel comfortable making therapeutic decisions with imperfect information. The goal of this narrative review is to provide a framework of questions that physicians can use to employ TDM effectively in practice."
"BACKGROUND Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease of the colon that infrequently affects children. The disease requires immunosuppressive therapy to achieve remission and keep the disease in remission. Currently, many therapies are approved for use in pediatric patients with UC, including steroid, 5-aminosalicylic acid (5-ASA), azathioprine, and biologic therapy with anti-tumor necrosis factor (TNF) inhibitors. Despite their efficacy, many patients have refractory severe disease that fails therapy and may require surgical interventions. Recently, the small molecule Janus Kinase (JAK) inhibitor tofacitinib has been approved for moderate to severe UC that fails biologic therapy in adults. However, the safety and efficacy of this drug has not been tested in pediatric UC patients. CASE REPORT We describe a case of a 13-year-old girl with 2-year history of severe UC who had secondary loss response to both infliximab and adalimumab over 2 years, despite adequate trough serum drug levels and the concomitant use of azathioprine. She was also dependent on steroid to control her disease. Infectious work-ups were always negative for infectious organisms. She was then successfully treated with tofacitinib 5 mg orally twice daily. She went into complete clinical, endoscopic, and steroid-free remission. CONCLUSIONS This case report highlights the safety and efficacy of tofacitinib in pediatric patients with severe refractory UC, potentially avoiding proctocolectomy in this young patient population. Future research should study the role of tofacitinib in patients with moderate to severe UC in children."
"Vascular complications of Behcet'sdisease, including intracardiac thrombus formation, are one of the significant causes of mortality and morbidity in this population. Similar to other vasculitic disorders, Behcet's disease is primarily treated with immunosuppressants. While the benefit of adding anticoagulants in Behcet's disease with thromboembolism remains debatable, some literature encourages its use with concomitant intracardiac thrombus. Herewith, we present the case of a young male who was diagnosed with bilateral pulmonary embolism in addition to right ventricle intracardiac thrombus upon his scheduled dose of infliximab infusion. He was managed by adding azathioprine to his regimen together with oral prednisolone and warfarin with a target international normalized ratio of 2-3. This case report addresses the importance and outcome of early identification of Behcet's disease's vascular complications and immediate initiation of anticoagulation accordingly."
"Infliximab is an efficacious therapy for inflammatory bowel disease and may play a role in management of some extraintestinal manifestations. While higher trough levels of infliximab are associated with higher rates of disease remission, the association between trough levels of infliximab and arthralgia activity characterised as an extraintestinal manifestation has yet to be defined.
We aimed to assess the association between serum trough levels of infliximab and peripheral arthralgia activity in patients with inflammatory bowel disease.
In this cross-sectional study, we identified patients with inflammatory bowel disease on infliximab therapy with known history of arthralgias attributed to an extraintestinal manifestation. Collected variables included disease phenotype, medications (such as thiopurines or methotrexate), Harvey Bradshaw Index, partial Mayo score, C reactive protein, trough levels of infliximab and anti-infliximab antibodies. The primary outcome was active patient-reported arthralgia.
Out of 267 patients included, 65 (24.4%) had active arthralgias at the time the trough level of infliximab was measured. No significant differences in trough levels were seen between those patients with and without arthralgias. Patients on combination therapy with methotrexate or thiopurines or those with detectable anti-infliximab antibodies were not more likely to have inactive arthralgias (OR 0.99, 95% CI 0.57 to 1.74, p=0.99 and OR 1.94, 95% CI 0.9 to 4.1, p=0.09, respectively).
This study suggests that although therapeutic drug monitoring of infliximab can have a role in the management of Crohn's disease and ulcerative colitis, it does not seem to be useful in managing arthralgias associated with inflammatory bowel disease."
"Chronic granulomatous disease (CGD) is an inborn error of immunity caused by inactivating genetic mutations in any one of the components of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Phagocytic cell reactive oxygen species generation is impaired in the absence of a functional NADPH oxidase complex. As a result, patients with CGD are at high risk of developing deep-seated infections with certain bacteria and fungi. Additionally, aberrant inflammation and granuloma formation may occur in multiple organs including the bowels, with inflammatory bowel disease seen as a common inflammatory complication of CGD. Traditionally, TNF-α inhibitors are considered effective biological therapies for moderate-to-severe inflammatory bowel disease. While limited case series and reports of patients with CGD have shown improvement in fistula healing with use of TNF-α inhibitors, several patients have developed severe, even fatal, infections with CGD-related pathogens while on TNF-inhibitor therapy. In this case report, we describe an adolescent male with X-linked CGD and steroid-refractory colitis with perirectal fistula and abscesses, who was initiated on treatment with infliximab, a TNF-α inhibitor. Following his first two infliximab doses, the patient developed a "
ABP 710 (AVSOLA
"Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn's disease (CD).
This was a systematic review and individual-patient data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (October 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction of remission in patients with short-duration (≤18 months) vs long-duration disease (>18 months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome.
We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab (6168 patients with CD and 3227 patients with UC). In CD, remission induction rates were higher in pooled placebo and patients in active arms with short-duration disease of ≤18 months (41.4% [244 of 589]) compared with disease duration of >18 months (29.8% [852 of 2857], meta-analytically estimated odds ratio, 1.33; 95% confidence interval, 1.09-1.64). The primary outcome, proportional biologic/placebo treatment effect on induction of remission, was not different in short-duration disease of ≤18 months (n = 589, odds ratio, 1.47; 95% confidence interval, 1.01-2.15) compared with longer disease duration (n = 2857, odds ratio, 1.43; 95% confidence interval, 1.19-1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable, regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cutoffs and when modeled for individual patient's covariates, including prior anti-tumor necrosis factor exposure.
There are higher rates of induction of remission with biologics and with placebo in early CD, resulting in a treatment to placebo effect ratio that is similar across disease durations. No such relationships between disease duration and outcomes was found in UC. PROSPERO registration: CRD42018041961."
"This article highlights one health system's response to the market influx of biosimilars with the establishment of a process for formulary review and selection of preferred agents and support for therapeutic interchanges.
Through assessment of available literature, insurance payor coverage, and manufacturer-anticipated approvals of biosimilars, a strategic stance was developed to guide biosimilar order preparation, review, adoption, and implementation. The electronic medical record (EMR) is prepared for biosimilar implementation at least 6 to 12 months ahead of anticipated formulary review. The review includes assessment of a class (reference product and available biosimilars) after at least 2 biosimilars become available. Key health-system departments and clinicians are enlisted to support review of clinical, safety, and economic implications. Implementation of a preferred product relies on standard education, formulary availability, and staff awareness to address any perceived patient safety concerns and gather provider support. The standard steps developed now apply to all future biosimilar reviews, adoption plans, and ongoing monitoring. Barriers evaluated include changes in payor coverage and challenges in preparation of the EMR for future biosimilars, meeting precertification team education needs, and providing operational support for pharmacy inventory.
To date, use of 5 preferred biosimilar products has led to significant cost savings to the institution, and the process has been endorsed by providers. The institution's successes can be attributed to clear communication with stakeholders and the development of a deliberate process, led by a multidisciplinary leadership team, for managing formulary, safety, and operational barriers in a thoughtful and systematic manner."
"The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype.
To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota.
We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included.
We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients.
Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments."
"Anti-tumor necrosis factor-α (TNF-α) is a life-changing treatment leading to quality-of-life improvement. Nonetheless, this treatment is associated with a high risk of infection, especially tuberculosis.
Our study aimed to determine the frequency of active tuberculosis in our patients with chronic rheumatic disease and treated with TNF-α.
We conducted a retrospective study including patients with Rheumatoid Arthritis and Spondylarthritis diagnosed according to ACR/EULAR 2009 criteria and ASAS 2010, respectively, and treated with biological agents for at least 6 months. We collected data regarding tuberculosis screening and the occurrence of active tuberculosis during follow-up.
82 patients were included (37 men and 45 women). The mean age was 42 ± 3.4 years. At inclusion, no patient had a medical history of tuberculosis. The diagnosis of latent tuberculosis infection was established in 17 patients (20.7%). Prophylactic treatment was prescribed in all these cases for three months. Two cases (2.4%) of active tuberculosis occurred under biologic (infliximab). It was two severe forms of tuberculosis. The first case had miliary tuberculosis associated with hepatic and peritoneal involvement. The second one had pleural tuberculosis. These two patients received anti-tuberculosis therapy, and the biological treatment was interrupted. Given the high disease activity, the anti-TNF-α was restarted after 3 and 4 months. There was no recurrence of tuberculosis after 7 years of follow-up.
The use of TNF-α blockers is associated with a risk of disseminated forms of tuberculosis. Tuberculosis screening, which is recommended before the biological onset, is also necessary under this treatment. Restarting the anti-TNF-α after appropriate treatment of tuberculosis seemed to be safe."
"Real-world and long-term data on biologic treatment changes - including switching, discontinuation, dose escalation, and interval change (both increasing and decreasing) - are required to understand treatment patterns for psoriasis (PsO) in Canada. The study objectives were to evaluate the time to first biologic treatment change and to document these changes in Canadian patients with moderate-to-severe chronic plaque PsO. Charts from 13 Canadian sites were queried retrospectively (2005-2019); a period covering all biologic classes commonly used for PsO in Canada. Included were patients diagnosed with, and currently using biologics for, moderate-to-severe chronic plaque PsO. Time to first treatment change, nature of treatment change, number of lines of treatment, proportion of patients on each drug, and drug survival were collected. Based on 1149 medical charts, adalimumab had the longest time to first treatment change (49.3 months; 95% confidence interval, 37.4-67.4). Approximately half of the patients had a treatment change, and nearly 75% of these changes were either an interval change or a biologic switch. Lack of efficacy was the most prevalent primary reason for biologic switch (67.3%), whereas 6.7% of patients switched due to adverse events. Drug survival for etanercept and infliximab was approximately twice as long for patients who had dose optimization (i.e., dose escalation or interval change) than patients without dose optimization. The survival curve of adalimumab was similar to the one of ustekinumab after 48 months of treatment, showing approximately 60% of patients remaining on treatment after 132 months, with or without dose optimization. Assessing treatment patterns of all commonly used biologics for moderate-to-severe chronic plaque PsO in Canada between 2005 and 2019 showed that approximately half of the patients required a treatment change (mainly interval change or biologic switch) while the other half remained on treatment."
"Knowledge gaps exist in the use of biologics for pregnant patients with Crohn's disease (CD), especially the usage of ustekinumab (UST) and infliximab (IFX) infusion during the late gestation period. In this case series, we investigated perinatal and neonatal outcomes and pharmacokinetics of these biologics in pregnant CD patients.
Pregnant CD patients under treatment with IFX or UST during January 2017 to December 2019 were monitored. Growth and development of their babies were followed up to six months. Drug concentrations were measured in maternal peripheral and cord blood at delivery and infants' blood at six months of age.
Four cases were kept IFX treatment until late gestation (median last dose: 31.2 weeks). One case received UST until 23 weeks of gestation. All cases were in clinical remission but moderately undernourished. Babies were delivered by cesarean section at full term without any complications or congenital abnormalities. No growth or developmental defects and no susceptibility to infections were observed by six months. However, two babies whose mothers received IFX after 30 weeks of gestation were detected IFX in their blood at six months of age (0.94 and 0.24 pg/ml). Concentrations of UST in maternal and cord blood were 267.7 and 756.5 ng/ml, respectively. UST was not detected in the infant at six months of age.
Administration of UST or IFX to pregnant patients with CD is safe, particularly IFX to be given in the late gestation period. Understanding of the pharmacokinetics of biologics in maternal-infant interactions may improve the management of pregnant CD patients."
"Hydrocephalus is reported in approximately one-tenth of neurosarcoidosis patients. However, data on clinical characteristics and outcome are lacking. In this retrospective study, we present 11 patients with neurosarcoidosis and hydrocephalus on neuroimaging. Median age was 52 years and seven were female (64%). Presenting symptoms consisted of headache in 8 out of 11 (73%), vertigo in 5 (46%), gait abnormalities in 4 (36%), diplopia in 2 (18%) and decreased visual acuity in 1 (9%). Cranial imaging showed obstructive hydrocephalus in 10 (91%) and non-obstructive hydrocephalus in 1 (9%) out of 11, obstruction occurred at the level of the fourth ventricle in 6 out of 10 (60%). Treatment consisted of glucocorticoids in all the patients with additional methotrexate or azathioprine in 6 (55%) and infliximab in 1 (9%) patient. Neurosurgical intervention was performed in 10 out of 11 (91%) patients. Treatment led to remission, improvement or stabilization of disease in 9 out of 10 (90%) of patients. One patient died due to cerebral herniation despite neurosurgical decompression and CSF shunting. Median modified Rankin scale score at last follow-up was 2 (range 0-6). A systematic review and meta-analysis of studies on hydrocephalus due to neurosarcoidosis identified 36 patients that compared to our patients had a lower median age at onset and a higher mortality. Acute obstructive hydrocephalus due to neurosarcoidosis is a potentially fatal medical emergency requiring neurosurgical intervention and initiation of immunosuppressive therapy. If patients survive the initial phase, the outcome is generally favorable."
"Infliximab (IFX) is the first-line treatment for patients with Crohn's disease (CD) and is noted for its relatively high cost. The therapeutic efficacy of IFX has noticeable individual differences. Known single-gene polymorphisms (SNPs) are inadequate for predicting non-response to IFX. In this study, we aimed to identify new genetic factors associated with IFX-therapy failure and to predict non-response to IFX by developing a multivariate predictive model.
In this retrospective study, we collected and analysed the data of Chinese patients with CD who received IFX therapy at one hospital between June 2013 and June 2019. Primary non-response (PNR) and non-durable response (NDR) were evaluated using a simple endoscopic score for CD (SES-CD). A total of 125 SNPs within 44 genes were genotyped. A multivariate logistic-regression model was established to predict non-response to IFX. An area-under-the-receiver-operating-characteristics curve (AUROC) was applied to evaluate the predictive model performance.
Forty-two of 206 (20.4%) patients experienced PNR and 15 of 159 (9.4%) patients experienced NDR. Nine SNPs were associated with PNR (
Genetic polymorphisms are significantly associated with response to IFX among Chinese CD patients."
"Anti-tumour necrosis factor (TNF) therapy has greatly improved treatment outcomes in patients with inflammatory bowel disease (IBD), but long-term use is associated with cutaneous reactions, susceptibility to infections and frequent injections or hospital visits. Several non-controlled studies have demonstrated that dose reduction is feasible for a subset of patients, provided that early detection of a disease flare is possible. Here, we aim to compare the effectiveness of interval lengthening with standard dosing in maintaining remission in young patients with IBD.
In this international, prospective, non-inferiority, partially randomised patient preference trial, we aim to recruit 148 patients aged 12-25 years with luminal Crohn's disease or ulcerative colitis in sustained remission (ie, three consecutive in-range faecal calprotectin (FC) results or recently confirmed endoscopic remission). In the interventional arm, the dosing interval will be lengthened from 8 to 12 weeks for infliximab users and from 2 to 3 weeks for adalimumab users. In the control group, standard dosing will be continued. Rapid tests will be performed for FC every 4 weeks and for anti-TNF trough levels every 12 weeks. The primary outcome is the cumulative incidence of out-of-range FC results at 48-week follow-up. Secondary endpoints include time to get out-of-range FC results, cumulative incidence of adverse effects, proportion of patients progressing to loss of response and identification of predictors of successful interval lengthening.
The protocol has been approved by the Medical Ethics Review Committee of the University Medical Centre Groningen and is pending at the other participating centres. Results will be disseminated in peer-reviewed journals and presented at scientific meetings.
EudraCT number: 2020-001811-26; ClinicalTrials.gov Identifier: NCT04646187. Protocol version 4, date 17 September 2021."
"A large proportion of patients with inflammatory bowel disease (IBD) relapse after drug discontinuation despite achieving a stable state of infliximab-induced clinical remission. Resuming the use of the same tumor necrosis factor-alpha (TNF-α) inhibitors in patients who relapse following TNF-α inhibitor discontinuation was suggested as a treatment strategy. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of infliximab retreatment in patients with IBD.
A systematic literature search to shortlist relevant studies was conducted using the MEDLINE, Embase, CINAHL, and SCOPUS databases for studies published from inception to August 2020.
Nine studies were included in the meta-analysis. The pooled clinical remission rate of infliximab retreatment in patients with IBD was 85% (95% confidence interval (CI), 81-89%) for induction treatment and 73% (95% CI, 66-80%) for maintenance treatment. A clinical remission rate following infliximab reintroduction was achieved in a greater proportion of patients with Crohn's disease (87%; 95% CI, 83-91%) than in those with ulcerative colitis (78%; 95% CI, 61-91%) for induction treatment, but the difference was not statistically significant. Infusion-related reactions after infliximab retreatment occurred in 9% of patients with IBD (95% CI, 3-16%).
Infliximab retreatment showed high clinical remission rates with tolerable infusion-related reactions in patients with IBD who achieved remission with initial infliximab treatment but relapsed after its discontinuation. We suggest infliximab as a viable alternative in patients with IBD who previously responded well to infliximab treatment."
"Nowadays, tumor necrosis factor-alpha (TNFα) inhibitors have revolutionised the treatment of inflammatory arthritides by demonstrating efficacy with an acceptable toxicity profile. However, autoimmune phenomena and clinical entities have been reported ranging from an isolated presence of autoantibodies to full-blown autoimmune diseases, including drug-induced lupus (DIL). Case Presentation: A 62-year-old woman with rheumatoid arthritis (RA) refractory to methotrexate and prednisone was treated with adalimumab (ADA). 4 months later, she presented acute cutaneous eruptions after sun exposure, positive ANA (1/640 fine speckled pattern), Ro (SSA) and anti- Smith (Sm) antibodies with no other clinical or laboratory abnormalities. The diagnosis of DIL was made, ADA was discontinued, and she was treated successfully with prednisone plus local calcineurin inhibitors. Conclusion: Thus, we review the literature for cases of DIL development in patients treated with TNFα inhibitors. Rheumatologists should be aware of the possible adverse events and the requirement of careful clinical evaluation and monitoring."
"CT-P13 (Remsima
Biosimilars are biological medical agents that are designed to closely replicate a reference medicine while potentially reducing treatment costs. CT-P13 (Remsima"
"The prevalence of the chronic inflammatory bowel diseases (CIBD) Crohn's disease (CD) and ulcerative colitis (UC) is on the rise worldwide. In Germany CIBDs are also a significant healthcare problem. The pathogenesis is complex and involves genetic factors, environmental aspects and changes in the immunological constitution. Furthermore, the gut microbiota plays a role in the maintenance of intestinal inflammation. Fortunately, several new drugs, in particular biologicals, have been approved for the treatment of CIBDs. The treatment of UC is mainly based on 5‑aminosalicylic acid formulations, preferably as a topical form for distal colitis and proctitis as well as local budesonide formulations. In the case of extensive spread, high disease activity and refractory disease antibodies (biologicals) are successfully used, similar to CD. In addition to anti-tumor necrosis factor antibodies (infliximab, adalimumab, golimumab), vedolizumab, an anti-integrin antibody and the interleukin 12/23 antibody ustekinumab can be successfully used. The intravenous and also subcutaneous administration of antibodies are increasing in importance and are now available for all forms. Furthermore, the Janus kinase inhibitor tofacitinib is an orally administered option for UC. Clinical scores, endoscopy, ultrasound, laboratory parameters and calprotectin determination in stool are employed to evaluate treatment response (treat to target approach). Ultimately, the long-term goal is mucosal healing. Despite advances in the pharmaceutical treatment, a significant number of patients with CIBD still suffer from treatment refractory courses and need surgery at some time during the disease.
Die Prävalenzen der chronisch-entzündlichen Darmerkrankungen (CED) Morbus Crohn (MC) und Colitis ulcerosa (CU) steigen weltweit an. Auch in Deutschland stellen die CED ein großes gesundheitspolitisches Problem dar. Die Pathogenese ist komplex und involviert genetische Faktoren, Umweltaspekte und Veränderungen in der immunologischen Konstitution. Weiterhin spielt das Darmmikrobiom eine Rolle bei der Aufrechterhaltung der Entzündung. In den letzten Jahren sind erfreulicherweise weitere Medikamente für die Behandlung der CED zugelassen worden, vor allem Biologika. Die Therapie der CU stützt sich hauptsächlich auf 5‑Aminosalicylsäure-Präparate, bevorzugt auch in topischer Form bei distaler Kolitis und Proktitis, sowie lokale Budesonidformulierungen. Bei ausgedehntem Befall, hoher Krankheitsaktivität oder refraktärem Verlauf kommen ähnlich wie beim MC auch Antikörper (Biologika) mit gutem Erfolg zum Einsatz. Neben Anti-Tumor-Nekrose-Faktor-Antikörpern (Infliximab, Adalimumab, Golimumab) werden der Integrinantikörper Vedolizumab sowie der Interleukin-12/23-Antikörper Ustekinumab erfolgreich verwendet. Einen zunehmenden Stellenwert erhält neben der intravenösen auch die subkutane Anwendung der Antikörpertherapien, die mittlerweile für alle Präparate zur Verfügung steht. Des Weiteren ist bei CU der Januskinaseinhibitor Tofacitinib eine orale Option. Der Therapieerfolg wird multimodal anhand von Endoskopie, Sonographie, Laborparametern, Calprotectinbestimmung im Stuhl und klinischen Scores beurteilt („treat-to-target approach“). Langfristig gilt das Ziel einer mukosalen Heilung. Trotz der Fortschritte in der medikamentösen Therapie leidet immer noch ein signifikanter Teil der Patienten mit CED unter therapierefraktären Verläufen und benötigt im Verlauf eine chirurgische Therapie."
"Treatment for moderate-to-severe ulcerative colitis (UC) includes medical therapies such as immunosuppressive agents or surgical options such as colectomy. While prior studies have indicated a mortality benefit with elective surgery, the timing and effectiveness of colectomy in the UC treatment algorithm have not been assessed. We hypothesize that the ideal placement of colectomy occurs prior to the exhaustion of all medical therapies.
We designed a Markov model to assess the ideal position of colectomy. The base case was a 50-year-old male with steroid-dependent moderate-to-severe UC without prior treatment with immunomodulator or biologic therapies. We developed 4 separate algorithms incorporating elective colectomy: (1) prior to biologics, (2) after infliximab monotherapy failure, (3) after infliximab and azathioprine combination therapy failure, and (4) after medically refractory to all medical therapies including vedolizumab. Transition probabilities were obtained from published literature. First-order Monte Carlo simulations of 100 trials of 100,000 individuals were used to calculate quality-adjusted life-year (QALY) estimates. One-way sensitivity analyses were conducted for all variables.
Algorithm 3 (colectomy following combination therapy) was the preferred strategy with 1.864 QALYs (95% CI [1.863, 1.865]) over a 3-year period and the preferred strategy in the probabilistic sensitivity analysis 92.77% of the time.
This simulation suggests that early incorporation of colectomy for patients medically refractory to infliximab and azathioprine combination therapy may yield greater quality of life for patients with steroid-dependent UC. These findings suggest avenues for more patient-centered preference work and a combined medical-surgical approach to UC."
"Although tumor necrosis factor inhibitors (TNFi) have favorably altered the treatment landscape for patients with axial spondyloarthritis (axSpA), there is limited data regarding TNFi persistence and reasons for discontinuation. This is an observational time-to-event study utilizing data collected for a prospective multiple-disease registry of US Veterans with axSpA treated with TNFi therapies and recruited over a 10 year period. Clinical, serological, and comorbid parameters were collected. Corporate Data Warehouse Pharmacy files provided courses of the 5 TNFi agents, and response to treatment was documented. Individual TNFi persistence was established utilizing univariate and multivariate Cox proportional models, and reasons for discontinuation were obtained by physician chart review. Two-hundred and fifty-five axSpA patients received 731 TNFi courses. A majority of patients (84.3%) had TNFi persistence at 12 months; 63.5% and 47.1% at 24 and 36 months, respectively. Compared to adalimumab, infliximab demonstrated greater persistence, certolizumab the least. Age, smoking status, BMI, comorbidity burden, inflammatory markers and HLA-B27 did not predict TNFi persistence or discontinuation. Stroke and peripheral arterial disease increased the probability of TNFi discontinuation. Secondary non-response (SNR) was the most common reason for discontinuation (46% of all courses); non-adherence (6%) and clinical remission (2%) were uncommon. Pain score at enrollment, myocardial infarction, African American race and inflammatory bowel disease (IBD) predicted TNFi response. While initial persistence of TNFi treatment was high, a large proportion of the patients discontinued initial TNFi therapy by 3 years, primarily due to loss of efficacy. While further research identifying potential predictors of TNFi discontinuation in axSpA is warranted, access to alternate disease-modifying therapies is needed."
"TNF inhibitors are relatively safe drugs, but asymptomatic infliximab-induced high serum creatine kinase (CK) levels have been reported in >30% of patients with inflammatory bowel disease (IBD). Whether high serum CK levels are a specific effect of treatment with TNF inhibitors has not been studied in detail. CK levels were therefore compared between infliximab- and vedolizumab-treated IBD patients.
In this retrospective, monocentric study, 131 IBD cases (82 with Crohn's disease (CD), 49 with ulcerative colitis) of the Basel University Hospital IBD cohort treated either with infliximab or vedolizumab were included. Serum samples for measuring CK, lactate dehydrogenase (LDH), C-reactive protein (CRP), and fecal calprotectin (FCal) levels were collected longitudinally and analyzed using mixed additive models.
No significant differences in CK levels between infliximab and vedolizumab-treated patients were observed over time. Infliximab-treated males, however, showed significantly higher CK levels than females and former smokers treated with infliximab showed significantly lower CK levels than nonsmokers. No such differences were observed in vedolizumab-treated patients. LDH and CRP were not significantly different between infliximab- and vedolizumab-treated patients, while adjusted groups showed substantially higher LDH levels with increasing age and significantly lower LDH levels in patients with longer disease duration. Infliximab patients with CD showed significantly lower CRP. However, significantly higher FCal concentrations were noted in infliximab patients independent of diagnosis, gender, disease duration, smoking behavior, and age.
In our cohort, high serum CK levels are not an infliximab- or vedolizumab-specific effect."
"Therapeutic drug monitoring (TDM) of infliximab (IFX) trough levels and anti-drug antibodies in conjunction with symptoms, disease history, and investigations can aid decision-making. This study evaluated 1-year outcomes of patients with decisions that were altered on the basis of TDM results, in order to investigate whether outcomes from TDM-based decisions to adjust or stop IFX treatment are durable.
We retrospectively collected clinical outcomes 12 months post treatment decisions based on proactive TDM. Patients whose initial treatment decisions were altered on the basis of TDM results were compared with those where the decision remained unchanged. Events of interest were inpatient admissions with active inflammatory bowel disease (IBD), further changes to biologic therapy, and IBD-related health-care costs.
Of 189 patients, 54 (28%) had initial treatment decisions altered in the light of TDM results. The 135 patients whose initial decision was not altered in light of TDM results served as the comparator. There were no differences in hospitalization rates or subsequent biologic switches between the altered decision groups and the comparator group. IBD-related health-care costs were higher in those whose initial decision was altered (median GBP 7,912 vs. GBP 6,521; 
Our study demonstrates good outcomes from changes to IFX treatment based on TDM. Patients with a decision to stop, switch, or continue with an adjusted IFX dose experienced comparable clinical outcomes but had higher drug-related expenditure than those whose treatment decision was not altered in light of TDM."
"Ustekinumab is a monoclonal antibody used as treatment for various inflammatory conditions. We present a pediatric patient with Crohn's disease who did not tolerate infliximab and was then changed to ustekinumab. He developed anaphylaxis to the medication after the second dose. A drug desensitization protocol was created by the allergy team leading to successful administration of both intravenous and then subcutaneous ustekinumab. As monoclonal agents become mainstays of therapy for inflammatory conditions, there are increased reports of allergic reactions. Prior reports and protocols of ustekinumab desensitization have not been reported. This case report highlights successful desensitization to ustekinumab as well as the importance of a multidisciplinary approach to addressing treatment needs of patients who develop life-threatening reactions to such medications."
"Traditional methods of developing predictive models in inflammatory bowel diseases (IBD) rely on using statistical regression approaches to deriving clinical scores such as the Crohn's disease (CD) activity index. However, traditional approaches are unable to take advantage of more complex data structures such as repeated measurements. Deep learning methods have the potential ability to automatically find and learn complex, hidden relationships between predictive markers and outcomes, but their application to clinical prediction in CD and IBD has not been explored previously.
To determine and compare the utility of deep learning with conventional algorithms in predicting response to anti-tumor necrosis factor (anti-TNF) therapy in CD.
This was a retrospective single-center cohort study of all CD patients who commenced anti-TNF therapy (either adalimumab or infliximab) from January 1, 2010 to December 31, 2015. Remission was defined as a C-reactive protein (CRP) < 5 mg/L at 12 mo after anti-TNF commencement. Three supervised learning algorithms were compared: (1) A conventional statistical learning algorithm using multivariable logistic regression on baseline data only; (2) A deep learning algorithm using a feed-forward artificial neural network on baseline data only; and (3) A deep learning algorithm using a recurrent neural network on repeated data. Predictive performance was assessed using area under the receiver operator characteristic curve (AUC) after 10× repeated 5-fold cross-validation.
A total of 146 patients were included (median age 36 years, 48% male). Concomitant therapy at anti-TNF commencement included thiopurines (68%), methotrexate (18%), corticosteroids (44%) and aminosalicylates (33%). After 12 mo, 64% had CRP < 5 mg/L. The conventional learning algorithm selected the following baseline variables for the predictive model: Complex disease behavior, albumin, monocytes, lymphocytes, mean corpuscular hemoglobin concentration and gamma-glutamyl transferase, and had a cross-validated AUC of 0.659, 95% confidence interval (CI): 0.562-0.756. A feed-forward artificial neural network using only baseline data demonstrated an AUC of 0.710 (95%CI: 0.622-0.799; 
Deep learning methods are feasible and have the potential for stronger predictive performance compared to conventional model building methods when applied to predicting remission after anti-TNF therapy in CD."
"To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA).
We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens.
Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3-6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3-8) and 2 (1-6), and 20 (13-30) mg/day and 20 (15-25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6-13) and 11 months (IQR 6-18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection.
This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA."
"Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10-20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease.
In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8-12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244.
Between March 1, 2017, and Aug 31, 2020, 105 patients were randomly assigned to treatment and 103 were included in the intention-to-treat population (54 in the infliximab group, 49 in the second IVIG group). Two patients randomised to infliximab did not receive allocated treatment. The primary outcome was met by 40 (77%) of 52 patients in the infliximab group and 25 (51%) of 49 patients in the second IVIG infusion group (odds ratio 0·31, 95% CI 0·13-0·73, p=0·0076). 31 patients with fever beyond 24 h received crossover treatment: nine (17%) in the infliximab group received second IVIG and 22 (45%) in second IVIG group received infliximab (p=0·0024). Three patients randomly assigned to infliximab and two to second IVIG with fever beyond 24h did not receive crossover treatment. Mean fever days from enrolment was 1·5 (SD 1·4) for the infliximab group and 2·5 (2·5) for the second IVIG group (p=0·014). Mean hospital stay was 3·2 days (2·1) for the infliximab group and 4·5 days (2·5) for the second IVIG group (p<0·001). There was no difference between treatment groups for markers of inflammation or coronary artery outcome. 24 (44%) of 54 patients in the infliximab group and 33 (67%) of 49 in the second IVIG group had at least one adverse event. A drop in haemoglobin concentration of at least 2g/dL was seen in 19 (33%) of 58 patients who received IVIG as either their first or second study treatment (three of whom required transfusion) and in three (7%) of 43 who received only infliximab (none required transfusion; p=0·0028). Haemolytic anaemia was the only serious adverse events deemed definitely or probably related to study treatment, and was reported in nine (15%) of 58 patients who received IVIG as either their first or second study treatment and none who received infliximab only.
Infliximab is a safe, well tolerated, and effective treatment for patients with IVIG resistant Kawasaki disease, and results in shorter duration of fever, reduced need for additional therapy, less severe anaemia, and shorter hospitalisation compared with second IVIG infusion.
Patient Centered Outcomes Research Institute."
"Pyoderma gangrenosum (PG) is a rare, and often challenging to diagnose, inflammatory disorder with relatively high rates of morbidity and mortality. Central to the diagnosis of PG is histologic evaluation and exclusion of other entities. Large-scale studies investigating the proportion of patients receiving a thorough diagnostic work-up, as well as prevalence studies regarding comorbidities and systemic treatment in PG using claims-based data, are sparse. Our objective was to identify patients diagnosed with PG and describe the diagnostic work-up and prevalence of common comorbidities and therapies in this population using claims-based data in a retrospective cohort study. In order to better understand practices of diagnostic work-up, we captured rates of skin biopsy, tissue culture, and/or surgical debridement prior to initial diagnosis. We also identified the prevalence of PG-associated comorbidities and initial immunosuppressive therapy given for PG. Of the 565 patients diagnosed with PG, 9.4% underwent skin biopsy, 8% tissue culture, and 1.4% both skin biopsy AND tissue culture prior to diagnosis. Inflammatory bowel disease was the most prevalent comorbidity (16.3%). The most common treatment administered was systemic corticosteroids (17%). Although practice guidelines explicitly delineate histology and exclusion of infection as important diagnostic criteria, only a minority of patients in this study underwent skin biopsy and/or tissue culture prior to receiving a diagnosis of PG, suggesting that patients may receive a diagnosis of PG without having tissue evaluation. Such discordance between practice guidelines and ""real-world"" practice inevitably increases the risk for misdiagnosis of PG and misdirected treatment with immunosuppressants for presumptive PG in cases of PG mimickers. Moreover, comorbidities associated with PG may occur, or be identified in, a lower proportion of patients as compared with what is reported in the existing literature. Study limitations include a population restricted to < 65 years with commercial insurance and the reliance upon ICD diagnostic coding to capture the population."
"Psoriasis is a common long-lasting, inflammatory disease that mainly affects the skin. The incidence of this condition has increased significantly over time and at this point, it affects approximately 1% of children. Psoriasis can appear at any age, including childhood and adolescence, with a higher frequency in girls, an earlier onset being associated with severe psoriasis. The pathology is the result of the interaction between genetics and trigger factors such as infections, stress, diet, obesity, and chemical irritants. Paradoxically, tumor necrosis factor (TNF)-α inhibitors (infliximab, adalimumab) may induce psoriasis in children. Psoriasis is a long-term condition with periods of exacerbation; thus, the quality of life can be affected and patients should receive psychosocial support. Although most children have mild disease and topical treatment is efficient, some cases are challenging to treat. The aim of this review was to provide an overview of the current knowledge concerning the epidemiology, etiology, pathogenesis, clinical features, comorbidities, and treatment of psoriasis in children and also to emphasize the need for a multidisciplinary approach to this complex pathology."
"Sympathetic ophthalmia is a rare bilateral diffuse granulomatous panuveitis that usually results from surgical or penetrating trauma to one eye. The symptoms range from impaired near vision to pain, photophobia, and loss of visual acuity. Anterior segment manifestations include bilateral acute uveitis with mutton-fat keratic precipitates and posterior segment findings include vitritis, multifocal neurosensory retinal detachment, choroiditis, optic nerve edema, and Dalen-Fuchs nodules. The diagnosis is clinical. Ancillary investigations include fundus fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), ultrasound B scan, and autofluorescence imaging. The management options include corticosteroids (topical and systemic) as the first line along with immunomodulatory therapy started at the presentation of the disease. Recent advances include imaging with OCT-angiography, enhanced depth imaging-OCT (EDI-OCT, choroidal vascular index/CVI), targeting IL-23/IL-17 pathway, and use of biologics for the management of this rare entity. Recent advances in early diagnosis and prompt treatment has led to improved final visual outcomes in both the sympathizing and exciting eye. This review is aimed at giving a comprehensive overview of sympathetic ophthalmia along with a special emphasis on current treatment strategies and recent advances."
"To compare the treatment outcomes of TNF inhibitors and tocilizumab (TCZ) in patients with Takayasu arteritis.
Takayasu arteritis patients who were refractory to conventional immunosuppressive (IS) drugs and received biologic treatment were included in this multicenter retrospective cohort study. Clinical, laboratory and imaging data during follow-up were recorded. Remission, glucocorticoid (GC) sparing effect, drug survival was compared between TNF inhibitor and TCZ treatments. Also, a subgroup matched comparison was performed between groups.
One hundred and eleven (F/M: 98/13) patients were enrolled. A total of 173 biologic treatment courses (77 infliximab, 49 TCZ, 33 adalimumab, 9 certolizumab, 3 rituximab, 1 ustekinumab and 1 anakinra) were given. Tocilizumab was chosen in 23 patients and TNF inhibitors were chosen in 88 patients as first-line biologic agent. Complete/partial remission rates between TCZ and TNF inhibitors were similar at 3rd month and at the end of the follow-up. GC dose decrease (≤4 mg) or discontinuation of GCs was achieved in a similar rate in both groups (TNF inhibitors vs TCZ: 78% vs 59%, p = 0.125). Drug survival rate was 56% in TNF inhibitors and 57% in TCZ group (p = 0.22). The use of concomitant conventional ISs did not affect the drug survival (HR =0.78, 95% CI =0.42-1.43, p = 0.42). The match analysis showed similar results between groups in terms of relapse, decrease in GC dose, surgery need and mortality.
The efficacy and safety outcomes and drug survival rates seem to be similar for TNF inhibitors and tocilizumab in patients with Takayasu arteritis."
"A healthy diet is recommended for patients with Crohn's disease (CD) in remission.
To evaluate the diet quality of patients with CD.
Cross-sectional study with patients with CD and clinical remission using the biological agent infliximab. The diet quality was assessed using the Diet Quality Index-Revised (DQI-R). DQI-R was calculated based on 24-hour dietary recalls (24HR), being classified as ""inadequate diet"" (≤40 points), ""diet requiring modifications"" (41 to 64 points) and ""healthy diet"" (≥65 points). Weight, height and waist circumference (WC) of patients were assessed. For comparison between groups, Student's t-test or Mann-Whitney was used. For correlation between continuous variables, Pearson or Spearman coefficient was used. Values of P<0.05 indicated statistical significance.
A total of 43 patients participated in the study. The final DQI-R score was 49.1 points - ""diet requiring modifications"". No patient received the classification of ""healthy diet"" (maximum score =59.7), 55.8% presented ""diet requiring modifications"" and 44.2% ""inadequate diet"". When comparing the ""inadequate diet"" and ""diet requiring modifications"" groups, a lower mean age was observed in the ""inadequate diet"" group (37.6±14.8 versus 47.4±10.5 y, P=0.02). It was found that 44.2% of the patients were overweight (body mass index [BMI] ≥25 kg/m²) and had increased WC (women: WC ≥80 cm and men: WC ≥94 cm). A positive correlation was found between the final DQI-R score and BMI (P=0.046; r=0.346).
Patients with CD in clinical remission using infliximab are not adopting a diet considered healthy, which points to the need for an individualized nutritional approach."
"Symptoms, diagnostic and therapy of perianal disease in patients with inflammatory bowel diseases "
"Biologic agents are increasingly used for many autoimmune and inflammatory conditions, as they are both steroid sparing and can potentially induce and maintain remission. Notably tumor necrosis factor (TNF) alpha antagonists are particularly useful in inflammatory bowel disease (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Infliximab is a chimeric monoclonal antibody that targets TNF alpha (cytokine involved in modulation of inflammatory responses) and neutralizes its effects. As infliximab is a generic TNF alpha inhibitor, it can cause non-specific immune mediated side effects in addition to its intended therapeutic effect on the target organ (i.e., the gut in IBD). We present a case of a gentleman developing a rare dermatological side effect of an acneiform reaction, after the use of infliximab for his CD. Monitoring anti-TNF alpha antibodies may help identify patients at a higher risk of developing adverse reactions. In addition, gut specific biologic agents (vedolizumab) may be the next preferable step in individuals with IBD who demonstrate reactions and/or intolerance to non-specific TNF alpha inhibitors."
"Vaccination is the most effective method to prevent and control the SARS-CoV-2 infection and biologics are not considered a contraindication for vaccination. The burning question is that safety data are lacking since patients taking drugs affecting the immune system were excluded from clinical trials leading to vaccine approbation. Moreover, it seems that vaccination could worsen psoriasis. We conducted a survey to investigate the safety of SARS-CoV-2 vaccines in psoriatic patients treated with biologics. A total of 150 patients with stable plaque psoriasis treated with biologics for at least 2 months were evaluated in a 3 months period. Fifty patients (22 F/28 M; age: 33-83 years) only underwent the first and second doses of SARS-CoV-2 vaccines. All patients discontinued their biological agents 10 days before and 10 days after each dose of vaccine. Of these, 24 patients were treated with anti-TNF, 14 with anti-IL17, 7 with anti-IL12-23, and 5 with anti-IL23. After the vaccines, all patients were evaluated at day 2, 7, and 14 for local and/or systemic side effects and/or adverse drug reactions to SARS-CoV-2 vaccines. None of the patients experienced any side effects or a psoriatic flare. Only one patient treated with infliximab biosimilar referred an exacerbation of psoriasis after vaccine. The remaining 100 patients reported that they did not get the vaccine yet. Our preliminary data confirm that SARS-CoV-2 mRNA vaccines are safe for patients with chronic plaque psoriasis treated with biologics and did not trigger psoriasis, although these data should be validated in a larger population. We encourage an early SARS-CoV-2 vaccines administration in all psoriatic patients on immunosuppressant drugs."
"SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment."
"Administering medications prior to infliximab infusions to prevent infusion-related infliximab reactions is a common practice in the United States. However, the premedication protocol varies among different institutions. The purpose of this study was to demonstrate whether the use of methylprednisolone was effective as a premedication to prevent infusion reactions while infliximab was administered to children with inflammatory bowel disease. The effect of concurrent use of other immunomodulators on the rate of reaction incidents was also studied. This was a retrospective chart review, assessing children younger than 21 years diagnosed with inflammatory bowel disease from January 2008 to April 2018. The incident rate of infusion reactions was also compared between two cohorts: those who received the premedication of methylprednisolone and those who did not. Subgroup analysis of concomitant immunomodulators, infliximab dose and frequency, and anti-infliximab assay were also performed. A total of 34 subjects received methylprednisolone as a premedication and 151 subjects did not. No statistically significant difference of allergic reactions was found between the two groups (p = .727). Concomitant immunomodulator therapy lowered the likelihood of developing reactions (p = .048). This study was conducted to help pediatric gastroenterology and infusion nurses better understand and implement evidence-based approaches in the premedication protocol for infusions of anti-tumor necrosis factor-α (anti-TNF-α) antibody products."
"Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic exposure. We aimed to assess the comparative efficacy and safety of biologics in patients with Crohn's disease.
We did a systematic review and network meta-analysis of phase 2 and phase 3 randomised controlled trials done in adults (≥18 years) with moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450) treated with tumour necrosis factor (TNF) antagonists, anti-integrin, anti-interleukin (IL)-12 and IL-23p40, or anti-IL23p19 agents, either alone or in combination with immunosuppressants, as their first-line biologic or after previous biologic exposure, compared with placebo or an active comparator. The minimum duration of therapy was 14 days for trials reporting induction of remission in active disease and 22 weeks in trials reporting maintenance of remission. We searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, without any language restrictions. Summary estimates of the primary and secondary outcomes were extracted from the published reports; individual patient-level data were not sought. The primary endpoint was induction of clinical remission in patients with active disease (CDAI <150) and maintenance of remission in patients with response to induction therapy, with data extracted from published reports. A network meta-analysis with multivariate consistency model random-effects meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values.
The search strategy yielded 18 382 citations, of which 31 trials were eligible for inclusion. On the basis of 15 randomised controlled trials including 2931 biologic-naive patients, infliximab monotherapy (odds ratio [OR] 4·53 [95% CI 1·49-13·79]), infliximab combined with azathioprine (7·49 [2·04-27·49]), adalimumab (3·01 [1·25-7·27]), and ustekinumab (2·63 [1·10-6·28]) were associated with significantly higher odds of inducing remission compared to certolizumab pegol (all moderate confidence); infliximab and azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab (3·76 [1·01-14·03]; low confidence). On the basis of ten randomised controlled trials including 2479 patients with previous biologic exposure, adalimumab after loss of response to infliximab (OR 2·82 [95% CI 1·20-6·62]; low confidence), and risankizumab (2·10 [1·12-3·92]; moderate confidence), were associated with higher odds of inducing remission than vedolizumab. No differences between active interventions were observed in maintenance trials. Most trials were at low or uncertain risk of bias.
Although biologic treatment choices in patients with moderate-to-severe Crohn's disease must be individualised for each patient, this analysis suggests that either infliximab with azathioprine or adalimumab might be preferred as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab might be preferred as a second-line therapy, for induction of clinical remission.
None."
"The coronavirus disease (COVID-19) has once again reminded us of the significance of host immune response and consequential havocs of the immune dysregulation. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) inflicts severe complications to the infected host, including cough, dyspnoea, fever, septic shock, acute respiratory distress syndrome (ARDs), and multiple organ failure. These manifestations are the consequence of the dysregulated immune system, which gives rise to excessive and unattended production of pro-inflammatory mediators. Elevated circulatory cytokine and chemokine levels are accompanied by spontaneous haemorrhage, thrombocytopenia and systemic inflammation, which are the cardinal features of life-threatening cytokine storm syndrome in advanced COVID-19 diseases. Coronavirus hijacked NF-kappa B (NF-κB) is responsible for upregulating the expressions of inflammatory cytokine, chemokine, alarmins and inducible enzymes, which paves the pathway for cytokine storm. Given the scenario, the systemic approach of simultaneous inhibition of NF-κB offers an attractive therapeutic intervention. Targeted therapies with proteasome inhibitor (VL-01, bortezomib, carfilzomib and ixazomib), bruton tyrosine kinase inhibitor (acalabrutinib), nucleotide analogue (remdesivir), TNF-α monoclonal antibodies (infliximab and adalimumab), N-acetylcysteine and corticosteroids (dexamethasone), focusing the NF-κB inhibition have demonstrated effectiveness in terms of the significant decrease in morbidity and mortality in severe COVID-19 patients. Hence, this review highlights the activation, signal transduction and cross-talk of NF-κB with regard to cytokine storm in COVID-19. Moreover, the development of therapeutic strategies based on NF-κB inhibition are also discussed herein."
"The superiority of anti-TNF-α agents to thiopurines for the prevention of postoperative recurrence of Crohn's disease (CD) after ileocolonic resection remains controversial. In this meta-analysis of individual participant data (IPD), the effect of both strategies was compared and assessed after risk stratification.
After a systematic literature search, IPD were requested from randomized controlled trials investigating thiopurines and/or anti-TNF-α agents after ileocolonic resection. Primary outcome was endoscopic recurrence (ER) (Rutgeerts score ≥i2) and secondary outcomes were clinical recurrence (Harvey-Bradshaw Index/Crohn's Disease Activity Index score) and severe ER (Rutgeerts score ≥i3). A fixed effect network meta-analysis was performed. Subgroup effects were assessed and a prediction model was established using Poisson regression models, including sex, smoking, Montreal classification, CD duration, history of prior resection and previous exposure to anti-TNF-α or thiopurines.
In the meta-analysis of IPD, 645 participants from 6 studies were included. In the total population, a superior effect was demonstrated for anti-TNF-α compared with thiopurine prophylaxis for ER (relative risk [RR], 0.52; 95% confidence interval [CI], 0.33-0.80), clinical recurrence (RR, 0.50; 95% CI, 0.26-0.96), and severe ER (RR, 0.41; 95% CI, 0.21-0.79). No differential subgroup effects were found for ER. In Poisson regression analysis, previous exposure to anti-TNF-α and penetrating disease behavior were associated with ER risk. The advantage of anti-TNF-α agents as compared with thiopurines was observed in low- and high-risk groups.
Anti-TNF-α is superior to thiopurine prophylaxis for the prevention of endoscopic and clinical postoperative CD recurrence after ileocolonic resection. The advantage of anti-TNF-α agents was confirmed in subgroup analysis and after risk stratification."
"We report a 14-year-old man with Crohn's disease (CD) who developed right upper arm pain while being treated with the anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, infliximab. There were no symptoms suggestive of active CD, but the inflammatory response was high, and a contrast-enhanced CT showed the occlusion of the right brachial artery. We diagnosed the patient as having Takayasu's arteritis (TA) and started treatment with corticosteroids, then tapered off the steroids as the symptoms of TA resolved. Later, TA flared up, and his treatment was changed from infliximab to an anti-IL-6 receptor antibody, tocilizumab. The change to TCZ stabilized TA, but exacerbated CD. It is difficult to control both diseases at the same time, and the choice of biologics for treatment must be carefully considered."
"Model-informed precision dosing (MIPD) may be a solution to therapeutic failure of infliximab for patients with ulcerative colitis (UC), as underexposure could be avoided, and the probability of endoscopic improvement (pEI; Mayo endoscopic subscore ≤ 1) could be optimized. To investigate in silico whether this claim has merit, four induction dosing regimens were simulated: 5 mg/kg (label dosing), 10 mg/kg, covariate-based MIPD (fat-free mass, corticosteroid use, and presence of extensive colitis at baseline), and concentration-based MIPD (based on the trough concentration at day 14). Covariate- and concentration-based MIPD were chosen to target the same median area under the infliximab concentration-time curve up to endoscopy at day 84 (AUC"
"Infliximab (IFX) and adalimumab (ADA) refer to the classic drugs to treat moderate-severe inflammatory bowel disease (IBD), which have been proven to be effective to control IBD. However, the side effects exerted by IFX and ADA should be monitored in therapies, especially the paradoxical reaction of the skin system (e.g., psoriasis). Psoriasis is recognized as the most common skin lesion, capable of significantly affecting the quality of patients' life.
This study searched literatures published in English language with the qualifications on PubMed, Embase, Web of Science, Google, and Geenmedical databases. Over 2 co-authors assessed the quality of the articles and extracted the data independently. The data acquired were statistically analyzed with the statistical software of Revman and Stata.
The ADA Group achieved a higher incidence of psoriasis (odds ratio [OR] = 0.658, 95% confidence interval [CI] [0.471-0.919]); Females achieved a higher incidence of psoriasis than males (OR = 1.941, 95%CI [1.326-2.843], P < .05); Smoking up-regulated the incidence of psoriasis (OR = 1.679, 95%CI [1.237-2.279], P < .05); The interval of medication was over 1 year, and the interval of medication applying IFX was longer than that of the ADA Group; most cases could be relieved by using local hormone, phototherapy, or systemic hormone therapy under the strategy of biological agents.
The frequency of reported in IBD exceeds those of other autoimmune diseases, and the ADA treatment for IBD is safer than IFX. Psoriasis is more common in females than in males. Smoking refers to one of risk factors of psoriasis."
"To evaluate for increased rectal bleeding following enoxaparin thromboprophylaxis in children hospitalized for ulcerative colitis (UC).
Retrospective cohort study (2007--2016) of 218 inpatients with active UC. Patients receiving enoxaparin were compared with a nonenoxaparin-treated patient group. Severity of UC was determined using the Pediatric Ulcerative Colitis Activity Index (PUCAI). Hemoglobin (Hb) values and packed red blood cell (pRBC) transfusions were reviewed for a 7-day period following hospital admission. A linear mixed effect model was used to compare change in Hb values between the groups. Risk of pRBC transfusion was compared using a log-rank test and Cox proportional hazard regression. A sub-analysis was also conducted restricting to patients with severe UC to provide more generalizable insight into safety profile of enoxaparin.
Children hospitalized for UC and receiving enoxaparin were more likely to have severe disease, received infliximab therapy and be admitted after 2010. Use of enoxaparin showed there was not a difference (P = 0.60) in the fall of Hb detected among those with acute severe colitis (initial PUCAI ≥65) during the week following admission. Moreover, there was no difference in the risk of requiring a pRBC transfusion with enoxaparin use (log-rank test all patients: P = 0.80; severe UC: P = 0.88; Cox proportional hazard regression all patients: P = 0.72; severe UC: 0.85).
There was no difference in Hb levels or need for blood transfusions in children hospitalized for severe UC (PUCAI ≥65) whether or not they received enoxaparin for thromboembolism prophylaxis."
"Thymoma-associated autoimmune enteropathy is a rare paraneoplastic syndrome that is characterized by severe chronic diarrhea, malabsorption, and specific histological findings. Because of its rarity, it is difficult to diagnose. We describe an adult patient with protracted diarrhea and weight loss that developed recurrent sepsis and progressive colonic stenosis due to thymoma-associated autoimmune enteropathy. Ultimately, the diagnosis thymoma-associated autoimmune enteropathy was established by characteristic intestinal histology, anti-enterocytes antibodies, and thorax imaging. Radical thymectomy was performed without improvement. Therapy with azathioprine and infliximab induced clinical remission with complete recovery of the colonic stenosis."
"Anti-tumor necrosis factor (TNF) treatment for inflammatory bowel disease (IBD) increases the risk of tuberculosis (TB) infection. In the present study, we analyzed the clinical characteristics and risks of TB in Korean patients with IBD who received anti-TNF treatment.
The study included patients with IBD who were treated using anti-TNF agents between January 2001 and June 2018 at the Asan Medical Center. Overall, 1434 patients with ulcerative colitis or Crohn's disease were enrolled. We calculated the incidence of active TB infection after anti-TNF treatment and compared the clinical characteristics of the TB group with those of the non-TB group.
Twenty-one patients (1.46%) developed active TB infection, and the incidence rate of active TB was 366.73 per 100,000 person-years. In total, 198 patients (14.9%) were positive for latent tuberculosis infection (LTBI), of whom only eight (4%) did not complete LTBI treatment. The age at which the anti-TNF therapy was started was significantly higher in the TB group than in the non-TB group (HR 1.041, 95% CI 1.014-1.069, p = 0.002), and as age increased, so did the incidence rate of active TB infection (linearity p < 0.001). There was no significant difference in the incidence rate of LTBI between the TB and non-TB groups (HR 0.896, 95% CI 0.262-3.066, p = 0.862).
In patients with IBD, the incidence rate of TB increased with age at anti-TNF therapy initiation. Active treatment of LTBI may lower the incidence of TB in patients with IBD who are to undergo anti-TNF therapy."
"To describe the ophthalmological characteristics in a Juvenile idiopathic arthritis (JIA) cohort and to evaluate how therapeutic advances have changed the course of the uveitis.
Analysis of a retrospective cohort study of consecutive JIA pediatric patients including JIA-associated uveitis (JIA-U) and comparison with a previous study in the same uveitis center assessed before the wide-spread of biological therapy.
The total of 49 JIA patients were analyzed, of whom 18 JIA-U, compared with a JIA-U past cohort of 66 patients. Systemic corticosteroids were used significantly less in the current JIA-U group (p = 0.008) than in the past one. JIA-U present cohort was on therapy more frequently with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) than the past group (p = 0.039), mostly treated with methotrexate (93.3%). Furthermore, a larger use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) was described in the current JIA-U group (p = 0.005) also associated with csDMARDs (p = 0.003). Adalimumab was used more (72.7%) in the present JIA-U cohort compared to a larger treatment with infliximab (61.5%) in the past (p = 0.005). Higher number of uveitis recurrences was observed in the previous cohort compared to the current one (p = 0.005). Fewer complications were described in this study than in the previous: posterior synechiae (p = 0.007), cataract (p < 0.001), band keratopathy (p < 0.001), and elevated intraocular pressure (IOP) (p = 0.047).
Current therapies reduced the uveitis recurrences and ocular complications including cataract due also to the lower use of corticosteroids. The new close collaboration with the pediatric rheumatologic center in the same University has contributed to the care improvement and decrease of uveitis complications."
"Drug repurposing is an attractive option for identifying new treatment strategies, in particular in extraordinary situations of urgent need such as the current coronavirus disease 2019 (Covid-19) pandemic. Recently, the World Health Organization announced testing of three drugs as potential Covid-19 therapeutics that are known for their dampening effect on the immune system. Thus, the underlying concept of selecting these drugs is to temper the potentially life-threatening overshooting of the immune system reacting to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This viewpoint discusses the possibility that the impact of these and other drugs on autophagy contributes to their therapeutic effect by hampering the SARS-CoV-2 life cycle."
This study will evaluate the efficacy of infliximab in reducing the incidence of grade II-IV acute graft versus host disease by day +100 post-transplant in patients undergoing allogeneic hematopoietic stem cell transplant.
"Major depression is increasingly recognized to be a chronic and highly recurrent condition, which results in significantly increased health problems. One possible mechanism that may contribute to treatment resistance is increased production and release of chemicals called proinflammatory cytokines in patients with major depression. These chemicals mediate the body's response to infectious agents like bacteria and have been shown to be increased by psychological stress. They produce the symptoms that we associate with being sick, including fever, malaise and changes in sleep and appetite. Several lines of evidence indicate that proinflammatory cytokines may contribute to the development of major depression and may thus represent a novel target for the pharmacological treatment of the disorder.||The TNF-alpha antagonist, Infliximab (Remicade®), is an infusion style drug approved by the FDA for the treatment of inflammatory conditions like Crohns disease and rheumatoid arthritis. The researchers are conducting a study to see if the infliximab (Remicade®) is more effective than placebo in acutely reducing symptoms of depression in patients who have elevated proinflammatory markers and have not responded to, or been unable to tolerate, at least two previous treatments in the current depressive episode. Proinflammatory markers are measured by a simple blood test for C-Reactive Protein (CRP) levels in the body.||After appropriate screening to determine eligibility, 64 subjects with treatment resistant depression will be randomized to receive three infusions of either infliximab (Remicade®) or placebo (salt water) in the Emory Infliximab Infusion Center in the Division of Digestive Diseases, Emory University School of Medicine. Subjects will be followed for 12 weeks with evaluations at weeks 0 (baseline), 1, 2, 3, 4, 6, 8, 10 and 12. The first infliximab (Remicade®) infusion will occur at the first (Baseline) visit. The second infusion will occur at Study Week 2 (the third visit). The third infusion will occur at Study Week 6 (Visit 6). The choice of three infusions, and the infusion schedule, is based on current recommendations for the use of infliximab (Remicade®) in conditions for which it has received FDA approval. Subjects will be evaluated for twelve weeks by trained clinicians for changes in depression symptoms and improvements in quality of life. In addition, a physician will evaluate subjects each visit to make sure they are remaining healthy. Blood will be drawn at baseline prior to infusion and all subsequent visits to check labs for safety but also to evaluate potential relationships between changes in inflammatory activity and therapeutic response. After Study Week 12, participants will be monitored by phone, every 4 weeks during the 22-Week Post Study Follow-up Phase to assess physical and psychiatric symptoms in the period following the final infusion. At the baseline and Week 8 visits, subjects will be admitted to the Atlanta Clinical Translational Science Institute (ACTSI), a research unit in the Emory Hospital, for an extended evaluation. The purpose of coming to the ACTSI will be for researchers to evaluate whether treatment with infliximab improves endocrine function, inflammation, sleep and thinking abilities in people who are depressed. For all other visits (Week 1, 2, 4, 6, 10 and 12), participants will come for an office visit in the Winship Cancer Institute."
"Corneal melt is a complication that could affect very ill eyes and lead to the thinning of the cornea (the clear window covering of the eyes). This thinning can lead to severe consequences such as the leakage of the liquid inside the eye (ocular perforation), or even blindness. Corneal melt can be caused by certain infections or as a sterile process. This project only includes patients with a sterile corneal melt (without an infection) caused by diseases such as rosacea, Sjogren's syndrome, rheumatoid arthritis, Crohn's disease, Stevens Johnson syndrome, as well as toxic epidermal necrolysis or mucous membrane pemphigoid.||Infliximab is an antibody against tumour necrosis factor alpha and has been used to treat or prevent corneal melt in certain patients with inflammatory of auto-immune disease. In this situation, infliximab was used intravenous (using veins) in order to treat the whole body.||This study's hypothesis is that infliximab can safely be used as eye drops for the treatment of sterile corneal melt."
"The aim of this study is to a.) evaluate whether early serum infliximab levels are predictive of avoidance of colectomy, b) evaluate whether serum albumin levels correlate with serum infliximab levels, and c) evaluate whether serum tumor necrosis factor levels are inversely correlated with serum infliximab levels.||In patients hospitalized for severe ulcerative colitis and treated with high-dose infliximab, we predict that early serum infliximab levels (24, 48, and 72 hour) will be positively associated with clinical response and avoidance of colectomy."
"A multi-centre retrospective review of fistulizing Crohn's disease (CD) patient charts will capture data to measure health care resource utilization associated with the use of Infliximab for treatment of CD. Three health science centres/hospitals from Ontario are targeted to participate in the study, each site is expected to provide 30-40 patient charts with a target of 108 charts total."
"Penetrating keratoplasty is a cornea surgery involving several inflammatory complications, of which the most important is glaucoma. Researchers wish to determine whether it is safe to administer infliximab (an anti-inflammatory drug) eye drops after surgery, and whether this eye drop could prevent the occurrence of glaucoma."
The aim of this study is to assess the relationship between microscopic Geboes index of inflammation and clinical course of ulcerative colitis in patients treated with infliximab. The investigators propose to test the hypothesis if infliximab is able to induce histological remission and then change the clinical course of ulcerative colitis.
"Switching to Adalimumab has proven to be efficacious in Crohn's disease (CD) patients with intolerance or loss of response to Infliximab. Currently there are no studies on the efficacy of switching to Infliximab in patients with loss of response or primary non-response to Adalimumab. Even in rheumatology, where switching between all classes of anti-TNFα biologicals is common practice, there are no scientific data on switching from humanized to chimeric anti-TNFα antibodies.||The purpose of this study is to document the efficacy of such a switch and to identify the possible predictive factors for success.||If treatment with Adalimumab fails (despite optimal dose and interval) and the treating physician therefore decided to switch to infliximab, the patient may be enrolled in this observational study. At regular intervals (every Remicade), the patient will be clinically re-evaluated. The disease activity score will be calculated: Crohn's disease activity index (CDAI). At regular intervals, the results of interim blood tests will be documented (3x). The succession will be 1 year. At week 10, 26 and 52, additional serum samples will be taken for determination of antibodies against Adalimumab and Infliximab. The serum levels of Adalimumab (week 0) and Infliximab (week 10, 26 and 52) will be determined.||For this study there is no specific therapy change. The study wants only to document the results of a therapy switch that, in current clinical practice, is made by the treating physician."
"The Boston Keratoprosthesis type I (KPro) is a prosthetic cornea used to treat several causes of corneal blindness. Some categories of patients, including those with auto-immune diseases such as Stevens-Johnson syndrome, toxic epidermal necrolysis syndrome and mucous membrane pemphigoid, have a higher risk of failure for the KPro. Because of chronic inflammation, the cornea supporting the KPro may melt, leading to a higher risk of infection, loss of the KPro and loss of the eye.||Infliximab is an antibody against tumor necrosis factor alpha and is used intravenously to control inflammation in several diseases. It has been used in some cases of corneal melting with significant success.||This study's hypothesis is that infliximab can be successfully used as an eye drop (instead of the usual administration through veins) and that its regular use may prevent melt in eyes with a Boston Keratoprosthesis type I and underlying auto-immune disease."
"To collect information on the safety and effectiveness of Infliximab BS for Intravenous Drip Infusion 100 mg ""Pfizer"" against psoriasis vulgaris, psoriasis arthropathica, pustular psoriasis, or erythrodermic psoriasis under actual status of use."
"Prospective, open-label-, 1-arm, multicenter observational study to determine the dose and interval of Infliximab infusions for subjects with plaque psoriasis."
"To collect information on the safety and effectiveness of Infliximab BS for Intravenous Drip Infusion 100 mg ""Pfizer"" against rheumatoid arthritis under actual status of use."
The purpose of this study is to improve the investigators understanding of the relationship between Crohn's disease and blood levels of the drug infliximab (Remicade). The investigators want to determine whether measuring drug levels can be helpful in understanding how patients respond to this treatment.
"The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow."
"To collect information on the safety and effectiveness of Infliximab BS for Intravenous Drip Infusion 100 mg ""Pfizer"" against Crohn's disease or ulcerative colitis under actual status of use."
"The proposed study is intended to test the idea, based upon current knowledge of the biology and physiology of corneal ulceration in SJS/TENS patients who receive a keratoprosthesis, and on the known effects of infliximab on matrix metalloproteinases, that infliximab therapy for such patients may reduce the likelihood of corneal ulceration, and hence extend the period of prosthesis retention and vision recovery."
"There is a great individual variability of pharmacokinetic of infliximab in patients treated for ankylosing spondylitis (AS). Moreover, some patients have a treatment with methotrexate (MTX), others have not.||Thus, the aim of this study is to assess the effect of MTX on the pharmacokinetic properties of infliximab in 30 patients treated for AS, 15 with MTX, 15 without."
"This trial is designed to measure improvement of hip involvement in patients with ankylosing spondylitis (AS) after receiving 4 doses of infliximab. Participants will receive infliximab 5 mg/kg (as an intravenous perfusion over a period of 2 hours) at Weeks 0, 2, 6, and 14, consistent with the approved dosing regimen described in the label. Participants will be evaluated for hip pain, functional capacity and stiffness before and after 14 weeks (4 doses) of treatment. Further treatment after 4 doses is based on standard clinical practice as determined by the trial site."
"Objectives: To examine the effect of accelerated infliximab induction in children with moderate to severe UC. Design: A multi-center, prospective, randomized, open label study. Setting: Pediatric gastroenterology centers. Participants: Children 6 year to 17 years (Overall, 84 patients) with moderate to severe UC who are corticosteroid dependent/resistant thus planned to receive infliximab induction. Intervention: Group 1 (intervention) will receive an accelerated induction at 0,1,3 weeks (5 mg/kg) and then at week 7,11,15. Group 2 (standard) will receive a per protocol induction at 0,2,6 weeks (5 mg/kg) and then at week 14. Drug levels will be obtained prior to each infusion in each group (up to week 20). Further maintenance will be planned according to drug levels at weeks 15 and 14, respectively. Follow-up will continue without further interventions till 52 weeks following induction. Main outcome measure: Clinical remission, on infliximab at week 20. Secondary outcome measures: 1. Colectomy free rates at week 20 and 52. 2. Clinical remission on infliximab at week 52. 3. Drug levels and anti-drug antibodies prior to last study infusion. 4. Anthropometric and laboratory measures including calprotectin at the end of induction, week 20 and week 52 5. Changes in fecal microbiome, virome and bile acids content. Sample size: In order to demonstrate 30% difference in clinical remission rate between groups is significant, we will need to study 36 children in each group to be able to reject the null hypothesis that the failure rates between the groups are equal with probability (power) of 80% and a type I error probability of 0.05."
"Palmoplantar psoriasis is a variant of psoriasis affecting palms and soles. It is one of the most debilitating variants of psoriasis which very often interferes with daily activities and with the ability to work. This type of psoriasis is very difficult to treat as topicals have difficulty penetrating the thick epidermis of palms and soles and are therefore not very effective. The response to standard agents (methotrexate, cyclosporine and acitretin) is also usually limited. A number of these patients have very severe hand and feet disease with mild to no involvement elsewhere on the body.||Given the efficacy of infliximab in psoriasis, the purpose of this study is to evaluate if infliximab is safe and if it will improve severity and quality of life in patients with palmoplantar psoriasis, a debilitating variant of psoriasis."
"Inflammatory bowel disease (IBD) is a chronic condition that causes inflammation of the intestinal tract. Common types of IBD include Crohn's disease, ulcerative colitis, and indeterminate colitis. Infliximab (Remicade®) is a biologic medication that is approved by the U.S. Food and Drug Administration (FDA) for the treatment of IBD. Previous research with infliximab has shown it to be an effective treatment for pediatric IBD, however, it can become less effective if the level of the medication in the body is not high enough or if a patient develops antibodies (proteins made by the immune system that attack foreign substances in the body) to the medication. Currently, if a patient with IBD is taking infliximab and develops either abnormal lab values or reports a worsening of symptoms the doctors will measure the level of infliximab in the blood as well as any infliximab antibodies to determine if dosing changes, to either the dose of the medication or the frequency of dosing, are needed. This process is called reactive drug monitoring. The purpose of this research study is to find out if proactive drug monitoring in patients being treated with infliximab for IBD works better for controlling IBD. Proactive drug monitoring is measuring the level of infliximab in the blood as well as infliximab antibodies on a regular basis, before symptoms worsen or lab results come back abnormal, to see if dosing changes can be made that may prevent the worsening of IBD."
"This is a prospective open-label study to evaluated the efficacy and safety of infliximab(Remicade) in treating of patients with early ankylosing spondylitis (AS). Infliximab was injected intra-venous on baseline, 2nd week, 6th week, 12th week and 24th week, with dosing of 5mg/kg. The major outcome index is ASAS20, and minor outcome indexes include ASAS50 and ASAS70, BASDAI20,BASDAI50 and BASDAI70. And MRI of sacroiliac joint is not necessary. The adverse events at any time were recorded."
The purpose of this study is to determine the superiority and efficacy of infliximab induction therapy in chinese participants with moderate to severe plaque-type psoriasis (scaly skin rash) compared with placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial).
"Patient with undifferentiated arthritis and the presence of anti-citruline (anti-CCP) antibodies are at high risk to develop RA. The presence of anti-CCP is associated with a higher rate of erosion and a higher risk of progressive and severe RA.||The investigators have demonstrated in the CIERA study that MTX/IFX combination therapy is superior to MTX alone to reduce MRI signs of synovitis and bone edema and is clinically more effective.||The immunopathogenesis of undifferentiated arthritis is poorly understood. However, synovial studies from patients with early arthritis suggest that UA and RA may share common immunopathogenic mechanisms. One biopsy study of asymptomatic joints in patients with early arthritis demonstrates synovitis in more than half of the joints samples with prominent T cell and macrophage infiltration, similar to Rheumatoid Arthritis (RA).||Thus intensive treatment with anti-TNF antibodies (infliximab) may have an impact on multiple immune mechanisms driving synovitis in undifferentiated arthritis and may influence the clinical outcome.||Recently, Methotrexate has been demonstrated to improve the course of undifferentiated arthritis and prevent the development of RA. Short regimen of more intensive therapy with Infliximab could alter the radiological, immunopathological and clinical outcome."
"This study will evaluate the efficacy, tolerability, and effect on the quality of life of infliximab in adults with moderate-to-severe psoriasis who are resistant to etanercept after 12 weeks of treatment or have failed 24 weeks of treatment with etanercept. Infliximab will be administered as an intravenous infusion of 5 mg/kg at Baseline (Week 0), Visit 3 (Week 2), Visit 4 (Week 6), Visit 6 (Week 14), and Visit 8 (Week 22)."
"Middle Eastern subjects with moderate-to-severe chronic plaque psoriasis will be administered infusions of infliximab (Remicade) at 5 mg/kg of body weight at Weeks 0, 2, 6, 14, and 22. The safety and efficacy of infliximab monotherapy will be evaluated."
"1 Project summary 1.1 Rational. Accent 1 study has demonstrated the superiority of Infliximab over placebo in a systematic treatment strategy of Crohn 's disease every 8 weeks during one year. However the optimal strategy beyond one year of treatment is not established. Particularly, the need for carrying on systematic treatment with infliximab in all the patients has not been demonstrated.||1.2 Primary objective. Determine factors associated with a low risk of clinical relapse after stopping infliximab in CD patients in remission (CDAI<150) and regularly treated with infliximab for at least one year.||1.3 Main objective and main judgement criteria. Determine predictive factors for relapse within one year after stopping infliximab. Main judgement criteria is the clinical relapse after stopping infliximab. Clinical relapse is defined either by a CDAI>250 or by a CDAI between 150 and 250 if this CDAI is confirmed over two consecutive weeks with an increase of at least 70 points over baseline for the two consecutive measures.||1.4 Secondary objectives and judgement criteria. Determine the time to-relapse Determine predictive factors for short-term relapse (<2 months)after stopping infliximab.||Determine response to infliximab retreatment in these patients. Determine tolerance to infliximab retreatment in these patients. Determine predictive factors for an absence of response to retreatment. Determine predictive factors for infliximab retreatment intolerance. Determine sustained response in the retreated patients.||1.5 Type of study Open-label prospective study of stopping regular treatment. Inclusion period: minimum one year, possibly prolonged to reach 100 patients. Patients will be followed up every two months for at least 18 months after stopping infliximab.||1.6 Justification of the number of patients Number of patients to include is at least 100. This recruitment should be reached within one year. This number should allow to disclose predictive factors associated with a relative risk of at least 2 if this factor is equilibrated (50% at risk patients) or 3 is this factor is disequilibrated (90% at risk patients)."
"Studies show the presence of immuno-inflammatory disturbances in individuals with Bipolar Disorders (BD). Increased levels of circulating proteins known as cytokines that promote inflammation have been consistently reported in individuals with bipolar disorders. A particular cytokine referred to as Tumor Necrosis Factor (TNF)-alpha is among those cytokines that have been consistently identified across depressive, manic, and euthymic periods. Disturbances in inflammation however, are not seen in all individual with bipolar disorder. Those individuals with signs of inflammation also often present with higher prevalence of medical disorders that are also associated with inflammation. Those individuals with significant signs of inflammation may respond to anti-inflammatory treatments. In this study, individuals with bipolar depression who exhibit signs of high inflammation will be enrolled and treated with either an anti-inflammatory biologic known as infliximab or placebo (saline)."
"The aim of this study is to quantify how infliximab therapy is being used in the UK and the consequent impact on health care resources, which will help to inform budget holders and payers on the costs associated with the treatment of Crohn's Disease."
This project is designed to test the hypothesis that infliximab is clinically useful for patients with refractory childhood uveitis.
"Subjects with moderate-to-severe chronic psoriasis not responding to standard or biologic therapy will be eligible to enroll in this study. Subjects will receive infliximab infusions (5 mg/kg of body weight) at Weeks 0, 2, 6, and 14 followed by a 12-week follow-up period. The efficacy of infliximab will be evaluated by the Psoriasis Area and Severity Index (PASI)."
Combination Methotrexate and Infliximab:Influence of immunogenicity on the efficacy of infliximab in patients with Ankylosing Spondylitis.
"To evaluate the predictive value of clinical, functional (HAQ), laboratory and US variables in relation to disease activity and radiographic outcome in patients with RA who start treatment with Remicade at 24 weeks."
This study aims to test the hypothesis that the accelerated infusion of infliximab is not inferior to the conventional 2 hour infusion with respect to the frequency of infusion reaction.
The purpose of this study is to determine if intravitreal infliximab is a safe and effective treatment for macular edema secondary to diabetes.
"This 14-week non-interventional study will observe patients with rheumatoid arthritis (RA) who are being treated with infliximab for the first time, in order to learn about their disease characteristics. Patients in this study will be treated for RA with infliximab and in a usual manner as decided by their physician."
The primary objective of this study is to examine the efficacy of infliximab for the treatment of persistent uveitis in children. Participants (4-18 years of age) will be randomly assigned to either 5mg/kg or 10mg/kg dose of infliximab to be administered by intravenous infusion at four week intervals. Participant responses will be measured at at four to eight week intervals for up to ten months.
"This is a long-term, randomized, multi-center, open-label study of infliximab treatment in adults with moderate to severe plaque-type psoriasis. This study is the long-term extension of Study P04271 (NCT00251641); Study P04271 is a Phase 3b, randomized, parallel-group, multicenter, open-label, 26-week study comparing the efficacy and safety of infliximab versus methotrexate in the treatment of adult subjects with moderate to severe plaque-type psoriasis. The objectives of this study are to assess the efficacy and safety of long-term maintenance therapy versus intermittent therapy with 5 mg/kg infliximab in a moderate to severe plaque-type psoriasis population.||During an interim safety evaluation of the trial, a higher incidence of serious and severe infusion reactions was observed in the intermittent treatment arm, consisting of a re-induction cycle (maximum of 4 infusions at 0, 2, 6 and 14 weeks) after a period of no treatment compared with the maintenance arm (infusions every 8 weeks without an interruption of treatment). Consequently, the sponsor has terminated the trial. The label will be updated to reflect this new information relating to the use of a re-induction regimen with infliximab."
The purpose of this study is to identify whether an Accelerated or Intensified Infliximab induction regimen is superior to Standard induction in Acute Severe Ulcerative Colitis in an open label multi-centre randomised controlled trial.
The purpose of this study is to evaluate the efficacy of infliximab in induction regimen by assessing the mean decrease in Disease Activity Index for intestinal Behcet's disease (DAIBD) score of 20 or more in participants with active intestinal Behcet's disease who are refractory to conventional therapies.
"Subjects with psoriasis will receive intravenous infliximab 5 mg/kg given over a 2-hour period at Weeks 0, 2, and 6 (induction therapy) to evaluate the efficacy of infliximab at Week 18. Subjects who achieved >=75% improvement in Psoriasis Pustulosa Palmoplantaris Area and Severity Index (PPPASI) score at Week 8 AND had deterioration of PPPASI score of 50% from Week 8 until Week 12 were to receive an additional infusion at Week 12."
"This is a Phase 4, multi-center, open-label, one-arm, pilot study in patients with active ankylosing spondylitis refractory to conventional treatment. Remicade will be given at Weeks 0, 2, and 6 and then every 8 weeks up to Week 54. The number of patients showing ASAS-20 clinical response at Week 14 will be evaluated."
The purpose of this study is to determine if intravitreal infliximab is a safe and effective treatment for macular edema secondary to uveitis.
"ASART-1 clinical study is a phase 1 study which carried out to establish the pharmacokinetic equivalence and equal safety profile of BCD-055 (infliximab manufactured by JSC BIOCAD, Russia) and Remicade when used as multiple IV infusions for the treatment of ankylosing spondylitis."
"Acute Graft Versus Host Disease (GVHD) is a serious medical condition that is a common development after Bone Marrow Transplant (BMT). Acute GVHD happens when the donor cells attack and damage your tissues and organs after transplant.||Acute GVHD often causes: Skin rashes, nausea, vomiting, abdominal pain, diarrhea (may have blood), liver damage that can cause inflammation in the liver or jaundice (yellowing of the skin or eyes), damage to other organs||Steroids are the first line of treatment for acute GVHD. About a quarter of the patients that develop acute GVHD may not respond to steroid and have steroid refractory GVHD (SR-aGVHD). Patients with SR-aGVHD may need other medications. SR-aGVHD, is a potentially life threatening condition. There is no standard treatment and it may not respond to treatment.||The goals of this study are to find out if Infliximab and basiliximab can treat SR-aGVHD.||Participants in this study will receive combination therapy (2 drugs: infliximab and basiliximab) once a week for four weeks."
"Patients harboring dolichoectactic vertebrobasilar (DVB) aneurysms are at risk of suffering SAH, ischemic stroke, and/or brainstem compression and many patients are not offered invasive treatment due to the futility of existing surgical methods. Consequently, there is demand for development of medical therapy for DVB aneurysms"
The study will assess the efficacy and safety of PF-06438179 and infliximab in combination with methotrexate in subjects with active rheumatoid arthritis who have had an inadequate response to methotrexate.
"prospectively compared Exclusive Enteral Nutrition with Infliximab in the clinical outcomes, mucosal healing, nutrition improvements, adverse effects and gastrointestinal microbiota changes on Chinese Children With active Crohn's Disease"
Retrospective observational study in which the efficacy of infliximab is studied in patients with inflammatory bowel disease and its subcutaneous levels are monitored.
"This study will be performed to evaluate and document the safety and efficacy of infliximab (Remicade®) in the treatment of chronic inflammatory diseases in big cohorts in the daily routine practice of rheumatologists, gastroenterologists, and dermatologists."
This study evaluates the safety of infliximab in infants and children with acute Kawasaki Disease.
"Intra-articular (IA) injection of medication is a common procedure in the management of joint disorders. In particular, the procedure is effective in the treatment of inflammatory conditions, with long acting corticosteroids most commonly used. These agents have been shown to reduce the signs and symptoms of inflammation, expressed primarily in the synovium of the joint, and are probably capable of slowing the progression of damage to joint cartilage and bone in some of these inflammatory conditions. Arthritis that is refractory to IA corticosteroid injections may respond to surgical, chemical, or, radioisotope synovectomy, procedures in which the inflamed synovial tissue is eradicated. It has been noted that infliximab, a monoclonal antibody directed to Tumor Necrosis Factor (TNF) - α, has high affinity for the TNF-α rich inflamed synovium. Recently, clinical benefit from IA injections of infliximab has been reported in some cases that were refractory to IA injections of corticosteroids. Similarly, the effectiveness of IA infliximab in suppression of joint inflammation has also been demonstrated in patients who could not receive systemic therapy with infliximab. These reports examined the effect of a single injection of infliximab100 mg injected into a large inflamed joint or 2 IA injections 24 hours apart.||We propose to further evaluate the use of IA infliximab in patients with intractable knee monoarthritis, explore the optimal mode of its employment, and assess the degree of infliximab systemic absorption from the IA injection. In a pilot study 40 knees will be evaluated, 20 injected with infliximab and 20 injected with a corticosteroid comparator reflecting the current standard of care."
The purpose of this study is to compare the proportion of patients with an infusion reaction in Rheumatoid arthritis (RA) patients treated with Golimumab Intravenous (IV) or Infliximab.
The purpose of this study is to evaluate whether trough serum infliximab concentrations at the time of loss of clinical response will identify pediatric participants with inflammatory bowel disease (IBD) who would benefit (regain clinical response) from dose escalation above the currently approved dose [5 milligram (mg)/kilogram (kg) every 8 weeks (q8wk)] and the safety of that dose escalation.
"Infliximab is a chimeric monoclonal antibody directed towards Tumor Necrosis Factor -alpha that is largely used in inflammatory diseases such as rheumatoid arthritis (RA).||A relationship between dose and clinical outcomes was shown in populations of RA patients but there is an interindividual variability of this relationship. At an individual level, this dose-effet relationship can be separated into the dose-concentration (pharmacokinetic or PK) and the concentration-effet (pharmacokinetic-pharmacodynamic or PK-PD) relationships.||Serum trough concentrations of infliximab have been shown to be variable between patients receiving the same treatment regimen. This PK variability may be explained by several factors (e.g. genetic and immunological factors). The concentration-effect relationship may also be variable and the sources of this variability need to be studied as well. To date no detailed infliximab PK analysis has been published. The sources of variability of the dose-effect relationship need to be characterized to optimize infliximab dosing regimen in patients.||The FAKIR study is a multicenter prospective observational study that will focus on patients treated with infliximab. Its aims are:||to characterize the PK and PK-PD variability of infliximab in RA, using clinical criteria and biomarkers, assessed over time ;|to study the influence of the polymorphism of FCGRT (the gene encoding FcRn) on the PK variability of infliximab; to study the influence of the polymorphism of FCGR3A (the gene encoding Fc gamma RIIIa) on the PK-PD variability of infliximab; and to study the influence of antibodies toward infliximab on the PK and PK-PD variabilities of infliximab."
This study aim to identify the therapeutic effect of azathioprine during infliximab(IFX) treatment in Crohn's disease (CD).Half of patients will receive azathioprine and infliximab combination therapy at the same time. The other half patients will be given infliximab therapy first and then receive azathioprine 14 weeks later.
"Ankylosing spondylitis (AS) is a chronic inflammatory disease that involves the sacroiliac joints, axial skeleton, entheses and peripheral joints. Current therapy for AS is mainly NSAIDs and physiotherapy which are oft insufficient. Treatment with the TNF-alpha blocking agent infliximab was shown to have definite clinical efficacy in patients with active AS on a short- and a long-term-basis over 2 years. We want to show that treatment with infliximab on a long-term basis over 4 years is safe and efficient and can prevent radiographic progression over a long period of time. Further we want to learn about the outcome after discontinuation of anti-TNF-alpha therapy."
"The primary purpose of the project is to determine what is the best schedule for restarting infliximab in patients with inflammatory bowel disease (IBD) specifically ulcerative colitis and Crohn's disease, who have undergone infliximab infusions before. The primary endpoint would be the failure rate; the need to discontinue infliximab or change treatment. A secondary aim will be to determine if infliximab drug and antibody levels can predict clinical outcomes at 1 year. Other secondary outcomes include comparing short-term and long-term steroid free remission rate, and serum and fecal inflammatory markers in response to infliximab."
"This clinical trail intends to evaluate interventions based on the Infliximab trough levels for an individualized therapy adaption for pediatric IBD-patients undergoing anti-TNF-alpha-therapy. Main aim of the individualized strategy is to attain and maintain early disease control in order to keep as many patients as possible in disease remission, and to avoid primary and secondary therapy failure."
"This observational study will explore the Swedish national population of patients with rheumatoid arthritis (RA) on infliximab maintenance therapy in order to identify patients who may be eligible for a dose reduction study. Patients will be asked a variety of questions regarding their treatment dosing and disease activity, and then asked whether or not they would consider participating in a dose reduction study. Patients in this study will be described in terms of demographic and disease characteristics."
"Proliferative vitreoretinopathy (PVR) is the most common cause for failure of rhegmatogenous retinal detachment repair and is characterized by the growth and contraction of cellular membranes within the vitreous cavity on both sides of the retinal surface as well as intraretinal fibrosis.||Multiple therapeutic agents have been tried as an adjunctive to retinal detachment surgery for PVR with no consistent efficacy. Tumor necrosis factor-α (TNF-α), which is a prominent inflammatory cytokine, is secreted in response to trauma, infection, and inflammation. It is a key mediator of ocular inflammation and its interactions with the retinal pigment epithelium (RPE) cell contribute to the initiation of PVR. This may occur through the action of TNF-α on the RPE cells inducing changes in cellular morphologies that lead to the formation of fibroblastic cells.||Infliximab (Remicade; Janssen Biotech, Horsham, PA, USA) is a mouse-human chimeric antibody that neutralizes the biological activity of TNF-α by high-affinity binding to the soluble and transmembrane forms of TNF-α, therefore preventing the effective binding of TNF-α with its receptors. Infliximab is used in the treatment of various ocular and systemic inflammatory conditions. Furthermore, intravitreal infliximab has been used for the treatment of various ocular diseases and has proven to be generally safe for the short term in inflammatory ocular conditions. A recent study showed that intravitreal infliximab can inhibit the development of PVR and reduce levels of cytokines in an experimental dispase-induced PVR model.||The purpose of this randomized controlled trial is to evaluate the efficacy of intravitreal infliximab injection as an adjunct to pars plana vitrectomy in the treatment of PVR associated with primary rhegmatogenous retinal detachment."
"The purpose of the study is to assess whether a proactive therapeutic drug monitoring strategy, introduced early during treatment, improves Infliximab (IFX) durability, efficacy and safety in children and young adults with inflammatory bowel disease. Patients with an indication to receive IFX, based on current clinical practice recommendations, will receive the drug either based on IFX concentrations determined before every IFX infusion, starting from the third infusion, or at standard dosing. Approximately 90 patients will be included in this research study. Patients enrolled will be in the study for approximately 12 months."
The objective of this study is to investigate the effect of infliximab to the children who don't respond to the first dose of intravenous immunoglobulin (IVIG) (2g/kg) in Kawasaki disease.
"This is an open-label, controlled sub-study to the parent protocol (P04041, NCT00779935) to examine the expression profile of genes in patients in the active stage of ankylosing spondylitis (AS) compared to the healthy population as control, moreover to examine the changes in expression profile during anti-tumor necrosis factor (TNF)-alpha treatment (Remicade)."
"The objective of this study is to compare the efficacy of Infliximab-Biosimilar to Infliximab-Innovator and to demonstrate its noninferiority, in patients with ulcerative colitis or Crohn's disease in remission under treatment with infliximab up to 3 months."
"Takayasu arteritis (TA) is a chronic inflammatory disease affecting large and medium caliber arteries, particularly the aortic arch and its main branches. Clinical manifestations are caused by the marked thickening of the wall of the involved vessels, resulting in lumen narrowing and ischemia of the tributary districts. Therapy is based on the use of corticosteroids, immunosuppressants, and biologic drugs including infliximab, a monoclonal antibody blocking tissue necrosis factor (TNF)-alpha. Biosimilar infliximab is commercially available and used in the treatment of various immune-mediated conditions. There are currently no data on the efficacy and safety of biosimilar infliximab in the treatment of TA.||The investigators propose this monocentric, observational, prospective, open label study to evaluate the efficacy and safety of biosimilar infliximab in the treatment of 30 patients with TA. Specifically, the study will include: I) TA patients refractory to treatment with corticosteroid and/or immmunosuppressive therapy, not previously treated with infliximab; II) TA patients already receiving treatment with originator infliximab.||Biosimilar infliximab will be administered at dosages usually employed in the treatment of TA. Specifically, patients not previously treated with the originator drug will receive biosimilar infliximab intravenously at a dose of 5 mg/Kg at time 0, at week 2, at week 4; thereafter, treatment will be administered every 4-6 weeks at a dose of 5-10 mg/kg based on clinical judgement. In patients previously treated with the originator drug, biosimilar infliximab will be administered at the same dosages.||To evaluate the efficacy of therapy, changes in clinical manifestations, laboratory examinations, and imaging findings including angio-magnetic resonance imaging (MRI) of thoracic and abdominal vessels and total body PET/CT scan will be evaluate at time 0 as well as 6 and 12 months following treatment initiation. In order to evaluate the safety of the study treatment, the investigators will stringently evaluate possible side effects of treatment, including infusion reactions, changes in laboratory tests, infection, cancer, autoimmune manifestations, neurological and cardiovascular symptoms.||The total duration of follow up for each patient will be 52 weeks from enrolment."
The purpose of this study is to understand the safety and effectiveness of infliximab when used in clinical practice. This is a post-marketing surveillance study.
The OPTIMIZE Trial compares whether iDose dashboard-driven infliximab dosing (iDose-driven dosing) is more effective and safer than standard infliximab dosing for inducing and maintaining disease remission in moderately to severely active CD.
"This is a prospective Phase 4, open-label, non-randomized, observational, multi-center study of infliximab in participants with plaque-type psoriasis to assess the clinical response in real-world practice of long-term maintenance therapy with infliximab 5 mg/kg body weight in a psoriasis population, prescribed in a regimen in accordance with the product monograph (PM) for Canada, the approved summary sheet of product characteristics (SPC) for countries in the European Union (EU), or per label according to local guidelines for all other participating countries."
"This is a national, multi-center, observational, prospective photographic atlas study in subjects who are treated with infliximab for moderate-to-severe psoriasis in daily clinic according to local country regulations and reimbursement."
"The main purpose of the study was to compare rheumatoid arthritis symptom improvement in participants who were given ABP 710 to those who were given infliximab, 22 weeks after starting treatment."
"The present study was designed to assess the efficacy of infliximab in a 2-period study :||An initial period with comparison of infliximab versus placebo and allowing the determination of the primary criteria|Then an extension period in which the 2 arms will receive infliximab (in the placebo group : 5 perfusions and in the experimental group 3 supplemental perfusions). Finally, the 2 groups will receive 5 injections of infliximab There is little evidence in the literature of when and how infliximab should be administered in sarcoidosis. We hypothesized, from our personal experience in 30 cases (18 of which were reported in a retrospective trial (14), that infliximab would have a very quick activity. So it appeared reasonable to evaluate the primary criterion at 6 weeks after initiation of the treatment."
"This study evaluates the effectiveness and safety of infliximab in the treatment of acute pancreatitis in adults. A third of participants will receive one single dose of infliximab via infusion, another third will receive a higher dose of infliximab via infusion and the final third of participants will receive a placebo infusion."
This multicenter prospective clinical trial investigates the accuracy of ultrasound to predict relapse after discontinuation of infliximab and the efficacy/safety of readministration of infliximab in patients with rheumatoid arthritis in a low disease activity state.
The main purpose of this study is to record the use of Infliximab (IFX) in the treatment of Chinese children with Crohn's disease (CD) in routine clinical practice and to summarize the clinical efficacy and safety of IFX in the treatment of pediatric CD.
"Pemphigus vulgaris (PV) is a rare skin disorder that causes blistering of the skin and mucous membranes. Infliximab is a man-made antibody used to treat certain types of immune system disorders, including rheumatoid arthritis and Crohn's disease. This study will determine if infliximab given in combination with prednisone is a safe and effective treatment for adults with PV."
"Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that results from immune dysregulation. Arguably, the development of Tumor Necrosis Factor (TNF) antagonists (including infliximab, adalimumab and golimumab) revolutionized the management of immune-mediated chronic diseases in the past two decades.||However, about one third of patients will not respond to a first anti-TNF treatment and 10% to 30% will loose response to anti-TNF during the follow-up.||Historically, a switch between anti-TNF was performed to recapture remission and response to anti-TNF. Recently, a new biologic therapy blocking another target has been approved and is now reimbursed during ulcerative colitis, namely vedolizumab. Vedolizumab is an anti-integrin agent avoiding the recruitment of lymphocytes specifically in inflamed gut tissue.||Emerging data suggest that a switch of therapeutic class (meaning a change of biologic target with Non-TNF-targeted biologic) in case of clinical failure or insufficient response to anti-TNF may be the best choice. This idea of a switch out of the anti-TNF class is also supported by data on drug monitoring that may help physician decision making in case of loss of response. However, no trial is currently available and ongoing to assess the best therapeutic strategy. The aim of the proposed study is to assess the best biological based strategy in patient losing response to a first subcutaneous anti-TNF (golimumab and/or adalimumab)."
The purpose of this study is to evaluate the effectiveness and safety of infliximab (Remicade) in patients with Juvenile Rheumatoid Arthritis (JRA).
The purpose of this study is to determine if treatment with infliximab improves macular edema which is refractory to laser photocoagulation in patients with diabetes.
"This is a monocentric, two-arm, non-randomised, non-blinded, historically controlled, interventional trial. The purpose of this trial is to investigate the effect of model-informed infliximab dose de-escalation on the infliximab exposure and therapeutic outcome as compared to standard dose de-escalation in patients with inflammatory bowel diseases."
"This is a study to compare the effect of infliximab versus placebo on synovial inflammation as measured by dynamic contrast enhanced (DCE)-MRI of one wrist. The primary hypothesis is that over 14 weeks of therapy, the change from baseline in the volume transfer rate in enhancing synovium is larger due to treatment with infliximab than with placebo."
"Rheumatic Polymyalgia(PMR) is a relatively common chronic inflammatory disorder of unknown origin which predominantly develops in elderly subjects and presents with severe pain and stiffness in the neck, shoulder and pelvic girdles, along with increased acute phase reactants. Systemic manifestations such as fever, anorexia and weight loss are characteristic signatures of PMR.||Corticosteroids (CS) constitute the standard treatment of PMR. Although in most patients the symptoms of the disease disappear after one or two years of treatment, a proportion of patients remain CS-dependent with the subsequent CS toxicity. Open label studies have suggested that tumour necrosis factor (TNF) antagonists lead to sustained improvement and CS sparing effect in patients with refractory PMR.||The investigators conducted a randomised, double-blind, placebo controlled trial with infliximab in CS-dependent patients with PMR. Patients with CS-dependent PMR (defined as requiring ≥ 5 mg/day after at least 2 years of treatment to maintain remission or ≥ 7.5 mg/day after at least 6 months) were randomly assigned to receive Infliximab (5 mg/kg i.v) at 0, 2, 6, 14 and 22 weeks (n = 12) or placebo (n = 11) together with CS that were reduced according to a predefined schedule. The primary outcome was the proportion of responder patients -defined as individuals with both complete clinical and analytical remission without receiving CS for at least three months- at 24 weeks. Secondary outcomes were cumulative CS doses and adverse events proportion."
"Crohn's disease (CD) is a lifelong condition of inflammation in the bowel. CD can affect any part of the gastrointestinal tract from mouth to anus. Symptoms can include: tiredness, stomach pain, diarrhea (which may be bloody if the disease is severe), fever, weight loss, skin rashes, arthritis and inflammation of the eye.||Infliximab-IFX (Remicade®) is a medication that is used to treat CD in adults and children. In adults it has been shown that the amount of this drug a person has in their blood can show how well it is working for them. Health Canada has approved Infliximab -IFX for the treatment of CD in children 9 and older. In Canada, doctors may prescribe Inflixmab to younger children when other therapies do not resolve their disease symptoms. This is called ""off-label"" use of Infliximab.||IFX levels in the body and consequently its efficacy can be influenced by many biological characteristics within the patient's body. In about 17% of those treated with IFX, the patient's immune response against IFX may lead to a three to fivefold increased risk of loss of response. This immune response to the medication often occurs when drug levels are undetectable in the body. Thus it is in order to achieve best results with this treatment, physicians need to be able to adjust dosing specific to each patient. A recent study has shown that 29% of children have an undetectable IFX level at the 4th medication infusion. Up to 40% of patients receiving scheduled IFX have undetectable drug level prior to their next infusion.||In order to minimize the loss of response, we hope to conduct an observational cohort study of pediatric patients treated with IFX.||This open label, cohort study aims to:||Determine the pharmacokinetics of IFX in children with CD and the factors that affect IFX levels during the first three loading infusions|Obtain data to create a model that can guide and adjust the IFX dose and frequency to achieve optimal trough level between 5 and 10 ug /ml at 14 weeks."
"PHASE: IV||TYPE OF STUDY: With direct benefit.||DESCRIPTIVE: Multicenter, randomized, open label study.||INCLUSION CRITERIA: Steroid-refractory ulcerative colitis.||OBJECTIVES: To compare the efficacy of cyclosporine with infliximab in steroid- refractory attacks of ulcerative colitis.||STUDY TREATMENTS:Cyclosporine 2mg/kg/day intravenous(IV)for 7days then Neoral 4mg/kg/day orally for 3 months. Infliximab 5mg/kg at Weeks 0, 2 and 6.||NUMBER OF PATIENTS: 50 patients in each group i.e. a total of 100 patients.||INCLUSION PERIOD: 24 months.||STUDY DURATION: 27 months.||MAIN EVALUATION CRITERIA:||Clinical response at D7 according to the Lichtiger Index score AND Clinical Remission at D98 according to the Mayo Disease Activity Index score||SECONDARY EVALUATION CRITERIA:||Clinical remission at D98 (according to the Mayo Disease Activity Index score) Endoscopic response Colectomy rate Tolerance"
"The goal of this research study is to test the clinical effectiveness of a drug called infliximab (Remicade) in chronic beryllium disease (CBD). This drug may reduce tumor necrosis factor-alpha (TNF-a), which is associated with more severe disease and inflammation in the lung. Receiving infliximab may help with symptoms, and may improve clinical testing data normally ordered by your doctor, such as breathing tests. Baseline and follow-up testing will look for improvements in breathing tests (pulmonary function testing), exchange of oxygen in the lungs (exercise test), chest x ray, and lung inflammation."
"Tumor necrosis factor (TNF) alpha is a pro-inflammatory cytokine playing a significant role in the pathogenesis of the spondyloarthropathies (SpA). Infliximab is a TNF alpha blocking monoclonal antibody efficacious and safe as treatment of adult-onset SpA.||In this study we will try to demonstrate that infliximab administered at 5mg/kg to patients with juvenile onset SpA over a period of 12 weeks will have more efficacy than placebo and that it will be well tolerated. At the end of this phase, patients will go into a 52-week open extension to demonstrate sustained efficacy, safety, and tolerability of infliximab We will include 34 patients with juvenile onset SpA unresponsive to standard treatment. Efficacy will be assessed by counting the number of actively inflamed joints and a number of other parameters."
Remicade is a common medicine used for the treatment of inflammatory bowel disease. This medication is given as an intravenous infusion over 2 hours. Studies have suggested it is safe to give the infusion at a faster rate. The investigators would like to see if the infusion can be given over 1 hour. The investigators expect that increasing the rate of infusion WILL NOT lead to an increase in infusion reactions and will be just as safe and effective as the standard 2 hours dose.
"Subjects will be given 3 infusions of infliximab according to the label at week 0, 2, and 6. Subjects will be followed for a maximum of 18 weeks or until relapse. This study will assess the ability of the Power Doppler Ultrasonography (PDUS) to be a reliable marker of enthesitis response and relapse in subjects treated with infliximab."
"The goal of this study is to implement instruments that would increase the treating physician's awareness of the necessary tuberculosis screening when starting a new patient on infliximab (Remicade) therapy who has not reacted sufficiently to disease-modifying preparations, including methotrexate."
"This is a prospective, open-label, 1-arm, multicenter observational study to determine the average Remicade dosage and time span between 9 infusions in subjects with rheumatoid arthritis (RA)"
"Intravitreal injection of up to 2 mg of infliximab has proved to be safe in animal models (rabbits and primates). These studies have shown no evidence of intraocular inflammation or toxicity by clinical, electrophysiological, and histopathological examination for up to 90 days even with 3 repeated monthly injections. However, the study conducted by Rassi et al was the only one to report the development of severe intraocular inflammation in one eye out of 12 rabbit eyes at 90 days following 3 intravitreal injections (2mg monthly). Unfortunately, clinical studies conducted on patients, so far, have raised serious concern about its safety and adverse effects.||These clinical studies have shown various and inconsistent results in terms of the safety and efficacy of intravitreal infliximab. These studies were conducted on patients with refractory as well as naïve cases of age related macular degenerations choroidal neovascularization (AMD CNV), diabetic macular edema (DME), central retinal vein occlusion (CRVO), angiomatous malformations, pseudophakic macular edema, and uveitis. The doses used ranged from 0.5mg to 2mg. The initial study by Theodossaidis et al in 2009 did not report any intraocular inflammation in 3 patients receiving 2 intravitreal injections of 1 and 2 mg for refractory AMD CNV with 7 months follow up period.(8) Later several clinical studies have reported severe intraocular inflammation following intravitreal injections of infliximab in non-uveitic patients.These collected data have initiated a call for cautious use of intravitreal infliximab.||On the other hand, studies investigating intravitreal infliximab in uveitis patients have shown improvement in vision, reduction in macular thickness on optical coherence tomography (OCT), and reduction in inflammation. In this study, we have investigated the safety and efficacy of 3 consecutive intravitreal infliximab injections (1 mg/0.05 mL, 6 weeks apart) in carefully selected group of patients with refractory uveitis in Behcet's disease."
"Since the end of 2019, Egypt and the whole world have been suffering from the Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization (WHO), since the emergence of this new pandemic, there have been more than 97 million confirmed cases of COVID-19 patients and two million death globally; around 160 thousand of these cases are in Egypt.||Tocilizumab play role among the unique therapeutic alternatives for the management of cytokine release syndrome (CRS), a life-threatening complication of chimeric antigen receptor (CAR) - T cell therapy. CRS occurs as a result of uncontrolled immune activation with release of pro-inflammatory cytokines and chemokines. Up till now, clinical trial and expertise with tocilizumab in COVID-19 patients has been limited. Despite preliminary encouraging results, recent studies suffered from limitations such as the absence of consistent treatment outline, a short post-treatment follow-up, and the absence of a comparison group.||A recent study discussed the possible beneficial effect of tumor necrosis factor (TNF) inhibitors in severe COVID-19. Specifically, TNF may aggravate lymphopenia through direct killing via TNF/TNFR1 signaling in T cells, and T cell dysfunction reveals an important yet underestimated target for immunomodulatory therapeutic approaches. Accordingly, anti-TNF may be considered as an encouraging therapeutic option in severe COVID-19.||These promising clinical findings encouraged us to use infliximab (IFX), a chimeric monoclonal anti-TNF antibody, as an experimental therapy in patients with moderate and severe COVID-19 in the absence of IBD.||In this study, we compare the outcomes of a large cohort of patients with moderate and severe COVID-19 pneumonia treated with tocilizumab in addition to standard management, with those of concomitantly hospitalized patients who received infliximab and tocilizumab in addition to standard management."
"A prospective, multi-centric, cohort study to observe the efficacy difference between intensive classic DMARDs and Infliximab(IFX) with methotrexate(MTX) treatment in sever rheumatoid arthritis(RA) 28 joints disease activity score>5.1(DAS28>5.1) patients with poor prognostic factors.Primary objective is compare the difference of clinical remission rate between classic DMARDs and Infliximab with MTX treatment in severe RA patients with poor prognostic factors at week 30."
The purpose of this study is to determine whether the addition of infliximab to standard primary therapy of intravenous immunoglobulin (IVIG) and high dose aspirin will reduce resistance to therapy in acute Kawasaki disease (KD).
"Infliximab (IFX) is highly effective in inducing and maintaining remission in patients with inflammatory bowel disease (IBD). However, a large proportion of patients will eventually lose response to IFX. Therefore, strategies to improve the outcome of maintenance treatment with IFX are required. Retrospective analyses suggest that adjusting IFX treatment in order to achieve IFX trough levels (TL) above a well-defined therapeutic threshold will improve the outcome of IFX treatment."
"The measurement of serum concentrations of infliximab (IFX)has now become a routine part of optimal use of that drug. Trough values are used in two situations: (a) reactively where there is loss of response to infliximab - therapeutic concentrations are indicate likely non-response to the drug, whereas low levels are associated with the chance of regaining response by increasing dosage; or (b) proactively, where dose optimisation in the maintenance phase is performed to ensure ongoing efficacy and/or cost-effective use (where high levels lead to reduction in dosage without loss of efficacy).||With the introduction of biosimilar infliximab into clinical practice, it is important to demonstrate that the biosimilar behaves similarly in the assay used as does originator infliximab to which the assays were developed. While unlikely to be different due to identical protein core, such confirmation is needed before such assays can be used in clinical practice with confidence.||AIMS||To compare the concentrations of biosimilar IFX (MSD-IFX) with that of originator IFX (orig-IFX) when added to serum form healthy subjects and those with IBD when measured by commonly-used commercial assays.|To compare the effect of freeze-thawing and storage at 4 oC on concentrations of MSD-IFX."
This is an open-label program of Remicade in the treatment of patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX) to determine the onset of efficacy of infliximab.
"Crohn's disease is an inflammatory (swelling and soreness) disorder of the digestive tract. Affected patients suffer from abdominal pains, diarrhea (sometimes bloody), weight loss. It is a lifelong disease with frequent flares during the course of the disease. Crohn's disease is mostly treated with medications, sometimes surgery is needed. Infliximab is a medication for treating severe Crohn's disease. This medicine is effective by blocking special substance (tumor necrosis factor) released from certain white blood cells in the body. Infliximab is given via a vessel at week 0, 2, 6 initially, then every 2 monthly for maintenance. However, some of patients with Crohn's disease do not respond infliximab. Currently there is no test to reveal which patients will respond to treatment. This study aims to analyze and compare particular subgroup of white cells and its products during and after infliximab treatment which may determine the responsiveness to infliximab treatment."
"More than half of rheumatoid arthritis (RA) patients complain of sleep disturbance and this cardinal complaint is associated with fatigue, pain, and depressed mood in patient with chronic inflammatory disorder. Despite the frequency of this complaint, there is limited efforts to evaluate sleep or the abnormal increases in the expression of pro-inflammatory cytokines play a key role in the progression of RA, we hypothesize that the cytokine network is one physiological system that is associated with sleep disturbances in RA patients. Pro-inflammatory cytokines signal the central nervous system and are associated with increased symptoms of pain, fatigue, and depressed mood in rheumatic patients. The specific aims of the study are to examine the contribution of cytokines on sleep by administering a TNF antagonist vs. placebo to probe the action of pro-inflammatory cytokines on sleep in RA Patients. Examination of sleep and its consequences for pro-inflammatory cytokine activity within the framework of an observational and experimental research design will have implications for understanding the psycho-biological mechanisms that link sleep and the clinical manifestations of RA. Results from this study will guide the developments of interventions that target disordered sleep with potential effects on disability in RA."
The purpose of this research is to test the safety and effectiveness of the investigational combination of pembrolizumab and infliximab in treating metastatic melanoma.
"This is an open-label, prospective, observational study with the primary objective to characterize the pharmacokinetics of infliximab in patients with Acute Severe Ulcerative Colitis."
"Descriptive: A 24-month multicentre, observational, prospective cohort study. Population: IBD Patients under stable clinical and biological remission Study treatments: Patients who will be proposed to switch, or who have just switched, from the intravenous originator Remicade® or one of its biosimilars to the subcutaneous infliximab Remsima®SC as part of routine care. All consecutive patients in IBD centers participating in the study will be proposed to participate in the study during their regular outpatients' visits.||Objectives:The primary objective of PEREM study is to determine the rate of persistence of subcutaneous infliximab at 48 weeks after switching from IV infliximab to subcutaneous infliximab Remsima®SC."
"This study will evaluate the Efficacy and Safety of Infliximab versus Cyclophosphamide in Subjects with Idiopathic Refractory Scleritis.||The term scleritis describes a chronic inflammation that involves the outermost cost and skeleton of the eye. Scleritis is classified anatomically as either anterior or posterior based on the principal location of the inflammation. Thirty to forty percent of scleritis cases are associated with systemic autoimmune conditions including rheumatoid arthritis and granulomatosis with polyangiitis. Infectious causes including herpes virus and varicella zoster account for 5 to 10% of patients. The remaining 50% of cases are classified as idiopathic.||CIRIS, is the first prospective randomized, head to head study, comparing infliximab to cyclophosphamide in refractory idiopathic scleritis. There is no firm evidence or randomized controlled trials directly addressing the best biologic agent in severe and refractory idiopathic scleritis. If left untreated or insufficiently treated, scleritis can progress to peripheral ulcerative keratitis, uveitis and glaucoma. Visual loss occurs in approximately 10% of patients with anterior scleritis and in up to 75% of patients with posterior scleritis. The incidence of burden in ocular inflammation (uveitis and scleritis) has been dramatically reduced in the recent years with the use of biologics, raising the question of whether these compounds should be used earlier in the treatment of severe non infectious scleritis. Contrasting with other immunosuppressors, cyclophosphamide and infliximab act rapidly and are highly effective in steroid's sparing.||Despite a strong rationale, these compounds are not yet approved in idiopathic refractory scleritis, which guarantees the innovative nature of this study that aims selecting or dropping any arm when evidence of efficacy already exists."
"This is a prospective, randomized, double-blind, parallel group, multicentre global phase 3 clinical study to evaluate the efficacy, safety and immunogenicity of BOW015 (infliximab-EPIRUS) compared to Remicade in subjects with active Rheumatoid Arthritis (RA) despite Methotrexate (MTX) therapy."
The purpose of the study was to evaluate the ability of a maintenance dosage regimen of infliximab to achieve and sustain at least 40% improvement from baseline in the total joint count in patients with active Rheumatoid Arthritis (RA) during methotrexate tapering.
The current observational program was determined to collect data on the real life dosing regimen of Remicade in patients with Crohn's disease (CD) in the hospital and non-hospital setting.
This study will gather information on the safety and efficacy of patients with rheumatoid arthritis (RA) who are starting treatment with infliximab for the first time. Patients will be treated in the usual manner according to local guidelines and normal clinical practice.
The aim of the study is to investigate in subjects receiving their first course of peg-interferon α-2b plus ribavirin therapy for chronic HCV infection
This is a pilot study to estimate the efficacy of infliximab in inducing and maintaining healing of lesions in the mucosa of subjects with Crohn's disease involving their small bowel.
"This is a prospective, open-label, 1-arm, multicenter observational study to determine the dose and time interval of Remicade (Infliximab) infusions in psoriatic arthritis (PsA)."
Injections of medicine into the middle of the eye (intravitreal injections) are commonly used in a multitude of retinal diseases. We are looking for new treatments that may be beneficial in treating retinal disease and improving patients' vision.||Infliximab (Remicade) is a genetically engineered antibody against a molecule in the body called TNF-α. It neutralizes the effects of TNF-α by binding to it. Intravenous Infliximab has been used for inflammatory arthritic conditions and Crohn's disease since 1998. We do not know if infliximab injections into the eye are safe. We are performing this pilot study to determine if they can be safe.
"Inflammatory bowel disease (IBD) is a common disease in Canada, leading to significant morbidity as a result of remitting and relapsing intestinal inflammation. Currently, tumor necrosis factor (TNF) antagonists such as infliximab, make up 30% of the biologic agents available to individuals with IBD. There is a high risk of losing response or having a hypersensitivity reaction to infliximab, necessitating treatment discontinuation. This is due, in part, to the formation of anti-drug antibodies (ADAs). ADA formation can result in loss of response to therapy which may eliminate an intestine-saving therapy and increases their risk of progressing to surgical resection. There are few tools clinicians can implement to minimize the risk of ADA formation. The current approach is to add a second drug (known as combination therapy), specifically an immunomodulator (methotrexate or azathioprine), exposing the patient to additional medication-related risks, intensive monitoring with bi-weekly blood work and potential side effects including infection and malignancy.||Preliminary data from our group as well as others suggests that individuals who carry a variant in the class 2 human leukocyte antigen (HLA) gene (HLADQA1*05A>G, rs2097432) are more likely to form ADAs to infliximab. Pre-emptive screening for this variant may allow clinicians to more selectively use combination therapy, recommending it only in IBD patients at high risk of developing ADAs to infliximab. Additionally, this may result in fewer drug-associated adverse events.||With this project, we aim to explore the value of prospective HLADQA1*05 screening (pharmacogenomic screening) in IBD patients being considered for treatment with infliximab and using the result to guide the application of combination therapy compared to IBD patients treated with infliximab (with or without a second agent) as per current practice. We will assess the incidence of infliximab ADA formation, as well as the incidence of infliximab loss of response, treatment discontinuation, and adverse drug events. Additionally, we will assess the time to each of these events."
"This is an open-label, interventional study where a subset of participants will be randomized to one of two treatment-optimization strategies. Participants with moderate to severe Crohn's disease (CD) will receive induction treatment comprised of 3 infusions of infliximab at Weeks 0, 2, and 6. The participants will be evaluated at Week 10. Participants who are in clinical response will enter the observational phase of the study where they will receive standard of care treatment, as per the infliximab product monograph. Participants who lose response, may qualify for entry into the interventional phase of the study, where they will be randomized to one of the following treatment-optimization arms: 1) dose increase: infliximab 7 mg/kg, every 8 weeks or 2) shortened interval: infliximab 5 mg/kg every 6 weeks.||Note: Due to early study termination, no statistical analysis was performed for the interventional part of this study, therefore, endpoints dedicated to this phase of the study have not been analyzed."
"Aims: The main aim of this study is to access the predictive value of Treg and Breg for the clinical effect of Infliximab in the treatment through analyzing the relationship between Breg and Treg and the efficacy of Infliximab.||Design: It is a prospective, observational study. In the treatment group, 32 patients with Crohn's disease (CD) about to start Infliximab-treatment are recruited. They have blood samples drawn at week 0 and 14 of Infliximab treatment. 33 healthy individuals serve as a control group. Controls are only investigated once. All treatment and follow-up are according to national guidelines. The frequencies of Treg and Breg are investigated using flow cytometry. Subjects data are extracted from various registries."
"The objective of this study is to prove reasonability of registration in Russian federation this new indication (ankylosing spondylitis [AS]) through evaluation of safety and efficacy rate of Remicade 5mg/kg, given as an intravenous infusion over a 2-hour period followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 6 to 8 weeks (maximum 9 infusions)."
"The aim of this clinical trial is to assess the efficacy and safety of Infliximab biosimilar in patients of resistant Hidradenitis suppurativa. The main question it aims to answer are:||how effective is infliximab biosimilar in treating resistant Hidradentis suppurativa|Is infliximab biosimilar safe in these patients Patients will receive weekly injections of Infliximab Biosimilar Remsima, according to weight, for first 4 weeks, and then fortnightly for next 10 weeks. Patients will be followed up for 10 weeks post treatment for assessment of safety and efficacy"
"This is a prospective, open-label, 1-arm, multicenter observational study to determine the dose and time span of Remicade between infusions for ankylosing spondylitis (AS)."
The purpose of this study is to evaluate the effectiveness and safety of infliximab in Chinese patients with active ulcerative colitis (swelling and ulceration of large intestine and rectum).
"Rationale: Crohn's disease (CD) is a chronic, debilitating inflammatory bowel disease (IBD) which is diagnosed during childhood in up to one in ten patients. The use of anti-tumor necrosis factor (TNF)-α agents has significantly ameliorated CD management. Infliximab (IFX) is the first anti-TNF-α agent registered for pediatric CD. The current dosing recommendation of IFX is extrapolated from adult studies, and it is a weight-based dose (5 mg/kg) delivered during induction (infusion at weeks 0, 2, and 6) and maintenance (every 8 weeks). However, pediatric patients have a 25-40% lower drug exposure compared to adults, particularly children under 10 years of age, resulting in diminished efficacy and an increased risk of developing a complicated disease course. The investigators hypothesize that an intensified IFX induction scheme (instead of the current dosing recommendation) is more effective in the treatment of pediatric CD patients.||Objective: The primary study objective of our study is to assess the efficacy of an IFX intensified induction scheme vs. a standard dosing schedule in improving drug exposure without treatment escalation in pediatric CD patients. Secondary objectives are clinical and biochemical remission without treatment escalation, development of antibodies to IFX (ATI) and adverse reactions.||Study design: An international, multicenter, prospective, open-label trial. Study population: Anti-TNF-α naïve children (age 3-15 years) with CD and an indication to start IFX treatment.||Intervention: IFX will be given intravenously at 10 mg/kg at week 0, and 5 mg/kg at weeks 2, 4, and 8 to all patients (induction). Maintenance will start at week 12, and then ideally continue every 6 weeks till week 24 (end of study). IFX trough levels will be measured at weeks 4, 12, and 24. During the maintenance, the IFX dose and/or interval adjustments, the IFX discontinuation or the start of a co-medication (i.e., an immunomodulator) will be possible on indication (i.e., primary nonresponse, secondary loss of response, intolerance to study medication) at the physicians' discretion. Follow-up will continue for the duration of the study (week 24).||Main endpoint: Proportion of patients with IFX TL ≥ 5 µg/mL at week 12 without treatment escalation."
"Subjects must be 18- 75 years old and have a history of both inflammatory bowels disease (Crohn's or ulcerative colitis) and pyoderma gangrenosum.||This is a 6 month open label study of an intravenous (IV) medication. Visits occur every 2 weeks initially, then every 1-2 months later in the study."
"This is an open-label, multicenter, parallel-group comparison study of the efficacy, safety, and tolerability of infliximab therapy in adult patients suffering from chronic plaque psoriasis (psoriasis vulgaris). Patients will be assigned to GROUP I (""high need"") or GROUP II (""low-need"") by the investigator according to their previous psoriasis treatment."
"The purpose of this study is to determine whether infliximab can favourably and safely be discontinued in patients with Crohn's disease in sustained complete clinical, biochemical, and endoscopic remission on infliximab.||Further to examine the clinical utility of measuring levels/activity of infliximab and activity of anti-infliximab Ab in patients in sustained complete remission, in order to investigate whether pharmacoimmunological data can predict the clinical outcome and rationalize therapeutic management of these patients with respect to continuation or discontinuation of infliximab therapy. Additional, to investigate the optimal time-point, out of three, to measure this activity."
"The aim of the study is to test whether neutralizing TNF-alpha with infliximab affects insulin resistance and phenotypical manifestations of the metabolic syndrome as fasting plasma insulin, total body fat, plasma lipid profile or vascular endothelial function in obese male subjects."
"Participants from an ongoing observational study (P05319) who have a limited (adequate but less than optimal) response to infliximab will be randomized to either increase the frequency of infliximab infusions from every 8 weeks to every 6 weeks, or to add weekly methotrexate to their current treatment plan. While receiving infliximab study treatment(s), patients in this study will attend regularly scheduled office visits for various clinical tests for safety and effectiveness evaluations."
"This phase I/II trial studies the side effects of infliximab and vedolizumab and to see how well they work in treating inflammation of the colon (colitis) caused by immune checkpoint inhibitor therapy in patients with cancer of the genital and urinary organs (genitourinary) or melanoma. Monoclonal antibodies, such as infliximab or vedolizumab, may help to treat immunotherapy induced colitis/diarrhea. This study may help to identify the optimal treatment strategy for immune checkpoint inhibitor-related colitis in patients with genitourinary cancer or melanoma."
This observational study is in line with the German educational plan with the aim to implement a tool to increase and monitor the awareness of tuberculosis screening and to reinforce the patient eligibility for a treatment with Remicade according to the Summary of Product Characteristics (SmPc).
"A phase 1, Randomized, Double-blind, Parallel group, Sing-dose study to compare the Pharmacokinetics and Safety of CMAB008 and Remicade in healthy subjects."
"In this study, healthy volunteers will receive a single intravenous dose of either PF-06438179 or infliximab (United States) or infliximab (European Union). During the course of the study, the pharmacokinetics will be assessed by sampling the levels of drug in the blood, and by comparing these levels among the different administration arms of PF-06438179 and the licensed infliximab products. Safety, tolerability, and immunologic response will also be evaluated throughout."
"The purpose of this observational study is to evaluate the safety and effectiveness of infliximab injection under actual conditions of use in participants, and to learn more about its adverse events."
This study evaluates the efficacy of the addition of infliximab to conventional initial treatment (intravenous immunoglobulin [IVIG] plus aspirin) in early regression of coronary artery lesion in patients with Kawasaki disease (KD).
The purpose of the study is to evaluate the effectiveness and safety of infliximab (Remicade) in patients with plaque-type psoriasis.
"The aim of the study was to evaluate the efficacy of infliximab (IFX) treatment, 5 mg/kg every 6 weeks, in patients with active ankylosing spondylitis (AS) and to determine whether IFX dose reduction and interval extension, 3 mg/kg every 8 weeks during the second year sustained the treatment effect. The study was started in 2003 an finished in 2008."
REMICADE (infliximab) is a drug used to treat active Crohn's disease and is being tested in an experiment to see if it may be useful in preventing relapse of Crohn's disease after surgical resection. This study will compare the effects (both good and bad) of REMICADE (infliximab) to those of placebo. Placebo looks like the drug being studied but has no active ingredients.
"This is a Phase 3b, randomized, parallel-group, multicenter, active-controlled, open-label study of the efficacy and safety of infliximab compared with methotrexate (MTX) in the treatment of moderate to severe psoriasis in adults who were diagnosed with moderate to severe plaque-type psoriasis for at least 6 months prior to screening (subjects with concurrent psoriatic arthritis may also be enrolled)."
"Background:||Standard therapy is ill-defined for patients with systemic lupus erythematosus (SLE) suffering from the membraneous form of Lupus nephritis (WHO class V). Therapeutic options used at present include azathioprine.||In a small, open label safety study, patients with lupus nephritis, including patients with membraneous lupus nephritis, have experienced a long-lasting therapeutic response, with sustained reduction in proteinuria, following a 10 weeks course of 4 infusions of infliximab in combination with azathioprine. This short course appeared safe with regard to SLE activity, despite increases in autoantibody levels.||Study hypothesis:||The combination of four infusions of infliximab (5 mg/kg of body weight)administered at weeks 0, 2,6, and 10, with azathioprine will be faster than azathioprine alone in reducing proteinuria to less than 1.5 g/day in patients with active lupus nephritis WHO class V (proteinuria > 3g/day).|This combination therapy will show a tolerable safety profile with regard to SLE activity and infections."
"Takayasu arteritis (TA) is a vasculitis of unknown origin, resulting in progressive thickening and stenosis of large and medium arteries (the aorta and its major branches, and the pulmonary arteries). First line therapy of TA consists of high dose corticosteroids (CS). Between 20 and 50% of cases respond to CS alone, with subsequent resolution of symptoms and stabilization of vascular abnormalities. Although second-line agents (methotrexate, azathioprine, mercaptopurine, mycophenolate mofetil) may result in initial remission, relapses remain common when prednisone is tapered. Thus, 50% of CS-resistant or relapsing TA patients may achieve sustained remission with the addition of methotrexate. During the last decade, biologics such as anti-tumor necrosis factor alpha (anti-TNFα) and anti-interleukin-6 (anti-IL-6) have been used as third-line treatment in refractory or relapsing TA. Almost 90% of CS-methotrexate resistant TA cases responded to infliximab, an anti-TNFα, and sustained remission was obtained in 37 to 76% of the cases. Tocilizumab, an anti-IL-6 has given similar results with 68% of sustained remission in refractory TA. Irrespective of classical cardiovascular risk factors, the systemic inflammation and CS use play a pivotal role in the occurrence of cardiovascular thrombotic events (CVEs). As CVEs overlap with TA complications it is primordial to drastically taper CS in that vasculitis. We therefore hypothesize that Infliximab or Tocilizumab can achieve a remission in more than 70% of refractory/relapsing TA cases to CS associated to a second-line agent. INTOReTAK, first randomized prospective study in TA, has an original design testing Infliximab and Tocilizumab propensity to achieve over 70% of sustained remission in refractory/relapsing TA and evaluating jointly the 2 arms. The primary objective of this study is to obtain, by arm, ≥ 70% of patients at 6 months after randomization with prednisone ≤ 0.1mg/kg per day and inactive disease (NIH score ≤ 1) during the last 3 months."
"In this trial, patients that are severely affected by the disease COVID-19 will either receive infliximab, an anti-inflammatory drug, or standard therapy. Infliximab is a drug that inhibits inflammation by blocking a molecule called TNFα. The patients receive the drug via an infusion into a vein. The primary goal of this trial is to see whether the drug infliximab affects how many people died from COVID-19 after 28 days by comparing patients receiving the drug in addition to standard therapy with patients only receiving standard therapy.||Furthermore, this trial will look at whether the drug is safe to use in these patients, whether it has an effect on the inflammation and whether it can affect how ill patients are after surviving the disease.||The trial is conducted in more than one hospital. As COVID-19 is responsible for a global pandemic, positive results of this trial could affect patients, healthcare and economic systems worldwide."
"The purpose of this study is to compare the effectiveness of iInfliximab plus methotrexate (MTX) in treatment of Rheumatoid rheumatoid Arthritis arthritis (RA) (it is an autoimmune disease that causes pain, swelling, stiffness and loss of function in joints) in participants with moderate disease versus participants with severe disease and to compare the efficacy and safety of the MTX subgroups."
This observational study is in line with the German educational plan with the aim to implement a tool to increase and monitor the awareness for tuberculosis screening and to reinforce the patient eligibility for a treatment with Remicade according to the Summary of Product Characteristics (SmPc).
"This is a randomized, double-blind, multi-center, placebo-controlled study with two parallel treatment groups (placebo and infliximab) in subjects with ankylosing spondylitis (AS) to evaluate the efficacy of infliximab 3 mg/kg."
This study is undertaken to compare the efficacy and onset of action of infliximab plus methotrexate (IFX + MTX) versus methotrexate alone (MTX) in methotrexate naïve active psoriatic arthritis patients.
"Aim: the main aim of this study is to investigate if immune cells (regulatory T-cells, Th17 cells and other immune cell types) or biomarkers can be used to predict the response or lack of response to treatment with Infliximab. If so, characteristics of the immune cells may also unveil the mechanisms behind lack of response to Infliximab.||Design: a prospective, observational study with three arms. In the treatment group, 35 patients with Crohn's disease about to start Infliximab-treatment are recruited. They have blood samples drawn at day 1 before first treatment, after 6 week, and again after 22 weeks of treatment. 12 healthy volunteers serve as a control group. Controls are only investigated once. All treatment and follow-up are according to national guidelines, and data from this study is not used by the clinicians.||Methods: the number of regulatory T-cells and pro-inflammatory T-cells (Th17 cells) is investigated using flow cytometry. From plasma and serum samples, various proteins (biomarkers), such as transforming growth factor beta (TGF-beta) and tumour necrosis factor alpha (TNF-alpha), are measured using immunoassays. Patient data (demographics and medical history) are extracted from various registries."
"The purpose of this study is to see whether serious graft versus host disease which is not well controlled with steroid treatment can be controlled with therapy with both daclizumab and infliximab. We hypothesize that a combination of daclizumab and infliximab will more effectively treat graft versus host disease than therapy with a single drug. The study also looks at whether chronic graft versus host disease develops, and survival at 6 and 9 months post-treatment."
The purpose of this study is to evaluate long-term safety information of infliximab in patients who have participated in infliximab clinical studies in ulcerative colitis.
"This is a 4 month open trial with TNF-blockade using infliximab (an antibody that blocks TNF) in adult patients with chronic myositis (polymyositis, dermatomyositis, inclusion body myositis) who have persisting muscle weakness and inflammatory active disease despite adequate treatment with immunosuppressives either currently or previously.||Infliximab is given as infusions, 5 mg/kg body weight, these infusions are repeated after 2, 6 and 14 weeks. The study involves 15 adult patients.||Primary outcome measure is muscle function assessed by muscle function index score.||Other outcome measures are Myositis Disease Activity core set: Patient's global assessment and physicians global assessment on visual analogue scales (VAS). Manual muscle test, Health assessment questionnaire (HAQ), serum levels of CPK, LD and extra muscular disease activity score. Muscle biopsy, Magnetic resonance imaging (MRI) of thigh muscles and Health related Quality of life, measured by SF-36."
"The purpose of this study is to test the safety and effectiveness of infliximab in patients with plaque psoriasis who have been receiving the drug etanercept for treatment of their plaque psoriasis for at least four months, without enough improvement in their psoriasis symptoms."
"This study aims to assess trough, TREM-1 levels and efficacy of IFX and ADA in IBD patients."
This is a study evaluating the long-term safety of infliximab (Remicade)
The aim of the study is to generate novel minimally-invasive serum protein signatures and biomarkers in children and adolescents with Crohn's Disease (CD) that correlate with and can predict and monitor patients who will have a prolonged response to Infliximab so that personalized medicine can be applied to patients with CD.
The purpose of this observational (a study that follows participants forward in time) study is to compare the functional improvement of hip joint using Harris hip score between 2 treatment groups (infliximab and conventional therapy) at Week 30 in ankylosing spondylitis (an autoimmune disease causing chronic inflammation at tendon ends and ligament attachment points) participants with hip involvement.
The purpose of this study is to evaluate the safety and efficacy (effectiveness) of Infliximab (Remicade) in patients with Giant Cell Arteritis. Infliximab (Remicade) targets specific proteins in the body's immune system to help control the development of inflammation to help reduce painful disease.
"The purpose of this study is to determine whether a top-down treatment approach, prescribing infliximab and azathioprine at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and azathioprine, in moderate-to-severe pediatric Crohn's disease (CD) patients."
"An open-label, non-randomised, uncontrolled, proof-of-concept study of eight patients with 'definite' HTLV-I-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Eligible patients will have either early disease (of less than 2 years duration) or progressive disease (with observed clinical deterioration during the preceding 3 months.||Following 2 baseline assessments including Magnetic Resonance Imaging (MRI) of the spinal cord and a lumbar puncture for examination of the fluid around the brain (CSF) participants will be treated with a total of 7 infusions of the anti-TNF-alpha antibody infliximab over a period of 48 weeks. After the last on therapy assessment at 48 weeks participants will be followed up for a further 24 weeks. Study assessments will be clinical, virological, immunological and radiological. MRIs of the spinal cord will be obtained at weeks 12 and 72. CSF will be examined, on therapy, at week 12."
The purpose of this study is to develop a predictive model that will allow optimized dosing of infliximab for individual patients
"This Phase 3, randomized, open-label, multicenter study in rheumatoid arthritis (RA) patients with low disease activity (Disease Activity Score 28 [DAS28] >2.8 and <3.5) is being conducted to evaluate induction of remission by adding infliximab to pre-existing treatment versus no additional treatment. All subjects eligible for this study, aged >35 to <=65 years, will have a diagnosis of RA according to American College of Rheumatology (ACR) criteria, and will be offered additional treatment with infliximab. Prior to the start of treatment, subjects must be on a stable regimen of disease modifying antirheumatic drugs (DMARDs) for at least 3 months. Subjects will be randomized (1:1) to basic therapy with or without infliximab for a total duration of 38 weeks followed by a follow-up period of up to 6 months. Subjects randomized to basic therapy + infliximab will receive infliximab 3 mg/kg at Weeks 0, 2, 6, 14, 22, 30, and 38. The primary objective of the study is to assess the rate of remission according to DAS 28 (<2.6) at the end of treatment (after 38 weeks). Safety assessments include the incidence of adverse events, serious adverse events, and clinically notable abnormal vital signs and laboratory values."
"The aim of this study is to investigate whether intensive, personalized IFX dosing by using a pharmacokinetics driven dashboard system during the induction phase in patients with acute severe UC leads to increased treatment success (as defined by clinical and endoscopic response at week 6) as compared to the standard dosing."
"This is a Phase IIIB, randomized, prospective, multicenter, single-country, open-label, controlled pilot trial designed to evaluate the effect of infliximab induction therapy on sustained virologic response (SVR) to treatment with pegylated interferon alfa-2b plus ribavirin in a group of 96 therapy-naïve subjects with genotype 1 hepatitis C virus (HCV) infection and high serum tumor necrosis factor (TNF)-alpha values."
The purpose of this study is to evaluate the effectiveness and safety of infliximab (Remicade) in patients with Ulcerative Colitis. Infliximab (Remicade) targets specific proteins in the body's immune system to help control the development of inflammation to help reduce painful disease.
The purpose of this study is to determine if Infliximab is safe and effective in the treatment of psoriatic arthritis. Infliximab (Remicade) targets specific proteins in the body's immune system to help control the development of inflammation to help reduce painful disease.
"A randomized, placebo-controlled pilot study to determine endoscopic recurrence of Crohn's disease 12 months after curative, resective ileal or ileocolonic surgery in patients receiving post-operative infliximab or placebo"
"Prospective, observational, parallel-group, postmarketing safety surveillance registry in participants treated with Remicade or standard therapy for active or fistulizing Crohn's disease (CD). The follow-up period is up to 5 years. The participants in the standard therapy group may switch over to Remicade any time during the follow-up period"
The purpose of this study is to establish whether RA patients with moderate to severe disease activity with unsustainable response to infliximab 3 mg/kg every 8 weeks have better efficacy with adalimumab 40 mg s.c. eow compared to infliximab 3 mg/kg i.v. every 6 weeks.
The purpose of this study is to determine if infliximab (anti-TNF) is effective in the treatment of plaque psoriasis.
This is a randomized controlled trial to compare the efficacy and safety of infliximab and immunosuppressives therapy alone or in combination for pediatric Crohn's disease.
"In this research proposal, the investigators will focus on methods to optimize the therapeutic response to anti-TNF antibodies, by determining a correlation of 6-mp metabolite levels with IFX trough levels, anti-IFX antibody levels and clinical response. The study will also evaluate (in vitro) the possible impact of vitamin D on the interaction of IFX with dendritic cells in both healthy subjects and patients with Crohn's disease (proliferation, maturation, cytokine profile, apoptosis, gene expression)."
To compare treatment outcome in patients with Crohn's disease with secondary loss of response to infliximab (i.e. initial good response follow by loss of response) treated according to current standards based only on clinical features versus treatment based on serum levels of infliximab and anti-infliximab antibody (Ab) status.
The purpose of this study is to evaluate the safety and effectiveness of infliximab (Remicade) in patients with Chronic Sarcoidosis. Infliximab (Remicade) targets specific proteins in the body's immune system to help control the development of inflammation to help reduce painful disease.
The purpose of this observational study is to assess the safety and effectiveness of biosimilar Infliximab in patients with rheumatoid arthritis(RA) in Jordan where no visits or intervention(s) additional to the daily practice will be performed
"This is a comparative pragmatic trial in patients with UC and CD on maintenance treatment with IFX. All IBD patients from cohort A with maintenance IFX treatment at a referral IBD clinic are prospectively included between June and August 2018. An ultra-proactive IFX TDM algorithm is applied as follows. All patients have an ELISA TL measurement at baseline, of which the result determined the follow-up pathway: (A) TL between 3-7μg/mL: continuation at same dose and interval; (B) TL >7μg/mL: interval prolongation allowed; (C) TL <3μg/mL: interval shortening with minimum 2 weeks, with the next IFX TL measured using a POCT. (i) If the POCT showed an IFX TL <3μg/mL, dose was optimized ad hoc using a linear dosing formula (Dosen = (TL target * Dose n-1) / TL measured), followed by a new POCT test at next visit with the same interval. (ii) If the POCT showed an IFX TL ≥3µg/mL, no additional dose was given and routine TL testing with ELISA was retaken at next visit. At every visit this algorithm was reapplied to all patients.||The patients from cohort A will be compared with the patients from cohort B. The patients in cohort B receive maintenance IFX treatment at a referral IBD clinic during the same period. Dose adjustment are done based on standard of care reactive TDM of IFX and clinical symptoms. Data will be collected retrospectively to avoid treatment optimization bias."
"BCD-055-2 is international multi-center comparative double-blind randomized clinical trial to evaluate efficacy and safety of BCD-055 (JSC ""BIOCAD"", Russia) and Remicade® in patients with ankylosing spondylitis.||BCD-055 is biosimilar of infliximab (JSC ""BIOCAD"", Russia)"
The purpose of this study is to evaluate the safety and effectiveness of infliximab (Remicade) in patients with Chronic Obstructive Pulmonary Disease (COPD). Infliximab (Remicade) targets specific proteins in the body's immune system to help control the development of inflammation to help reduce painful disease.
"The purpose of this study, in patients with rheumatoid arthritis who have had an incomplete response to etanercept and methotrexate (MTX), are to evaluate: safety and evidence of therapeutic benefit of infliximab and methotrexate, the levels (pharmacokinetics) of etanercept and infliximab and antibodies (immunogenicity) to etanercept and infliximab in patients blood, whether switching from etanercept to infliximab changes progression of structural damage over the study period, and whether specific markers in the blood (pharmacodynamics) correlate with therapeutic response or benefit."
"Study Design & Objectives:||Multi-centre, non-interventional, open-label, non-comparative, prospective cohort study with a clinical follow-up between 12 and 14 weeks.||To determine the performances of the RA-INF-Dx blood test intended to aid in the identification of patients with rheumatoid arthritis who are unlikely to show an initial response to infliximab and methotrexate combination therapy evaluated according to EULAR response criteria.||Ancillary study objective:||To constitute a biocollection of samples associated with all clinical and biological data collected at inclusion and at the evaluation visit."
The purpose of this study is to evaluate the effectiveness and safety of infliximab (Remicade) in patients with Ulcerative Colitis.
"In children receiving a hematopoietic stem cell transplant (HSCT), blood levels of TNFalpha (an inflammatory cytokine) at the onset of the acute GVHD (graft-versus-host disease) could be correlated with the severity of the disease. The hypothesis is that the highest infliximab (a biologic drug against TNFalpha) could be associated with a significant reduction in TNFa levels and, subsequently, with a faster remission of the symptoms and prevention of disease progression. Moreover, a rapid drop of infliximab serum concentration, documented by therapeutic drug monitoring (TDM), could be related to the active phase of GVHD and higher production of TNFalpha. Therefore, the study is aimed at investigating whether the drop in infliximab plasma concentrations could be associated with clinical response and production of TNFalpha.||HSCT children receiving infliximab to control GVHD are enrolled. Blood samples will be collected during treatment and they serve to measure drug and TNFalpha concentrations. Drug levels are analyzed by a population pharmacokinetic modeling and results are compared with plasma concentrations of TNFalfa and clinical response."
"The primary objective of this study was to assess the proportion of participants in the infliximab plus naproxen arm versus the placebo plus naproxen arm, in a population of participants with moderate-to-severe active axial spondyloarthritis and disease duration of ≤3 years, who achieve the Assessment in Ankylosing Spondylitis (ASAS) partial remission criteria."
The purpose of this study is to assess the safety and effectiveness of three different treatments for patients with Crohns disease who have not responded to previous treatment with a group of drugs commonly used to treat Crohn's Disease (5-ASA) and corticosteroids. Patients will receive either infliximab (a drug used to treat autoimmune diseases) or azathioprine (an immunosuppressant or drug used to suppress the immune system) or a combination of both for up to 34 weeks. This research study will involve approximately 500 patients. The main study involves up to 34 weeks (approximately 8 months). A study extension of an additional 20 weeks (approximately 5 months) is optional for patients who successfully complete the main study. A country-specific study extension of open label infliximab treatment for an additional 1 year is optional for patients who successfully complete the main study extension.
"This small, preliminary study will examine whether multiple infusions of infliximab (Remicade® (Registered Trademark)) can control inflammation in patients with active scleritis. The sclera is the tough white outer coat enclosing the eyeball. Infliximab is a combination of part human and part mouse proteins that block a natural body protein called tumor necrosis factor (TNF). TNF appears to be involved in scleritis, and stopping its action may help reduce the inflammation in the disease. The drug has been approved by the Food and Drug Administration for treating Crohn's disease and rheumatoid arthritis.||Patients 18 years of age or older with active non-infectious scleritis may be eligible for this study. Participants will undergo the following tests and procedures:||Medical history and physical examination.|Eye examination, including a vision test and examination of the retina (back part of the eye) and of the sclera and its blood vessels.|Questionnaire about vision and daily activities.|Tuberculin skin test.|Pregnancy test: Women who can have children are tested for pregnancy at study weeks 0, 14, 30, 38, and 46.|Infliximab treatment: Infliximab is infused over a 2-hour period through a needle in a vein, usually in the arm. The patient's vital signs are checked before the patient begins each infusion starts and again before leaving the clinic. After the first two infusions, if the disease remains quiet, other scleritis medications will be attempted to be reduced to half the original dose over 8 to 12 weeks and possibly to nothing if the patient continues to do well. Patients receive a maximum of 9 infusions over a 30-week period.|Blood draws: About 4 tablespoons of blood are drawn at each visit to test for the number and types of cells in the blood and to check for signs of inflammation and side effects of the study medicine.||Patients are seen in the NEI clinic for infusions and to check the response to therapy. This includes 13 clinic visits over 46 weeks, as follows: every 2 weeks for the first 2 weeks, every 4 weeks thereafter for a total of 30 weeks for infusions, and then every 4 weeks for 16 additional weeks.||Patients may stop therapy if their scleritis is not controlled 10 weeks into the study period; if they develop a flare of inflammation after initial control of the active scleritis; if their vision loss is too large; or if their medications increase or other medicines are added to control the scleritis. Patients whose vision decreases minimally, stays the same, or improves may remain in the study."
"This is a randomized, double-blind, parallel group, multicentre clinical study to evaluate the efficacy, safety, pharmacokinetics and immunogenicity of SB2 compared to Remicade in subjects with moderate to severe Rheumatoid Arthritis (RA) despite Methotrexate (MTX) therapy."
"The purpose of this study is to examine the relationship between anti-drug antibodies, serum drug concentrations, and clinical response for rheumatoid arthritis patients being treated with etanercept, adalimumab or infliximab."
"The aim of this study is to establish the efficacy and duration of effect of intra-articular (IA) infliximab vs intravenous infliximab vs current standard care (IA steroid injections) in seronegative oligoarthritis. All patients will have seronegative arthritis affecting less than 5 joints but including at least one knee. 10 patients will receive IA infliximab injections to the affected knee, 10 will receive IA steroid injections to the affected knee and 10 will receive a course of intravenous infliximab. Patients will not be aware of their group as this is a placebo-controlled study."
"Pediatric Ulcerative Colitis (UC) patients with moderate to severe disease activity at high risk of colectomy. Early use of biologic agents will likely be more effective. But there were no studies identified that compared a strategy of upfront biologic-based therapy versus gradual step-up therapy. In our study, newly diagnosed moderate to severe pediatric UC patients (6-18 years old) will be randomly divided into infliximab (IFX) treatment group (Top down group, TD) and corticosteroids (CS) treatment group (Step-up group, SU). Mucosal healing rate at week 12 will be compared between the two groups. The relapse rates and sustained durations of remission within one year will also be evaluated."
"Infliximab is the active ingredient in a drug currently sold by the trade names Remicade, Remsima and Inflectra. Infliximab neutralizes tumor necrosis factor (TNF) α, a chemical messenger (cytokine) in the immune system, and belongs to a class of drugs called ""TNF inhibitors"". 8-55% of patients receiving infliximab have an infusion reaction. Infusion reactions are unintended reactions that occur during infusion of the drug and up to 14 days after. The incidence varies widely in different studies and seems difficult to determine due to variations in reporting of reactions, different definitions of reactions and retrospective data collection. The aim of this study is to estimate the incidence of infusion related reactions and investigate risk factors and immunological mechanisms of infusion reactions to infliximab in patients with a chronic inflammatory disease."
The purpose of this study is to evaluate the safety and effectiveness of Infliximab (Remicade) in patients with Rheumatoid Arthritis. Infliximab (Remicade) targets specific proteins in the body's immune system to help control the development of inflammation to help reduce the pain of rheumatoid arthritis.
"The purpose of this study is to evaluate the effectiveness of the switch from the original infliximab ( REMICADE®) to its biosimilar (INFLECTRA®) in all the patients at Cochin hospital receiving REMICADE® for either a rheumatic, gastro-enterologic or ophthalmic condition"
A study to assess the safety and efficacy of the IV drug infliximab for the treatment of hidradenitis suppurativa
This research study is evaluating the effectiveness and safety of infliximab therapy compared with steroids in the treatment of ipilimumab-induced colitis in patients with III/IV melanoma.
"Ano-perineal lesions are the first signs of Crohn's disease in 1/3 to 1/2 of cases. They are most often associated with a poor prognosis of the disease and their management is complex and difficult because of the dilapidated and recurrent nature of lesions with significant repercussions on continence and quality of life.||The treatment of these lesions is most often medical and surgical, consisting of drainage of the suppurative lesions and/or the use of biotherapy +/- combined with an immunosuppressant."
"RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Infliximab may improve cancer-related weight loss, lack of appetite, and fatigue. It is not yet known whether docetaxel is more effective with or without infliximab in preventing weight loss and fatigue in patients with advanced cancer. (Infliximab treatment discontinued effective 10/05/05)||PURPOSE: Randomized phase III trial to determine the effectiveness of docetaxel with or without infliximab in preventing weight loss, loss of appetite, and fatigue in patients who have unresectable non-small cell lung cancer. (Infliximab treatment discontinued effective 10/05/05)"
"This is a multicenter, Phase III, randomized, double-blind, double-dummy, parallel-group study to evaluate the safety, efficacy, and tolerability of etrolizumab compared with infliximab in treating participants with moderate to severe ulcerative colitis (UC) who are naive to tumor necrosis factor (TNF) inhibitors. Participants will be randomized in a 1:1 ratio to receive either etrolizumab 105 milligrams (mg) by subcutaneous (SC) injection once every 4 weeks (Q4W) + placebo (intravenous [IV] infusion at Weeks 0, 2, and 6, then once every 8 weeks [Q8W]) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then Q8W) + placebo (SC Q4W). Time on treatment is 54 weeks."
"This is a post-marketing observational study of patients with Inflammatory Bowel Disease (specifically, Crohn's disease or Ulcerative Colitis) who have been prescribed CT-P13 (infliximab) or Remicade (infliximab) for treatment. CT-P13 (brand names Inflectra and Remsima) is a biosimilar medicine to Remicade, meaning it is a biologic medicine that contains the same active substance as Remicade (infliximab). The key study objectives are as follows:||To characterize the population and drug utilization patterns of patients treated with CT-P13 for Crohn's Disease (CD) or Ulcerative Colitis (UC) in the context of standard of care Remicade|To explore the long-term safety profile of CT-P13 in the treatment of patients with CD or UC in the context of standard of care Remicade|To assess the effectiveness of CT-P13 in the treatment of patients with CD or UC in the context of standard of care Remicade"
"This multicenter study is being conducted to determine whether infliximab exposure after an initial infusion is predictive of early clinical response in hospitalized pediatric patients with severe steroid-refractory UC or IBD-U. This pilot and feasibility study will establish the infrastructure, demonstrate feasibility, and collect preliminary data to support the full study."
"Approximately 3 million people in the United States are living with inflammatory bowel disease, which includes Crohn's Disease (CD). There are limited treatment options approved for use in children and adults with Crohn's disease. Physicians need better ways to inform decisions on treatment.||The main reason for this research study is to determine if a computer program that calculates an individualized dose based on a patient's blood testing results (precision dosing) can better achieve the best possible response to infliximab compared to standard dosing (conventional dosing)."
"BCD-055-3 is international multi-center comparative double-blind randomized clinical trial of efficacy and safety of BCD-055 (JSC ""BIOCAD"", Russia) and Remicade® in combination with methotrexate in patients with active rheumatoid arthritis."
The purpose of the study is to evaluate the safety and effectiveness of scheduled and as needed treatment of psoriasis with infliximab. Infliximab (Remicade) targets specific proteins in the body's immune system to help control the development of inflammation to help reduce painful disease.
The purpose of the study is to evaluate the effectiveness and safety of infliximab (Remicade) in children with moderately to severely active ulcerative colitis.
"This study will compare rheumatoid arthritis (RA) patients who have been treated in clinical practice with either infliximab or a combination of sulfasalazine and hydroxychloroquine, after having an active disease despite treatment with methotrexate for at least one month. To establish which patients respond to treatment, DAS28-ESR measurements (disease activity score using 28 joints and erythrocyte sedimentation rate) taken at treatment start and nine months thereafter, and the EULAR (European League Against Rheumatism) definition of a ""good response"" will be employed.||The purpose of the study is to verify if the same conclusion could be reached using data from patients treated in real world clinical practice as in a previous randomized controlled trial comparing the two treatment strategies (SWEFOT -- ClinicalTrials.gov Identifier: NCT00764725).||Inclusion criteria similar to the ones used in the emulated trial will be applied.||In real clinical practice, patients who receive infliximab may have more severe RA and may also differ in other ways from patients receiving sulfasalazine and hydroxychloroquine. To be able to compare the proportions of responders under each treatment in this ""real-world"" setting, the data will be re-weighted, so that patient characteristics become balanced between treatment groups."
"Low-Back Pain (LBP) is the leading cause of disability worldwide. Even though LBP relates to different underlying pathologies, there are a substantial number of patients with chronic complaints that have vertebral bone marrow lesions visualized as Modic changes (MC) on magnetic resonance imaging (MRI). Despite the clinical evidence that MC is painful, the etiology is unknown and there is currently no established treatment. It has been suggested that MCs are secondary to a biomechanically induced degradation with a subsequent autoimmune response, supported by evidence showing that Tumor necrosis factor (TNF)-α plays a critical role in intervertebral disc degeneration and MCs. Clinical trials suppressing inflammation with TNF-alfa blockers in patients with acute low back pain and sciatica provide evidence to support the initiation of a clinical trial assessing the effect of TNF-alfa blockers in patients with chronic low-back pain and MCs. Since TNF-alfa blockers is an established treatment for immune-mediated disorders like spondyloarthritis by reducing pain as well as bone marrow lesions, the researchers aim to assess whether this treatment is effective for chronic LBP with MCs. In addition refine diagnostic assessment and explore potential biomarkers, which will provide an increased understanding of underlying factors causing LBP, and ultimately result in better management and treatment for one of the most costly and challenging patient populations."
"RATIONALE: Monoclonal antibodies, such as infliximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.||PURPOSE: Randomized phase II trial to study the effectiveness of infliximab in treating patients who have myelodysplastic syndrome."
"Continuous treatment with the anti-tumor necrosis factor alpha monoclonal antibody infliximab is efficacious in ankylosing spondylitis (AS), whereas treatment discontinuation results in disease relapse, with variable delay. Objective of this study was to compare efficacy between a continuous treatment with infliximab, and a treatment adapted to symptoms recurrence. Addition of methotrexate (MTX)to infliximab was also tested."
"This Phase IIIb, randomized, multi-national, multi-center, blinded study of Infliximab (IFX) in subjects aged 18 and older with active RA is being conducted to assess whether increasing either the infusion dose or infusion frequency in patients presenting with a disease flare after an initial response to infliximab results in a significant improvement in disease activity.||Subjects responding to an initial infliximab treatment regimen, who flare during continuation of treatment at 3 mg/kg administered every 8 weeks, will be randomly assigned to one of 3 different dosing regimens of infliximab and will be treated for 4 or 5 consecutive infusions for a total duration of 24 weeks. The infliximab control group and the infliximab increased dose group are evaluator and subject-blinded. The increased frequency group is not blinded. Clinical assessments of disease activity will be based the European League Against Rheumatism (EULAR) criteria for response. Safety parameters will be assessed at every infusion.||A disease flare is defined by an increase in DAS28 with 0.6 or more at screening, when compared to the DAS28 score measured immediately prior to the last Remicade® infusion and depends upon the actual score as well. Since prior to enrollment, the subject received Remicade® as per routine clinical practice, the days on which infusions were administered and assessments are done during the induction period do not have to be exactly at Week 2, 6 and 14.||Drug: Infliximab Control (double-blinded)|Drug: Infliximab Increased Dose (double-blinded)|Drug: Infliximab Increased Frequency (open-label)"
"This study will test whether the drug combination of methotrexate and infliximab (anti-TNF-alpha antibody) is more effective than methotrexate alone for treating rheumatoid arthritis early in the disease. (The Food and Drug Administration has approved both treatment regimens for patients with long-standing rheumatoid arthritis.) The study will also evaluate how effectively magnetic resonance imaging (MRI) can detect differences in the development of bone damage in the two treatment groups by as early as 6 months.||Patients 18 years of age and older who have had rheumatoid arthritis for less than 2 years and who have four or more affected joints may be eligible for this 1-year study. Patients must have received methotrexate treatment in the past without complete success, and must not have been treated previously with Anti-Thymocyte therapy.||All participants will receive 20 Mg./week of methotrexate. In addition, patients will be randomly assigned to receive a monthly infusion of infliximab or placebo (a fluid that contains no active drug). After 6 months, all patients will receive active infliximab for the remaining half year of the study. Patients will also receive folic acid (1mg/day), Vitamin D (400 IU/day), and calcium supplements. They may continue to take prednisone (no more than 10 Mg./day) and non-steroidal anti-inflammatory drugs (NSAIDS). Medication dosages will be adjusted as needed if pain and joint swelling worsen. Over the course of the study, patients will come to NIH for 15 visits and undergo the following tests and procedures:||Joint examination-at every visit.|Drug side effects evaluation-at every visit during the study and after the study at 24 and 36 months by questionnaires to be filled out and returned.|Hand and feet X-rays at the first visit, at 6 months and at 12 months.|MRIs of the wrist to examine damage in the bone and synovial tissue (tissue lining the joint)-before treatment begins and at weeks 15, 27 and 54. For this study, the patient lies still in a narrow cylinder (the scanner) with a strong magnetic field. A contrast material (gadolinium) is injected into the blood to enhance the images of the synovium. The MRI takes about 45 minutes.|DEXA scans (dual emission X-ray absorptiometry) of the lower spine, one hip and one wrist to measure bone density and assess bone loss-before treatment begins and at weeks 27 and 54. This X-ray test takes about 5 to 10 minutes.|CTs (computed tomography) of one hand to assess joint damage in the wrist-before treatment begins and at weeks 27 and 54. Only half the patients in the study will have this X-ray study, which produces 3-dimensional images of the hand. It will be done to compare the location, size and change of damage in the wrist seen on CT with the information obtained on MRI. The procedure takes about 5 to 10 minutes to complete.|Blood tests-at every visit to evaluate treatment response and side effects."
"This study will examine whether infliximab (Remicade ) is safe and effective for the treatment of dermatomyositis and polymyositis. Infliximab blocks the effect of a protein called tumor necrosis factor (TNF), which is associated with harmful inflammation in many diseases.||Patients 18 years of age and older with active dermatomyositis or polymyositis that does not respond adequately to treatment with methotrexate and corticosteroids may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood and urine tests, chest x-ray, pulmonary function test, skin test for tuberculosis, HIV test, electromyography (described below), manual muscle testing, and functional assessments. Magnetic resonance imaging (described below) will be done to assess the degree and location of inflammation in the involved limbs. An electrocardiogram and echocardiogram will be done if recent ones are not available. Patients who qualify for the study will be asked to undergo two muscle biopsies (surgical removal and analysis of small pieces of muscle tissue), one before initiation of treatment and another on the 16th week .||Participants will be randomly assigned to receive either 3 mg/kg body weight of infliximab or a placebo (inactive substance) by infusion through a vein over 2 hours. The infusions will be given at the beginning of the treatment period (week 0) and at weeks 2, 6 and 14. At week 16, strength will be assessed by manual muscle testing. Patients who improved with treatment will continue with the same infusion dose on weeks 18, 22, 30, and 38. Those who do not improve will be assigned by random allocation to receive either 5 mg/kg body weight or 10/mg/kg body weight of infliximab on weeks 18, 22, 30 and 38. Those who did not improve who were previously on the placebo infusion will receive an extra dose of either 5 mg/kg or 10 mg/kg body weight of infliximab on week 16, while those patients who were previously on 3 mg/kg body weight of infliximab who failed to meet the improvement criteria will receive an infusion containing no medication on week 16. Patients will be admitted to the hospital for infusions at weeks 0, 14 and 38; the rest will be given on an outpatient basis. After the 38th week, all infusions will be stopped and patients will be assessed on the 40th week.||Participants will undergo some or all of the following tests and evaluations during treatment:||Blood tests every week to look for antibodies seen with muscle inflammation. Some of the blood samples will be stored for later testing, including genetic studies to find genetic differences related to inflammation.|Skin test for tuberculosis|Chest x-rays at the beginning of the study (if a recent one is not available) and again at weeks 16 and 40 to look for active infection, detect signs of past exposure or infection with diseases such as tuberculosis, and assess the presence of lung disease that might be related to the myositis.|MRI (usually of the legs) at the beginning of the study and again at weeks 16 and 40 to measure disease activity and extent of muscle involvement. This will also give an idea of the response to treatment. This test uses a magnetic field and radio waves to produce images of body tissues. During the procedure the patient lies on a bed surrounded by a metal cylinder (the scanner).|Muscle biopsy at the beginning of the study to diagnose muscle inflammation and again at week 16 to evaluate the response to treatment.|Electromyography if the patient has not had an EMG previously. For this test, small needles are inserted into the muscle to assess the electrical activity of the muscle|HIV test||Patients whose disease worsen with treatment or who develop serious drug-related side effects will be taken off the study and referred back to their primary care physician for further therapy. Patients who improve will be referred back to their primary physician at the end of the study for possible continued treatment. Participants will be asked to return for follow-up visits every 6 weeks for a total of 30 weeks to monitor long-term effects of the drug"
"This study will determine whether a stepwise increase of the drug infliximab (Remicade® (Registered Trademark)) controls juvenile rheumatoid arthritis more effectively than a fixed dose. It will look at the safety and effectiveness of increasing the dose to a maximum of 15mg/kg body weight per dose, examining the drug's effect on bone and cartilage, and whether it can improve abnormal growth, metabolism and hormones. Infliximab is approved for treating adults with rheumatoid arthritis and Crohn's disease.||Children between 4 and 17 years of age with active juvenile rheumatoid arthritis who do not respond adequately to standard therapy may be eligible for this study.||Participants will receive nine infusions of infliximab during this 62-week study. The drug is given intravenously (IV, into a vein) over 2 hours. The first three infusions will be at a dose of 5 mg/kg of body weight. Children who improve on this regimen will receive another 6 infusions at the same dose. Children who do not significantly improve on 5 mg/kg at the end of 6 weeks (the third infusion) may continue with phase 2 of the study, in which they will be randomly assigned to receive either: 1) 6 additional doses of the drug at 5 mg/kg per dose, or 2) a gradually increased dose to a maximum of 15 mg/kg. In addition, all children will continue to take methotrexate at the same dose as when they entered the study.||Participants will visit the NIH Clinical Center 12 times (about every 8 weeks) during the study for the following tests and procedures:||History and physical examination, including a complete joint exam|Puberty assessment - breast development in girls, testicle size in boys, and pubic hair|Height and weight measurements||Children will have imaging studies (x-rays, MRI and Dexa scan) at the beginning and end of the study and will collect a 24-hour urine sample before each infliximab infusion.||Patients may elect to have an endocrine evaluation. This involves Clinical Center hospitalizations for 1-1/2 days on visits 1, 4 and 12. Small amounts of blood will be drawn every 20 minutes (through an indwelling catheter to avoid multiple needle sticks) for 8 hours while the child sleeps. The blood will be examined for the normal rhythm of growth hormone and other substances in the body and how they are affected by arthritis.||Participants will complete a questionnaire once a year for 2 years to provide information on their health status and any problems that might be related to the study drug."
"The purpose of this study is to compare the effects of Infliximab and oral prednisone versus methylprednisolone and oral prednisone in patients with melanoma, lung cancer, or renal cell carcinoma who have immune related Grade 3-4 diarrhea for up to 3 days or persistent Grade 2 diarrhea for more than 5 days after treatment with Yervoy and/or Opdivo"
"Phase IV||Design : Prospective, open-label, randomized three-arms study||Main Inclusion criteria Luminal Crohn's disease patients with steroid free remission for at least 6 months and a combination therapy with infliximab and anti-metabolites for at least 8 months||Primary objective To demonstrate that Infliximab scheduled maintenance with or without antimetabolites is superior to antimetabolites alone to maintain sustained steroid-free remission over 2 years, while the latter is non inferior with regards to the mean time spent in remission over the same duration||Main co-primary end points Clinical relapse rate at 2 years Mean remission duration within 2 years Study treatment Infliximab, Mercaptopurine, azathioprine, methotrexate.||Number of subjects 225 randomized patients (75 per arm)||Study duration: 3 + 2 years Enrollment: 3 years Follow-up: 2 years"
The purpose of this study is to determine whether infliximab is effective on fat-free mass in the treatment of patients with moderate to severe COPD suffering from cachexia.
The primary objective is to compare the efficacy and safety of infliximab plus methotrexate to infliximab alone for the long-term control of signs and symptoms of Crohn's disease (CD) in patients with symptoms that are persistent enough to require corticosteroid therapy.
The investigators will compare the immunogenicity of influenza vaccine in adults and children with inflammatory bowel disease by timing of vaccine in relation to maintenance infliximab dosing. The primary objective is to compare the proportion of IBD patients on maintenance infliximab who mount serologic protection to each component of the influenza vaccination between patients vaccinated on day of infliximab infusion (Day 0 to 4) and patients vaccinated at the mid-point between infliximab infusions (Day 21 to 28). Serologic protection will be defined by a hemagglutination-inhibition titer ≥ 1:40. The secondary objective is to compare the proportion of IBD patients who mount an immunogenic response (≥ 4-fold increase from pre to post-vaccination titer) to each component of the influenza vaccination between patients vaccinated on day of infliximab infusion and those vaccinated at the mid-point.
"To compare retention rates of adalimumab, etanercept and infliximab as first-line biotherapy in rheumatoid arthritis (RA), to determine causes of discontinuation, retention-associated factors, and retention rates of possible second-line tumor necrosis factor α inhibitors (TNFi)."
A study of the safety and efficacy of Infliximab (Remicade) versus placebo in subjects with Ankylosing Spondylitis
The purpose of this study is to compare a 2 immunosuppressant regimen for the treatment of relapsing or refractory necrotizing antineutrophil cytoplasmic antibody (ANCA) associated vasculitides.
"Eosinophilic Esophagitis (EE) is a chronic inflammatory disorder of the esophagus with a constantly increasing prevalence. It has been demonstrated that the expression of the cytokine TNF-α is up regulated in EE and that this pro-inflammatory cytokine is highly expressed by the keratinocytes of the esophageal epithelium in patients with active EE. Furthermore, it has been shown that TNF-α is capable to induce eotaxin-3 production in keratinocytes. These results suggest that TNF-α plays a crucial role in the pathogenesis of EE. Based on these findings, the investigators plan a prospective T1 translational study with the purpose to evaluate the efficacy of an Infliximab monotherapy in adult patients with severe, corticosteroid-dependent EE."
The purpose of this study is to demonstrate similarity of NI-071 (proposed biosimilar to infliximab) to US REMICADE® (reference product) in terms of safety and efficacy in patients with rheumatoid arthritis (RA) not adequately responding to methotrexate (MTX).
A study of the safety and efficacy of infliximab (Remicade) in pediatric patients with moderate to severe Crohn's Disease
"The purpose of this study is to evaluate the effectiveness and safety of infliximab, the active ingredient in Remicade, for the treatment of cachexia in pancreatic cancer patients who are receiving chemotherapy with gemcitabine."
The purpose of this study is to evaluate the efficacy and safety of infliximab (Remicade) in patients with early rheumatoid arthritis.
This study will evaluate biomarkers that reflect changes in gut mucosal status during therapy with infliximab and determine whether changes in the levels of the selected biomarkers can be used to predict endoscopically assessed gut mucosal status changes.
"The purpose of this study is to compare the pharmacokinetics, safety, tolerability and immunogenicity of SB2 and Remicade (EU sourced Remicade and US sourced Remicade) in healthy subjects."
"This is the trial to see how our product is similar to remicade by comparing the results of blood samples when co-administered with methotrexate between 12.5 to 25 mg/week, oral or parenteral dose and folic acid in rheumatoid arthritis patients who are not receiving adequate response to methotrexate alone up to week 30."
"Long term data on efficacy and safety of anti-TNF treatment with infliximab in patients with ankylosing spondylitis (AS) beyond 5 years is lacking. These data are important because patients with AS usually are younger and withdrawal of anti-TNF therapy in these patients almost always leads to a disease relapse. Furthermore it is still unclear whether long term anti-TNF treatment in AS patients can inhibit radiographic progression. Patients who participated in the EASIC and the DIKAS trial respectively who were treated with infliximab within these studies for 7 and 10 years respectively are followed up by using clinical outcome parameters every 6 months assessing efficacy and safety of long term treatment. Furthermore radiographs of the spine, if done for clinical indication, are analyzed. It is hypothesized that anti-TNF treatment with infliximab is effective and safe over a time period of 9 and 12 years respectively and that long term anti-TNF therapy may inhibit radiographic progression of the spine."
A study of infliximab in patients with Fistulizing Crohn's Disease
"This open-label, single-arm, multicenter, multiple single-dose intravenous (IV) infusion, efficacy, and safety extension study of the Phase 1 Study CT-P13 1.1 is designed to assess the long-term efficacy and safety of multiple doses of CT-P13."
This is a study of infliximab (Remicade) in subjects with Crohn's disease
"To assess persistence of CT-P13 in patients with Rheumatoid Diseases (Rheumatoid arthritis [RA], ankylosing spondylitis [AS], and psoriatic arthritis [PsA]) who are naïve to biologics or are switching from stable Remicade to CT-P13. The main objectives of the study are:||To evaluate real-life drug persistence in RA, AS, and PsA patients who are either initiated with CT-P13 as their first biologic, or who are switched from stable Remicade|To characterise the patient populations and drug usage patterns of RA, AS, and PsA patients who are either initiated with CT-P13 as their first biologic, or who are switched from stable Remicade|To assess the safety of CT-P13 in RA, AS, and PsA patients who are either initiated with CT-P13 as their first biologic, or who are switched from stable Remicade for up to 2 years"
"The main purpose of this study is to examine the effects of infliximab on measures related to depression symptoms. Infliximab is also known by its brand name Remicade. Infliximab, or Remicade, is given to by an intravenous (IV) needle and is currently used to treat rheumatoid arthritis and Crohn's disease. Infliximab is thought to help these conditions because it reduces inflammation in the body. Infliximab (Remicade) reduces inflammation by blocking a chemical in the body called tumor necrosis factor (TNF)-alpha. This chemical produces inflammation. Inflammatory chemicals in the body like TNF-alpha appear to be increased in some people with major depression. Researchers believe that a drug like infliximab, which blocks TNF-alpha, may be helpful in treating depression.||This is a double-blind, placebo-controlled study in which participants will be randomized to receive one infusion of infliximab or placebo. The study will assess neuroimaging measures of corticostriatal circuitry before and after a placebo-controlled pharmacologic blockade of inflammation in 80 depressed patients."
"Acute graft versus host disease (GVHD) remains one of the most significant and potentially lethal complications of allogeneic bone marrow transplantation. Depending upon the type of transplant, the incidence of acute GVHD varies between 20 - 50% in related donor transplants, or as high as 70 - 90% in unrelated donor transplants. Acute GVHD affects the skin, liver and gastrointestinal (GI) tract and usually occurs within 20 - 40 days of the bone marrow infusion.||Steroids are the standard initial treatment of acute GVHD, with approximately 50% of the patients either free of disease or requiring no further therapy. In the remaining patients, the GVHD either does not respond or it comes back during the tapering of steroids. These patients have a much worse prognosis with a mortality rate greater than 70%. Studies using additional agents such as antithymocyte globulin (ATG), monoclonal antibodies, and anti-lymphocyte globulin showed no improvement over the use of steroids alone. This leads the investigators to look for new immunosuppressive agents that can reduce the risk and severity of acute GVHD.||The major purpose of this study is to evaluate the way the body uses and absorbs (the pharmacokinetic profile) a drug called anti tumor necrosis factor antibody (infliximab) for the treatment of acute GVHD. Infliximab is currently indicated for the treatment of immunologic-based diseases (rheumatoid arthritis, moderately to severely active Crohn's disease, and fistulizing Crohn's disease), assuming patients have had inadequate responses to conventional therapy. It is not approved for the treatment of GVHD.||This is a Phase I pharmacokinetic study that is coordinated by the Pediatric Blood and Marrow Transplant Consortium (PBMTC). The study will be conducted in the Blood and Marrow Transplantation (BMT) program at Children's Healthcare of Atlanta - Egleston, Emory University Department of Pediatrics. The goal is to enroll 1 - 2 patients on this study; accrual will be via the BMT program. Eligible patients must be less than 18 years of age.||Patients with newly diagnosed acute GVHD will be able to participate in the study. Patients will receive a single dose of infliximab in the clinic. Since this is a Phase I study, the patients will have blood samples drawn to measure the pharmacokinetics of the drug. A total of 16 blood samples will be drawn over 84 days. The samples will be labeled with a code, processed, frozen, and then sent in a batch to the PBMTC designated laboratory for testing. Patients will continue on any drugs they were getting for the prevention of GVHD. Additional doses of infliximab may be given. This decision will be based on the results of the blood testing."
"This project is designed to test the hypothesis that inhibition of binding between tumor necrosis factor alpha (TNF-alpha) and its receptors using Remicade (infliximab, chimeric mouse/human IgG1K monoclonal antibody directed against human TNF-alpha, Centocor, Malvern,PA) is clinically useful for patients with uveitis that is refractory to other forms of systemic immunosuppressive therapy."
"CT-P13 (Infliximab) is a monoclonal antibody currently being developed by CELLTRION, Inc. This open-label, single-arm, multicenter, multiple single dose intravenous (IV) infusion, efficacy, and safety extension study of the Phase 3 Study CT-P13 3.1 is designed to assess the long-term efficacy and safety of multiple doses of CT-P13."
To assess the relationship between the change in Crohn's Disease Activity Index (CDAI) scores and trough serum infliximab concentration in subjects who are scheduled to receive infliximab infusions at an interval of 8 weeks.
The purpose of this study is to compare the clinical findings involving the small bowel obtained with the Capso Vision Video Capsule Device to those results obtained with the PillCam SB2.
"This study will be performed to compare the efficacy and safety of the classical ""Step-Up"" approach for treatment of moderate-to-severe active ulcerative colitis using oral prednisolone + oral 5-aminosalicylic acid (5-ASA) or oral prednisolone + oral azathioprine (AZA) with a more intensive and early ""Top-Hold"" approach with intravenous infliximab (5 mg/kg) administered at Weeks 0, 2, and 6 and 8 weeks thereafter."
"This trial is extension part of the P04280 (placebo-controlled, double-blind, randomized study of chronic treatment with infliximab in approximately 140 patients, NCT00202852). This study will be conducted at 6 study centers in South Korea. After completion of the last follow-up visit at Week 30 and code break in main double-blind trial, subjects randomized to the placebo group and those who were treated with an infliximab-containing regimen who maintained clinical response at the time of study completion will be provided with open-label infliximab for treatment of their conditions and additional safety data will be collected."
"The costs and potential complications (side effects) of therapies currently used to treat Crohn's disease could be reduced if a non-invasive test existed that determined which therapies benefit patients and which do not. A non-invasive test is a test that does not involve cutting or entering the skin. Currently, once therapies are prescribed, doctors rely solely on clinical parameters to gauge whether the therapies are helpful. This includes evaluation of overall general well-being, abdominal pain, and number of liquid stools per day. There is no established and reliable non-invasive test that can predict whether a person is responding to therapy early in the course of treatment when these evaluations may be inconclusive.||During this research study we will look for changes in sugar metabolism on low-dose PET/CT before and 2 weeks after the first infusion of infliximab therapy. This is to find out if these changes can predict clinical response and steroid-free remission at two, six and 12 months, in patients with Crohn's disease."
"Behçet's disease (BD) is a systemic vasculitis of arterial and venous vessels of any size, involving young patients (from 15 to 45 years). BD significantly increases morbidity and mortality. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, nonsteroidal antiinflammatory agents and topical treatments are often sufficient for mucocutaneous and joint involvement, more aggressive approach with immunosuppressive agents is warranted for severe manifestations. Early recognition and vigorous use of immunosuppressives with high dose steroids have changed the prognosis of patients with severe BD. BD is a severe systemic vasculitis leading to blindness in up to 20% at 4 years and a 5-year mortality rate of 15% in patients with major vessel or neurological involvement. Cyclophosphamide has been used for life-threatening BD for 40 years. However, the outcome of severe complications of BD is poor. The European League Against Rheumatism (EULAR) recommendation for the management of BD advocated cyclophosphamide plus glucocorticoids for life-threatening manifestations (i.e neurological and/or major vessel involvement). TNFa antagonists have been used with success in severe and/or resistant cases. In addition, the incidence of blindness in BD has been dramatically reduced in the recent years with the use of anti-TNF. However, there is no firm evidence or randomized controlled trials directly addressing the best induction immunosuppressive therapy in severe BD manifestations. The investigators therefore aimed to assess the best induction therapy in severe and difficult to treat BD patients. The investigators hypothesize that up to 70% of the patients with life-threatening manifestations of BD receiving these compounds [anti-TNFa or cyclophosphamide] will achieve a complete remission of BD at 6 months and with less than 0.1 mg/kg/day of prednisone.||ITAC, is the first randomized prospective, head to head study, comparing infliximab, to cyclophosphamide in severe manifestations of BD. There is no firm evidence or randomized controlled trials directly addressing the best induction immunosuppressive therapy in severe BD. Cyclophosphamide failed to demonstrate sustainable remission over 70 % of life threatening BD cases. There is little published information on use of immunosuppressants other than cyclophosphamide for severe BD. TNFa antagonists have been used with success in severe and/or resistant cases. TNFa expression correlates with BD activity and other immunological data provide a strong rationale for targeting BD with biologics. Despite a strong rationale, these compounds are not yet approved in BD, which guarantees the innovative nature of this study that aims selecting or dropping any arm when evidence of efficacy already exists."
"This is a double-blind, double-dummy, prednisolone-controlled, multi-center, randomized, parallel-group clinical study to evaluate the therapeutic efficacy of repeated infliximab infusions in order to maintain Crohn's disease remission at the end of the study."
"Crohn's disease (CD) is a life-long inflammatory bowel disease disease with an unknown pathogenesis. The ultimate goal of therapy is to modify the natural history of CD thus reducing complications. Thalidomide is a small molecule with immunomodulatory and anti-angiogenetic properties. It is currently approved for the treatment of erythema nodosum leprosum, an immunological complication of leprosy and multiple myeloma. It has also been used in several other inflammatory diseases of the skin and of the mucosal membranes, such as Behcet disease, oropharyngeal ulcers in AIDS, cutaneous lupus, and graft versus host disease. Many case series and one pediatric randomized controlled trial proved the efficacy of thalidomide in the treatment of children with CD refractory to standard treatments. In these patients, clinical remission was achieved in about 50% of the cases and was maintained for a mean time superior of 3 years. Mucosal healing after 52 weeks of treatment was observed in 40% of the patients in clinical remission. Moreover, thalidomide was found to have a steroid-sparing effect and to decrease the need for surgical interventions. The clinical and endoscopic efficacy of thalidomide was also observed in children with failure to respond or intolerance to anti-TNF biological drugs.||The aim of this multicentric prospective randomized controlled is to evaluate the efficacy and safety of thalidomide vs infliximab in changing the natural history of CD in patients with poor prognostic outcome. Moreover, the study will evaluate the immunological and genetical mechanisms of CD, the mechanisms of action thalidomide in CD and will the pharmacokinetics, metabolomics and pharmacogenomics of thalidomide, and their impact on thalidomide safety and effectiveness."
"Deep endometriosis associated pain is believed to be caused by inflammation. Anti TNFa has been proved to be an effective treatment for other inflammation related conditions as Crohn's disease Endometriosis is associated with an inflammatory response in the pelvis, which is mediated by a number of cytokines including TNF-α. It has therefore been suggested that infliximab, an anti-TNF-α monoclonal antibody, might relieve pain in affected women."
"The purpose of this study is to determine whether a top-down treatment approach, prescribing infliximab (IFX) and azathioprine (AZA) at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and AZA or exclusive enteral nutrition (EEN) and AZA, in moderate-to-severe pediatric Crohn's disease (CD) patients."
This study is the trial to demonstrate how our product is similar to remicade by comparing the results of blood samples in active Ankylosing Spondylitis patients.
"The objective of the study is to identify and validate predictive markers of infliximab responsiveness in RA patients by 2 approaches: i) measuring biochemical, immunological and bone markers in sera because of their involvement in pathogenic mechanisms; ii) identifying gene-expression signatures in PBMCs by the transcriptomic analysis.||Patients with active RA (ACR criteria) were given i.v. 3 mg/kg infliximab associated with metotrexate at weeks 0, 2, 6, and every 8th week. Infliximab efficacy was evaluated at week 14, using the EULAR response criteria.||Just before the starting of infliximab treatment, the following parameters were measured in the sera: i) immunological tests: rheumatoid factor (IgA, IgG, IgM), anti-CCP, autoAb recognizing the 27 C-terminal fragment (ACAST-C27) and domain I (ACAST-DI) of calpastatin, anti-G6PI, anti a-enolase, anti-keratin and anti-perinuclear factor; ii) biochemical markers: CRP, MMP-1, MMP-3, TIMP-1, TIMP-2; markers of bone resorption: pyridinolin, deoxypyridinolin, osteoprotegerin, sRANKL, COMP. The predictive value of each parameter for a response/non-response to infliximab was analysed using Fischer's exact, Mann-Whitney and Chi2 tests.|A blood sample was collected just before the onset of infliximab treatment and total RNAs were extracted from the peripheral blood mononuclear cells. The [33P] radiolabeled mRNAs were hybridized (duplicate or triplicate) over a set of 10.000 human cDNA probes spotted at a high density on nylon membranes. Data were normalized and filtered to allow the comparison between RNA samples. Statistical analyses were performed with the R software and hierarchical clustering was performed with the Cluster and Tree View softwares."
"The metabolic response to ulcerative colitis, including increased proteolysis and lipolysis and changes in energy expenditure, plays a significant role in the resulting malnutrition from which these patients suffer. Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, has been found to be elevated in children with ulcerative colitis. TNF-alpha has been incriminated in the mechanism of weight loss in many different chronic diseases, and causes net protein and lipid catabolism. Anti-TNF-alpha antibody (infliximab) has been proven to be an effective therapy for ulcerative colitis.||The purpose of this study is to determine changes in protein and lipid metabolism, as well as resting energy expenditure, before and after therapy with anti-TNF-alpha antibody (infliximab) in children with ulcerative colitis. Performing this study will better define the changes in nutrition status observed in these children following remission of active ulcerative colitis, and potentially lead to changes in medical and nutritional management of these children"
To investigate whether sustained trough levels of IFX can be achieved using IFX (Infliximab) trough level measurements and adjustment of dosing based upon these levels by means of two different standardized algorithms in comparison with 'standard of care' IFX treatment and its effects on clinical and endoscopic outcomes.
"The SOLIDARITY PLUS Finland Long-COVID trial aims to assess the long-term effects of imatinib and infliximab, used during acute hospitalization due to COVID-19-infection, on long-COVID symptoms and quality of life (QoL) using questionnaires at six months, one and two years post-discharge. The primary research questions are whether imatinib or infliximab lower the risk of long-COVID symptoms and leads to better QoL in the long term.||Objectives include:||i) Long-COVID symptoms||To investigate the effect of imatinib (vs. usual care only) and infliximab (vs. usual care only) on the occurrence of symptoms that have been associated with the long-COVID syndrome. The questionnaires will take place at six months, one and two years after the hospital admission. The questionnaire will be the same that has been used in the SOLIDARITY Finland Long-COVID trial on remdesivir. The questionnaire was developed by our multidisciplinary team of physicians, including the representation of multiple specialties such as general practice, lung diseases, neurology, internal medicine, rheumatology, genetics, and clinical epidemiology, and two patient partners.||The symptom questionnaire - that will be completed by patients at one and two years - measures basic patient information (age, height, weight, smoking status, major comorbidity, and working status) and a wide variety of potential long-COVID-symptoms and their bother (1. Fatigue; 2. Attention deficits; 3. Memory problems; 4. Sleeping difficulties; 5. Depressive mood; 6. Anxiety; 7. Dizziness; 8. Headache; 9. Tinnitus; 10. Paresthesias; 11. Changes in taste/smell perceptions; 12. Postexertional malaise; 13. Palpitations; 14. Chest discomfort; 15. Nausea; 16. Skin rash; 17. Joint aches; 18. Muscle pains; 19. Continuous cough; 20. Respiratory tract mucous discharges).||ii) Quality of life||The EQ-5D-5L questionnaire will be used to compare patients' quality of life in imatinib, infliximab, and usual care arms.||EQ-5D-5L questionnaire assesses the following domains: 1. Mobility; 2. Self-care; 3. Usual activities; 4. Pain and discomfort; 5. Anxiety and depression; 6. The visual analog scale of subjective perception of overall health.||Additionally (at 1 or 2 years; depending on future funding and ethical approval decisions):||The Finnish healthcare registries (such as Statistics Finland Mortality Database, the HILMO Care Register for Health Care, and/or Digital and Population Data Services Agency (Finnish Digital Agency)) will be used to estimate long-term mortality and incidence of major comorbidity in treatment arms.|Lung function will be assessed using spirometry and diffusing capacity, as well as the six-minute walk test (6 mwt) in treatment arms.|Whole-genome genotyping will be performed for a genome-wide association study to investigate genetic correlates of long-COVID-19 -symptoms in treatment arms."
The purpose of this study is to compare the safety of NI-071 with Remicade® (infliximab) in patients with Rheumatoid Arthritis inadequately treated with Methotrexate.
"The purpose of this study is to evaluate the safety and effectiveness of infliximab (an anti-TNF chimeric monoclonal antibody [cA2]) in patients with active Rheumatoid Arthritis, despite methotrexate treatment."
"This study will determine if the drug infliximab is safe for treating inflammatory bowel disease (IBD) in patients with chronic granulomatous disease (CGD). IBD is an inflammation or irritation of the gut that leads to symptoms such as diarrhea, bloating and stomach cramps. CGD is an inherited disease affecting white blood cells called neutrophils in which patients are susceptible to repeated bacterial and fungal infections. They also have a higher incidence of some autoimmune diseases, such as IBD. Infliximab is approved to treat Crohn's disease, an IBD similar to that seen in patients with CGD.||Patients 10 years of age and older with CGD and IBD may be eligible for this study. Candidates are screened with a medical history, physical examination, blood and urine tests, electrocardiogram (EKG), tuberculosis skin test (PPD skin testing), and stool test for the presence of infections. Additional tests may be done, including colonoscopy (procedure using a flexible tube through the rectum to examine the lining of the gut) and imaging studies such as an x-ray, chest CT scan (test using a special x-ray machine), MRI (test using a magnetic field and radio waves), and barium studies (study using a drinkable solution of barium to help enhance the x-ray pictures of the gut).||Participants are divided into patients with IBD symptoms (Group 1) and patients without IBD symptoms (Group 2) for the following procedures:||Group 1||Patients are evaluated every 6 months with a medical history and physical examination for signs and symptoms of IBD. Patients who are taking moderate to high doses of steroid medications have their medication slowly lowered (tapered) and are evaluated every 3 months for a total of 2 years. Patients in this group who start to develop IBD symptoms are moved to Group 2 for treatment with infliximab (see below).||Group 2||Patients in Group 2 receive infliximab infusions at 2-week intervals for three doses. The drug is given over a 2-hour period through a catheter placed in a vein. Patients are evaluated with a medical history, physical exam, and blood tests the day of each dose. One week after the last dose, they have another evaluation, including a colonoscopy. Patients who respond well to infliximab may continue to receive the drug every 2 months for a total of 1 year, with evaluations at every dosing visit. At the end of the first year of receiving infliximab, all patients have follow-up evaluations every 6 months for a total of 2 years.||Group 3||Subjects who volunteer to undergo colonoscopy and research biopsies that serve as controls for evaluation of the patient gut samples."
"The introduction of infliximab (IFX) and other monoclonal antibodies (MAbs) targeting tumor necrosis factor (TNF) was a major advancement in the management of inflammatory bowel disease (IBD). These biologics were able to improve the health outcomes of many IBD patients for whom other treatments were neither satisfactory nor sufficient. Despite clear advantages and increased use of these treatments, physicians still see a loss of response in up to 50% of their IBD patients within one year of initiating these therapies. Most of these phenomena are attributed to low drug concentrations in the presence or absence of anti-drug antibodies (ADA).||The fundamental issue is that approved/on-label dosing of these drug therapies does not take into account the various factors that impact the way an individual's body responds and processes these therapies. Dashboard software systems can quickly integrate patient data and serve as a revolutionary decision-support tool for physicians. The Precision IFX dashboard prototype was specifically developed to facilitate dosing of therapeutic monoclonal antibodies by integrating patient's clinical characteristics and drug concentrations into pharmacokinetic (PK) algorithms. Using clinical observations and patient laboratories, the system provides multiple dosing regimens that could allow the patient to attain and sustain a therapeutic drug trough level.||Using the Precision IFX dashboard to analyze and forecast optimal dosing regimens with prospectively collected individual patient data, the clinician will select an appropriate dose to actively maintain therapeutic drug trough levels throughout the infliximab maintenance period. This study aims to examine the outcomes of one year of maintenance infusions in IBD patients dosed using the Precision IFX dashboard prototype and compare the results with historical controls."
"The purpose of this study is to assess the safety and efficacy of switching from Remicade to the biosimilar treatment Remsima in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn's disease and chronic plaque psoriasis"
"The aim of the study is confirmation of efficacy of induction therapy with three doses of infliximab In patients with Crohn disease aged 7-17 years, and comparison of efficacy and safety of two regiment of maintenance therapy:||Infliximab with immunomodulation|Infliximab alone"
"The primary objective of this study is to evaluate sustained clinical remission (for the definition see below) in patients with inflammatory bowel disease receiving long-term (> 2 years) scheduled treatment with infliximab.||Secondary objectives include:||to identify predictors of sustained clinical remission during long-term infliximab scheduled treatment|to identify predictors of loose of response during infliximab scheduled maintenance treatment|to identify predictors for maintaining clinical remission in patients who discontinue infliximab because of long-lasting steroid-free clinical remission|to evaluate percentage of surgery during and after treatment (total follow-up)|to evaluate safety of long-term infliximab scheduled treatment||List the clinical hypotheses||Infliximab is indicated and recommended in moderate to severe inflammatory bowel disease patients who not tolerate or are not responsive to conventional therapies. Most of randomized clinical trials about the use of infliximab in inflammatory bowel diseases are limited to 52 weeks and very few data come from some observational studies about results of prolonged (over one year) treatment with infliximab. No validated predictors of sustained clinical remission or loss of response are available so far. Moreover, few data are available about the hypothetical reduction of IBD related surgery in the ""biological era"".||In this proposal we suggest the following hypotheses:||infliximab scheduled treatment may be efficacious in maintain long-term clinical remission;|among clinical, laboratory and endoscopic data some predictors of sustained clinical remission during infliximab long-term scheduled treatment may be found;|among clinical, laboratory and endoscopic data some predictors of loss of response during infliximab long-term scheduled treatment may be found;|among clinical, laboratory and endoscopic data some predictors of sustained clinical remission after infliximab discontinuation because of long-lasting (> 6 months) steroid-free clinical remission may be found;|maintenance of remission with infliximab may reduce rates of surgery over time;|long-term scheduled treatment with infliximab may be safe and well tolerated. Results from this study may really help clinicians to make practical decisions in these particular clinical settings."
"Part 1 of this study is a 3-arm, randomized, active-controlled, parallel-group, multicenter, double-blind, double-dummy, 16-week study to compare the efficacy and safety of infliximab (IFX), as monotherapy or in combination with azathioprine (AZA) versus AZA monotherapy in adults with moderate to severe active ulcerative colitis (UC). Participants who qualify at the Baseline Visit will be eligible to be randomized to one of the three active treatment groups.||Participants in the IFX/AZA combination therapy and IFX monotherapy cohorts will receive IFX infusions at Weeks 0, 2, and 6 and daily oral AZA/placebo, respectively; participants in the AZA cohort will receive daily oral AZA and placebo infusions at Weeks 0, 2, and 6. At Week 8, all participants will be evaluated for response.||Participants responding to IFX treatment at Week 8, either as monotherapy or in combination with AZA, will receive one more IFX infusion at Week 14; non-responders to IFX therapy will receive placebo infusions at Weeks 8 and 10 and one additional IFX infusion at Week 14.||Participants responding to AZA monotherapy at Week 8 will continue on AZA therapy and receive one placebo infusion at Week 14; nonresponders to AZA will be eligible to receive IFX at Weeks 8, 10, and 14.||Part 2: Participants in remission on IFX monotherapy or IFX/AZA treatment at Week 16 will be randomized to either maintenance or intermittent open-label IFX treatment; randomization will be stratified based on oral AZA/placebo treatment in Part 1. Oral AZA/placebo treatment will continue to be double-blinded. All participants will continue to receive oral AZA/ placebo for the duration of the study.||Participants randomized to maintenance IFX treatment will receive scheduled IFX infusions every 8 weeks beginning at Week 22 (Week 6 for direct entry). If participants lose response, or if treatment has to be discontinued because of an adverse event, these participants are considered treatment failures, and should be followed up for safety at the scheduled 6-month visits (Weeks 38, 62, and 94 [Weeks 22, 46, and 78 for direct entry]). These participants will receive standard of care per their personal physician.||Participants randomized to intermittent IFX treatment will be evaluated every 8 weeks. Participants will receive IFX only upon relapse of disease. Treatment with IFX will be initiated at Weeks 0, 2, and 6 of the individual treatment cycle and will continue every 8 weeks until remission is regained. Throughout the study, individual treatment cycles will be repeated whenever a subject relapses.||In addition, to facilitate enrollment into Part 2, participants who received treatment outside of Part 1 and who are in remission on IFX with or without AZA/6-mercaptopurine (6-MP) will be allowed to enter directly into Part 2. In the Czech Republic, direct entry into Part 2 of the study is not allowed.||A higher than expected incidence of serious infusion reactions observed in the intermittent treatment arm of another study (Protocol P04563, NCT0358670) conducted in participants with moderate to severe psoriasis resulted in the termination of that study. Based on the similarities in study design between the intermittent treatment arm of P04563 and the intermittent treatment arm of Part 2 of this study, enrollment to Part 2 of this study was put on hold, for precautionary reasons. At the same time, all participants already enrolled in the intermittent treatment arm of Part 2 were asked to discontinue from the trial. In October 2009, a decision was made by the sponsor to terminate the whole study (Part 1 and 2). At that time, participants enrolled in Part 1 of the study were allowed to complete their treatment up to Week 16."
The purpose was to evaluate as to whether administration of infliximab of 12 week interval with supplementary VSL#3 is more effective or at least of similar efficacy when compared to conventional administration of infliximab only of 8 week interval.
"The purpose of this study is collection and analysis of information pertaining to pregnancy outcomes in women exposed to infliximab during pregnancy, relative to the background risk in similar but non-biologic exposed patients; and information pertaining to health status, during the first year following delivery, of infants born to women following prenatal exposure to infliximab and their unexposed counterparts."
"International multicenter open-label single-arm confidence-interval-estimation based Phase II clinical trial, aiming to estimate a plausible range of the proportion of patients experiencing efficacy failure in the population, to provide evidence for efficacy and safety of the induction regimen with rATG and infliximab and a go/no go rule for further clinical development."
"In severe refractory sarcoidosis not responding to conventional immunosuppressive treatment, the third-line tumor necrosis factor (TNF)-alpha inhibitor infliximab is an alternative. Treatment duration is not known, although it has been suggested that relapse rates after withdrawal could be high. We hypothesize that a prolonged course of TNF-alpha would be better for maintaining remission in sarcoidosis.||The population consists of histologically-proven adults sarcoidosis patients who were treated with infliximab and are in remission for at least 6 months with less than or equal to 10 milligrams of steroids (prednisone).||The present study is a phase 3, prospective, randomized, parallel groups, comparative, open-labelled 2 arms study superiority trial comparing a STOP to a REMAIN strategy. Patients will be randomized in the 2 groups in a 1:1 ratio."
"The purpose of this study is to determine if an anti-inflammatory drug, called infliximab, will reduce inflammation in the synovial lining in patients with an early stage of osteoarthritis of the knee. It will also help determine if the study medication decreases the accumulation of synovial fluid and prevents cartilage breakdown."
"Increased inflammation has been implicated in the pathophysiology of a number of neuropsychiatric illnesses including mood disorders, which affect almost 30 million adults in the United States alone. One mechanism by which inflammation may alter behavior is through increasing brain glutamate, a neurotransmitter that in excess has been implicated in neuronal toxicity and resistance to conventional antidepressant therapy. The goal of the proposed research is to test the hypothesis that inflammation alters behavior through increasing glutamate in specific brain regions, ultimately leading to behavioral changes.||The proposed research is designed to determine the cause and effect relationship between inflammation and CNS glutamate as well as the relationship between CNS glutamate and specific symptoms. To accomplish these aims, investigators will administer a single infusion of either the tumor necrosis factor (TNF) antagonist infliximab or placebo (n=30 per group) to patients with high inflammation (CRP>3mg/L). A CRP>3mg/L was chosen because it is considered high inflammation according to guidelines by the American Heart Association. Moreover, a CRP>3mg/L is associated with significantly increased basal ganglia glutamate and with a clinical response to infliximab. Inflammatory biomarkers, basal ganglia glutamate as measured by MRS, and motivation and psychomotor activity will be assessed at baseline and days 1 and 3 and weeks 1 and 2 following infliximab or placebo administration."
"The purpose of this study is to assess the efficacy, safety and pharmacokinetics of maintenance treatment with 3mg/kg, 6mg/kg or 10mg/kg of TA-650 in combination with methotrexate (MTX) after three infusions (weeks-0, 2, 6) of 3mg/kg in Rheumatoid Arthritis (RA) showing an insufficient response to MTX."
"This is a placebo controlled randomised clinical trial.Patients attending Yorkshire Early Arthritis Clinics and diagnosed with rheumatoid arthritis with symptom duration of 3-12 months will be recruited. They will be randomised to blinded therapy with either methotrexate and intravenous corticosteroid at baseline, or methotrexate and intravenous infliximab according to the standard treatment regime. Patients will be followed regularly, and at each visit, if the patients are not in remission, they will be given an intramuscular injection of corticosteroid. After 26 weeks, all patients will be unblinded and those with an inadequate treatment response will be treated according to a dose escalation algorithm until they achieve remission. Those in remission will continue on blinded therapy and if 6 months of remission is achieved the intravenous agent (infliximab or placebo) will be withdrawn."
"Background and aims: Acute severe ulcerative colitis (ASC) is a potentially life-threatening event. Poor pediatric data are available about the success rates of Infliximab (IFX) as a second line therapy. This study was performed in consecutively observed pediatric patients with ASC, treated according to the 2011 European Crohn's colitis Organization (ECCO)- European Society for Pediatric Gastroenterology, Hepatology and nutrition (ESPGHAN) guidelines on pediatric ASC¹ and aim to assess the long-term efficacy of IFX and clinical predictors of poor outcome.||Methods: Children hospitalized for an episode of ASC, defined as a Pediatric Ulcerative Colitis Activity Index (PUCAI) of at least 65 points, were enrolled. Clinical assessment through PUCAI and laboratory data (Erythrocyte Sedimentation Rate, C-Reactive Protein, hemoglobin, albumin, hematocrit, ferritin) was recorded at admission and at day 3 and 5. All patients were treated according to the above mentioned guidelines for ASC and received intravenous (iv) corticosteroids (CS) as first-line therapy. IFX was administered as second-line therapy in CS-refractory patients. In a 2-year follow up the overall colectomy rate and the efficacy of IFX in avoiding colectomy were evaluated."
The purpose of this clinical research study is to learn if Abatacept or Infliximab in combination with Methotrexate demonstrate a greater reduction in disease activity over placebo.
Ulcerative colitis patients treated with Infliximab (IFX) in deep remission after at least 12 months of treatment will be randomized to continue IFX or to stop IFX and start Azathioprine (AZA).||Each patient will be followed for 12 months.
"This study examined whether the anti-inflammatory medicines infliximab, sirolimus or daclizumab, when given with a participant's current therapies, would prevent the growth of new blood vessels in the eye in participants with age-related macular degeneration (AMD).||Participants 55 years of age and older with AMD and drusen larger than 63um may be eligible for this study. Vision in the study eye was between 20/20 and 20/400.||Participants were randomly assigned to one of three treatments - infliximab, sirolimus, or daclizumab - or to observation only. In addition, participants may have been treated by their ophthalmologist as needed for their AMD.||Infliximab and daclizumab were given intravenously (through a vein); infusions were given at enrollment in the study, then at 2 weeks, and then monthly.||Sirolimus was a pill that was taken every other day for the duration of the study. At 6 months, participants were evaluated to see whether continuing treatment would be beneficial.||In addition to treatment or observation, participants underwent the following procedures:||Physical examination at enrollment and 6 months.||Photographs of the back of the eye, fluorescein angiography, indocyanine green angiography and measurement of retinal thickness at enrollment and months 1, 3 and 6.||Fluorescein angiography evaluated the eye's blood vessels. A yellow dye was injected into an arm vein and traveled to the blood vessels in the eyes. Pictures of the retina were taken using a camera that flashed a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.|Indocyanine green angiography identified feeder vessels that may have supplied abnormal blood vessels. This procedure is similar to fluorescein angiography, but uses a green dye and flashes an invisible light.|Optical coherence tomography measures retinal thickness. This test shines a light into the eye and produces cross-sectional pictures of the retina. These measurements are repeated during the study to determine whether retinal thickening is getting better or worse, or staying the same.||Tuberculin skin test and chest x-ray at enrollment and 6 months.||Blood tests at enrollment and months 1, 3 and 6."
"To assess if infliximab drug levels in subjects with Ulcerative Colitis predict risk of colectomy rate. Additionally, the investigators will estimate an optimal day 4 infliximab level based on the study results."
The first-line treatment strategy of moderate to severe UC was a important question at issue. The biological agents had potentiality to alter the disease course of UC. The AGA clinical guidelines had conditional recommend that IFX and other biological agene migtht be first-line therapy for high-risk UC patints but only had low grade evidence.We launched this multicenter prospective cohort trial to compare the efficacy and safety of infliximab (IFX) and corticosteroids(CS) when they was used as first-line therapy in UC patients.
"Comparison of trough level-based spacing and clinical-based spacing of infliximab infusions in patients with inflammatory bowel disease in deep remission A prospective, multicenter, open-label, randomized, controlled Study"
"The purpose of this study is to assess the efficacy, safety and pharmacokinetics after administration of 10mg/kg TA-650 every 8 weeks to patients with Crohn's disease showing an insufficient response to previous treatment with 5 mg/kg of REMICADE every 8 weeks."
"This phase II trial studies how well infliximab and intravenous immunoglobulin therapy work in treating patients with pneumonitis that does not respond to steroid treatment. Immunotherapy with monoclonal antibodies such as, infliximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Intravenous immunoglobulin therapy may improve pneumonitis. It is not yet known whether giving infliximab and intravenous immunoglobulin therapy will work better in treating patients with pneumonitis."
"TNFα inhibitors have revolutionized the management of patients suffering from inflammatory diseases in the field of rheumatology. Infliximab remains widely used in France, and infliximab biosimilars have been routinely used since 2015 in Cochin Hospital with an interchangeability strategy validated by two real life studies. REMSIMA® 120 mg is the first authorized subcutaneous (SC) form of infliximab to be administered at a fixed dose of 120 mg every 2 weeks. Scarce information is available regarding the safety and efficacy of proposing a switch from IV infliximab to SC REMSIMA® in the subsets of patients suffering from different rheumatic diseases in daily care. The primary objective of the SIC2 study will be determine the retention rate of Remsima SC at 6 months. The investigators will recruit adult patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis."
The purpose of this study is to determine whether Infliximab (monoclonal anti-tumour necrosis factor alpha antibodies) are safe and effective in the treatment of anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis.
This study evaluates 2 therapeutic strategies (increase infliximab dose or add an immunosuppressant) in patients with inflammatory bowel disease in loss of response to infliximab. Addition of an immunosuppressant may be more efficient at long term and is less expensive.
"Kawasaki disease (KD) is a self-limited illness that affects the heart blood vessels (coronary arteries) of infants and children and is now the most common cause of acquired heart disease in children. A mixture of proteins from human blood (Intravenous immunoglobulin, IVIG) is a treatment that reduces the rate of the major complication of the disease: a bulging of the wall of the coronary arteries called an aneurysm. However, 10-20% of children are resistant to this treatment and the fever returns. These children have the highest rates of aneurysm formation and thus should be treated aggressively. Unfortunately, there are no guidelines for the best secondary treatment for these resistant patients because the problem has never been adequately studied. Most physicians choose either a second infusion of IVIG or an engineered antibody called infliximab that inactivates a molecule that promotes inflammation. This trial will randomize (assign by chance like the flip of a coin) IVIG-resistant patients to receive either a second IVIG infusion or infliximab and the response to treatment will be compared to learn which treatment stops the fever the fastest. In addition, parents and caregivers will provide observations about their child's response to the different treatments."
"Islet transplantation has been investigated as a treatment for Type 1 diabetes mellitus in selected patients with inadequate glucose control despite insulin therapy. However, the perennial hope that such an approach would result in long-term freedom from the need for exogenous insulin, with stabilization of the secondary complications of diabetes, has failed to materialize in practice. The goal of the present study is therefore to improve the safety and efficacy of clinical islet-alone transplantation by minimizing dependence on calcineurin-inhibitor therapy - thereby avoiding potential nephrotoxicity, and furthermore improving success with single-donor islet infusions by avoiding all diabetogenic immunosuppression. Campath-1H, combined with Infliximab induction therapy provides a unique opportunity to minimize dosing of maintenance long-term immunosuppression while further promoting islet engraftment."
The purpose of this study is to assess the effectiveness of treatment in patients with active rheumatoid arthritis who are having an inadequate response to at least 3 months of treatment with etanercept or adalimumab in addition to methotrexate.
This study investigated the expression of T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) in the colonic mucosa and/or the peripheral blood of children with Crohn's disease during anti TNF-α (infliximab) therapy.
"The purpose of the study is to compare the effects of methotrexate (MTX) alone or in combination with intravenous (IV) methylprednisolone (MP) or infliximab (IFX) on MRI-detected synovitis, bone edema and erosive changes in early rheumatoid arthritis (RA) patients."
"CMAB008 is an infliximab biosimilar candidate. The host cell of Remicade is mouse myeloma SP2/0 cell, however, the host cell of CMAB008 is CHO (Chinese hamster ovary cell). It seems that CMAB008 has lower immunogenicity and higher safety, because Remicade comprises more complex-type and hybrid-type glycans than CMAB008. However, it is not yet known whether CMAB008 is not inferior to Remicade. This randomized, double-blind trial investigates the efficacy and safety of CMAB008 for moderately to severely active rheumatoid arthritis, compared to Remicade."
"The goal of the present study is to evaluate the best regimen for infliximab monotherapy, and to evaluate if limited combination therapy with IFX and an Immunomodulator for the first 6 months of therapy, in prior Immunomodulator failures, is superior to monotherapy with Immunomodulator cessation from the second infusion, in preventing loss of remission to IFX."
"This is a Phase II, randomized, active-controlled, double-blind, double-dummy, parallel-group, multicenter study in the United States enrolling patients with active RA. The study will enroll approximately 290 patients at approximately 130 sites."
"Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory disease and TNF-alpha has been recognized as a triggering cytokine in the induction of joints inflammation and is involved in the pathogenesis of RA.||Treatment for RA aims to reduce disease activity, prevent or manage joint deterioration and lower the risk of major comorbidities such as heart disease and stroke.||The strategy of targeting cytokines has significantly increased RA patient outcomes. Therefore management with biological disease-modifying antirheumatic drugs ""bDMARD"" (Etanercept, Infliximab, Adalimumab) should be considered, If the treatment goal is not met with the first conventional synthetic drug modifying antirheumatic drugs (csDMARD) strategy, or if there are poor prognostic factors.||The multi-biomarker disease activity test could be used to help standardise individual treatment decisions, especially in patients who failed to respond well to the traditional treatment.||Iraq does not currently have specific guidelines, which might pose a risk to patients' safety. More data about the choice of bDMARD is needed in terms of tracking therapeutic response, or whether TNF or other pro-inflammatory cytokines like interleukin-6 (IL-6) is the main factor for the development and severity of RA.||These data are important to improve the overall status of the patient, better choice of treatment and biomarkers to detect.||There is limited information on the treatment patterns of rheumatoid arthritis (RA) across Iraq including the Kurdistan Region. Therefore, the aim of this research is to evaluate the efficacy, and clinical responses of RA patients who have been treated with different anti-TNF, as well as on answering the research hypothesis, Can plasma TNF-alpha and IL-6 be used as markers of therapeutic response to TNF alpha antagonist in patients with RA?"
"The purpose of this long-term observational study is designed to collect additional information on incidence of cancer and cause of death among patients who have participated in clinical trials of infliximab in the treatment of COPD. Patients must have received at least 1 dose of study agent (ie, placebo or infliximab) in the primary studies to be eligible for participation in this long-term follow-up study. Information on deaths and cancers will be collected twice yearly for a period of 5 years from each patient's last safety visit in the primary study."
"This is a prospective, single-arm, post marketing observational study in adult patients with active rheumatoid arthritis (RA) who are discontinuing treatment due to lack of efficacy, intolerance or to an incomplete response with either infliximab or etanercept.||The aim of this post-marketing observational study is to obtain data on clinical outcomes, compliance and tolerability to determine the effectiveness of switching from infliximab or etanercept to adalimumab. In this cohort, the different treatment strategies are to be studied in the context of the routine clinical practice in the different participating places."
"This is a Phase 3b, multicenter study of the efficacy of golimumab 2 mg/kg IV in subjects with active rheumatoid arthritis who are receiving methotrexate and have inadequate disease control (defined as an erythrocyte sedimentation rate [ESR]-based Disease Activity Score in 28 joints [DAS28] ≥ 3.2 and ≥ 4 swollen and ≥ 4 tender joints) despite current anti-TNFα therapy with infliximab 2 - 4 mg/kg every 4 weeks, 2 - 5 mg/kg every 5 weeks, 3 - 6 mg/kg every 6 weeks, 3 - 7mg/kg every 7 weeks, or 4 - 8 mg/kg every 8 weeks.||To be eligible for participation, subjects must have previously demonstrated initial and/or temporary improvement in disease signs and symptoms, who have since exhibited a diminished response despite continued treatment. It is estimated that 200 subjects will be enrolled in the study at approximately 85 global sites."
The purpose of this study is to assess equivalence of pharmacokinetics between NI-071 and infliximab(the comparator) in Japanese healthy volunteers
The purpose of this study is to investigate similarity between NI-071 and infliximab(the comparator) in terms of efficacy in patients with Rheumatoid Arthritis not adequately responding to Methotrexate.
"To demonstrate that CT-P13 is equivalent to China-approved Remicade at Week 14, in terms of efficacy as determined by clinical response according to the change from baseline in disease activity."
"The FIN-RACo trial is an investigator initiated multicenter (n=15 centers in Finland) prospective study on the treatment of patients with early rheumatoid arthritis (RA) with combination therapy with disease modifying antirheumatic drugs starting with methotrexate, sulphasalazine, hydroxychloroquine and prednisolone (COMBI). During the first 6 months, the patients are randomized to treatment with infliximab/placebo added on the combination treatment. The study is prospective for 5 years, with extension to 10 years. The target is to induce remission in both treatment arms. To reach this target, the investigators use frequent changes of doses and anti-rheumatic drugs and use of intra-articular glucocorticoid injections. The primary endpoints are the proportions of patients with remission at 2 and 5 years in both treatment arms."
The purpose of this observational study is to assess the safety and effectiveness of biosimilar Infliximab in patients with inflammatory bowel disease (IBD) in Saudi Arabia where no visits or intervention(s) additional to the daily practice will be performed.
"Anti-TNF treatment (infliximab (IFX), adalimumab (ADA)) has become standard therapy for refractory pediatric and adult Crohn's disease (CD) patients, and is used for the induction (primary response) and maintenance of remission. When effective, clinical and endoscopic remission is reached within weeks. However, primary non-response is observed in 20% of pediatric patients, and in 40% of adult CD patients, suggesting a more robust acute response to anti-TNF therapy in children as compared to adults.During maintenance treatment, 60 - 80% of patients have secondary loss of response, necessitating dose adjustments to maintain clinical response. Anti-TNF treatment is also increasingly used in ulcerative colitis (UC), and has been shown to induce remission in active disease. For UC, the comparison between the efficacy in children versus adults is more difficult to report as studies in children are scarce. Anti-TNF treatment is associated with rare but potentially fatal side effects, infusion reactions, and is an expensive treatment. To avoid overtreatment it is necessary to early identify non-responders to treatment, and therefore it is important to develop predictive biomarkers of treatment response."
"Inflammatory bowel disease (IBD) and psoriasis (Ps) are common, chronic, immune- mediated barrier diseases with shared inflammatory pathways. Current therapeutic interventions with anti-cytokine antibodies (TNF-α, IL-23/IL-12) reflect the intent to disrupt specific pathways of inflammatory immunopathology. Individual responses to biological treatment can be thereby be exploited in a systems biology approach that employs a targeted mechanism of action (MOA) to decipher molecular signatures of therapeutic responses in the context of a distinct disease entity. Using a translational approach to investigate clinical and molecular phenotypes during therapeutic interference with cytokine signaling and leukocyte trafficking, the investigators aim to trace common and unique signatures of drug- and therapy-specific responses.||Patients will undergo endoscopic evaluation of the mucosal surface and gastrointestinal wall by conventional HD-colonoscopy, endoscopic ultrasound and confocal laser endomicroscopy prior to and during specific therapies with biologicals. In parallel, mucosa samples will be obtained to define molecular phenotypes during the course of therapy."
"Prior to the first infusion, patients will be randomized into one of two groups (placebo or infliximab). All patients will continue to receive the same does of methotrexate (MTX) during the study as received prior to the study. The objective of the study is to evaluate the efficacy and safety result of infliximab with Korean patients in reducing clinical signs and symptoms of rheumatoid arthritis (RA) at 30 weeks following the onset of treatment and to review whether the result is comparable to the result of the ATTRACT trial."
The goal of the present study is to evaluate if addition of methotrexate can restore remission after loss of response to infliximab after dose escalation.||another goal is to evaluate if low dose methotrexate can maintain remission achieved by regular dose methotrexate by 6 months.
"This is a prospective, safety surveillance registry in participants with moderate-to-severe active ulcerative colitis (UC)."
"The immunogenicity of anti-tumor necrosis factor alpha (anti-TNF) therapy in inflammatory bowel disease (IBD) is an important cause of loss of response to therapy that may lead to escalation of dose or discontinuation of therapy. Antibodies may develop to infliximab (ATI) or to adalimumab (ATA) and cause this loss of response, also known as a secondary loss of response. An alternative approach is the addition of immunomodulator (IM) therapy to counteract the antibody response and regain efficacy of the biologic medication. The investigators' goal is to treat patients' who have lost response to adalimumab or infliximab with an immunomodulator with the goal of eliminating the circulating antibodies to the anti-TNF and restoring efficacy."
To determine whether treatment of patients who have toxic epidermal necrolysis with a drug called remicaide increases the number of patients who are alive 30 days laters.
"Goal is to prospectively determine if stool calprotectin and change in bowel wall thickness and hyperemia, as seen on small bowel ultrasound, at week 0, 14, and 54 can be used to predict response at week 54 to infliximab in pediatric patients with small bowel Crohn's Disease."
"Approximately 3 million people in the United States are living with inflammatory bowel disease, which includes Crohn's Disease, with many of those being young children and adolescents. Physicians need better ways to inform decisions on treatment.||The main reason for this research study is to determine if a computer program that formulates a dose based on a patient's blood testing results can better achieve the optimal drug level as compared to standard dosing."
This study is to assess noninferiority in efficacy and to assess overall safety of CT P13 compared to Remicade in patients with active Crohn's disease up to Week 54.
"This registry is a multi-center, prospective, observational program that will gather and analyze data on subjects with Crohn's disease being treated with Remicade® as per approved product monograph in Canada. In contrast to a controlled clinical trial, there is no imposed experimental intervention and treatment with Remicade® is determined solely by the subject's physicians. Thus, the data captured and reported in this registry will reflect a ""real world"" approach to the treatment of Crohn's disease with Remicade®."
"PHASE : IV TYPE OF STUDY : With direct benefit. DESCRIPTIVE : Multicentre, randomized, open label study. INCLUSION CRITERIA : Acute severe ulcerative colitis. OBJECTIVES : To compare the efficacy and safety of early administration of the combination therapy with infliximab and azathioprine with steroids and azathioprine in patients with acute severe ulcerative colitis treated with intravenous steroids.||STUDY TREATMENTS : All patients :||Intravenous steroids (0.8 mg/kg/day of methylprednisolone or equivalent) for 5 days.||Combination therapy arm:||Infliximab 5 mg/kg plus Azathioprine 2-2.5 mg/kg/day.||Azathioprine arm:||Steroids tapering for 3 months and Azathioprine 2-2.5 mg/kg/day."
"Crohn's disease (CD) is an incurable debilitating disorder affecting an increasing number of children. The etiology remains elusive, but a genetically determined aberrant immune response against microbiota appears to be responsible. TNFα plays a pivotal role in the cytokine cascade of the inflammatory process and mediates multiple processes central to the pathogenesis of CD. The natural history of pediatric CD is characterized by recurrent flare-ups that severely impair patients growth, pubertal development and nutritional status. Epidemiological observations have shown that the course of CD, despite conventional treatment, inevitably progresses to the development of severe complications and surgery. Infliximab is the most widely used biological agent in moderate-to-severe pediatric CD. At present biologics are used after the failure of conventional drugs (step-up approach) and represent the peak of the CD therapeutic pyramid. The early use of biologics (top-down approach) has been demonstrated to be effective in adults with CD. The project aims at evaluating if a top-down approach may achieve mucosal healing before irreversible tissue damage present in late CD and thus alter the natural course of the disease, compared to the conventional approach. The study can also add information about the safety of infliximab used as first-line therapy and may add data on the benefit and costs of a reversal of the traditional therapeutic pyramid in pediatric CD, guiding the clinician in deciding in whom, when and how to introduce early aggressive treatment in daily practice."
Capsule endoscopy has been shown to be the first-line endoscopic procedure for small bowel disease. This study was aimed to compare the performance between the frequency-altering AKE-1 capsule and the Pillcam SB2 in patients with suspected small bowel disease.
"There is little data published on the long term durability of infliximab in pediatric patients. In particular a focus on durable remission, frequency of dose/frequency change and switch within class. Moreover 10 years of safety experience is rarely reported in children.||The overall objective is to evaluate the persistence of infliximab as well as dosing strategies in pediatric inflammatory bowel disease (IBD) patients and safety of infliximab Regarding persistence of infliximab the investigators will be focusing on the proportion of patients who continue to have a durable response or remission to infliximab.||The investigators will be assessing this by measuring the frequency of dose escalation, proportion of patients needing frequency change and proportion of patients switched to adalimumab or certolizumab.||Safety outcomes will focus on frequency of malignancies, infections and immunogenecity"
"This study is aimed to assess the hypothesis that instillation of fibrin glue with the induction of local conditions using Infliximab, may be useful in the treatment of perianal Crohn's disease."
"Patients with rheumatoid arthritis who have been well controlled with methotrexate plus infliximab may remain in remission or low disease activity without infliximab. And the chance of sustained remission increase by the addition of another DMARD, bucillamine, at the time of discontinuing infliximab. The BuSHIDO trial is the prospective, randomized, controlled study comparing MTX monotherapy and MTX plus bucillamine combination therapy as to the rate of disease flare after discontinuing infliximab."
"This study is designed to collect tissue samples from the biopsy specimen that was used to diagnose hepatosplenic T-cell lymphoma (HSTCL), additional patient information, and if possible, to obtain additional samples including a single blood sample, a buccal swab sample and/or a bowel tissue sample. Samples obtained will be stored by the sponsor for future testing. In addition, demographic and clinical patient information will be collected. The study will be conducted in North America. Patients eligible for enrollment include males or females with IBD of any age who have a confirmed diagnosis of HSTCL. Patients will be identified through the sponsor's adverse event reporting systems. Cases reported to the sponsor's Medical Information Center will be queried to ascertain if the reporter is interested in participating in the study. Where appropriate, cases may also be identified through the sponsor's new or on-going clinical trials and registries. Samples may be collected from living patients or from stored tissue of deceased patients. This study will not restrict or introduce any therapeutic interventions, including medications. All patients will continue to be managed by their personal physicians. No healthy subjects will be enrolled in this study."
"Small bowel ultrasound (SBUS) is emerging as a well tolerated, non-invasive, radiation free, low cost measure to assess inflammatory bowel disease (IBD), and is being used as first-line imaging in Europe. SBUS findings have been shown to correlate with endoscopic findings, and a small number of recent studies have looked at change in bowel wall thickness (BWT) in response to anti-tumor necrosis factor (anti-TNF) therapy. However, the use of SBUS to detect response to anti-TNF therapy has not been tested in pediatric patients. The purpose of this study is to apply the use of SBUS to pediatric patients with Crohn's disease and to assess response to treatment with infliximab. The investigators will also measure C-reactive protein and fecal calprotectin at baseline, and additionally measuring IFX levels and anti-infliximab antibodies (ATI) at week 14 to assess change in biochemical response to infliximab treatment, as well as correlation between these markers with changes in patient reported outcomes via a weighted pediatric Crohn's disease activity questionnaire (wPCDAI) and changes in BWT. This study is novel in that it will be the first study in pediatric patients to use SBUS to assess response to IFX therapy, and will also be the first study to correlate SBUS findings with therapeutic drug monitoring (TDM). This study has the potential to propagate the use of SBUS in the pediatric population, as the use of TDM in concert with small bowel imaging post-induction will allow the investigators to tailor therapy early in the treatment course."
"Specific Aim 1. To determine the transcriptome of peripheral blood mononuclear cells isolated monocytes and target tissues in IMIDs.||Specific Aim 2. To analyze the change in gene expression profiles in patients with Crohn's disease, psoriatic and rheumatoid arthritis before and after infliximab therapy."
"The first 12 weeks of this study will compare the efficacy of etanercept 50 mg once-weekly to placebo in subjects with rheumatoid arthritis who have not responded well to infliximab or adalimumab plus methotrexate. This comparison will be performed for all subjects and separately for subjects who are anti-drug antibody positive for one of these medications. From week 12 to week 24, all subjects will receive etanercept 50 mg once-weekly. The effect of anti-drug antibody status on the efficacy of etanercept as well as the safety profile of etanercept in these subjects will also be evaluated throughout the study."
TNF alfa blockers are widely used for treatment of severe psoriasis. These biologics are well-tolerated with few side effects.||Unfortunately not all patients respond adequately to treatment with tnf alfa blockers. Some do not respond at all while others respond initially but gradually lose effect despite increased dose and more frequent administration.||The cause of treatment failure is largely unknown and it may be production of tnf-alfa neutralizing antibodies. This has been demonstrated in patients with rheumatoid arthritis and inflammatory bowel disease who lost response after treatment with tnf-alfa blockers.
"Prospective, multicentre trial which the biologic treatment will be initiated by clinical indication. The treatment selection anti-TNFα (infliximab, adalimumab or golimumab), vedolizumab and ustekinumab will be made at the discretion of the clinician. There will be no random assignment of treatment. The drugs will be used in the approved indications and conditions of use."
"Background: The treatment of inflammatory bowel diseases (IBD) is based mainly on 3 compounds: 1- 5 aminosalysilates . 2- immunomodulators (Azathioprines). 3- Biologic therapies (Infliximab, Adalimumab) . There are no established data in the literature whether these therapies effects sperm quality. Given that a large number of the patients are young men in the reproductive stage of their lives , It of importance to investigate these effect.||Aim: To investigate the effect of chronic treatment of any of the three therapy mentioned above, on sperm quality ."
The objective of the SMART trial is to compare a combination therapy using azathioprine and subcutaneous infliximab versus ileocecal resection in patients with symptomatic small bowel Crohn's disease.
To assess the clinical efficacy of subcutaneous (sc) certolizumab pegol administration over 26 weeks in patients suffering from Crohn's Disease (CD) and previously treated with infliximab
Utilization of health resources in a testing based strategy versus an empiric dose escalation strategy to manage Crohn's disease and Ulcerative Colitis in subjects with loss of response to infliximab or adalimumab.
The purpose of this study is to determine if PF-06687234 is effective and safe as add-on therapy to infliximab in subjects with active ulcerative colitis who are not in remission.
"The purpose of this study is to evaluate the proportion of Rheumatoid Arthritis (RA) subjects achieving a ""good"" or ""moderate"" DAS28 response (EULAR28 criteria) at Week 16 with etanercept 50 mg subcutaneously (SC) once weekly in patients who have failed infliximab."
"The primary objective of this study is to make adalimumab available to patients suffering from moderately to severely active Crohn's Disease who have failed to respond to, lost response to, or are intolerant to infliximab, and to evaluate safety"
The purpose of this study is:||To ascertain whether the quantitative assessment of enhancing synovial volume and perfusion indices on serial Magnetic Resonance Imaging (MRI) examination are useful indicators of responsiveness to treatment in early Rheumatoid Arthritis (RA) using biologic therapy and Methotrexate (MTX) compared with Methotrexate(MTX) alone.|To assess the cost-effectiveness of Tumor Necrosis Factor (TNF) blockers compared with Methotrexate(MTX) monotherapy for Rheumatoid Arthritis(RA).
An open-label multi-center single-cohort study to assess the safety and efficacy of certolizumab pegol for the treatment of signs and symptoms of active Crohn's disease in Greek patients who have previously responded to infliximab but who no longer have a sustained response or became intolerant to infliximab
The purpose of this study is:||To elucidate the immunomodulating properties of anti-TNF-α therapy in patients with psoriatic arthritis (PsA).|To ascertain whether magnetic resonance imaging (MRI) is a sensitive tool in measuring early response after therapy with anti-TNF-α in the PsA wrist using the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) guidelines for rheumatoid arthritis (RA).|To assess whether the lipid and other cardiovascular risk profiles would improve after anti-TNF-α therapy in patients with PsA.
"During transplant surgery, there is a period of time when a donated kidney is removed from a donor's body and stored until the time of the transplant surgery. The storage procedure results in buildup of various proteins within the kidney that can injure the donated kidney after it is transplanted. One of these proteins is tumor necrosis factor-alpha (TNF-alpha).||The purpose of this study is to evaluate whether taking infliximab, which blocks tumor necrosis factor alpha (TNF-alpha), just prior to transplant surgery, along with usual transplant medicines will protect the donated kidney from damage caused by TNF-alpha and help keep the transplanted kidney healthy for a longer period of time."
Loss of total mass of muscles (catabolism) is a serious clinical problem in patients with active inflammatory bowel disease (IBD). The investigators have earlier shown that the liver plays an important role in this stress-catabolism by increasing the production of urea during the inflammatory process.||The purpose of this study is to examine the effect of the anti-inflammatory drugs prednisolone and infliximab on the regulation of the urea synthesis in patients with active ulcerative colitis and Crohn's disease.
"RATIONALE: Infliximab may help improve energy levels in patients who have undergone treatment for breast cancer.||PURPOSE: This phase II trial is studying how well infliximab works in treating cancer-related fatigue in postmenopausal women who have undergone treatment for stage 0, stage I, or stage II breast cancer."
"Background: It remains uncertain whether vitD3 supplementation is beneficial for remission of Crohn's disease (CD). The influence of vitD3 supplementation on Infliximab (IFX) efficacy was retrospectively analyzed in Chinese CD patients. Methods: Patients with moderate-to-severe CD, who were bio-naïve and prescribed with IFX treatment for at least 54 weeks were recorded. VitD3 supplementation was defined as patients additionally took oral vitD3 (125 IU/d) within 3 days after the first infusion and persisted in the whole follow-up period. Disease activity was assessed using Harvey-Bradshaw Index (HBI). Serum cytokine profiles were quantitatively analyzed in a subset of all patients at baseline and 54-week after intervention."
"Study type : A 30 months, multicentre, open-label strategic randomized controlled trial||Population : Chron's Disease (CD) patients with an i2 endoscopic postoperative recurrence in the year following ileocolonic resection (6-12months after ileocolonic resection).||Treatments :||Stratification at inclusion according to prophylactic therapy.||Patients randomized in 2 arms:||Status quo arm: if the patient received no prophylactic therapy, no treatment will be started; if the patient received a prophylactic therapy, the same will be continued at the same dose.|Therapy escalation arm: infliximab-CT-P13 will be started with two intravenous infusions of 5 mg per kg bodyweight at week 0 and week 2 and subcutaneous injections of 120 mg every 2 weeks from week 6 onwards.||Main objective : To evaluate the proportion of CD patients without endoscopic postoperative recurrence (i0-i1) at 12 months in the arm receiving therapy escalation compared to status quo arm in patients having an i2 endoscopic postoperative recurrence 6-12months after ileocolonic anastomosis with restoration of faecal stream."
The aim of the study is to evaluate the efficacy of new immunosuppressive protocol based on two applications of anti-CD52 MabCampath (Alemtuzumab) a single dose of anti-TNF-α Remicade (infliximab) monoclonal antibodies in the early posttransplant period followed by either monotherapy based on tacrolimus or sirolimus.
The aim of this study is to understand which therapies will suppress effector cells and promote regulatory T cells and To test whether patients with a better response to therapy and longer psoriasis-free periods develop a higher numerical ratio of regulatory to effectors T-cells and/or regulatory cells more able to suppress the effectors.
"This study monitors the efficacy and safety of Golimumab in maintaining deep remission and quality of life in Ulcerative Colitis patients in deep prolonged remission with Infliximab. Patients will be followed up for one year and they will be assessed with biochemical tests (C-Reactive Protein , Full Blood Count , Faecal Calprotectin),endoscopic evaluation (MAYO Score) and finally histologically."
"A study to describe the one-year persistence in participants treated by Flixabi (infliximab) or Imraldi (Adalimumab) as prescribed by the physician for each of the 5 following indications: Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Crohn's Disease (CD) [adults and children] and Ulcerative Colitis (UC) [adults for both treatments and children only for Flixabi]."
The study prospectively compares two treatment algorithms for newly diagnosed Crohn's disease: one 'aggressive' treatment with early introduction of immunomodulators and biologicals and one 'standard treatment' with corticosteroids and only later introduction of immunosuppressives and biologicals if disease activity requires that.
Anti-TNF therapy induces intestinal wall remodeling that correlates with clinical response and can be detected in patients undergoing serial computed tomography enterography (CTE).
"Infliximab and other TNF-inhibitors have revolutionised the treatment of several immunological inflammatory diseases. Still, more than half of the patients either do not respond sufficiently to infliximab therapy or loose efficacy over time. The large individual variation in the serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be main reasons for these treatment failures. An individualised treatment strategy based on systematic assessments of serum drug concentrations, therapeutic drug monitoring, has been proposed as a clinical tool to optimise efficacy of infliximab treatment. Therapeutic drug monitoring seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy still remain to be shown. The NOR-DRUM study is planned as a national, randomised controlled multicentre trial in two parts aiming to assess the effectiveness of therapeutic drug monitoring in order to achieve remission in patients with immunological inflammatory diseases starting infliximab treatment (part A) and in order to maintain disease control in patients on maintenance infliximab treatment (part B). The results of the NOR-DRUM study will hopefully contribute to an implementation of a personalised medicine approach to treatment with infliximab and other biological drugs."
"This study investigated the mucosal gene expression defects associated with active Crohn's disease (CD)and ulcerative colitis (UC), and studied the effect of infliximab induced downregulation of inflammation and mucosal healing on these abnormalities, using whole genome gene expression microarrays."
"The purpose of this study is to describe infliximab and abatacept dosing patterns (i.e., dosing amount and frequency) and costs among a population of managed care enrollees with RA. This study will also identify changes in infliximab and abatacept dosing over time and the implication these changes may have on the costs of medication administration."
The goal of this study will be to assess the safety and efficacy of high-dose interval Vitamin D3 therapy in children and young adults with Inflammatory Bowel Disease being treated with serial Remicade infusions.
"Comparative, randomized study patients are scheduled to have two capsule endoscopies within 2 to 14 days from each other using two different endoscopies the Pillcam SB2 (Given Imaging, Israel) and the Capsocam (Capso Vision Saratoga United States) The order in which the devices are administered is randomly allocated."
"assessment of inflammatory bowel disease patients in activity and remission by abdominal ultrasound examine non-invasive and in physiological condition by measuring the colon wall thickness in diagnosis and follow up the patient also including extra intestinal features such as the splanchnic vessels,mesentery and lymph nodes . Doppler u.s can evaluate bowel wall vascularity In activity and remission . peripheral hemogram in relationship to activity inflammatory bowel disease asses anemia ,increase monocyte and decrease mean platelet volume( MPV) . also,the investigator will evaluate the outcome of different lines of treatment traditional and biologic therapy (response to treatment,times of activity and complications)"
"The purpose of this study is to evaluate efficacy of golimumab in inducing clinical remission as assessed by the Mayo score, in pediatric participants with moderately to severely active ulcerative colitis (UC). In addition, the safety profile of golimumab, in pediatric participants with moderately to severely active UC will be assessed."
"The Swefot trial was designed to compare two treatment strategies for patients with early rheumatoid arthritis (less than 1 year symptom duration): the use of a combination of traditional antirheumatic medications (DMARDs), versus a combination including a newer ""biological"" anti-TNF medication. In order to make this trial consistent with current practices in rheumatology, all patients were first given the most commonly used antirheumatic medication, methotrexate (MTX). After 3-4 months those patients who had not responded adequately to this treatment were randomized to receive either MTX plus sulfasalazine plus hydroxychloroquine, or MTX plus infliximab. Again, to be truly life-like, the trial allowed patients who could not tolerate one of the added medications to switch in treatment - but keeping with the same strategy - so that sulfasalazine plus hydroxychloroquine could be replaced by cyclosporin A, and infliximab by etanercept. The primary outcome in this trial was the percentage of patients who, after one year of treatment, achieved a ""good response"" as defined by Eular."
"This is a Phase 1b, open-label study of immune checkpoints inhibitors Nivolumab+Ipilimumab administered in combination with the anti-TNF-α either Infliximab or Certolizumab, in patients with advanced melanoma."
"Janssen Inc. plans to collect data on about 3000 to 5000 infliximab infusions per year, starting in the third quarter of 2005. It is expected that about 12 sites from the Remicade Infusion Network (R.I.N.) will participate. This registry will be a multicentre, prospective, observational program that will gather and analyze data on subjects being treated with infliximab."
"This 14-week study will observe the gene expression of certain immune cells in patients with rheumatoid arthritis who receive etanercept, infliximab, and adalimumab. Patients at the National Institute of Rheumatology and Physiotherapy, Budapest, who are already scheduled to receive an anti-TNF agent will be asked to participate in this study. Patients will receive their treatment (etanercept, infliximab, or adalimumab) as scheduled, and have blood samples collected during the study and analyzed by the laboratory. Patient's response to their treatment will also be studied based on x-rays and other examinations."
The purpose of this study is to determine which early infliximab pharmacokinetic level is most associated with clinical remission at weeks 30 and 54 in pediatric IBD patients.
"This is an open label randomized trial to evaluate the efficacy and treatment duration with vedolizumab to patients with immune mediated colitis. The trial will include 82 patients randomized into two arms, either standard treatment with prednisolone (plus infliximab in severe cases) or vedolizumab treatment up front."
"Post-authorization, prospective and unicenter clinical trial, in which patients with UC will be included. The treatment with anti-TNFα (infliximab, adalimumab or golimumab) or JAK-inhibitors (tofacitinib) will be initiated by clinical practice and the choice will be made at the discretion of the investigator at the center where the patients will be recruited (Hospital Universitario de La Princesa). In the case of the group of patients treated with tofacitinib, the selection will be made following the action protocol implemented in our center, in which this drug is usually reserved for those cases refractory to anti-TNFα and/or vedolizumab. There will be no random assignment of treatment. The drugs will be used in the approved indications and conditions of use."
"The purpose of this study is to evaluate the long-term safety and clinical status of pediatric patients with Inflammatory Bowel Disease (IBD). Particular attention will be directed to recording safety outcomes reported in association with infliximab and other prescribed IBD therapies. In addition, information on disease status and quality of life will be collected."
"This is Phase 3, Randomized, Placebo-controlled study to demonstrate superiority of CT-P13 over Placebo SC in Patients With Moderately to Severely Active Crohn's Disease"
"This is Phase 3, Randomized, Placebo-controlled study to demonstrate superiority of CT-P13 over Placebo SC in Patients With Moderately to Severely Active Ulcerative Colitis"
"Many studies reveal that infliximab (IFX, an immunoglobulin gamma-1 antibody)can response well to Crohn's Disease(CD) patients who are intolerant of corticosteroids and immunosuppressant,or steroids-dependent .More over,A complex fistula in CD is an indication for early IFX therapy in conjunction with surgical drainage.Some papers claim that IFX may prevent enterectomy CD patients from relapsing. Those with risk factors which at diagnosis associated with "" disabling disease ""include age < 40 years, initial need for steroid therapy, and the presence of perianal disease are recommended to use IFX early.||IFX is approved by State Food And Drug Administration(SFDA) in 2007 ,but the safety is still controversial by then.Some studies proclaim that the side effect may be infections,acute infusion reactions,anaphylactic reactions,autoimmunity,drug-induced lupus,congestive heart failure,abortion and demyelination,etc.||So some problems still need to be settled as follows:1)all the the infliximab dates are from other countries,there is rare date from the Chinese,especially the large quantity of random controlled studies and the CD patients with enterectomy.2)despite of the large number of databases from the international ,when to stop and the predictor of the response is still obscure.3)The high cost of IFX may hinder its applications,especially for the moderate to severe active CD patients who take mesalazine and/or immunosuppressant to maintain remission.In addition,the pathogenic age segments in the occurence of CD: from 15~ 50 years old ,so they suffer from the disability of self-improvements.||The main object of the clinical trial is to complete the database of Chinese CD patients ,especially the safety and efficacy of IFX and those with enterectomy.Then we can record the clinical manifestations of the moderate to severe CD patients with the use of IFX or conventional drugs,including the dose,course and Concomitant treatment.We can also study the predictor and the appropriate time to stop using IFX .We can make the mode of cost-benefit help the patients choose the best project."
"The role of exclusive enteral nutrition (EEN) in the induction of remission in pediatric patients with Crohn's disease had been well documented. But the role of EEN in children with Ulcerative Colitis (UC) was not clear. In this study, EEN will be combined with corticosteroids or infliximab in the induction of remission in pediatric UC patients with moderate to severe disease activity. The mucosal healing rate at week12 will be compared between the two groups (combine with EEN group VS non-combine group)."
The purpose of this study is to analyze the frequency of the formation of antibodies against three different anti-TNF biologic agents used for the therapy of juvenile idiopathic arthritis.
"Hyrimoz™ was developed as a biosimilar to HumiraTM (INN: adalimumab) and Zessly™ was developed as a biosimilar to RemicadeTM (INN: infliximab). Within the Biosimilar Development Program of Hyrimoz™ and Zessly™, two clinical confirmatory efficacy and safety studies were conducted: Hyrimoz™ in plaque psoriasis and Zessly™ in rheumatoid arthritis. Both confirmatory Phase III studies demonstrated equivalent efficacy and similar safety and immunogenicity of Hyrimoz™ to HumiraTM and Zessly™ to RemicadeTM, respectively.||The current study is designed to provide a systematic and consistent overview of the real-world data in biologic-naïve patients with moderate-to-severe Crohn's disease (CD). The data collected in this observational trial will be used to increase the knowledge of the effectiveness of Hyrimoz™ and Zessly™ in clinical routine care in patients with moderate-to-severe CD."
Molecular imaging with infliximab antibody with FITC has the potential to predict therapeutic responses to infliximab antibody and can be used for personalized medicine in ulcerative colitis.
"The purpose of this study is to determine the safety, tolerability, and efficacy of natalizumab in individuals diagnosed with active Crohn's Disease that are not in remission (CDAI greater than/equal to 150) and are currently taking Remicade. It is thought that natalizumab may stop the movement of certain cells, known as white blood cells, into bowel tissue. These cells are thought to cause damage in the bowel leading to the symptoms of Crohn's disease.||Patients who complete this study may be eligible for long-term natalizumab therapy via extension protocol ELN100226-351."
Can genetic markers be used to predict anti-TNF response? A cohort was established to identify SNPs associated with anti-TNF therapy in patients with inflammatory bowel disease.
"Endocopic remission rates of moderate to severe ulcerative colitis are low. Biologics including Vedolizumab, infliximab, and adalimumab are effective in induction and maintainence of ulcerative colitis. The role of 5-ASA in promoting a higher rate of endocsopic remission is unclear. We aim to evaluate the efficacy of combination of 5-ASA and biologics in treating ulcerative colitis."
"The primary endpoint will be evaluated through the following variables: PUCAI score, IFX levels, and steroid treatment.||Clinical response to IFX will be evaluated through the PUCAI score. The response will be considered clinically significant if PUCAI points continue maintained below 30 during the study period. The IFX response will also be determined by IFX serum levels. A therapeutic IFX level, i.e. for achieving an adequate clinical response, is established above 6 μg/mL. Finally, the necessity, or not, of a steroid treatment during the study period will also be indicative of successful efficacy with GMA."
The primary aim is to evaluate if introduction of eHealth in its form of the web application Constant-Care (https://ibd.constant-care.com) could reduce the length of hospitalization in patients with acute severe Ulcerative Colitis treated with infliximab. This is relative to historical controls extracted from medical records.||Patients will self-measure on the web-application while hospitalized as well as after discharge. At the web-application different questionnaires are filled out and a fecal calprotectin (FC) analysis is performed on a smartphone. The final follow up is one year after admission.
"Crohn's disease and ulcerative colitis affect about 1.6 to 3 million people in the United States with many of those being young children and adolescents. Physicians need better ways to inform decisions on therapy selection and recognize ongoing intestinal injury while on treatment.||The main reason for this research study is to see if a blood test or stool test, which measures specific proteins, taken just before starting a new treatment for Crohn's disease can predict a patient's ability to achieve complete intestinal healing. The investigators also want to see if the intensity of gut inflammation can be detected by measuring a separate set of proteins in the blood."
The purpose of this study is to evaluate the effectiveness and safety of anti-TNF chimeric monoclonal antibody (cA2) compared to placebo in the treatment of patients with fistulizing Crohn's disease.
"Introduction Acute severe ulcerative colitis (ASUC) occurs in 15-25 % of all ulcerative colitis (UC) patients. Initial treatment with intravenous corticosteroids fails in 30-50 % of patients, for whom the next line of treatment is biological therapy or colectomy. Acute colectomy has a higher risk of morbidity and mortality than a scheduled colectomy. Data suggest that an accelerated administration of biological treatment in corticosteroid non-responders compared to clinical practice, 5-7 days with intravenous corticosteroids, may be superior in inducing disease remission, thus potentially avoiding acute colectomy. However, there are currently no patient friendly and objective diagnostic tool to preselect patients for such a treatment. The aim of this study is to examine if gastrointestinal ultrasound (GIUS) could preselect corticosteroid non-responders to biological treatment after 48 hours to increase effectiveness of the second line therapy and thereby reduce the morbidity and mortality of ASUC.||Methods and analysis The study is a clinician blinded observational multi-center study derived from the Department of Gastroenterology, Herlev Hospital, Denmark. Fifty ASUC patients will be included at the time of hospitalization and followed for 12 months. Baseline clinical activity scores, endoscopic scores, blood samples, fecal-calprotectin, vital parameters and GIUS measurements will be obtained prior to administration of intravenous corticosteroids. All examinations except fecal-calprotectin and endoscopy will be repeated at 48 ± 24 hours, 5-7 days and 3 months after treatment start. Endoscopic scores and fecal-calprotectin will be obtained after 3 months and an additional fecal-calprotectin after 6 ± 1 days. Treatment outcome will be registered at each event and after 12 months. Patients will be divided into corticosteroid responders and non-responders and compared to GIUS measurements at each event using non-parametric statistics (Mann-Whitney and Wilcoxon test) and time to endpoints by survival statistics (Kaplan Meier). ROC statistics will determine the best cutoff values for GIUS parameters for optimal sensitivity, specificity and accuracy.||Ethics and dissemination The study is approved by the National committee on health research ethics (H-18031264). Results will be published in relevant scientific journals and presented at international conferences. Fully anonymized data will be accessible from authors upon request."
"To characterize circulating DC subsets from healthy controls and IBD patients and to assess, following an ex vivo challenge, the effect of anti-TNF (infliximab, adalimumab and golimumab), anti-p40 -IL-12/IL-23- (ustekinumab) and anti-α4β7 (vedolizumab) immunomodulators on both the GI production of soluble immune mediators and the mucosal capacity to alter the recruitment capacity of circulating DC subsets. It is expected that such approach will provide further information on the action mechanisms of such therapies on IBD patients, allowing a better understanding of the pathophysiology of this disease and the identification of tissue-specific therapeutic targets, thus avoiding collateral problems associated with systemic immunomodulation."
"Ankylosing Spondylitis (AS) is a chronic painful progressive inflammatory arthritis of unknown etiology primarily affecting the spine and sacroiliac joints. In addition to formation of new bone leading to syndesmophytes and ankylosis; osteoporosis is also a prominent feature in AS-thus showing the paradox of new bone formation at abnormal sites coexisting with reduced bone mass & increased fracture risk. Osteoporosis is a common complication of AS, with an incidence between 18.7% and 62%. TNF alpha has a central role in disturbing this balance in bone metabolism--resulting in accelerated alveolar bone loss and decreased strength- i.e. osteoporosis. The investigators hypothesis that anti TNF therapy is effective in active AS resistant to conventional therapy and helps in improving the bone density and over all bone health."
"The primary objective is to assess if discontinuation of anti- tumor necrosis factor alpha (TNF) treatment in ulcerative colitis patients in sustained clinical remission, with the option to restart treatment in the case of relapse, is non-inferior to continued anti-TNF treatment. Secondary objectives are to assess the efficacy and safety of restarting anti-TNF treatment after a relapse"
This study compares the similarity of the proportion of subjects who achieved ACR20 at week 30 in the two groups.
"This is a prospective, observational, multicenter study conducted in adult patients with ulcerative colitis (UC) or Crohn's disease (CD). The study plans to recruit 300 subjects in the United States and Canada in which the participating physician has decided to treat with INFLECTRA. The study will evaluate treatment patterns, adherence, disease activity, remission status, relapse status, treatment satisfaction, and healthcare resource utilization. Patient outcomes will be assessed at four time points (quarterly) for approximately 52 weeks after the decision to initiate treatment with INFLECTRA."
"The purpose of this study is to evaluate the efficacy of TA-650 using Pediatric Crohn's Disease Activity Index (PCDAI) in pediatric patients with moderate to severe Crohn's disease after TA-650 administration at a dose of 5 mg/kg at week 0, 2, and 6, then every 8 week after week 14 up to week 46, and at a dose of 10 mg/kg if the effect is attenuated. The safety and pharmacokinetics are also evaluated."
"In March 2020, children exposed to the virus that causes the COVID-19 illness, SARS-CoV-2, presented with fever and significant inflammation about a month after exposure to the virus. Some children were sick enough to require care in the intensive care unit for what came to be known as Multisystem Inflammatory Syndrome-Children (MIS-C).The clinical presentation shared many features with Kawasaki disease (KD), a self-limited inflammation that can cause ballooning of the arteries of the heart. Thus, physicians reached for many of the therapies used to treat children with KD. Despite the surge of COVID-19 cases and children continuing to present with MIS-C, there are no data that guide the choice of therapy. Thus, the investigators have designed a study to determine which combination of therapies is most effective in helping children with MIS-C recover quickly."
"Vasculitis occur when the body's immune system, rather than protecting the body, attacks blood vessels, causing injury to the vessel and the part of the body it supplies with blood. Vasculitis is rare, and there are a number of different types, which can affect both adults and children. We treat vasculitis with steroids and drugs aiming to damp down the activity of the immune system, but they often cause side effects. Some patients do not improve with this treatment, or cannot tolerate it and their vasculitis worsens; this is known as refractory vasculitis. Patients with refractory vasculitis are at high risk of health complications from the disease and its therapy and are in need of newer more effective treatments with fewer side effects.||Biologics are drugs which are designed to precisely target parts of the immune system and may have fewer side effects. Biologics have been used for several years to treat vasculitis, particularly anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis or AAV. However, for many of the rarer types of vasculitis, and especially those vasculitis disease types that are not ANCA-associated, there is little information to support use of biologic therapies as effective treatments.||The purpose of this trial is to find out whether biologics are effective and represent value for money for participants with refractory vasculitis. The trial will include patients with Non-ANCA-associated vasculitis (NAAV)"
"Proposal for Sub-Study to be conducted with the WHO Solidarity Plus Trial:||Apart from the data been collected as per the WHO Solidarity Trial Plus protocol, Nepal Health Research Council will conduct a sub-study to evaluate some components which are felt to be important in the local context but have not been included as part of the Solidarity Trial Plus. Rather that conducting a separate study, the following components can be evaluated by collecting additional data as a part of sub-study in the local context."
"The objective of this study is to compare in very early polyarticular juvenile idiopathic arthritis (JIA) the efficacy, safety, and cost-benefit-ratio of three treatment strategies: biologic combination, combination of conventional disease-modifying drugs (DMARDs), and methotrexate alone."
"BACKGROUND/RATIONALE:||Treatment outcomes of patients with inflammatory bowel disease (IBD) have improved enormously during the past decade due to the use of anti-tumour necrosis factor (anti-TNF) therapy. As a result, 67 to 91% of paediatric patients and 66% of adult patients is still in sustained remission two years after the initiation of anti-TNF therapy. Prolonged use of anti-TNFs comes with disadvantages such as dose dependent susceptibility to infections and dermatological adverse effects. Preliminary, mostly uncontrolled studies suggest that dose reduction by dosing interval lengthening is a realistic option in a relevant proportion of patients with IBD, provided that intensive follow-up is applied.||OBJECTIVE:||To evaluate whether a faecal calprotectin (FC) guided strategy of anti-TNF dosing interval lengthening is non-inferior in maintaining remission in patients with IBD, compared with an unchanged dosing interval."
"Patients with spondyloarthritis, already treated by TNF blocker (adalimumab, etanercept or infliximab), and in stable low disease activity for at least 6 months, will be randomized into 2 groups: either keeping on their usual treatment with stable doses or progressive spacing of injections of their treatment. Follow-up will be done every 3 months during 12 months, with regular monitoring of disease activity and, in patients from the group ""spacing"", modification of the rhythm of injections according to health state and predefined protocol."
"This is a Phase I/III Study to Evaluate Efficacy, Pharmacokinetics and Safety between CT-P13 SC and CT-P13 IV in Patients with Active Rheumatoid Arthritis (RA)."
"ACTIV-1 IM is a master protocol designed to evaluate multiple investigational agents for the treatment of moderately or severely ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The research objectives are to evaluate each agent with respect to speed of recovery, mortality, illness severity, and hospital resource utilization. Each agent will be evaluated as add-on therapy to the standard of care (SoC) in use at the local clinics, including remdesivir (provided). The SoC may change during the course of the study based on other research findings. Comparisons of the agents among themselves is not a research objective.||The study population corresponds to moderately and severely ill patients infected with the coronavirus disease 2019 (COVID-19) virus. Recruitment will target patients already hospitalized for treatment of COVID-19 infection as well as patients being treated for COVID-19 infection in Emergency Departments while waiting to be admitted to the hospital. Patients both in and out of the ICU are included in the study population."
This study will assess the safety and efficacy of QAX576 if patients with fistulizing Crohn's disease.
The purpose of this study is to evaluate safety and efficacy of etanercept in patients with psoriasis who had an unsatisfactory response to adalimumab and infliximab.
"Crohn's disease (CD) is a chronic recurrent intestinal inflammation involving the whole digestive tract, with high disability rate, high surgical rate and high recurrent rate postoperatively. Preventing postoperative recurrence in CD patients is an important clinical problem needed urgent intervention. Azathioprine (AZA) and infliximab (IFX) effectively prevent postoperative recurrence in CD patients, but the postoperative recurrence rate is still as high as 41%. Oral supplement of n-3 polyunsaturated fatty acids (n-3 PUFA) owns the advantages of high compliance and low economic cost. We aim to evaluate the effect of routine treatment (AZA/IFX) combined with long-term dietary n-3PUFA on the prevention and treatment of postoperative recurrence of CD, which help optimize the treatment strategy for the prevention of postoperative recurrence."
The purpose of this study is to determine whether a diet intervention (the Fasting Mimicking diet) will help induce clinical and biochemical response to tofacitinib therapy or second line biologic therapy with ustekinumab or infliximab in patients with ulcerative colitis. Study period will be 8 weeks during induction of tofacitinib or ustekinumab or infliximab. The primary aims of this study are to determine clinical response and improvement in fecal calprotectin and C-reactive protein levels. Secondary outcomes will include assessment of changes in the stool microbiome.
"The aim of this prospective study is to evaluate the feasibility and efficacy of metoprolol, a beta-1 adrenergic receptor blocker, in the treatment of cytokine release syndrome (CRS) caused by chimeric antigen receptor T (CAR T) cell infusions, its effects on the serum levels of Interleukin-6 (IL-6) and other cytokines."
"The purpose of this study is to determine possible alterations in cardiac function in patients with Rheumatoid Arthritis and Ankylosing Spondylitis under anti-TNF therapy, without clinical heart disfunction at baseline, using highly sensitive non-invasive methods."
"The rationale for this study is to further explore if development of antibodies against TNF-α blocking agents is associated with reduced clinical effect/worsened clinical outcome. An important aspect of the study is to carry out an exploratory analysis of the immunogenicity of the 4 recommended TNF-α blockers in the treatment of RA in Denmark, using the same cell-based assay."
"Resistant hypertension (RH) is characterized by high blood pressure (BP) in spite of concurrent use of three or more antihypertensive agents of different classes, combined at optimal doses. Currently it has been largely discussed the influence of inflammation in RH. The BP variation promotes increased expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukins 1 and 6. It was showed that treatment with TNF-α inhibitor improves BP and endothelial function, and reduces arterial stiffness in patients with rheumatoid arthritis. Recently, it was demonstrated that TNF-α levels are increased in RH subjects compared to normotensives. This study aims to assess whether the acute inhibition of TNF-α changes hemodynamic parameters, such as mean BP levels in RH."
Clinical study of anti-tumor necrosis factor therapy in patients with Takayasu arteritis.||This study is single arm (anti Tumor necrosis factor therapy only) clinical trial. Enrolled patients will be 11
"The effectiveness of thalidomide in treating inflammatory bowel disease has been widely recognized. Meanwhile, many serious adverse drug reactions were notified， but no reports on ovarian reserve function.Therefore, this study was to investigate the influence of thalidomide on function of ovarian reserve."
"Inflammatory bowel disease(IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is characterized by chronic and recurrent nonspecific intestinal inflammation with high disability rate. During the past few decades, the prevalence of IBD is increasing, especially in developing countries, which brings great burden to patients themselves and medical insurance. Currently, biological medications such as TNFα inhibitors (infliximab, adalimumab, etc.), integrin receptor antagonist (vedolizumab) and interleukin 12/interleukin 23 inhibitor (ustekinumab) are commonly used in IBD treatment as well as traditional drugs such as glucocorticoid, immunosupressive agents and 5-Aminosalicylic Acid, and surgury. However, health-econimic analysis is lacking in Chinese IBD patients and more research is needed for making treatment choice.||Meanwhile, the etiology, disease progression and prognosis prediction has not totally been clarified. The efficacy prediction model of vedolizumab and infliximab has been analyzed, whose prediction markers include level of albumin, smoking, surgery history, fistula, etc. However, no model has included predictors concerning disease pathway or pharmacological pathway in patients accepting different therapy. So a model to predict IBD progression and prognosis concerning pharmacological pathway is going to be explored."
"A two-stage design. An open, non-randomized, 3+3 dose escalating scheme will be used in the first stage of the study. A randomized (1:1) phase II open label study of DSC compared to Investigator choice Best Available Therapy (BAT) in allogeneic hematopoietic stem cell transplant recipients with Grades II-IV steroid refractory acute graft vs. host disease in the second part of the study. Patients in each phase will receive 2 doses of DSC. In the second part (Phase II) additional doses (up to 6 doses) may be given depending on response.||No cross-over are planned in the second stage of the study."
"Phase 1 randomized, open-label, multicenter, parallel-group study designed to evaluate efficacy, pharmacokinetics and safety between CT-P13 subcutaneous (SC) and CT-P13 intravenous (IV) in patients with active Crohn's Disease (CD) and active Ulcerative Colitis (UC)."
The purpose of this study is to evaluate whether the risk of serious infections in rheumatoid arthritis patients with tocilizumab is higher than in those with tumor necrosis factor inhibitors using the nationwide real-world data.
"Steroids are still the first line treatment for established severe acute-graft-versus-host-disease (aGVHD), with a response rate of 30-50%, and there is no established and effective therapy for severe steroid-refractory (aGVHD). The outcome for patients is poor and overall survival low, with few patients alive at 2 years.||In the case of failure after corticosteroid treatment, different therapeutic options have been introduced as second or third-line strategies. In this scenario, infusion of ex vivo expanded mesenchymal stromal cells (MSCs) has emerged as an additional tool for treatment of GVHD.||The purpose of this work is conduct a study in patients with refractory and/or resistant GVHD corticosteroids treatment. It will be randomized into two groups: one group that will receive the MSCs and the other group will follow the acute GVHD steroid-resistant and/or refractory treatment according to the routines of the Bone Marrow Transplantation (BMT) service of Hospital de Clinicas de Porto Alegre. It will be evaluated aspects of immune recovery early after MSCs infusion."
"The efficacy of TNF alfa inhibitors in the treatment of psoriasis has been documented in many studies.||Their effect on dendritic cells has been scarcely studied. TNF- α has a central role in dendritic cell biology, both for their maturity and mobilization of peripheral tissues to secondary lymphoid organs.||The primary objectives of this study are:||To document absolute number, density of immune infiltrate and dendritic cells and inflammatory cytokines expression pattern (particularly IFN α and IL-32) in psoriasic lesions vs normal skin of the same patient|To describe changes in such cell numbers and expression patterns upon 16 weeks treatment with TNF alfa inhibitors."
"biological DMARDs may be stopped in Rheumatoid Arthritis (RA) patients treated with a combination of synthetic DMARD plus bDMARDs which are in persistent clinical remission. The research question of this study is, whether musculoskeletal sonography is a useful biomarker predicting a disease flare after cessation of bDMARD therapy."
"ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, are chronic, idiopathic, relapsing inflammatory conditions of the gastrointestinal tract. The mechanism is multifactorial and may result from the combined interaction of environmental, genetic, epithelial barrier defects, dysregulated immune responses, and microbial factors"
"The results of the SONIC trial represented a significant advance in the management of patients with chronic inflammatory bowel disease by demonstrating the superiority of the combination of an alpha TNF anti-TNF with immunosuppressive therapy in naive patients (infliximab and azathioprine) compared to monotherapy in terms of clinical and endoscopic remission (40% versus 22%, p = 0.017). The benefit of this combination therapy is both pharmacological (addition, or even synergy of the two treatments) and immunological (reduction of the risk of immunization to biotherapy).||Data on the use of immunosuppressive methotrexate treatment are divergent. Indeed, a previous randomized trial suggested that the combination of anti-TNF alpha including infliximab and methotrexate was no more effective than anti-TNF alpha monotherapy in patients with Crohn's disease. However, the superiority of this combination has been clearly demonstrated over monotherapy in rheumatology for a long time.||In practice, more and more practitioners are prescribing this combination (antiTNF and MTX) in IBD patients because of tolerance problems, particularly to azathioprine or in patients with a dual expression of their disease, both digestive and joint.||The interest of my thesis work is therefore to be able to clarify these grey areas and to be able to modify or comfort therapeutic choices in practice."
The goal of this study is to test whether adalimumab can induce clinical remission in subjects with active Crohn's disease who have been initially treated with infliximab and either lost response or discontinued its use as a result of intolerance to the drug.
"To quantify the incremental cost of infections in patients treated with etanercept, adalimumab or infliximab versus abatacept."
"The pharmacogenomics of the Colombian population with rheumatoid arthritis (RA), understood as the individual response to drugs depending on the genome of each patient, can be an explanation for the problems of effectiveness and safety that appear during the pharmacotherapeutic treatment of RA.||Currently, there are limited studies on the pharmacogenomics of the Colombian population; Therefore, it is necessary to identify and classify the genetic polymorphisms characteristic of Colombian patients with RA, which influence the response of methotrexate, infliximab, etanercept, adalimumab and thus contribute to precision medicine and medical prescription according to the Specificity of the genome of each patient.||This project aims to determine the association of genetic polymorphisms with the response to inhibitors of tumor necrosis factor alpha (TNFα) and methotrexate. To do this, a prospective study of cases and controls will be performed in patients in 3 hospital of Colombia with pharmacotherapeutic treatment of methotrexate, infliximab, etanercept, adalimumab, in monotherapy or combination therapy.||As a result, it is expected to contribute to the performance of specific genetic tests for RA and the generation of a pharmacogenomic basis of the Colombian population with RA."
"to investigate, whether one of the two alternative therapy strategies (antibiotic plus immunostimulation versus antibiotic plus immunosuppression) in chronic reactive arthritis is therapeutical superior to conventionel standardtherapy (DMARD).|to investigate, whether one or more of the different therapy strategies cause an altered detection of bacterial DNA in the joint or colon.|to measure the antigen-specific and -unspecific immune response (predominantly t-cell response) during therapy and correlate it with the clinical course.|to gain knowledge from these analyses and the clinical course concerning the pathogenesis and the point of attack for possible therapies in chronic reactive arthritis.|to compare cytokine-profiles of CD4- and CD8-positive T-cells from patients treated with infliximab to those treated with etanercept."
"The metabolic response to Crohn's disease, including increased proteolysis and lipolysis and changes in energy expenditure, plays a significant role in the resulting malnutrition from which these patients suffer. Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, has been found to be elevated in children with ulcerative colitis. TNF-alpha has been incriminated in the mechanism of weight loss in many different chronic diseases, and causes net protein and lipid catabolism. Anti-TNF-alpha antibody (infliximab) has been proven to be an effective therapy for ulcerative colitis.||The purpose of this study is to compare changes in protein and lipid metabolism, as well as resting energy expenditure, before and after therapy with anti-TNF-alpha antibody (infliximab) or corticosteroids in children with recurrent Crohn's disease. Performing this study will better define the changes in nutrition status observed in these children following remission of active Crohn's disease, and potentially lead to changes in medical and nutritional management of these children."
"Ulcerative colitis (UC) is an inflammatory disease involving the colonic mucosa, with bleedings and ulcerations. Consequences are destroyed mucosal barrier and increased permeability. Several cytokines are described to mediate the progressive course of ulcerative colitis and it is considered nowadays an immunologic disease. Patients with UC have often low levels of vitamin D and elevated prevalence of osteoporosis.||In vitro studies demonstrate that vitamin D has an immunomodulating effect, and may have a direct healing action on colonic mucosa has been described in animal studies. One can therefore rise a hypothesis that vitamin D supplementation could be crucial in patients with UC. To our knowledge, it has not been performed randomized clinical trials to study these possible effects of vitamin D and it has not been studied the effects of vitamin D on the relapse frequency and immunological composition of colic mucosa in patient with moderate to severe ulcerative colitis.||Objectives for our study are as follows: To examine if high-dose vitamin D supplementation in patients with moderate to severe ulcerative colitis:||reduces relapse frequency and increase the duration of the Infliximab induced remission|mediates and changes the cytokines composition in the colic mucosa|decreases the excretion of calprotectin in feces and reduces the concentration of inflammation markers|augments bone mass"
"Conventional intestinal manometry is the current gold standard for the evaluation of intestinal motility, and identifies patterns of intestinal dysmotility. However intestinal manometry involves intestinal intubation with consequent discomfort for the patients, and requires considerable technical expertise and knowledge for interpretation of the data. Hence, to date this method has limited indications and is restricted to very few referral centers around the world.||A novel method for evaluation of intestinal motility has been developed based on endoluminal image analysis using the endoscopic PillCam capsule, In contrast to manometry, this technique is minimally invasive, the technical aspects are simple, and the analysis is fully automated by a computer program.||The technique has been validated in a group of patients with intestinal dysmotility and healthy subjects, and has demonstrated over 90% sensitivity and specificity.||This technique needs now to be validated in a large multinational population, to further develop a robust discrimination algorithm for widespread diagnostic application. Furthermore, whereas manometry only recognizes neuropathic, myopathic and obstructive motor patterns, endoluminal image analysis may identify different categories of patients depending on the clinical presentation and the etiologic factors involved.||This study is designed to provide evidence that the algorithm, using images created by PillCam SB2 capsules, is at least as good as small bowel manometry in diagnosing severe dysmotility."
Multicenter cohort of patients followed for 6 months during the pandemic in France with biocollection of sera and peripheral blood mononuclear cells
"One of the main potential causes of these failures of BP therapy response is the development of Anti-drug Anti-body (ADAb) in some patients. ADAb may decrease the efficacy of BPs by neutralizing them or modifying their clearance and they may be associated with BP-specific hypersensitivity reactions. The prediction, prevention and cure of anti-drug (AD) immunization are thus major goals in BP development. This prospective study (ABI-RA) will assess the occurrence of ADAb using standardized and validated assay(s) and also cellular, genetic and molecular parameters in RA/JIA patients treated with adalimumab, etanercept, infliximab and rituximab or tocilizumab, to address the mechanism of immunogenicity. Patient-related factors that might predispose an individual to an immune response will be taken into account: underlying disease, genetic background, immune status, including immunomodulating therapy and dosing schedule."
"Background:||Rheumatoid arthritis (RA) is often treated with drugs known as tumor necrosis factor (TNF) inhibitors, that can help decrease joint pain and swelling and can even result in RA remission. However, TNF inhibitors may increase risk of serious infections or some types of cancer.|It is not clear if people whose RA has been in remission for a long time need to stay on the TNF inhibitor to remain in remission. If they can stop taking the TNF inhibitor without having their symptoms come back, they will be spared the side effects of these medicines. Some studies have shown that people can stay in remission after stopping a TNF inhibitor, but other studies have not confirmed it. Researchers want to see if people with RA in remission on a TNF inhibitor can stay in remission without this medicine. Also there may be a clinical, imaging (MRI, ultrasound), laboratory profile that will help to determine which patients remain in remission after stopping these drugs.||Objectives:||To see whether RA remission can continue after discontinuing use of a TNF inhibitor.|To determine if clinical, imaging and immunological measurements can predict which participants will flare and which will remain in remission after discontinuing TNF inhibitor.||Eligibility:||-Individuals at least 18 years of age who have RA that is being controlled with TNF inhibitors. We plan to randomize 291 patients.||Design:||The study has seven visits over about 2 years. Six visits occur in the first year of the study, about 12 weeks apart. The final study visit is 1 year after the end of the treatment phase.|At the first visit, participants will be screened with a physical exam and medical history. They will complete a questionnaire about their RA symptoms. A blood sample will be collected. They will continue to take their RA medicines during this time.|The second visit will repeat tests from the first visit. These tests will confirm that the RA is in remission. Imaging studies will be performed on the hands, wrists, feet, and their connected joints. After this visit, participants will stop taking their TNF inhibitors and will start to have injections of a study drug. This drug will be either the participant's original TNF inhibitor or a placebo.|There will be follow-up visits at weeks 12, 24, and 36. Participants will have a medical history and joint exam. They will also provide blood samples and answer questions about their RA symptoms.|At the sixth visit (week 48), participants will repeat the tests and imaging studies from the second visit. They will stop taking the study injections.|Continued RA treatment after this visit will be decided by the participant and his or her rheumatologist. Participants may take any recommended medicine, including the TNF inhibitor they had been taking before the study. They will also receive a questionnaire to complete at home and mail back before the final study visit.|At the final visit (week 100), participants will repeat the tests and imaging studies from the second and sixth visits."
"The purpose of this study is to evaluate the long-term course of patients with psoriasis and psoriatic-arthritis in systemic treatments such as, methotrexate, cyclosporin A, fumaric acids, acitretin, systemic PUVA, etanercept, infliximab, adalimumab and ustekinumab. A patient will be included at first initiation of the treatment and will remain in the registry for 10 years, regardless of subsequent therapy.||The registry will also evaluate safety clinical outcomes and health related quality of life."
The purpose of this study is to evaluate the effectiveness and safety of anti-TNF chimeric monoclonal antibody (cA2) compared to placebo in patients with active Crohn's disease.
"This registry is a multi-center, prospective, longitudinal, observational program that will gather and analyse data on participants treated with infliximab, golimumab, golimumab Intravenous (I.V) or ustekinumab. Treatment will be prescribed by the physician according to actual clinical practice or standard of care for Rheumatoid Arthritis (RA), Axial Spondyloarthritis (AxSpA) , Psoriatic Arthritis (PsA); there will be no randomized assignments to treatment. At baseline and approximately every 6 months thereafter, information will be collected to assess safety, clinical outcomes, quality of life, comorbidities, pharmacoeconomics and treatment regimens among cohorts of participants receiving infliximab, golimumab, golimumab I.V or ustekinumab for the treatment of RA, AxSpA and PsA."
"This trial is a randomised, single-center, placebo-controlled, double blind, parallel group study in patients with asthma symptomatic on inhaled steroids.||This trial will examine the efficacy and safety of 5 mg/kg doses of infliximab in patients with inhaled corticosteroid-dependent asthma. The primary objective of this study is to obtain pharmacological evidence for a role of the pro-inflammatory cytokine TNF-alpha in patients with asthma symptomatic on inhaled steroids and to evaluate the safety and tolerability of repeated intravenous administration of infliximab."
"Approximately 30% of patients with rheumatoid arthritis have an inadequate response to anti-TNF (primarily or loss of response), leaving two alternatives: rotation to a second anti-TNF or change of biologic, with a different mechanism of action, such as abatacept, rituximab and tocilizumab. No controlled trial compared these two strategies face to face. The present objective is to investigate the issue whether one of these strategies could have a better efficacy in a pragmatic trial in the setting of current practice."
To study the long-term clinical outcome of patients with ulcerative colitis treated with first trial of biological therapy.
"Drug serum concentrations will be measured at several time-points for inflammatory disease patients treated with anti-TNF agents. The purpose is to determine which patients that will clinically benefit from either discontinue treatment, adjusting the dose, switch to another anti-TNF agent or a different class of medication."
The investigators expect that a culturally specific group intervention targeting African American smokers will result in greater smoking cessation rates compared to a standard intervention.
Study hypothesis - this study will assess the presence of endothelial dysfunction in patients with Crohn's disease before and after 12 weeks treatment of anti TNF α.
"This randomized, controlled study aims to evaluate the impact of therapeutic intervention (step up) for the patients who are clinical remission with Magnetic Resonance Enterocolonography (MREC) active. In addition, to evaluate the impact of therapeutic step down for the patients who archived clinical and MREC remission. The primary endpoint is the rate of clinical remission at 104 weeks."
The purpose of this study is to find biological response patterns of patients with rheumatoid arthritis to drugs with different biologic modes of action. This study should help to predict therapeutic responses and to find the right therapy for the right patient.
"The purpose of this study is to demonstrate that patients with Spondylarthropathies in remission under antiTNF therapy, can maintain the remission with a maintenance dose inferior to the currently recommended dose schedule."
"The aim of the study is to explore whether the influence of gender, tobacco smoking and obesity on treatment response in tumor necrosis factor inhibitors (TNFIs) can be explained by high degree of inflammation, human leucocyte antigen (HLA) type, autoantibodies, TNF and TNFI concentration and presence of ADA."
"We established a nationwide biologics and targeted synthetic DMARDs registry (in the form of an inception cohort) to study the safety profiles in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis patients receiving biologics or targeted synthetic DMARDs. As this registry is to observe the ""real world"" use of anti-rheumatic treatments under routine clinical practice, no hypothesis to prove is planned."
"This study will be a multicentre prospective randomized trial to assess the percentage of patients with IBD who, after stopping anti-TNF treatment, have sustained clinical remission at one year compared to those in which the treatment is continued at stable doses"
"Ulcerative colitis (UC) is a chronic, progressive immunologically mediated disease affecting nearly 1 million Americans. Up to one third of patients with UC will require hospitalization for severe disease (termed 'acute severe colitis (ASUC)'), often within the first year after diagnosis. Investigators will develop a large multi-center cohort of patients with ASUC with homogeneously collected detailed longitudinal clinical and laboratory data."
Retrospective review of the outcome of use of immunosuppressive drugs in treatment of sarcoidosis
"This prospective, multi-center, observational study will evaluate the efficacy and the safety of MabThera (rituximab) in participants with rheumatoid arthritis who have not responded or have been intolerant to a first anti-TNF alpha therapy. Participants have commenced MabThera or an alternative anti-TNF alpha treatment as a second biological therapy. Data will be collected for 12 months."
This study compares two administration methods of CT-P13. Half of participants will receive CT-P13 by pre-filled syringe while the other half will receive CT-P13 by auto-injector.
"National, prospective, multicentre observational study designed for eligible patients treated with Inflectra.||Its objectives are to describe under real conditions of use, the profile of patients treated with Inflectra and the response to treatment."
"The purpose of this study is to evaluate the long-term clinical, economic and humanistic outcomes of various treatment regimens, including infliximab, in Crohn's disease in real world medical practice."
"The investigators will be administering oral high dose interval vitamin D, concurrently when participants are receiving biologic therapy for their inflammatory bowel disease. The investigators will be collecting some additional bloodwork and questionnaires at the time of participants infusions."
"Multicenter, randomized, double-blind, placebo-controlled, 5-arm, dose-ranging study to assess the efficacy of subcutaneous injections of Golimumab (CNTO 148), 50 or 100 mg, at either 2- or 4- week intervals in subjects with active RA despite MTX therapy."
"Kawasaki disease (KD) affects infants and young children causing inflammation of the skin and blood vessels including the coronary arteries of the heart. Despite the currently available therapy, about one third of children develop enlargement of the coronary arteries that can lead to serious complications such as coronary artery stenosis, heart attack and even death.||Kawasaki disease is the most common heart disease in children in the USA and it is especially common among the children of Hawaii. Every year, 50-90 children are diagnosed with KD in Hawaii and unfortunately there is no medication available to successfully prevent coronary artery damage in a subset of cases.||During the first few weeks of the illness, cells of the immune system attack the coronary arteries and release a special substance (MMP) that is responsible for the coronary artery enlargement. There is a common antibiotic, doxycycline that can specifically block the action of this special substance (MMP). Research done on animals with KD showed that doxycycline was able to block this special substance and prevent enlargement of coronary arteries. Research in adults with enlargement of the main artery in their abdomen also showed that doxycycline may improve the outcome. Based on these studies doxycycline may be a promising therapy for children with KD, who develop enlargement of the coronary arteries.||The investigators' proposed research study will assess the usefulness of doxycycline in preventing the progressive enlargement of coronary arteries in children with KD. The investigators plan to perform a small (pilot) study to evaluate how good is doxycycline in preventing coronary artery enlargement. The investigators will treat 50 children with KD and enlarged coronary arteries for three weeks with doxycycline and assess the change in coronary arteries as well as the blood levels of the special substance (MMP). If doxycycline proves to be beneficial in this small study, the investigators are going to design a large research study involving multiple institutions on Hawaii and the mainland and will recruit more children to be certain about the value of the proposed treatment. The investigators' proposal may change the treatment protocol of KD and could present a possible treatment for children with enlarged coronary arteries preventing potentially devastating consequences."
OBJECTIVES:||I. Evaluate the efficacy of chimeric monoclonal antibody (cA2) compared with placebo in closure of enterocutaneous fistulae in patients with Crohn's disease.
"In this cross sectional and longitudinal study, patients with inflammatory bowel disease on biological treatment with infliximab or adalimumab will be included.||After inclusion, the dosage of their existing biological therapy will be adjusted following regular trough-level and antibody-level monitoring, according to a treatment algorithm.||Disease activity markers, fatigue and QoL will be assessed during the study. The hypothesis is that therapeutic drug monitoring may improve clinical disease outcome after one year of follow-up."
"Study hypothesis: PillCam SB3 is a new capsule designed to provide an improved image quality, and improved SB and duodenum tissue coverage due to Adaptive Frame Rate (AFR) of 2-6 fps, which will create more images for evaluation, and therefore should improve diagnostic accuracy.||Proposed Design: to enroll up to 230 patients with symptoms suggesting the presence of small bowel disease.||Preparation for procedure will include 12 hours fasting prior to the capsule ingestion||Patients will undergo a standard capsule endoscopy. Patients will be allowed to drink clear liquids 2 hours post ingestion, and eat 4 hours post ingestion.||Diagnostic yield of the SB3 will be calculated The Physician's subjective assessment of capsule performance will be captured"
The aim of the study is to analyze the mechanism of action of infliximab at the endomicroscopic level and to analyze mucosal healing - i.e. structural and functional changes in the mucosa in IBD patients - and associated processes such as permeability and bacterial invasion of the mucosa. In this study the role of the above mentioned parameters and further the establishment of endomicroscopic scores will serve to define new prognostic markers in view of long term remission upon infliximab treatment.
"Inflammatory bowel disease (IBD) is a chronic immune-related disease, which mainly affects the digestive tract. There are mainly two forms of the disease, including Crohn's disease (CD) and ulcerative colitis (UC).||Biologics have revolutionized the treatment of inflammatory bowel disease with good efficacy and safety. However, 20-50% of patients may not response to or lose response to biologics. Unfortunately, there has been no factors or measures that may predict the efficacy or safety of biologics.||In this study, a large prospective cohort study is conducted to evaluate the efficacy and safety of biologics (infliximab, adalimumab, vedolizumab, ustekinumab, and other approved biologics) in patients with inflammatory bowel disease in the real clinical practice. Meanwhile, a multi-omics approach involving transcriptomics, microbiome, proteomics, and metabolome, are adopted to explore biomarkers or factors that predict the therapeutic efficacy or safety of biologics. The mechanism underlie the disease will also be explored."
"Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by inflammatory arthritis and enthesitis involving the spine. AxSpA prevalence is around 0.17% of the French population. Tumor necrosis factor (TNF) was the first target defined in axSpA. Since one third of axSpA patients failed to the first TNF blocker, many axSpA patients received a second biological Disease-Modifying AntiRheumatic Drugs (bDMARDs). Until few months, the only choice was to use a second TNF blocker.Since 2003, pharmaceutical companies investigated efficacy of TNF blockers already used in rheumatoid arthritis. Etanercept is a fusion protein with TNF receptor type II p75 and IgG1 Fc fragment, whereas adalimumab, infliximab, and golimumab are monoclonal antibodies. Certolizumab is a fusion between a fab fragment targeting TNF and a Peg fraction. All demonstrated efficacy versus placebo in a randomized double blinded study||In case of failure to the first TNF blockers, rheumatologists will follow the ""Treat-to-Target"" principle. This approach already demonstrated its benefit in rheumatoid arthritis or in psoriatic arthritis. This concept was also suggested for axSpA with low levels of evidence and recommendation. So rheumatologist will provide the best treatment in case of failure to the first TNF blockers, which is a daily clinical situation. Since few months, rheumatologists have the choice between targeting IL-23/17 axis compared to a second TNF blocker."
"RABIOPRED is an in vitro non-invasive blood test, which aims to identify patients with rheumatoid arthritis (RA) who are not likely to respond to anti-TNFα and methotrexate combination therapy."
"This study will determine if medical treatment of colitis (inflammation of the colon resulting in loose bowel movements, rectal bleeding, and belly pain) that is used for other colitis conditions, such as Crohn's disease and ulcerative colitis, is safe and effective for treating colitis in patients with Hermansky-Pudlak syndrome (HPS). HPS is a hereditary disorder that causes albinism, visual impairment, and abnormal bleeding. Some patients also develop colitis, pulmonary fibrosis, and kidney disease.||Patients with HPS and colitis who are 18 years of age or older may be eligible for this study. Participants receive treatment for their colitis symptoms with one or more of several study drugs, which include mesalamine (5-ASA), corticosteroids, infliximab and 6-mercaptopurine, adalimumab and tacrolimus. The drugs are added to the treatment plan one at a time to find the combination that works best for the individual patient. Patients who respond to one or more of the medications may continue treatment with that same combination for up to 6 months.||Regular clinic visits are scheduled for blood tests, symptoms ratings questionnaires and periodic physical examinations and colonoscopies to measure the response to treatment and evaluate any side effects."
"The purpose of this study is to further evaluate the safety of infliximab, ustekinumab, and guselkumab in patients with plaque and other forms of psoriasis. The study also includes patients receiving other therapies, such as non-biologic and other biologic agents. The registry also evaluates patient and disease characteristics, including patient-reported assessment of psoriatic arthritis (PsA); and clinical and quality of life outcomes."
"Spondylarthropathy (SpA) comprises a group of rheumatic diseases mainly affecting the spine and sacroiliac joints. In most of the patients disease activity alternates, and some patients have symptom free periods. Tumor-Necrosis-Factor-alpha (TNF-alpha) antagonists have significantly improved the treatment options for patients with spondyloarthritis. TNF-alpha antagonist therapy is costly, implies an increased risk of infections, including reactivation of tuberculosis, and the risk of long-term adverse events, as cancer, is fully clarified. It is highly relevant to explore to which extent anti-TNF-alpha therapy can be discontinued in SpA patients without immediate relapse of disease activity. Two studies have investigated discontinuation of a TNF-alpha antagonist (infliximab and etanercept) in ankylosing spondylitis, reporting flares in the majority of patients within the 1-year follow-up period, with the longest times to relapse in patients with the lowest disease activity. The effect of adalimumab discontinuation has never been studied, and, furthermore, the effect of TNF-alpha-antagonist discontinuation has never been studied in patients with early spondyloarthritis not fulfilling the New York criteria."
"Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease in adults and is characterized by chronic inflammation of the joints leading to their destruction, resulting in a major loss of function.||The investigators propose a pilot study for studying changes in bone microarchitecture with High Resolution peripheral micro Computerized Tomography (HR-pQCT) in patients with RA treated with anti-TNF(Tumor Necrosis Factor), with the measurement of micro-architectural parameters in subchondral area near an inflammatory joint during the first 12 months of initiation of an anti-TNF therapy (Infliximab®, Etanercept®, Adalimumab®)."
"Crohn's disease is a chronic inflammatory condition of the intestines that causes abdominal pain, diarrhea, tunnels around the anus (fistulas), and extraintestinal symptoms. Effective medical treatments exist to treat the disease; however they can have significant side effects.||Previous studies have shown that sexual function is impaired in patients with Crohn's disease. It is likely that both the symptoms related to the disease, medications used to treat the disease, and surgery all impair sexual function in a variety of ways. For example, body image may be impaired, patients may be worried about bowel incontinence or unpleasant odors associated with diarrhea, patients may have significant pelvic pain secondary to perianal fistulas, or they may have painful intercourse from adjacent inflammation or scarring in the pelvis. The impact of medical treatment on patient's ability to regain sexual function is not known.||The investigators propose a 6 month study to compare sexual function before and after treatment in patients with Crohn's disease about to initiate therapy with an anti-TNF drug for treatment of perianal fistula or intestinal Crohn's or about to initiate therapy with steroids.||The investigators anticipate that the investigators will show that therapy with an anti TNF agent will result in a more rapid and greater return of sexual function than steroids. This information will be important to help counsel patients about the optimal treatment to begin for treatment of their Crohn's disease. Furthermore, it would be the first study to evaluate the impact of medical therapy on sexual function."
To evaluate whether stringent follow-up consisting of combined laboratory and ultrasound surveillance is superior to clinical monitoring alone to maintain clinical remission in rheumatoid arthritis.
"This study is an adaptive, randomized, open-label, controlled clinical trial, in collaboration with countries around the world through the World Health Organization."
"The purpose of this study is to examine the association with EBV infection, monitor the occurrence of lymphoma and assess lymphoma risk in patients with rheumatoid arthritis and/or Crohns disease and you have taken infliximab."
"""RUN-CD"" is an investigator initiated ""Non interventional Trial"" on biologics in Crohn´s Disease (CD) patients in Germany with a prospective documentation of effectiveness in induction and maintenance therapy of biologics, especially of Ustekinumab, with a special interest on predictors of long-term responses and favorable disease outcome and documentation of severe side effects caused by the therapy with biologics."
"The aim of this study is to evaluate the influence of anti tumor necrosis factor-alpha (TNF-α) treatment on blood pressure, endothelial function and immune cell phenotype in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis."
"To compare the efficacy of switching to a different molecular target (from TNF to IL6) versus cycling to a second TNF inhibitor in patients with active RA, who have not adequately responded to a previous treatment with a first anti-TNF."
"The purpose of this study is to establish the safety of the combined drug approach (anti-thrombin III, infliximab, apotransferrin, human recombinant erythropoietin beta, C1-inhibitor, glutathione, alfa-tocopherol, melatonin and epoprostenol)aimed to reduce ischemia-reperfusion injury during liver transplantation in eligible recipients."
"The purpose of this study is to establish the effectiveness of the combined drug approach (anti-thrombin III, infliximab, apotransferrin, human recombinant erythropoietin beta, C1-inhibitor, glutathione, alfa-tocopherol, melatonin and epoprostenol)aimed to reduce ischemia-reperfusion injury during liver transplantation in eligible recipients."
"The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of TA-650 at increased dose of 10 mg/kg every 8 weeks in patients with psoriasis in whom effect of the treatment was confirmed after the treatment with Remicade® at 5 mg/kg every 8 weeks but decreased thereafter."
"The purpose of the study is to establish a Danish cohort of spondylarthropathy (SpA) patients who are being treated with TNFalfa blockers. By following the TNFalfa blocking treated patients the researchers want to identify better biomarkers for disease activity and disease progression. In addition, the researchers want to identify predictors for disease progression."
"To compare the proportion of rheumatoid arthritis (RA) patients prescribed opioids, benzodiazepines, and antidepressants before versus after starting each of the following biologics: abatacept, infliximab, etanercept, adalimumab, utilizing an administrative claims database."
"With this prospective, randomized, multicentre, parallel group pragmatic non-inferiority trial, the investigators will evaluate if endoscopy-driven introduction of biological therapy is not leading to more postoperative endoscopic recurrence at week 86 compared to systematic prophylactic biological therapy in patients with CD undergoing an ileocolonic resection with ileocolonic anastomosis. Secondary analyses will include influence on clinical, biological and surgical CD recurrence, serious adverse events, direct costs, work productivity, and quality of life. If the investigators can demonstrate the non-inferiority of an endoscopy-driven approach, this patient-tailored management could be advocated, while a more expensive systematic introduction of biological therapies could be limited.||Finally, endoscopic images provided through the SOPRANO CD study, will be used to develop a new scoring system evaluating postoperative endoscopic recurrence."
"Current evidence on tapering of tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) is still hampered by heterogeneity in tapering regimens, selection and performance biases, and lack of data on optimized treatment dosing strategies especially in real-world clinical settings. This study aims to contribute to the ongoing investigation of disease-activity-guided tapering of TNFi in axSpA in the form of a prospective, randomized controlled trial."
"Breastfeeding is beneficial to both mother and baby. However, many breastfeeding women are affected by long-term health conditions and need to take medications. Sometimes, concerns about transfer of drugs to infants via breast milk lead the mothers to either avoid breastfeeding or stop their medication.||Inflammatory Bowel Disease (IBD) is a chronic condition that is marked by an abnormal response of the body's immune system, and high levels of certain proteins that cause inflammation (Cytokines like Tumor Necrosis Factor-alpha or TNFα). A group of drugs called ""biologics"" target and stop these proteins from causing inflammation, and have been successfully used to treat this condition. Inflammatory proteins may be present in breast milk of healthy women in variable levels, and may play a role in development of infant's brain and immune system.||This study is being conducted to investigate:||Concentration of some of the inflammatory proteins in breast milk of mothers with IBD and healthy controls|Interaction between these proteins and biologics in breast milk of women with IBD|Potential role of these proteins (and their interaction with biologics) on development of infant learning and memory function It has been presumed that concentrations of TNFα and some other cytokines are higher in breast milk of women with IBD, and the biologics can normalize these high levels.||Due to precautions for COVID-19, the study now consists of only two mandatory study visits and two optional study visits. The mandatory visits include two home visits in the first 4 months postpartum to complete a participant questionnaire and collect a small sample of breast milk at each visit. The optional study visits consist of two visits at the Hospital for Sick Children for evaluation of learning and memory function of the infant at the ages of 12 and 18 months. Additionally, mothers will be required to complete for their infant subscales of The Ages and Stages Questionnaires®, Third Edition (ASQ®-3) either in person or over the telephone at the ages of 12 months and 18 months."
"EBI2 is a risk gene for inflammatory bowel diseases (rs9557195). Patients of the Swiss IBD cohort study have been genotyped for the allelic status of EBI2. The investigators will test the influence of rs9557195 genoty (TT or CC allel), inflammatory activity and current treatment (infliximab vs. vedolizumab) on expression and activity of EBI2 on blood lymphocytes, mRNA expression of EBI2 and UBAC2 (located on the opposite DNA strand of EBI2) and activity of lymphocytes on a migraton assay."
"The investigators plan a prospective study designed to optimize and translate noncontrast, novel Magnetic Resonance Imaging (MRI) techniques for detecting and measuring intestinal inflammation as well as for allowing early prediction of response to medical therapy in small bowel Crohn's Disease (CD)."
"Comparing the structural effects of TNFi and tocilizumab on the periarticular bone by performing a comprehensive analysis of the periarticular bone changes in RA patients treated with either TNFi or tocilizumab in a longitudinal Setting, using high-resolution peripheral quantitative computed tomography (HR-pQCT), a very sensitive method for visualizing and quantifying bone microstructure in RA patients. Quantitatively assessing the changes of erosions volume, osteophytes size and the area of cortical fenestration in a group of TNFi-treated and a group of tocilizumab- treated RA patients."
reviewing the outcomes of patients with uveitis caused by autoimmune diseases treated at Assiut University Hospital at the Ophthalmology and Rheumatology and Rehabilitation Departments.
"To assess the effects of a 16-week individualized, intensive strength training program in patients with rheumatoid arthritis. Primary and secondary outcomes include: strength and body composition, function, disease activity, pain, quality of life.||We hypothesized that improvements would be seen in all of the above outcomes."
"This trial studies the role of the gut microbiome and effectiveness of a fecal transplant on medication-induced gastrointestinal (GI) complications in patients with melanoma or genitourinary cancer. The gut microbiome (the bacteria and microorganisms that live in the digestive system) may affect whether or not someone develops colitis (inflammation of the intestines) during cancer treatment with immune-checkpoint inhibitor drugs. Studying samples of stool, blood, and tissue from patients with melanoma or genitourinary cancer may help doctors learn more about the effects of treatment on cells, and help doctors understand how well patients respond to treatment. Treatment with fecal transplantation may help to improve diarrhea and colitis symptoms."
"Participants maintaining stable disease activity of Ankylosing Spondylitis (AS) with standard-dose tumor necrosis factor inhibitor (TNFi) treatment will randomly split into two groups: maintaining standard-dose TNFi, versus reduced-dose TNFi. The proportion of participants not underwent flare between the two groups will be analyzed."
"Up to one third of patients with Ulcerative Colitis (UC) will require hospitalisation for severe disease (ASUC - Acute Severe Ulcerative Colitis), often within the first 12 months of diagnosis. 30-40% of people admitted to hospital with ASUC will require colectomy during the emergency admission. Investigators will develop a multi-centre prospective inception cohort of patients with ASUC with homogeneously collected detailed longitudinal clinical, endoscopic and laboratory data."
"This is an open-label, phase IV trial. Adult patients, with moderately to severe, steroid dependent, acute ulcerative colitis not previously exposed to anti-TNF, will receive subcutaneous golimumab treatment, according to EU marketing authorization from baseline through week 14.||At week 16, patients achieving clinical and endoscopic remission will continue with Golimumab, 50 mg or 100 mg (depending on body weight) every 4 weeks, through week 52.||Patients not achieving clinical and endoscopic remission will be treated with infliximab, according to marketing authorization, and followed through week 52. This is not considered as an interventional arm but, since infliximab in Italy is considered as the first-line treatment for UC patients, as the usual clinical practice."
The study was to explore the efficacy of adalimumab in subjects previously treated with infliximab and failed infliximab treatment due to lack of efficacy or intolerance. To explore the safety of adalimumab in subjects previously treated with infliximab.
"In Canada and worldwide there is a need for updated independent real-world comparative effectiveness and safety data related to biologic drugs including biosimilar drugs. Biosimilar drugs hold potential to improve access to needed therapies at reduced cost enabling savings to be reallocated to other needs. However updated real-world evidence on comparative effectiveness and safety of biosimilar drugs is lacking. Investigators aim to demonstrate feasibility of creating network of clinical cohorts and other resources to provide real-world information on use of biosimilar drugs in Canada.||The core revolves around clinical datasets but investigators will complement with other data sources. Investigators will review data from National Prescription Drug Utilization Information System database that contains prescription claims-level data collected from publicly financed drug benefit programs in different provinces to conduct an environmental scan of the use of biosimilars and respective legacy drugs and other anti-Tumor Necrosis Factor agents covered by provincial drug plans from 2014-2017. Initial analysis will help to confirm that use of biosimilars is lower than corresponding legacy drugs.||Biologic drugs are relatively new and expensive drugs; biosimilar medicines are similar to original biologic drugs but cost less. If patients receive biosimilar drugs rather than originator biologics healthcare systems may be able to save money. Those savings can be used for other health care needs to benefit more Canadians. However investigators do not have detailed information on safety and effectiveness of these biosimilar drugs. The aim of study is to compare safety and effectiveness of biosimilar drugs to originator biologic drugs. Investigators will study patients with inflammatory rheumatic diseases (RA and AS) and Inflammatory Bowel Disease (CD and UC) and across Canada on these drugs. Primary focus is on patients without history of biologic drug use but investigators will also study patients switching to biosimilar drug from an originator biologic drug. Investigators will measure how long patients stay on treatment, if patients require new treatment, if the patients' disease control improves and occurrence of side effects such as infection that could be related to these drugs."
Registry with evaluation and genetic information of patients with advanced sarcoidosis and matched sarcoidosis
"Patients with Crohn's disease (CD) and ulcerative colitis (UC) are often treated with medications that suppress the immune system. These patients are therefore at increased risk for developing infections, such as influenza, pneumonia, and hepatitis B, which may be prevented by vaccination. While awareness is increasing among gastroenterologists of the importance of vaccinations in the IBD patient, there continues to be some question of the effectiveness of vaccination in immunosuppressed patients. It has been previously shown that patients on immunosuppressive therapy with certain biologic medications (the TNF-blockers: infliximab and adalimumab) had an impaired immune response to vaccination as compared to healthy controls, as the mechanism of immunosuppression for these agents is systemic. Vedolizumab, a biologic medication for CD and UC approved in May 2014, targets the α4β7 integrin, a key component of gut immunity, and as such it has been hypothesized that with this agent effects are gut specific. There is limited data that suggests that in healthy patients given vedolizumab do not have an altered response to parentally administered vaccines, however there are no studies in the CD and UC population describing this. Additionally, IBD patients treated with vedolizumab are frequently also on concomitant therapy with an immunomodulator (6-mercaptopurine, azathioprine, or methotrexate), and these patients ability to mount an immune response has not been demonstrated."
"Objective: To determine the effect of C-reactive protein (CRP) status, and infliximab treatment on the pharmacodynamics and pharmacokinetics of verapamil, a model drug for L-type calcium channel blocking, in Crohn's disease (CD) patients compared to healthy patients.||Hypotheses:CD patients will have elevated plasma verapamil concentrations, but diminished dromotropic response to verapamil; the concentration of circulating norepinephrine, used as a surrogate marker of sympathetic nervous activity, will be similar between the healthy patients and the CD patients; the sympathetic nervous system of the heart will be similar to healthy patients; Crohn's disease patients with normal CRP will have higher drug response compared to high CRP (>3 mg/l) patients; and that infliximab-treated patients will have higher verapamil response than those with similar symptom profiles who are not infliximab treated."
"The purpose of this study is to estimate and compare the incidence of overall malignancy, serious infection, and opportunistic infections between new users of ustekinumab and new users of other biologic therapies among adult participants with Crohn's disease (CD) or ulcerative colitis (UC)."
"Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with recurrent mucosal inflammation. Clinically, the disease is characterized by bloody diarrhea, abdominal pain, and constitutional symptoms such as fever and weight loss. Treatment strategies vary based on disease activity and target various aspects of the inflammatory cascade. Options include: anti-inflammatory drugs (mesalamine), immunosuppressive or modulatory medications (corticosteroids, thiopurines, cyclosporine) and biologic agents (Anti-TNF). Disease severity can be wide ranging, and nearly 25% of UC patients are hospitalized for acute severe disease. Of these patients, 30% will undergo colectomy after the acute episode, a quarter of which will experience post-operative complications. Although there has been great progress in treatment of UC over the past decade, even with the anti-TNF agent infliximab, the one-year remission rate for patients not responding to conservative management is barely 20%. Furthermore, corticosteroids have significant long-term consequences and immune suppressive drugs such as 6-mercaptopurine, azathioprine and infliximab have been associated with serious adverse events including life-threatening infections and lymphomas. With growing evidence that the pathogenesis of UC is multi-factorial and involves a complex interaction of genetic and environmental factors, newer treatment modalities are being evaluated to target the mucosal immune response and mucosal inflammatory regulatory system.||Hyperbaric oxygen offers a promising new treatment option since it targets both tissue hypoxia and inflammation. Recent small scales studies evaluating the impact of hyperbaric oxygen treatment in acute ulcerative colitis flares demonstrated improved outcomes. The mechanisms underlying the improvement are not known. In this study, we will treat ulcerative colitis flares with hyperbaric oxygen and measure changes in both markers of tissue hypoxia and inflammation. We hypothesize that hyperbaric oxygen will (a) improve outcomes, and (b) show reductions in markers of both tissue hypoxia and inflammation."
Main purposes of this study are :||Analysis of relapse risk of anal fistulae with prospective follow-up of patients undergoing pelvic MRI every 6 months for one year. This monitoring also determines if the presence of path of fistulae visible on MRI during inclusion visit is associated to increased risk of perianal abscess under infliximab or adalimumab treatment.|Evaluation of interest of new magnetic resonance imaging sequences for detection of persistent anal fistulae under infliximab or adalimumab treatment.||Secondary purposes are:||Description of patients with one or more paths of fistulae visible with MRI after at least one year of treatment with infliximab or adalimumab administered for anal fistulae and showing a complete healing of fistulae at clinical examination of inclusion visit.|Identification of predictive factors (included the presence of paths of fistulae visible with MRI during inclusion visit) of relapse of anal fistulae during the 1-year-follow-up after inclusion visit.
"The current available therapies for inflammatory bowel disease (IBD), including immunomodulator and biologic medications may have toxicities limiting use or inadequate effect. We propose a novel approach to the treatment of IBD by using transcutaneous vagal nerve stimulation (VNS). Research has previously identified that VNS using a surgically implanted stimulator can improve symptoms and decrease inflammation in people with inflammatory diseases. This study will evaluate the use of non-invasive nerve stimulation through the skin (rather than through an implanted device) as a potential therapy in pediatric patients with Crohn Disease or ulcerative colitis. We will be evaluating how this nerve stimulation affects symptoms, markers of inflammation found in the blood and stool including cytokine levels, and heart rate variability. The primary hypothesis of the study is the use of transcutaneous VNS will decrease inflammation in people with IBD leading to improved signs and symptoms of disease. The primary endpoint of the study is to evaluate the change in fecal calprotectin after 16 weeks of nerve stimulation. Secondary endpoints include changes in symptom scores, blood cytokine levels, and heart rate variability."
"Rheumatoid arthritis (RA) is a chronic and disabling disease. tumor necrosis factor-a(TNF-a) inhibitors have demonstrated an outstanding performance in relieving joint inflammation and retarding bone erosion involved in RA. However, there is still about one-thirds of RA patients had a poor response to TNF α inhibitors. The Investigators hope to discover prediction protein with a domestic genetic background and finally establish prediction system with Chinese characteristics."
"The purpose of this study is to evaluate the efficacy and safety of golimumab (CNTO 148) in subjects who have active rheumatoid arthritis and have been treated previously with at least 1 dose of a biologic anti-TNFa agent (etanercept, adalimumab or infliximab)."
"The goal in these studies will be to assess the relative levels of the Stat4 alpha and Stat4 beta isoforms in PBMCs from patients with Crohn's Disease, ulcerative colitis, celiac disease or from control patients. We hypothesize that the beta to alpha ratio will be higher in patients with active disease and that there will be a correlation between the ratio and the severity of disease."
"The purpose of this study is to evaluate CROWN's efficacy in supporting the repair and maintenance of the intestinal mucosa of patients with moderately to severely active Crohn's Disease receiving anti-Tumor Necrosis Factor (TNF) therapy (infliximab, adalimumab, certolizumab)"
"Tumor necrosis factor (TNF)-alpha has been strongly implicated as a major contributing factor for the development of radiculopathy. In animal studies, the application of TNF-alpha to nerve roots results in pain behavior indicative of radiculopathy. The use of TNF-alpha inhibitors (etanercept and infliximab) have been shown to prevent this pain behavior. Open-label studies in humans have shown both etanercept and infliximab provide excellent, long-term relief in patients with acute radiculopathy from herniated disc. However, a recent placebo-controlled study failed to demonstrate any significant difference from placebo. The investigators have already established the safety of neuraxial etanercept in a trial that has just been completed (not yet published). The objective of this study is to determine whether small doses of epidural etanercept, an anti-TNF-a medication, is an effective treatment for LBP caused by nerve root irritation (i.e., radiculopathy)."
"The objective of this study is to analyze the factors influencing the medical and non-medical direct costs of patients treated with biotherapy during the last twelve months (infliximab or adalimumab), including biosimilars (infliximab biosimilars: Inflectra ™ and Remsima ™) for treating Crohn's desease or ulcerative colitis"
"Crohn's disease is an immunologically mediated inflammatory bowel disease with a reported incidence of 4.0-7.0, 7.1, and 1.34 per 100,000 persons in Europe, the U.S., and Korea, respectively. Uncontrolled chronic inflammation finally causes various complications in intestine such as bowel obstruction, fistulas, abscesses, and anal fissures.||The incidence of perianal fistula was reported in 13%- 39% of patients with Crohn's disease. Medical treatment for Crohn's fistulae initially focused on surgical intervention accompanied by symptomatic treatment with antibiotics and immunosuppressants. The most serious problem after surgical intervention is the relatively high incidence of postoperative anal incontinence caused by sphincter injury during the procedure. Conversely, available pharmacological therapies for Crohn's fistulae based on biologic agents such as infliximab do not generally reach ideal goal of treatment (e.g., complete closure of the fistula). A high recurrence rate after treatment with infliximab has also been reported, even after long-term maintenance therapy, which suggests that infliximab monotherapy does not provide adequate healing.||The ACCENT II study demonstraded a complete fistula healing in 25% of patients. To reach a better clinical outcome, combination treatment with infliximab and surgical intervention is highly recommended for management of Crohn's fistulae. Nonetheless, even this strategy does not result in a satisfactory healing for many patients.||The ideal therapeutic goal of treatment is not only complete closure of the fistula without recurrence but also preservation of anal sphincter function. Unfortunately, currently available medical or surgical treatment is not likely to offer a cure for perianal fistulae and, as noted above, recurrence is frequently reported.||Together with active research in the field of bone marrow-derived mesenchymal stem cells (BM-MSCs) and hematopoietic stem cells, autologous or allogenic adipose tissue-derived stem cells (ASCs) have been studied for management of Crohn's disease and other disorders.||Of particular relevance to this study, ASCs could be considered to be safe and efficacious therapeutic tools for the treatment of Crohn's fistulae. Importantly, ASCs do not cause fecal incontinence after injection into the lesion site in Crohn's disease patients. A phase I dose-escalation clinical study with ASCs manufactured by Anterogen Co., Ltd. (Seoul, Korea) demonstrated the safety and therapeutic potential of these cells for the treatment of Crohn's fistulae. A phase II study demonstrated a good rate of cronh's related fistula closure using a ASCS injection.||Actually the best accepted treatment of Crohn related perianal fistula, is the surgical procedure in association whit medical therapy."
"This is an open-label study of 20 patients designed to demonstrate the safety, tolerability and preliminary evidence of benefit of adalimumab in the treatment of subjects with Ulcerative Colitis, both in patients who have never received anit-TNF agents and in those who have lost response or developed intolerance to previous infliximab therapy."
"An Agency for Healthcare Research and Quality executive summary indicated that better comparative effectiveness trial designs are needed to determine the relative merits of existing versus new and expensive biologic drug therapies for rheumatoid arthritis (RA). There are now 9 biologic therapies approved for treating RA. Four classes of biologics (TNF antagonists, B-cell inhibitors, T-cell co-stimulator blocker, and Interleukin-6 receptor blocker) are approved for use in RA patients with moderate or severe disease activity. Several critical questions have arisen, such as 1) what therapy should be prescribed after failure of methotrexate and/or other oral disease modifying antirheumatic drugs (DMARDs) to adequately control disease activity; 2) what is the level of efficacy of the various biologic therapies when compared in head-to-head trials; and 3) what are the mechanisms associated with failure of methotrexate and/or other oral DMARD therapy and responsiveness to biologic therapies. The MAZERATI study will provide the foundation for answering these questions and determining the mechanisms associated with these biologic therapies."
"This study (UNITI-1) will compare the effects (both positive and negative) of an initial treatment with ustekinumab to placebo over 8 weeks, in patients with moderately to severely active Crohn's disease who have either failed or could not tolerate at least one TNF-antagonist medications in the past (specifically, infliximab, adalimumab, or certolizumab pegol)."
"RECOVERY is a randomised trial investigating whether treatment with Lopinavir-Ritonavir, Hydroxychloroquine, Corticosteroids, Azithromycin, Colchicine, IV Immunoglobulin (children only), Convalescent plasma, Casirivimab+Imdevimab, Tocilizumab, Aspirin, Baricitinib, Infliximab, Empagliflozin, Sotrovimab, Molnupiravir, Paxlovid or Anakinra (children only) prevents death in patients with COVID-19."
"Inflammatory bowel disease (IBD), consisting of two major forms, Crohn's disease (CD) and ulcerative colitis (UC), affects more than 1.6 million people in the United States alone. Though the precise mechanisms underlying the inflammation and immune responses in IBD are still being investigated, various inflammatory mediators, including pro-inflammatory cytokines, and genes have been implicated in the disease process. At present, there are no reliable mechanisms to predict response to individual IBD medications. The investigators seek to evaluate whether inflammatory cytokines change longitudinally during treatment with anti-cytokine agents in both treatment primary responders and primary non-responders. In addition, the investigators will be evaluating the pharmacogenetics of treatment response to these agents."
"In this prospective, open, controlled, cross-sectional observational study patients with psoriasis or IBD, who received either anti-TNF-alpha inhibitors or alternates (purine-, folic acid analogues, phototherapy, fumaric ester, mesalazine) for their underlying disease were included.||Anogenital HPV-induced lesions, mucosal HPV DNA and serological status of mucosal low-risk (HPV6) and high-risk HPV (HPV16, HPV18) were determined."
"SPECIFIC AIMS:||To reverse hyperglycemia and insulin dependency in patients with Type 1 Diabetes Mellitus by islet cell transplantation;|To eliminate the incidence of hypoglycemia coma and unawareness in patients with Type 1 Diabetes Mellitus by islet cell transplantation;|To assess long-term safety and function of successful islet cell transplants in patients with Type 1 Diabetes Mellitus;|To determine whether the natural history of the microvascular, macrovascular and neuropathic complications of Diabetes Mellitus are altered following successful transplantation of islet cells; and|To assess the effect of infliximab in preventing early islet destruction, and thereby eliminating the need for a second donor's islet cells.|To assess the effect of etanercept in preventing early islet destruction.|To assess the effect of exenatide to improve islet graft function and survival in subjects that have returned to using exogenous insulin.|To assess the ability of exenatide to improve islet survival at time of transplantation."
"The objective of this study is to explore and describe the disease characteristics, treatment and outcomes of participants with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's Disease or ulcerative colitis as the major disease treated with REMICADE, SIMPONI or STELARA in clinical practice in the emerging regions of North Africa, the Middle East, and Western Asia."
"Crohn's disease (CD) is a chronic disease with a heterogeneous clinical presentation, relapse rate and treatment response. Insufficient control of mucosal inflammation results in irreversible bowel damage and complications and at present no markers are available to predict such a complicated disease course at diagnosis. Therefore, to prevent overtreatment of low risk patients, step-up treatment with subsequent introduction of corticosteroids, thiopurines maintenance and TNF-blockers if a previous category fails is standard care. Combination treatment with thiopurines and a TNF-blocker is more effective than monotherapy but associated with a higher risk for infectious complications. Landmark studies convincingly showed an improved long-term outcome if the TNF-blocker infliximab is introduced early after diagnosis. The standard step-care approach thus prolongs steroid exposure and delays start of disease modifying biologicals in high risks patients. Given the higher efficacy of combination therapy with a thiopurine of infliximab and potential allergic reactions and lower response rates after re-initiation of this chimeric biological, temporary monotherapy with this TNF-blocker has not been studied as first line treatment before. Adalimumab is a humanised monoclonal antibody and subsequently, combination therapy of adalimumab + thiopurines has only a marginal effect on anti-drug anti-body formation. Furthermore, combination therapy with adalimumab does not enhance the clinical response. Therefore, periodic treatment with adalimumab in combination with close monitoring after drug-discontinuation, in newly diagnosed CD might improve outcome, reduce drug-related side effects while still preventing overtreatment.||The aim of this study is to compare the long-term efficacy and safety of periodic adalimumab as initial treatment in newly diagnosed CD patients compared to standard step-care with corticosteroid/budesonide as the initial treatment"
"The purpose of this study is to evaluate the the efficacy of TA-650 using Clinical activity index (CAI) score and other evaluation indicators in pediatric patients with moderate to severe ulcerative colitis after TA-650 administration of at a dose of 5 mg/kg at weeks 0, 2, and 6, and then every 8 weeks at weeks 14 and 22. The safety and pharmacokinetics are also evaluated."
"Despite the advent of newer biologic therapies such as infliximab for Crohn's disease, a form of autoimmune inflammatory bowel disease, a proportion of patients are refractory to such therapy and require surgery. The hypothesis is that mesenchymal stromal cell therapy using third party human cultured cells will be safe and effective"
The rationale of the protocol is based on the reported beneficiary results of case-patients by the administration of other anti-TNF drug (infliximab) in separate cases on the grounds of a probable autoimmune predisposition of the disease. The objective of this study is to clarify the potency of etanercept for the therapy of hidradenitis suppurativa.
"This is a prospective interventional open-label randomized trial. The patients treated with anti-||PD-1 (programmed-death receptor type 1) or anti-PD-L1 (programmed-death ligand) antibodies in case of new acute onset interstitial changes or new seriuos respiratory system related symptoms will be recruited for this study to perform diagnostics. At the recruitment the patient will be randomized 1:1 to investigatory or control arm, the randomization will be stratified upon three criteria:||severity of suspected pneumonitis at baseline (grade 2 vs. grade 3-4)|response for oncological treatment (partial response (PR) and complete response (CR) vs. stable disease (SD) and progression disease (PD))|chronic respiratory system disorders Both groups will be treated in the same way in terms of diagnostic procedures. In case of interstitial lung diseases related to immune checkpoint inhibitor is confirmed with the severity of grade 2-4 in the modified CTCAE criteria the patient will get the treatment, accordingly to the randomization: ARM A - INVESTIGATORY GROUP the start dose will be 1-4 mg/kg of body weight of prednisone, depending on clinical condition and pneumonitis severity, the induction treatment will last for 5-7 days, in case of severe condition - no improvement after 48-72 h of initial treatment - introduction of immunosuppressive agent is recommended - cyclophosphamide, mofetil mycophenolate or infliximab. A continuation treatment with dose tapering is than recommended, starting from 60mg q 24h of prednisone for 2-4 weeks, and dropping the dose 10mg q 24 h not faster than over 14 days; the maintenance dose of prednisone 10mg q 24 h should be hold for 8 weeks and withdraw should last for 4 weeks. This arm will be treated with corticosteroid for at least 12-24 weeks.||ARM B - CONTROL GROUP the starting dose will be 1-4mg/kg of body weight of prednisone , depending on clinical condition and pneumonitis severity, the induction treatment will last 5-7 days; in case of severe condition - no improvement after 48-72 h of initial treatment - introduction of immunosuppressive agent is recommended: cyclophosphamide, mofetil mycophenolate or infliximab. A continuation treatment with dose tapering is than planned, starting from oral dose of 30-60mg q 24h of prednisone, and dose reduction of 10mg q 24 h each 1 week. This arm will be treated for 6-12 weeks.||During the treatment and after its termination the function of respiratory system, interstitial changes in radiologic examinations, anticancer response, survival time, pneumonitis relapse and glucocorticosteroid side effects will be monitored and evaluated. The observation will last up to 52 weeks."
"This pilot project intends to examine the utility of a systems medicine approach to identify regulatory networks and their perturbation in psoriasis and atopic dermatitis, and to obtain a comprehensive perspective on disease and disease control by integrating and modelling data across multiple cellular levels and time following specific blockade of single pathophysiological factors through use of licensed biologics during routine care as systems biology challenge. To this end, ultra-deep phenotyping and prospective molecular characterization in short time-intervals and different disease equilibrium states will be carried out in targeted small sets of patients. The different layers and types of clinical and molecular information will then be integrated (integrative personal omics profiling iPOP) for generating insights into disease pathways and for extraction of molecular signatures that correspond to clinical severity scores. It will provide a good starting point for planning future trials aimed at identifying biological patterns useful for guiding targeted treatment."
"This is a 16-week, open-label study to identify factors that help predict clinical responses to DMARD therapies for RA (Rheumatoid Arthritis) patients. All patients will receive a starting dose of DMARD medication(s) which may be adjusted by the investigator as needed. If a subject becomes intolerant to a DMARD medication the subject will be withdrawn from the study at the discretion of the investigator. Visits (prior to week 16) where withdrawal is determined to be necessary will be considered end of study. End of study data (week 16) as well as study serum will be collected. (Serum only collected on those subjects who have consented to the addendum Serum and DNA of this study). A portion of the blood collected at baseline, week 8 and week 16 with the addendum portion of the study is for future research and will be utilized attempting to look to detect the generation of superoxide radicals. The radicals have been shown to be associated with inflammation and may correlate with the progression of RA. If this is true, then treatment with RA should decrease the levels of these radicals signaling response to treatment."
"The purpose of this study is to investigate how RA affect the brain structures in RA-patients and if anti-inflammatory treatment that target TNF-α or JAK OR physical training of hands has positive impact on neuropsychiatric symptoms and morphological changes in the brain caused by the disease.||The goal of this research project is to improve the knowledge of morphological changes in brain developed in connection to RA and to identify clinical and serological markers to predict development of those changes and finally, to investigate if anti-rheumatic interventions counteract destructive processes in the central nervous system (CNS) and improve the patient's health with respect to functionality, pain experience and psychological well-being."
"The purpose of this study is to explore whether LY2127399 is effective in relieving signs and symptoms of rheumatoid arthritis (RA) in patients with a history of inadequate response or intolerance to at least 1 Tumor Necrosis Factor-Alpha (TNFα) inhibitor therapy. Examples of these TNFα inhibitor therapies that are currently on the market include Enbrel® (etanercept), Remicade® (infliximab), and Humira® (adalimumab)."
"Psoriasis is a common inflammatory disease of the skin and joints with a prevalence of 1-3% in the caucasian population of Northern Europe and the US. Similarly to other inflammatory diseases there is now substantial and accumulating evidence that psoriasis has a systemic inflammatory component.||It is known that patients suffering from psoriasis have increased prevalence of traditional cardiovascular risk factors, such as hypertension, dyslipidaemia, obesity, tobacco use and diabetes mellitus. This would logically explain an increased rate of cardiovascular events, but even when adjusting for theses risk factors, psoriasis carry an independent risk for developing cardiovascular disease.||Recent large epidemiological studies have shown a strong correlation between psoriasis and myocardial infarction.||Atopic dermatitis has been linked to ischemic stroke in one study, but besides this, the disease has not been associated with cardiovascular disease.||In conclusion, convincing and increasing evidence is supporting that psoriasis induce accelerated atherosclerosis and hence cardiovascular disease and mortality. In particular, this is seen in young patients with early disease onset.||Psoriasis is believed to be driven by cytokines produced by Th1 and Th17 lymphocytes. A number of these cytokines are suggested to be atherogenic. In contrast, another chronic inflammatory disease, atopic dermatitis, is predominantly driven by Th2 lymphocyte derived cytokines, some of which may inhibit atherosclerotic processes. It is therefore, of interest to compare the presence of cardiovascular disease in these two inflammatory skin diseases.||Hypothesis: That the risk of developing cardiovascular disease and especially coronary artery disease is increased in psoriasis patients and that this process can be influenced by treatment of psoriasis with biological treatment."
"The purpose of this program is to provide early access to ustekinumab where it is commercially unavailable for the treatment of participants with moderately to severely active Crohn's disease who have failed treatment with conventional Crohn's disease therapy (example, immunomodulators or corticosteroids) and Tumor Necrosis Factor alpha (TNF alpha) antagonist therapy (e.g., infliximab, adalimumab, certolizumab pegol, or their biosimilars), or who are intolerant to, or have a contraindication to these treatments. During the course of this early access program (EAP), through the reporting of serious adverse events (SAEs) and non-serious adverse drug reactions (ADRs) by participating physicians, information on the safety and tolerability of ustekinumab will be captured."
The purpose of this study is to examine reports of the cancer called hepatosplenic T-cell lymphoma (HSTCL) in the Dutch National Database of Pathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief or PALGA) during the years 1995 to 2008.
"This study will compare the efficacy and safety of re-treatment with 2 doses of MabThera (rituximab) in patients with active rheumatoid arthritis (RA) who have previously experienced an inadequate response or intolerance to anti-tumor necrosis factor (anti-TNF) therapies etanercept, infliximab or adalimumab therapy. All patients will receive infusions of 1000 mg intravenous (IV) MabThera on Days 1 and 15; at Week 24 patients who have demonstrated a moderate or good response will be randomized to receive re-treatment with either 1 or 2 additional infusions of 1000 mg IV MabThera. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals."
"This is a non-interventional, retrospective study of adult participants with IBD. IBD consists of either ulcerative colitis (UC) or Crohn's disease (CD). The study will review the clinical data previously collected during February 2007 to March 2020 of approximately 724 participants who have had treatment with adalimumab, infliximab, golimumab, or vedolizumab in Taiwan."
"Anti-cytokine antibodies, such as Infliximab (an anti TNF alfa chimeric antibody) and Adalimumab (an anti TNF alfa humanize antibody), have been developed and used in clinical practice for the treatment of patients with Crohn disease (CD). Unfortunately, their efficacy is limited. Based on these concepts, a new drug has been developed for IBD treatment. Vedolizumab (VDZ) is able to recognize the α4β7 heterodimer, and selectively blocks gut lymphocyte trafficking.||The hypothesis of this study is that VDZ therapy may be to halt CD disease progression during time and modifying its natural history, using Lemann Index."
"The RATIO registry is a French registry designed by a multidisciplinary group to collect data on opportunistic and severe bacterial infections and lymphoma in patients treated with TNF-a antagonists ( infliximab, etanercept and adalimumab). A total of 486 medical units in metropolitan France participate in the RATIO registry. All diagnosis are retained after validation by 2 qualified infectious disease or haematologist physicians (on the basis of the standardized case report form, the hospitalisation summary, and the microbiological and radiological results). Risk factors for developing these conditions when treated by TNF-a antagonists will be identified in a case control study. Incidence of these diseases will be calculated."
"Up to 60% of patients with Seronegative Spondyloarthritides have inflammation in the colon or ileum. This is usually asymptomatic, but in 5 to 10% of patients with SA, Frank IBD will develop. Lesions of the bowel could also be present in the SA patients because of the potential injury posed by the NSAIDS, a common used medication in this setting.||It is the bowel involvement in patients with SA that we propose to characterize, partly because there are scant communicated data in the medical literature, especially regarding small bowel lesions."
"Randomized, placebo-controlled dose-ranging study of 2'-FL in IBD, Crohn's Disease (CD) and ulcerative colitis (UC). The overarching hypothesis is that 2'-FL supplementation in IBD will be safe and well tolerated, while increasing fecal Bifidobacterium abundance and butyrate in a dose dependent manner. The investigators will test 1, 5, or 10 gm 2'-FL compared to 2 gm dextrose placebo as a daily dietary supplement in pediatric and young adult IBD participants in stable remission receiving infliximab, adalimumab, or infliximab-dyyb biosimilar anti-TNF therapy."
"This study will evaluate the efficacy and safety of MabThera in patients with active rheumatoid arthritis who have had an inadequate response to one prior anti-TNF alpha inhibitor. MabThera-naive patients will be stratified into 3 arms, according to previous inadequate response to a)etanercept, b)infliximab or c)adalimumab. Patients will be treated with MabThera (1g infusion) on day 1 and day 15, and will continue their basic methotrexate therapy. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals."
"Patients with spondylarthritis (SpA) (including ankylosing spondylitis, psoriatic arthritis, arthritis as part of inflammatory bowel disease and reactive arthritis) have axial involvement (the spine) as well as peripheral inflammation in joints and entheses (where the tendons and ligaments are anchored to the bone). Patients with high disease activity of SpA may need biological treatment (anti-TNF alpha), which are very expensive medications. Thus it is necessary to have a sensitive method for assessing the response to treatment. Ultrasonography (US) is a validated and reliable method for assessing disease activity in joints and tendons, and may be used to follow the treatment response.||The present study will include patients with SpA starting on anti-TNF alpha treatment (as first biologic medication or when switching to a new biologic treatment). The study is an extension of the ongoing NORDMARD study (Norwegian longitudinal observational study of arthritic patients starting disease-modifying treatment). The patients will be examined by use of US of 38 joints and 14 entheses at baseline and after 3, 6 and 12 months.||The objectives are to explore US as a method to assess peripheral inflammatory activity for evaluation of response to medication as well as to compare the US pathology with clinical and laboratory findings."
In patients treated with the monoclonal antibody infliximab (Remicade®) -which binds to and blocks tumor necrosis factor alpha (TNF-alpha) - an infusomat filter is routinely used to prevent the very same early adverse events observed in individuals receiving intravenous immunoglobulins (IVIG). We recently used such a filter in a patient suffering from malaise and vomiting in the context of an IVIG substitution therapy. In this patient symptoms improved and IVIG-induced complement-activation was reduced (unpublished observation).||Based on this simple observation we hypothesize that this simple and approved filter-system may be efficient in retaining complement-activating immunoglobulin G (IgG) aggregates in IVIG-preparations. This effect may reduce complement activation - and consecutive inflammation - thereby diminishing adverse events.||In this prospective study we propose to investigate how complement activation and side effects after IVIG infusion relate in individuals receiving conventional (i.e. unfiltered) vs. filtered IVIG-preparations.
"TNF inhibitors have improved treatment options for patients with inflammatory bowel disease (IBD) and three TNF inhibitors, infliximab, adalimumab and golimumab are available for treatment of ulcerative colitis in Switzerland. However, these drugs have been tested under ideal conditions in randomized controlled trials. Real-world data are needed to complement this information. It is the aim of the investigators to study, whether patients with ulcerative colitis can be effectively treated with golimumab in a real world setting in Switzerland.||The investigators used data from the Swiss IBD cohort study (SIBDC) in Switzerland and identified all SIBDC patients with UC treated with Golimumab and performed a retrospective chart review. The investigators acquired patient reported outcomes and objective measures for inflammation at baseline, at 6-10 weeks and at 6 and 12 months after golimumab treatment. Primary endpoint was clinical response (i.e. meaningful improvement) at 6-10 weeks. Secondary endpoints were clinical response at 6 and 12 months and clinical remission (i.e. free of symptoms of disease)."
"TNF inhibitors have improved treatment options for patients with inflammatory bowel disease (IBD) and three TNF inhibitors, infliximab, adalimumab and golimumab are available for treatment of ulcerative colitis in Switzerland. However, these drugs have been tested under ideal conditions in randomized controlled trials. Real-world data are needed to complement this information. It is the aim of our study to test, whether patients with ulcerative colitis can be effectively treated with golimumab in a real world setting in Switzerland.||The investigators will use data from the Swiss IBD cohort study (SIBDC) in Switzerland. They will identify all SIBDC patients with UC treated with Golimumab and perform a retrospective chart review. The investigators will acquire patient reported outcomes and objective measures for inflammation at baseline, at 6-10 weeks and at 6 and 12 months after golimumab treatment. Primary endpoint will be clinical response (i.e. meaningful improvement) at 6-10 weeks. Secondary endpoints will be clinical response at 6 and 12 months and clinical remission (i.e. free of symptoms of disease)."
"Due to the rigor of the clinical development program of adalimumab for the indication of AS, the population of subjects with active AS that could enroll in previous phase 3 studies was limited. Therefore, it is necessary to further evaluate the use of adalimumab in a setting that mimics day-to-day clinical practice to obtain further safety and efficacy data by allowing subjects meeting the characteristics noted below to enter this study:||Subjects who failed another TNF inhibitor (etanercept, infliximab)|Subjects with advanced spinal ankylosis|Subjects with AS associated disorders (i.e., uveitis, IBD, and psoriasis)"
"Since biological disease-modifying anti-rheumatic drugs (bDMARDs) are available in rheumatoid arthritis (RA) strategy an emerging question is the definition of remission in RA. Today some criteria were already proposed and the last one was proposed in 2011.||All these criteria integrated only clinical criteria without imaging assessment. In this context, ultrasound joint is daily performed without definition of remission. A discrepancy exists between clinical remission and persistence of active disease with ultrasound joint presence of a Doppler effect indicating inflammation and the risk of progression of joint damage. A definition of remission in RA could include erosions regression in subchondral bone (at best measured by high resolution peripheral quantitative computed tomography (HR-pQCT)).||The main hypothesis is that the reduction of erosion size assessed by HR-pQCT will be observed only in the absence of local inflammation measured by Doppler ultrasound in the erosion.||Tumor Necrosis Factor (TNF) blockers have strongly improved RA therapy outcome in terms of clinical improvement and structural damage (progression of radiographic lesions). Recent data showed that there could be joint bone rebuilt in case of inflammation suppression. HR-pQCT is a new technique emerging for bone erosions assessment in RA. Erosions size and volume could be reduced with anti-TNF, but with a large interindividual variability. There was no correlation between the activity of clinical or ultrasound synovium and evolution of erosion HR-pQCT."
"The aim of this post-marketing observational study (PMOS) was to obtain further data on long-term safety, efficacy, and quality of life outcomes for adalimumab in routine clinical use in participants with moderate to severe chronic plaque psoriasis after unsustainable clinical response to other biologic disease modifying anti-rheumatic drugs (BDMARDs). There are few data so far showing the effects of switching from other BDMARDs to adalimumab in patients with moderate to severe chronic plaque psoriasis. This study was designed to evaluate the long-term effectiveness of adalimumab in participants with moderate to severe chronic plaque psoriasis using the Psoriasis Area and Severity Index (PASI) in participants previously treated with efalizumab, infliximab, or etanercept and who either never achieved satisfactory response, achieved satisfactory response initially but lost it over time, or discontinued treatment due to intolerance/side effect(s) or other reasons, for example after regular stop of etanercept."
"Adalimumab is one of the pharmacological treatments for rheumatoid arthritis (RA) of more recent marketing authorization, and as a result of this, there are only efficacy and safety data from clinical trials with controlled conditions.The study will evaluate the safety and effectiveness of adalimumab in the common clinical practice of RA treatment in Spain, with several types of patients showing concomitant treatments or diseases and compliance. Among the tumor necrosis factor antagonists safety studies, adalimumab safety has been the less investigated in the common clinical practice because of, as a result of its recent marketing, it was not included in the BIOBADASER (Data Base for Biological Products in Spain, Rheumatology Spanish Society), Biologic Products Database of the Spanish Society of Rheumatology ) in which was determined an association between infliximab therapy and the risk of developing active tuberculosis. To ensure the maintaining of the strict common physician practice (no prescription induction), and following the recommendations of the SER (Sociedad Española de Reumatología, Spanish Society of Rheumatology) consensus documents, it will be selected only those patients that were already in treatment with adalimumab (HUMIRA),(except patients involved in clinical studies with Adalimumab), and had shown good response, or those that fulfilled treatment indication in accordance with the SER recommendations and following the Summary of Products Characteristics of adalimumab (HUMIRA)."
"Crohn disease is an inflammatory chronic disease of the bowel the complex physiopathology of which brings in immunological, genetic and environmental factors. At present, the appeal to biotherapics anti-TNFa (infliximab and adalimumab) or anti-IL-12/23 (ustekinumab) in MC represents a major therapeutic progress at the origin of a significant improvement of the symptoms, the healing of the intestinal hurts and the quality of life.||Considering the new immunological targets of these biotherapics, the investigators put the hypothesis that an immunological profile (impulsive person and\or tissular) specific of the patients with one MC is associated with the answer to biotherapics. So, before beginning the treatment the patients expressing strongly the pro-inflammatory cytokine TNFa, would more may be answering machines in anti-TNFa and those with whom the immunological profile is very marked towards the way Th1/Th17 would more may answer favorably the ustekinumab. The identification of immunological profiles capable of predicting before treatment the answer under biotherapics could establish in MC but also in other inflammatory diseases a major step forward to guide the coverage."
"Hypothesis - Behcet's disease is a multisystemic chronic relapsing inflammatory disease, classified among the vasculitides. The clinical manifestations include mucocutaneous lesions, articular, ocular, vascular, gastrointestinal and/or central nervous system involvement.||The aetiology of Behcet's disease is unknown, however. Experimental evidence suggests that TNF-α may play an important role in the pathogenesis of the disease.||To date, case reports and small open-short term studies report the efficacy of anti-TNFα therapy (Infliximab and Etanercept), especially regarding ocular and mucocutaneous involvement in Behcet.||There are no double blind long term studies on larger number of patients regarding the efficacy of anti-TNFα, especially Humira in healing arthritis +/- other manifestations of the disease."
"Ulcerative colitis (UC) is a chronic inflammatory condition causing continuous mucosal inflammation of the colon, which is accompanied by episodes of bloody diarrhoea and abdominal pain. Both infliximab and adalimumab have been used with success for moderate-to-severe UC refractory to conventional therapy. More recently, golimumab, another anti-TNF antibody, has been added to the treatment armamentarium.||In the multi-centre, double-blind, placebo-controlled PURSUIT trial, patients with moderate-to-severe UC randomized to induction therapy with golimumab (200-100 mg, or 100-50 mg at week 0 and 2) achieved clinical response, clinical remission and mucosal healing more frequent than patients randomized to placebo. In the PURSUIT maintenance trial, patients randomized to golimumab every four weeks (100 or 50 mg) maintained clinical response through week 54 significantly more often than patients randomized to placebo. Data on the use of golimumab in daily clinical practice are unavailable.||The aim of the retrospective Belgian multi-centre BE-SMART trial is to evaluate the mid-term outcome of golimumab in patients with moderate-to-severe colitis. The primary endpoint will be steroid-free golimumab continuation at week 26. Secondary endpoints will include (steroid-free) clinical remission, (steroid-free) clinical response, (steroid-free) mucosal healing, (steroid-free) complete mucosal healing hospitalization-free survival, and colectomy-free survival."
"RATIONALE: Studying samples of blood from patients with cancer, hepatitis C, or Crohn disease in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer and other diseases.||PURPOSE: This laboratory study is looking at the effect of biological therapy on biomarkers in patients with untreated hepatitis C, metastatic melanoma, or Crohn disease."
"Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis, which has a estimated prevalence of 0.3 - 1 %. The clinical course varies, but PsA is often a progressive, erosive arthritis causing severe disability and increased mortality.||The biologic treatment infliximab and etanercept have recently been introduced for treatment of PsA and psoriasis, and current data indicate a higher efficacy than with previously available therapies. No clinical trials on adalimumab in PsA are yet published (2005), but preliminary data are encouraging. The improved treatment options have increased the need for sensitive methods for diagnosis, monitoring and prognostication of PsA, so that the efficient therapies can be initiated at the optimal time point and monitored optimally. Ultrasonography (US) and magnetic resonance imaging (MRI) and a number of biomarkers are promising, but not yet sufficiently studied, methods for this.||The hypothesis is that adalimumab will be an effective treatment option for PsA. Novel imaging- and biomarkers can provide additional information, compared to clinical measures and radiography, concerning activity, destructive progression and prediction of therapeutic response in PsA patients receiving adalimumab. The perspective is a potential improvement in diagnosis, monitoring and prognostication of patients with PsA."
"Loss of response under anti-TNF is frequent. 20% of patients with clinical relapse present an immune mediated pharmacokinetic failure. In the last AGA recommendations, switch to another anti-TNF drug is suggested with no indication of immunosuppressive agent. In a recent study, 70% of patients with an immunogenic failure to a first anti-TNF agent developed a new immunogenic failure to the second anti-TNF drug using alone."
"BACKGROUND: Previous studies of short-term surgical outcomes after preoperative exposure to anti-TNF therapy in ulcerative colitis (UC) patients who have undergone IPAA have been conflicting. We sought to determine whether preoperative exposure to anti-TNF therapy affects histological measures of fibrosis in the colorectum, which may be a potential factor in adverse anastomosis complications following IPAA surgery.||METHODS: Individuals who received infliximab as maintenance therapy and who received their last dose within 180 days of the first stage of IPAA were selected. The control group comprised UC patients who were not exposed to anti-TNF therapy, matched by age, sex, BMI, disease duration, albumin levels, and post-operative leak outcome. Hematoxylin and eosin- (H&E) and trichrome-stained slides from the most distal, well-oriented, full-thickness section of colorectum from each patient's total colectomy specimen were evaluated. Blinded assessment of the degree of fibrosis in the lamina propria, the submucosa, the submucosa immediately adjacent to the muscularis propria, and the subserosa was performed by a single observer using a semi-quantitative pictorial scale."
"The objective of the study is to evaluate two therapeutic strategies: ""early switch"" or ""therapeutic intensification"" in patients with spondyloarthritis in case of secondary treatment failure suspicion to a first monoclonal antibodies anti-TNF definite by increase of ASDAS and positivity to ADAb.||Patients and Methods:||Multicentric randomized prospective study. Duration of inclusion 30 months. Duration of follow-up 24 months. 104 patients with spondyloarthritis treated with infliximab or adalimumab will be included if their ADAb dosage is positive, and they will be randomized (1:1) in two groups : ""early switch"" where treatment will be change to another anti-TNF, or ""therapeutic intensification"" where interval between two injections will be shortened. Patients will be evaluated clinically (ASDAS) and biologically (ADAb) at 12 weeks then at 24 weeks. Principal outcome will be the variation of ASDAS between baseline and end of the study. Number of patients to be included has been determined statistically from a preliminary study (power >98% for ASDAS variation of 20% on week 24).||Expected results:||On week 24, we expect a better response and a greater proportion of patients in remission in the ""early switch"" arm compare to the ""therapeutic intensification"" arm."
"Crohn's disease (CD) is a chronic illness, immunologically mediated, probably induced by the exposure of the intestine to an antigen or antigens similar to the intestine, to which immunologic tolerance is lost or a dysregulated immunity ensues. The disease has a variable course, from a mild, intermittently active illness requiring only symptomatic therapy to a fulminant illness requiring potentially dangerous immunosuppressive therapy, surgery or both. The molecular defect causing CD has not been characterized, but probably involves aberrant T cell function. Although CD often responds to immunosuppressive medication including corticosteroids, azathioprine and 6-mercaptopurine, to anti inflammatory drugs such as 5 aminosalicylate (5 ASA), or to some antimicrobial agents, including metronidazole, no therapy has been curative. In patients with severe CD, who have been unresponsive to corticosteroids, azathioprine, 5 ASA, metronidazole, and infliximab, we propose to compare the efficacy of Crohn's disease non-myeloablative autologous hematopoietic stem cell transplantation (CDNST) to standard therapy. Subsequent disease activity will be followed by (1) Crohn's disease activity index (CDAI), (2) a more global severity index, the Crohn's Severity Index, (3) type and amount of therapy for CD, and (4) clinical, hematologic and biochemical studies."
"Crohn's disease (CD) is a chronic relapsing-remitting systemic inflammatory disease, affecting any part of the gastrointestinal tract. Biological therapy with anti-tumor necrosis factor (TNF) alpha is the established treatment of choice for the management of moderate to severe Crohn's disease. However, its efficacy in an individual patient is the unpredictable and long-term outcome is still suboptimal. Identifying biomarkers which can predict treatment response is thus of utmost importance and can allow personalized management.||In inflammatory bowel disease (IBD), altered fecal microbiota signatures have been consistently reported. Moreover, overall bacterial diversity is consistently decreased during intestinal inflammation.||Fecal calprotectin (FC) is a calcium and zinc binding protein largely confined to the neutrophil granulocytes and macrophages and is a very sensitive marker for detection of inflammation in the gastrointestinal tract.||C reactive protein (CRP) is an acute phase reactant. CD Patients with elevated baseline CRP levels responded to infliximab treatment better and early normalisation of CRP correlated with sustained long-term response to infliximab therapy.||The investigators hypothesize that faecal microbial signatures in conjunction with faecal calprotectin and CRP may have a role in predicting response to biological therapy in CD patients."
"The goal of islet cell transplantation in Type 1 diabetics is to provide those affected with constant normal blood glucose levels, thereby reducing or eliminating altogether the need for injected insulin. This normalization may prevent or slow progression of diabetic complications, result in a healthier lifestyle, and lead to a better quality of life.||Participants who meet the inclusion criteria will undergo an extensive screening process which typically includes a series of blood tests, EKG, chest x-rays, and a psychological evaluation, among others. Those who are eligible for and chose to participate in the trial will receive an islet cell transplant and bone marrow infusion from the same donor, together with following immunosuppressive medications: tacrolimus, sirolimus, daclizumab and infliximab. Because the bone marrow infusion may successfully prevent the transplanted islet cells from rejecting, some participants may be able to stop taking the immunosuppressive medications after a year.||The islet cell transplant is done under local anesthesia in a special procedure radiology room. Several days after the islet cell transplant, the participant is admitted to the hospital as an outpatient in order to receive bone marrow via a simple intra-venous infusion procedure.||All participants will need to be seen at the Diabetes Research Institute after the transplant for follow-up testing and post-islet cell transplant care."
"Aims:Prospectively observe the effects of Vitamin D drops supplementation on the chronic course of Crohn's disease patients, analyze whether the effect of Vitamin D drops on CD patients is affected by factors such as disease site, disease activity, treatment, etc.Exploring the relationship between Fok I gene polymorphism and the efficacy of vitamin D supplementation. Provide a certain theoretical basis for ""precision treatment"" for CD patients in the future.||Design：It is a prospective cohort study. Investigators include a total of 60 participants with CD according to the inclusion and exclusion criteria, and divide them into two groups to assess their initial disease activity and detect related indicators. At the same time，investigators detect the Fok I gene polymorphism in all participants.One group is given Vitamin D drops 400IU per day orally, and the control group do not intervene. Participants' disease activity is assessed at baseline and related indicators are determined. The disease activity is re-evaluated at 2, 6, 14, 22, 30, and 38 weeks, and the serum indexes are re-evaluated.Investigators use statistical methods to analyze whether Vitamin D drops supplementation treatment can increase the serum 25 (OH) D level of CD participants who are treated with infliximab, improve the condition of CD participants,relationship with Fok I gene polymorphism，and analyze the effects of Vitamin D drops on participants with CD is affected by factors such as disease site, disease activity, and treatment."
"The endoscopic capsule is a new tool for exploration of the small intestine. The superiority of this technique on the radiological conventional examinations was shown in Crohn's disease. However no standardization of the lesions exists and no score of severity was proposed. The objective of this exploratory and multicentric study is to develop and validate an endoscopic score of severity especially dedicated to the examination by endoscopic capsule of the small intestine. Hundred twenty patients reached of disease of Crohn corresponding to various groups of severity will be included and will have an examination by video-capsule. The recorded examinations will be the standardized collection of all the lesions observed by independent readers, which will make it possible to evaluate the level of reproducibility of the detection of each lesion. Moreover, each reader will provide his total, qualitative and quantitative evaluations, of the severity of the attack of the small intestine. By using the data of only one reader, a score of severity will be built by simple linear function of the reproducible lesions observed. This score will be validated from the data corresponding to other readers of the same examinations, and those corresponding to another sample. Lastly, the aptitude of this score to detect the changes of the severity of the attack of the small intestine and to define the endoscopic cicatrization will be evaluated from data obtained among patients before and after treatment by infliximab or corticoids"
"In dermatology, biologic medications are used to treat conditions such as moderate-to-severe psoriasis. These medications generally function to decrease inflammation or disrupt the inflammatory cycle. Examples of biologic medications commonly used in dermatology include tumor necrosis factor-alpha (TNF-alpha), blockers/inhibitors (etanercept, infliximab, certolizumab pegol, golimumab), interleukin 12/23 blockers (ustekinumab) and interleukin 17A blockers (secukinumab, ixekizumab).||Due to biologic medication's efficacy and safety profiles, they have revolutionized dermatology and the general medical field. However, patients may be apprehensive about choosing a biologic medication for a variety of reasons. These include hearing negative information about the drug from friends or family, being nervous about injection, or seeing the drug or its side effects negatively portrayed in the media. Many patients are not aware that clinical trial evidence for biologics exist, and instead may rely on anecdotal evidence in choosing to take these medications.||Because fear of the drug is inherently subjective, it can be modified with appropriate reassurance and presentation of evidence. Physicians must be able to ascertain from where the fear originates and how it can be countered. By understanding what kind of information will allow patients to be confident in their decision to take a biologic, dermatologists can improve outcomes and initiate use of this drug. Furthermore, reducing fear of side effects or adverse events may improve adherence to treatment and may improve treatment outcomes. The investigators propose this study with the goal of learning whether patients are more confident in the potential success of biologic medications in treating their psoriasis after being presented with clinical trial evidence, anecdotal evidence, or both."
"Approximately 20-40% of patients with ulcerative colitis (UC) are obese. The investigators have demonstrated that obesity adversely impacts disease course in patients with UC, leading to higher risk of persistently active disease, surgery, hospitalization, and treatment failure, particularly in biologic-treated patients. Intentional weight loss is effective in improving disease outcomes in patients with inflammatory arthritis, but there is limited data on its impact in UC. While dietary interventions for weight loss have limited efficacy and endoscopic bariatric interventions may be too invasive in patients with UC with active gastrointestinal symptoms, pharmacological weight loss with a highly effective oral agent may be a novel strategy to induce weight loss and augment the efficacy of biologic therapy in UC.||Hence, the investigators are conducting a pilot, phase 2A, 22-week, randomized, placebo-controlled clinical trial of phentermine-topiramate in obese patients with active UC starting on a new biologic agent (infliximab, adalimumab, golimumab, vedolizumab).||The overall objective is to (1) evaluate the efficacy, safety and tolerability of phentermine-topiramate, and (2) to assess the impact of pharmacological weight loss on clinical outcomes, inflammatory burden and biologic trough concentration in patients with UC. The central hypothesis is that phentermine-topiramate will be safe, effective, and well tolerated in patients with UC, and weight loss would achieve higher rates of clinical and biochemical remission, and higher biologic trough concentration."
"Patients with inflammatory bowel disease (IBD) will be assessed for immunologic response to pneumococcal vaccination. Patients with IBD meet criteria as outlined by the Centers for Disease Control (CDC) for pneumococcal vaccination, yet the investigators have found that pneumococcal vaccination in this population is under-utilized. It is unknown whether or not IBD or IBD-related medications impact the immune response to this recommended vaccine.||Three groups of 25 patients each will be recruited. The first group will consist of outpatients with IBD who are receiving infliximab (Remicade TM) while on concommitant immunosuppressive therapy (with either 6MP, azathioprine, or methotrexate). This group is intended to represent a common 'heavily immunosuppressed' patient group with IBD.||The second group will consist of patients with IBD seen in our outpatient clinic who are not on any immune-suppressive medications. These patients meet CDC criteria for vaccination by virtue of having a chronic medical illness. The third group will consist of healthy age-matched (to the first group) controls.||After obtaining informed consent, patients will be screened with baseline lab tests including testing for antibodies against pneumococcus. At the baseline visit, patients will also undergo a brief medical history, physical examination, and assessment of their IBD disease activity.||Included patients will then undergo a one-time intramuscular vaccination with 23-valent polysaccharide pneumococcal vaccine (Pneumovax TM). One month later, subjects will return for a blood draw to assess for response to pneumococcal vaccination."
"Takayasu arteritis (TA) is a vasculitis of unknown origin, resulting in progressive thickening and stenosis of large and medium arteries (the aorta and its major branches, and the pulmonary arteries). First line therapy of TA consists of high dose corticosteroids (CS) (Mukhtyar et al, 2009). Between 20 and 50% of cases respond to CS alone, with subsequent resolution of symptoms and stabilization of vascular abnormalities (Shelhamer et al, 1985; Maksimowicz-McKinnon et al, 2007). Although second-line agents (methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide) may result in initial remission, relapses remain common when prednisone is tapered (Maksimowicz-McKinnon et al, 2007). Thus, 50% of CS-resistant or relapsing TA patients may achieve sustained remission with the addition of methotrexate (Hoffman et al, 1994). During the last decade, biologics such as anti-tumor necrosis factor alpha (anti-TNFα) and anti-interleukin-6 (anti-IL-6) have been used as third-line treatment in refractory or relapsing TA. Almost 90% of CS-methotrexate resistant TA cases responded to infliximab, an anti-TNFα, and sustained remission was obtained in 37 to 76% of the cases (Schmidt et al, 2012; Comarmond et al, 2012; Mekinian et al, 2012). Tocilizumab, an anti-IL-6 has given similar results with 68% of sustained remission in refractory TA (Abisror et al, 2013). Irrespective of classical cardiovascular risk factors, the systemic inflammation and CS use play a pivotal role in the occurrence of cardiovascular thrombotic events (CVEs) (Roubille et al, 2015). As CVEs overlap with TA complications it is primordial to drastically taper CS in that vasculitis. We therefore aim to analyses prospectively the long term outcome of refractory/relapsing TA patients."
"Understanding of how best to treat inflammatory bowel disease (IBD) has evolved over the last ten years. Evidence now suggests that the most effective therapy early in the course of Crohn's disease (CD) and ulcerative colitis (UC) involves the use of immune suppressing medications such as the anti-Tumor Necrosis Factor (anti-TNF) agents infliximab, adalimumab, and certolizumab. However, many CD and UC patients still ultimately require surgery despite the use of these medications. Side effects of the anti-TNF agents include increased risk of infections due to their effect on the immune system. Little is known about how use of these medications near the time of surgery may affect patients' risks of infection or other post-operative complications. The only available studies on this topic have given conflicting results. These studies have been limited by the fact that they have been small in size and retrospective. Retrospective studies primarily involve chart review as the method of identifying potential risk factors for infections and other complications after they have already occurred. This method limits both the type and quality of information/data that can be collected. The conflicting results have led to variance in practice patterns with regards to management of anti-TNF agents, the timing of surgery, and even the types of surgery.||By enrolling patients at the time of their surgery, collecting extensive information may be possible than previously studied on potential risk factors for both infectious and non-infectious complications following surgery. Risk factors to be studied will include individual patient characteristics, disease characteristics, surgical methods, novel characteristics of CT scans and MRIs and extensive medication exposures. The primary objective is to determine if exposure to anti-TNF agents prior to surgery increases the risk of infection post-operatively. And evaluate exposure to anti-TNF agents by both patient history of use and measurement of anti-TNF drug levels at the time of surgery. Monitoring of drug levels at the time of surgery has never been utilized in this way to evaluate the risk of anti-TNF agents in IBD. However, this has been done to assess the risk of other medications in different diseases.||If anti-TNF agents are found to pose a risk for infectious or non-infectious outcomes in IBD patients undergoing surgery, change maybe needed in the way these medications are used around the time of surgery. Additionally, by collecting comprehensive information on other potential risk factors besides medication use patients at greatest risk for bad outcomes can be identified and take protective measures when possible. The aims of this study address the CCFA challenge to better define the risks of medical and surgical therapies to improve the quality of care of IBD patients undergoing surgery."
The purpose of this study is to assess the long-term safety of vedolizumab versus other biologic agents in participants with Ulcerative Colitis (UC) or Crohn's Disease (CD).
"This study will explore how patients with rheumatoid arthritis evaluate, or rate, symptom improvements. Physicians generally evaluate patients health and treatment benefits based on laboratory measures, such as the number of tender or swollen joints, duration of morning stiffness, grip strength, pain severity and others. Less attention is given to whether these treatment results are meaningful to patients. This study will examine how much of an improvement in pain, stiffness, function, and other symptoms is needed before patients consider the change an important improvement.||Patients 18 years of age or older who were diagnosed with rheumatoid arthritis after age 16 and who have active arthritis (6 or more tender joints) may be eligible for this study. Of particular interest are patients beginning treatment with prednisone, methotrexate, leflunomide, infliximab, or etanercept, although patients receiving any type of treatment may be included.||Participants will be evaluated twice at the NIH Clinical Center, once at the start of the study and again at either 1 month or 4 months later, depending on the individual s treatment regimen. Permission will also be requested to review patients medical records for results of previous blood tests and x-rays. At each NIH visit, patients will undergo the following tests and procedures:||Medical history and physical examination, including evaluation of joint swelling and tenderness;|Questionnaires about rheumatoid arthritis symptoms;|Computer-based exercise to assess preferences for various state-of-health choices;|Grip strength test;|Walking test on level ground, with or without the use of a cane or walker;|Blood test to measure inflammation.||At the second visit, in addition to the above procedures, participants will complete a questionnaire to rate the importance of changes, if any, in pain, morning stiffness, fatigue, joint swelling, functioning, worry, depression, and overall impressions, since the first visit."
"Crohn's disease is an 'auto-immune' disorder of the gut. In this condition the body's own immune system is fighting its gut and causing inflammation and other symptoms. Patients who are refractory (not responding) to the medications usually used to control Crohn's disease (medicines like steroids, azathioprine, methotrexate, cyclophosphamide and antibodies like Infliximab), may consider being part of this study.||In this study, the investigators plan to wipe out (ablate) the 'faulty immune system' with medicines (immune-ablation) and then give back the patients own stored stem cells (that have been collected before) - a procedure called autologous (self) stem cell transplant (ASCT). Once the new immune system regrows again from the stem cells, it is hoped that the 'faulty' immune cells do not return again and do not fight the gut leading to remission from symptoms of Crohn's disease. The aim of this treatment therefore, is to reset or re-program the immune system, so that it does not fight the patient's own body.||Currently, there are very few trials and experience with this procedure in children and young adults. There have been a few studies that have shown benefit of ASCT procedure in adult patients. In some patients, the benefit lasted for 1-5 years; but 1 in 5 (20%) participants were not taking their medications for the Crohn's disease even 5 years after ASCT. Other 80% needed medications again, but in most cases with better disease control.||In order to potentially improve the long term outcomes of ASCT, the investigators are adding another medication (in addition to those used in adult studies) called IL-2 (Aldesleukin), which will be given as an every-other-day injection under the skin (subcutaneous) at very low doses for 6 weeks after the ASCT and can be taken at home. Low dose IL-2 is known to increase a type of immune cell called T-regulatory cells (Tregs) that make immune cells less reactive to self. Study doctors believe that increased population of Tregs after ASCT may lead to a better control of Crohn's disease- higher percentage of cures or disease control for a longer period of time compared to the previous adult trials.||Therefore, the goals of this study are-||To see if ASCT can be used safely and can provide substantial benefit in young adults who have refractory Crohn's disease.|To see if addition of IL-2 after the ASCT is safe and effective."
"There are fewer therapeutic options for patients with active ulcerative colitis (UC) compared to patients with active Crohn's disease (CD) and the investigators are facing a persistent unmet need for additional effective and affordable therapies for patients with UC. Methotrexate (MTX) 25 mg once weekly administered subcutaneously (sq) or intramuscularly (im) is an efficient therapy to induce and maintain steroid free remission in patients with CD. To evaluate the efficacy of a similar approach in patients with active ulcerative colitis the investigators conduct a double-blind, placebo controlled, randomized, multicenter, parallel group trial to investigate the safety and efficacy of 25 mg MTX applied subcutaneously once weekly in patients with active UC, who either failed 5-ASA therapy, or are steroid dependent or are intolerant or not responding to azathioprine/6-mercaptopurine therapy or have no response/ lost response to infliximab prior to the study inclusion. The study is designed as a drug withdrawal trial and includes two periods, the Induction Period (week 0-16) and the Maintenance Period (week 17-48). In the open label Induction Period every patient will receive a steroid taper, MTX 25 mg sq once weekly + daily folic acid 1 mg tablets for the induction of clinical response or remission. Patients responding to the open label MTX therapy and being off steroids between week 12-16 will be randomized at week 16 1:1 to Placebo sq once weekly + daily folic acid 1 mg tablets + 2.4 g mesalamine or to MTX 25 mg sq once weekly + daily folic acid 1 mg tablets+ 2.4 g mesalamine. The Specific Aims of the trial are: i) To evaluate the safety and tolerability of 25 mg MTX applied sq once weekly over a time period of 48 weeks; ii) To evaluate the relapse-free survival of MTX maintenance therapy compared to placebo over a time period of 32 weeks; iii) To evaluate the efficacy of MTX over a time period of 16 weeks to induce steroid free remission; iiii) To establish a DNA, plasma and serum library to enable the evaluation of clinical and pharmacogenomic models to predict the response to MTX therapy in patients with UC. With 25-30 participating centers actively enrolling, the investigators anticipate to complete enrollment for this study in a time period of 3 years. Completion of this trial will define the therapeutic value of MTX in UC, potentially changing the current therapeutic strategy in UC."
This study evaluates the intestinal microbiome and disease activity in patients with spondyloarthropathies receiving immunosuppressive therapy.||Patients will be analysed at two time points in reference to two predefined primary endpoints:||Changes in intestinal microbiome|Response to therapy||The investigators want to evaluate if successful treatment of spondylarthropathy coincide with specific changes in the gut flora.
"Crohn's Disease (CD) is an inflammatory bowel disease. It can lead to significant complications and discomfort in the stomach and intestines. Crohn's disease is a debilitating, incurable disease of immune cells; it affects almost 1 million people in the United States. CD is characterized by inflammation of the stomach and intestine as well as organs outside of the intestines such as the skin, eyes, and joints. Current therapies to treat CD aim to suppress the patient's immune cells but these therapies become ineffective for the majority of patients and lead to complications including the requirement for surgical bowel resection, impaired quality of life, and lifelong disability. Hematopoietic stem cell transplantation (HCT) is a procedure used to treat a number of medical conditions including Crohn's disease. To improve success of HCT in CD doctors considered combining transplant with other drugs to improve the chances of achieving remission and also maintaining the remission. The Investigators' plan in this study is to incorporate the drug Vedolizumab after transplant to test if this drug will improve remission and make patients healthier.||Patients may qualify to take part in this research study because Crohn's disease is active, because surgery is not a treatment option and because there is evidence that the disease has failed to respond to treatments for Crohn's disease including the following:||corticosteroids|azathioprine, 6-mercaptopurine, methotrexate|Anti-TNFα (infliximab, adalimumab, certolizumab, golimumab)|Anti-integrin agents (natalizumab, Vedolizumab) If patients meet entry criteria will undergo a baseline endoscopy, colonoscopy and MR or CT enterography. If documentation of active mucosal disease patients will then be tapered off of current medications and undergo stem cell mobilization. Mobilization will involve low dose chemotherapy, growth factors and require 1-2 week hospitalization. Patients will then undergo stem cell transplant which will involve high dose chemotherapy and require a 2-4 week hospitalization. After restoration of the immune system patients will be placed on vedolizumab per standard dosing (0,2,6 then 8 every weeks) for a total of 8 doses. Patients will have monthly study visits and a repeat colonoscopy and MR/CT scan at 6 months."
"In patients with Crohn's disease, anal fistulas are usually treated in three stages: 1) close examination of the fistula and drainage with a seton, 2) pharmacological treatment of the inflammatory component, and 3) closure of the fistulous tract by a sphincter-sparing technique. Setons are used to ensure the permeability of the fistulous tract, to decrease the rate of re-intervention due to the formation of new abscesses or tracts. A seton is a small, often elastic, thread used for drainage. It is inserted into the fistulous tract, passing from the external orifice of the fistula (close to the anus or, in some cases, the vaginal) through the fistula and exiting via the anal orifice.||Seton use seems to minimize colonization of the mucosa of the fistulous tract by the intestinal flora, leukocyte infiltration, and the spread of inflammation within the fistulous tract. Most clinical practice guidelines advocate the use of a seton, but the level of evidence for the efficacy of this approach remains low (D, EL5). Indeed, only a few open studies have reported seton use to be potentially beneficial. In the retrospective study of 32 patients by Regueiro et al., a surgery group with seton insertion before treatment with infliximab was compared with a group on infliximab, without a seton, from the outset. Response rates were better in the group of patients with a seton, with a lower rate of recurrence and a longer time to recurrence than for the seton-less group. Another retrospective study by Schwartz et al. compared two groups - seton (n = 326) and no seton (n = 1519) - in patient with at least six months of biotherapy in three states of the USA. There were more hospitalizations and higher costs generated by greater use of the healthcare system in the group treated without a seton than in those with a seton.||The systematic use of setons in the context of Crohn's disease was inspired by the management of cryptoglandular fistula. However, the protective value of setons in this context remains far from clear, due to a lack of studies providing high-level evidence. Furthermore, the impact of seton use on patient quality of life has been little evaluated.||Investigators aim to determine whether the insertion of one or more setons in anal fistulas in Crohn's disease patients significantly alters patient quality of life. Investigators will perform a randomized controlled trial comparing two strategies: drainage surgery with and without seton use."
"This study will evaluate: 1) whether computed tomography (CT) scanning is better than regular x-rays for measuring changes in the stiffness, or fusion, of the spine in patients with ankylosing spondylitis; and 2) if CT can be used to determine how fast extra bone forms in the spine of these patients. Better ways to measure spinal fusion are needed to be able to evaluate the effectiveness of medicines in slowing or stopping its progression. CT uses x-rays to provide detailed pictures of the inside of the body and are valuable for detecting spinal abnormalities because of the precision with which it can show these structures. For the procedure, the patient lies on a table that moves into a large, donut-shaped scanner that can move around the body to take pictures at different angles, which are viewed on a computer monitor.||Patients 18 years of age and older with ankylosing spondylitis who are not currently taking or planning to receive treatment with anti-TNF alpha medications (etanercept, infliximab, adalimumab) for 1 year may be eligible for this study. Participants have eight clinic visits, scheduled at study entry and at 4, 8, 12, 16, 20, 24, and 48 months, at the NIH Clinical Center for the following procedures:||Clinical assessment (all visits) - includes medical history and physical examination, measurement of spine flexibility with a tape measure and protractor, symptoms questionnaire|Blood tests for measures of inflammation, including red blood cell sedimentation rate and C-reactive protein level (all visits)|Urine pregnancy test in women of child-bearing age (visits 1, 4, 7, 8)|X-rays of the pelvis, low back, and neck (visits 1, 4, 7)|X-ray of the low back (visit 8)|CT scan of the low back (visits 1, 4, 7)|Magnetic resonance imaging (MRI) of the low back (visits 1, 4) - MRI combines a powerful magnet with an advanced computer system and radio waves to produce accurate, detailed pictures of organs and tissues. The patient lies on a table in a narrow cylinder containing a magnetic field, wearing earplugs to muffle loud noises that occur with electrical switching of the magnetic fields. He or she can speak with a staff member via an intercom system at all times during the procedure. During the scan, a contrast dye (gadolinium) is injected into the bloodstream through a catheter (plastic tube inserted in a vein) to brighten the images.||In addition, participants will complete a symptoms questionnaire by mail every 4 months for 2 years between visits 7 and 8."
"Background:||Psoriasis is a chronic, immunologically-mediated, inflammatory skin disease and targeted therapies e.g. tumor necrosis factor (TNF)-α and TH-17 antagonists have become increasing important agents in the management of psoriasis. TNF, interleukin-17 (IL-17) and TH-17 play major roles in defense against infection. Large-scaled clinical trials and post-marking surveillance had shown these agents may increase susceptibility to infections. Most studies evaluate the reactivation of tuberculosis but the influence of targeted therapies on the viral infection has not been extensively investigated.||TNF-α has been shown to contribute to the killing of cytomegalovirus (CMV)- and human papillomaviruses (HPV)-infected cells. Additionally, recent studies have shown a high prevalence of HPV DNA in psoriatic skin and increased HPV5 antibodies in patients with psoriasis. The prevalence of HPV in the skin was also affected by therapeutic modalities, such as psoralen-ultraviolet A (PUVA). Several case reports in which CMV, Epstein-Barr virus (EBV) and HPV infection complicated therapy with TNF-α antagonists have been reported. However, the study investigated the effect of TNF-α antagonists and other biologics on reactivation of latent viruses is limited. Only two studies investigated the short-term effect of infliximab on reaction of herpesviruses in patients of rheumatoid arthritis and Crohn's disease. The high prevalence of combination use of immunosuppressants, such as methotrexate alongside with TNF-α antagonists in these patients is different from patients with psoriasis. Additionally, various bacterium and fungi, such as Staphylococcus aureus, Malassezia are associated with provocation and/or exacerbation of psoriasis and recent studies had shown IL-17 is essential for the immune response to common fungus Candida albicans.||Aim:||The aim of this study is to prospectively investigate the effect of target therapies (TNF-α, TH-17 antagonist, IL-17 antagonists, tofacitinib and apremilast) on the activation of viruses, including CMV, EBV and HPV and the impact of biologics on the prevalence of surface colonization of microorganism, including HPV, bacteria and fungi, in patients with psoriasis.||Methods and procedures:||Our project consists of two related study. The first (Study 1), a prospective observational study, included patients with psoriasis who are going to undergo biologics therapy, the viral loads of CMV and EBV, HPV DNA detection in eyebrow hairs and skin scales, and bacterial, fungal cultures from skin scales were performed before the initiation, 12 and 24 weeks after initiation of the target therapies, 12 weeks after discontinuation of target therapies. This part of our project is to investigate the dynamic effect of biologics on the microorganisms in patients with psoriasis. The second part (Study 2), a case control study, recruits psoriasis patients who have started target therapies, they receive the sampling of blood, eyebrow hairs and skin scales for CMV, EBV and HPV investigations when they are enrolled. Control group compromised of age-and disease severity-matched psoriasis patients who are not treating with target therapies or other systemic antipsoriatic agents. Comparison of the prevalence of latent virus, virus reactivation, bacteria and fungi skin colonization between psoriasis patients who are treating with and without target therapies is performed. The aim of study 2 was to assess any difference of the status of latent virus or microorganism colonization in skins between psoriasis patients treated with and without target therapies."
"Spondyloarthritis (SpA) is one of the potentially debilitating inflammatory diseases that affect the whole body, primarily burdening the sacroiliac joints and the spine. It mostly affects young and middle aged adults. SpA can be classified to non-radiographic axial SpA (nr-axSpA) and radiographic axSpA (r-axSpA). The latter is ankylosing spondylitis (AS). The key to its early treatment is the radiological detection and management of sacroiliitis. To date, biologics is the most powerful anti-inflammatory drug. Recent research has shown that diffusion-weighted imaging (DWI) outperforms the sequence recommended by the Guidelines in diagnosing inflammation and assessing disease activity. Preliminary research conducted by our team has also demonstrated that apparent diffusion coefficient (ADC) is a valuable imaging biomarker. However, to date, no serum maker of comparable effectiveness has been identified. Damage-Associated Molecular Pattern (DAMP), including S100A8 and S100A9, high mobility group protein B1 (HMGB1) and Tenascin-C (TNC), may play a role in inflammation by regulating the TLR4/MyD88/NF-κB signaling pathways. The present study will enroll 20 patients with nr-axSpA and 20 patients with AS. It will utilize serum DAMP and ADC to assess disease activity before and after treatment as well as the change in and correlations of treatment outcomes, in order to identify objective and quantifiable serum and imaging markers that are beneficial in clinical applications. ADC is the primary outcome. The main hypothesis is that disease activity as measured by ADC will be reduced after 1 year of treatment from baseline as compared to before treatment at baseline. Study findings will indicate the utility of ADC as an objective indicator of disease activity for guiding therapeutic approaches and improving dosage adjustment in clinical applications."
"TNFi drugs remain the most prescribed first-line biologics for patients with rheumatoid arthritis (RA). However, up to 40% of RA patients fail to respond to TNFi treatment. One explanation of non-response is the development of anti-drug antibodies and low drug levels.||Studies have consistently shown that:||Serum drug levels of monoclonal antibodies (such as adalimumab, certolizumab, infliximab) and the presence of anti-drug antibodies in samples taken at 3 and 6 months correlate with subsequent response at 12 months.|Non-responders and those who develop anti-drug antibodies are less likely to receive concomitant methotrexate or, if they do receive it, are on lower doses than responder groups.||However, it has not been proven that knowing that a patient had low drug levels or anti-drug antibodies would have improved the outcome; neither has it been shown that introducing or increasing the dose of methotrexate would reduce the formation of anti-drug antibodies, thereby improving outcome.||Observational data has revealed that RA non-responders, who exhibit adequate serum drug levels and no detectable anti-drug antibodies, have lower probability of response to another agent with the same mechanism of action (MOA), and may benefit in switching to a drug with a different MOA (12). RA non-responders, who have low detectable serum trough levels and detectable anti-drug antibodies, may benefit in switching to a less immunogenic drug (13, 14). These patients may have a predisposition of developing immunogenicity against the introduced foreign protein (12). Neutralising anti-drug antibodies against the TNFi etanercept or the T-cell co-stimulation inhibitor abatacept have not been detected (10, 12, 15). Furthermore whilst the use and dose of methotrexate at initiation of TNFi, has been associated with lower levels of anti-drug antibodies in our work and others (10, 16), it is not known if increasing the MTX dose once immunogenicity has developed reduces anti-drug antibodies and leads to improved treatment response.||Whilst algorithms have been proposed based on these tests (4, 17, 18), they have not been confirmed in a randomised controlled trial setting to show that the intervention (testing) is effective. Based on our preliminary work in an observational dataset, this feasibility study will allow us to design a definitive study to answer the important issue of whether pharmacological testing can be utilised as robust biomarkers to optimise future patient outcomes.||The next essential step, therefore, is to prove that introducing these tests improves clinical outcome. It is very important to do so because some clinicians are already requesting that their immunology laboratories introduce such tests; yet the tests themselves are expensive and have not yet shown efficacy (19). Conducting a clinical feasibility trial is one of the essential first steps in development of a full clinical trial to undertake process evaluation and assess the proposed study design, required number of participants and ensure optimum project completion.||The proposed trial is a clinical feasibility trial with the aim to ensure a realistic assessment and capability to conduct the full clinical trial. Participants with RA, commencing adalimumab or certolizumab will be randomised to determine whether providing test results on adalimumab/certolizumab drug levels and anti-drug antibodies at 4 weeks, 3 and 6 months to clinicians caring for patients with RA (n=15 patients) starting on treatment with adalimumab/certolizumab, improves the course of disease activity, compared to standard care (n=15 patients). Clinicians will be provided with feedback and a treatment algorithm. The feasibility of the study will be assessed by a number of factors including evaluation of recruitment, attrition, data completeness and process evaluation. The results will be used to inform the number of participants required to fully evaluate the intervention."
"The primary endpoint of this study is to evaluate the prevalence of anxiety and depressive disorders, and their relationship with disease activity, in patients with rheumatoid arthritis treated with biological drugs"
"The study is to determine whether active surgical intervention promotes disease remission in patients with Crohn's Disease (CD).The management of CD involves both maintenance medication and medication used to control flares of the disease. The goal of maintenance therapy in CD is to maintain steroid- free remission, clinically and endoscopically. This requires regular clinical assessment including history, physical examination and at times colonoscopic examination. Other tools of assessment include blood (e.g. CRP, WCC) and stool (calprotectin) testing for inflammatory markers and imaging including MRI, CT or ultrasound.||The choice of maintenance treatment in CD is determined by disease extent, disease course (frequency of flares), failure of previous maintenance treatment, severity of the most recent flare, treatment used for inducing remission during the most recent flare, safety of maintenance treatment, and cancer prevention. The mainstay of maintenance medication are the 5-aminosalicylic acid compounds (5-ASA) such as mesalazine or sulphasalazine.||These compounds are commonly taken orally in formulations that predominantly deliver the active 5-ASA component to the colon. Alternatively, or in addition, mesalazine preparations can be delivered topically via enema or suppository if the disease only involves the left side of the colon (although it is only PBS funded for topical therapy during a flare and not for maintenance of remission - even though it also works in this setting). The majority of patients can be managed with maintenance 5-ASA compounds most of the time. For patients who have repeated flares of disease on 5-ASA maintenance therapy (1 or more flares in a year needing steroids), thiopurine medication such as azathioprine or 6-mercapropurine should be used. These medications induce systemic immunosuppression, reduce the incidence and severity of flares of colitis but also slightly increase the risk of some infections and malignancy. Anti TNF agents such as infliximab or adalimumab have been shown to have benefit in maintaining remission in CD (and are licensed for this indication by the TGA), however these agents are very expensive and not funded by the pharmaceutical benefits scheme in Australia and so, are not readily available. The anti TNF agents also give an increased risk of infection, particularly latent TB reactivation.||Mild flares of CD can be managed with higher doses of oral 5-ASA compounds or the addition of topical 5-ASAs given via enema or suppository. More severe flares are usually managed with a course of systemic corticosteroid. These can be given intravenously in acute, severe disease or orally in less severe flares. The steroids should then be tapered over time and discontinued. There is no indication for long term steroid use in CD and prolonged steroid use is associated with a number of complications including infection, osteoporosis, obesity, diabetes, poor wound healing, thinning skin, mood changes and insomnia. Severe flares of CD not responsive to steroids may respond to rescue therapy with the addition of either cyclosporin or anti-TNF therapy.||Patients in whom colonic inflammation cannot be controlled adequately frequently undergo total colectomy. This may be done electively (for refractory disease) or emergently in acute fulminant colitis. Colectomy entails surgical risk that is higher in the emergent setting; this risk includes infection, wound breakdown and a mortality rate. Colectomy is considered ""curative"" for CD especially if they have an ileostomy stoma created, however, it frequently also leads to complications both short- and long-term. In addition, in patients in whom an ileal-anal pouch is fashioned up to 50% will subsequently develop pouchitis at 4 years post surgery.||Patient eligibility was determined during a 5-week screening period, during which time details on patient demographics, medical history, and previous and concomitant medications were obtained,and the following assessments were completed: viral serology, stool culture, Crohn's Disease Activity Index (CDAI) patient diary and clinical score, Simple Endoscopic Score for Crohn's Disease (SES-CD), colonoscopy and colonic biopsy, stool collection for faecal biomarkers, vital signs, and laboratory evaluations.||All participants need to be subjected to rigorous assessments mentioned above at week 4, week 8 and week 12 after receiving active surgical intervention (two kinds: one is colostomy, and the other one is colonic exclusion)."
"Some medications taken by the breastfeeding women are excreted into milk, posing a potential risk of toxicity to the infant. The first line of evidence required for toxicity risk assessment is prediction of drug levels in milk. However, pharmacokinetic (PK) information of drug excretion into milk is largely lacking, or limited to data from case reports. This makes it difficult to provide population-level prediction of drug levels in milk. The lack of data on this topic jeopardizes not only maternal adherence to drug therapy during breastfeeding but also establishment of breastfeeding, even if the drug is considered safe during nursing. Clearly, this clinical problem in drug safety is an important women's health issue, affecting both mother and infant. ""Drugs in Lactation"" Analysis Consortium (DLAC) is a ""drug-in-milk"" monitoring network, which is designed as a platform for efficient collection of patient milk samples in a real world setting to generate population predictions of drug excretion levels into human milk."
"The rationale for this study is to investigate whether in psoriatic arthritis (PsA) patients in stable remission a reduction or complete discontinuation of immunosuppressive therapy can be achieved in a treat-to-target approach while maintaining in remission. Due to the lack of reliable data that answers the question of how to safely reduce medication in which patients, this study will test a pragmatic treatment algorithm that can be applied in clinical practice and that offers a gradual reduction with escape strategies in order to facilitate the maintenance of remission."
"An observational, prospective cohort study to evaluate the safety and efficacy of Remsima™ in patients with Crohn's disease (CD) or Ulcerative Colitis (UC)"
"The inflammatory bowel diseases represent a heterogeneous group of chronic , relapsing- inflammatory disorders of the gastrointestinal tract. Crohn's disease and ulcerative colitis are the two major clinical forms.The global incidence and prevalence of the inflammatory bowel diseases has increased over the last 2-4 decades . Despite the great progress in understanding the pathogenesis of these diseases, their etiology remains unclear . Considerable effort has been devoted to the development of an accurate ,noninvasive biomarkers that have increased diagnostic sensitivity and specificity .||Osteoprotegerin is a member of the Tumor Necrosis Factor Receptor superfamily of proteins. Osteoprotegerin is of particular importance in bone metabolism, inflammation , tumorigenesis, and other processes where cell differentiation, survival, and death are controlled. Osteoprotegerin activates inflammation in the gut by stimulating immune cells, cytokines, and the Necrosis factor-κappaB pathway .||Soluble Receptor activator of nuclear factor kappa-Β ligand is known as a type II membrane protein and as a member of tumor necrosis factor superfamily . Soluble Receptor activator of nuclear factor kappa-Β ligand has been identified to affect the immune system and a binding partner of ( Osteoprotegerin ), and controls cell proliferation.The interactions between Osteoprotegerin and Soluble Receptor activator of nuclear factor kappa-Β ligand, Soluble Receptor activator of nuclear factor kappa-Β have relevance to inflammatory pathways. Soluble Receptor activator of nuclear factor kappa-Β ligand- Soluble Receptor activator of nuclear factor kappa-Β ligand binding activates pathways that contribute to the survival of T-lymphocytes and dendritic cells ."
The overall purpose of this trial is to assess efficacy and safety of the combination of low doses of Methotrexate (MTX) with anti Tumor Necrosis Factor (TNF) alpha to improve initial efficacy and maintenance rate of anti-TNF alpha treatment in patients with psoriasis.
The purpose of this study is to describe treatment patterns associated with first-line and second line biologic use (vedolizumab or other biologic) and to describe the real-world clinical effectiveness of the use (first-line and second line) vedolizumab versus other biologics at least 6 months post-treatment initiation.
Fatigue is a common symptom and a leading concern in patients with inflammatory bowel disease (IBD) and often persists despite clinical and endoscopic remission.||This study evaluates the metabolomic profile of fatigued patients with IBD.
"The investigators propose an observational study including patients with inflammatory bowel disease under biological therapy with anti-TNF, anti-integrin α₄β₇ or anti-interleukin 12-23 (Ustekinumab), followed by an external Gastroenterology consultation at Centro Hospitalar Tondela-Viseu."
Metabolomics of systemic psoriasis treatment
The purpose of this study is to describe clinical course of newly diagnosed moderate to severe ulcerative colitis (chronic inflammatory disease of the colon) in tertiary referral hospitals in Korea for 5-year follow-up under usual care.
Crohn's disease (CD) is a chronic inflammatory bowel disease. CD pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota in predisposed hosts.||The purpose of this study is to evaluate de clinical efficacy of the fecal microbiota transplantation (FMT) as a maintenance treatment following anti-TNF agent withdrawal in CD's patient.
"This study is a pilot study to determine whether patients with TNFα excess have decreased calcium absorption in response to calcitriol (1,25-dihydroxyvitamin D, the active form of vitamin D) compared to normal controls. This initial pilot study is being done to determine if it is feasible to conduct a study where TNFα could be blocked (e.g., by anti-TNFα therapy such as Enbrel® or Remicade®) to improve vitamin D dependant calcium absorption and thus bone health."
"The primary objective of this study is to prospectively validate a novel intestinal ultrasound (IUS) Crohn's disease (CD) activity index and component items, correlating CD activity and responsiveness to therapy as evaluated by IUS with evaluations by ileocolonoscopy (IC) (Simple Endoscopic Score for Crohn's disease [SES-CD]) and magnetic resonance enterography (MRE) (Simplified Magnetic Resonance Index of Activity [MaRIA] score)."
"The purpose of this study is to examine the effect of anti-TNF therapy on rheumatoid arthritis using magnetic resonance imaging (MRI) and ultrasound imaging.||Anti-TNF therapies include a group of medications such as Enbrel, Remicade and Humira that affect your body's inflammatory response. These medications are routinely prescribed for the treatment of rheumatoid arthritis."
"This research study is for patients that have been diagnosed with chronic uveitis, a disease that causes inflammation in the eye. Patients are currently being treated with Remicade, Humira, Methotrexate and or similar chemotherapy type drugs to control this inflammation. Despite these medications, patients still have inflammation in their eyes. Patients are being asked to add an additional drug, thalidomide."
"Approximately, 40 to 50% of patients with rheumatoid arthritis (RA), the most frequent inflammatory arthritide, are non responders to the consensual 1st line of treatment : methotrexate. In these patients, it is well demonstrated that the addition of other immunomodulatory drug(s) often results in a significant improvement. However, the best option regarding the drug(s) to add remains unclear. Rheumatologists are currently used to adding a targeted therapy, such as anti-TNFα, and more recently abatacept or tocilizumab. Triple therapy using 3 conventional disease-modifying drugs (DMARDs), methotrexate or leflunomide+salazopyrine+hydroxychloroquine could be an alternative option to targeted therapies, all the more as they have a more favorable safety profile and a much lower cost. Uncertainty remains regarding the superiority of targeted therapies on triple therapy in methotrexate or leflunomide insufficient responders (IR). Investigators decided to address this issue by performing a randomized controlled pragmatic trial."
"A Phase 2b Parallel-Group, Double-Blind, Placebo-Controlled, Multicenter Study of SYN-004 Compared to Placebo for the Prevention of Clostridium difficile Infection (CDI) in Hospitalized Patients receiving IV ceftriaxone with a Diagnosis of a Lower Respiratory Tract Infection (LRTI)."
"A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multi-Dose Study of the Effect of Two Dosage Strengths of SYN-010 Compared with Placebo on Breath Methane Production in Breath Methane-Positive Subjects with Irritable Bowel Syndrome with Constipation (IBS-C)"
"A Single-Dose, Open-Label, Extension Study to Evaluate the Sustainability of the Effects of SYN-010 in Patients with Irritable Bowel Syndrome with Constipation"
The purpose of this study is to determine whether taking a growth hormone (GH) drug called somatropin causes the intestine of a person with Crohn's Disease (CD) to heal faster when compared to a person with Crohn's Disease that does not receive growth hormone drug.
"The objective of this study is to evaluate the effect of Tumor Necrosis Factor (TNF) inhibition on oral parameters in patients with RA and to examine changes in levels of proinflammatory cytokines in serum, gingival crevicular fluid (GCF), and saliva at an early time point (6-8 wk) and a later time point (14-16 wk) after the initiation of therapy in relation to concomitant assessment of Rheumatoid arthritis (RA) and oral clinical variables.||The purposes of the study are to:||Determine if oral periodontal parameters are affected by TNF inhibition;|Examine relationships between periodontal variables and RA variables with TNF inhibition;|Determine if there may be potential early response markers of clinical RA response seen using ultrasensitive analysis of oral or serum cytokines."
"This study will be an open label observational prospective study assessing the clinical efficacy of antiTNFα therapy and the alteration/impact on the synovial tissue, with specific regard to lymphoid aggregation, over a period of 12 months in patients with rheumatoid arthritis.||Rheumatoid arthritis (RA) is one of the most important chronic inflammatory disorders in the UK. It affects approximately 1% of adults and causes considerable morbidity, substantially reduces quality of life and has a significant mortality. It results in large direct medical costs as well as extensive indirect social costs. Despite the significant therapeutic progress following the introduction of antiTNFα, a cure for RA is still elusive. At present the reasons for the variation in clinical response are not known. The main aim of this study is to test the hypothesis that there are distinct molecular and cellular phenotypes present within the synovial tissue that define specific disease subsets and provide characteristic prognostic implications. In particular, the aim is to assess the relationship between the presence of ectopic lymphoneogenesis (ELN) within the rheumatoid synovial membrane and response to antiTNFα therapy."
This is a retrospective observational study looking at the characteristics and outcomes of participants taking Inflectra using the CorEvitas Rheumatoid Arthritis Registry.
"Objective: This randomized, controlled clinical study aimed to evaluate the performance of one universal adhesive applied with etch-and-rinse or self-etch strategy and one etch-and-rinse adhesive on fissure sealant retention over 24 months. Methodology: 144 sealants were placed on the permanent premolars and molars of 13 subjects. Teeth were divided into three groups SB2(control): Adper Single Bond 2, SBU-ER: Single Bond Universal/etch-and-rinse, SBU-SE: Single Bond Universal/self-etch. After the adhesive application, Fissurit FX was applied and light-cured. Clinical evaluations were done at baseline and at 1 week, 6-, 12-, 18- and 24-month recalls. Visual examination was performed on every visit for evaluation of the sealants. Evaluating criteria were: 1= completely retained; 2= partial loss; 3= total loss. The Pearson Chi-square test was used for each evaluation period."
"There are two main aims of this study.||First aim is to compare the risk of composite cancer outcomes, between patients treated with tofacitinib and patients treated with TNF inhibitors (TNFi) for rheumatoid arthritis (RA) among, 1) ""real world evidence (RWE)"" cohorts including routine care patient population from the US and, 2) ""Randomized controlled trial (RCT) DUPLICATE"" cohorts including routine care patient population who meet inclusion and exclusion criteria of the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis (""ORAL Surveillance"", NCT02092467) clinical trial.||Second aim is to examine the risk of common solid cancers (lung, colorectal, breast, prostate), hematological cancers, and non-melanoma skin cancer as separated endpoints when comparing tofacitinib with TNFi in patients with RA among, 1) ""real world evidence (RWE)"" cohort including routine care patient population from the US and, 2) ""Randomized controlled trial (RCT) DUPLICATE"" cohort including routine care patient population who meet inclusion and exclusion criteria of the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis (""ORAL Surveillance"", NCT02092467) clinical trial."
"There are two main aims of this study.||First aim is to compare the risk of cardiovascular events (including myocardial infarction or stroke), between patients treated with tofacitinib and patients treated with TNF inhibitors (TNFi) for rheumatoid arthritis (RA) among, 1) ""real world evidence (RWE)"" cohorts including routine care patient population from the US and, 2) ""Randomized controlled trial (RCT) DUPLICATE"" cohorts including routine care patient population who meet inclusion and exclusion criteria of the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis (""ORAL Surveillance"", NCT02092467) clinical trial.||Second aim is to examine the risk of myocardial infarction, stroke, heart failure hospitalization, coronary revascularization, and all-cause mortality as separate endpoints when comparing tofacitinib with TNFi in patients with RA among, 1) ""real world evidence (RWE)"" cohort including routine care patient population from the US and, 2) ""Randomized controlled trial (RCT) DUPLICATE"" cohort including routine care patient population who meet inclusion and exclusion criteria of the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis (""ORAL Surveillance"", NCT02092467) clinical trial."
"An Observational, Prospective Cohort Study to Evaluate Safety and Efficacy of RemsimaTM in Patients with Ankylosing Spondylitis"
"This is a phase 3, multicenter, randomized, open, prospective, controlled, parallel-group intervention study in 318 patients with Rheumatoid Arthritis. The study is composed of 3 phases: a pre-randomization phase for up to 10 days followed by a 1-year randomized, open three arm treatment phase for each patient, followed by a 5-year observational phase for all patients still in remission."
In this study patients with moderate to severe chronic graft-versus-host disease will be treated with a combination of prednisone and everolimus. Patients will be treated on the study for a maximum of 12 months and followed up for another 12 months.||The primary hypothesis of this study is that the addition of everolimus to prednisone increases response rates without increasing treatment related mortality or mortality due to relapse of underlying disease.
The aim of this study is to validate the ability of Capsule Endoscopy (CE) to accurately diagnose small bowel (SB) Crohns disease in patients with symptoms of abdominal pain and diarrhea.||The primary objective of the study is to evaluate whether Capsule Endoscopy prior to colonoscopy will improve diagnosis in patients with suspected Crohns disease when compared to standard diagnostic testing.
Compare the efficacy of adding small doses of prednisolone (10 mg) daily to the efficacy of adding one of the available anti TNF in the treatment of methotrexate inadequate responder rheumatoid arthritis patient.||Hypothesis:||Methotrexate + Prednisolone vs. Methotrexate + anti TNF
This study evaluates the intestinal microbiome and disease activity in patients with rheumatoid arthritis receiving immunosuppressive therapy. Patients will be analysed at two time points in reference to two predefined primary endpoints:||Changes in intestinal microbiome|Response to therapy||The investigators want to evaluate if successful treatment of rheumatoid arthritis coincide with specific changes in the gut flora.
"Objectives: To examine the effect of prophylaxis therapy on clinical and endoscopic disease recurrence in children with Crohn's Disease (CD) following ileo-cecal resection. Hypothesis: Post-operative pediatric patients treated with anti-Tumor necrosis factor (TNF) prophylaxis will demonstrate lower endoscopic recurrence rates at 1 year and lower clinical recurrence rates at 2 years compared with thiopurines treated patients. Design: A multi-center, prospective, observational study. Patients with either thiopurines or anti-TNF prophylaxis will be enrolled 0-6 months following ileo-cecal resection. Prophylactic treatment will be decided at the discretion of the treating physician and not as a part of the study. According to standard-of-care, patients will undergo a colonoscopic evaluation 6-9 month following surgery. Study visits will be performed at 6 months following resection, 12 months, 18 months and 24 months. Setting: Porto group and IBD interest group pediatric gastroenterology centers. Participants: Children 6 year to 18 years (Overall, 84 patients) with CD following limited ileo-cecal resection. Main outcome measure: 1. Endoscopic recurrence at 1 year (according to Rutgeerts Score: i2-i4). 2. Clinical recurrence at 2 years (according to pediatric Crohn's disease activity index-PCDAI: ≥10). Secondary outcome measures: 1. Re-operation rate at 2 years. 2. Exacerbation-free quartiles at 2 years. 3. Anthropometric and laboratory measures including calprotectin at each visit. 4. Changes in fecal microbiome- baseline, 1 year and 2 years. Inclusion criteria: 1. CD with phenotypes L1 and L3 following ileo-cecal resection. 2. No active perianal disease. 3. Prophylactic therapy with either thiopurines or anti-TNF. Exclusion criteria: 1. Pregnancy. 2. Active perianal disease (draining fistula or abscess). 3. Post-operative intra-abdominal complication (fistula or abscess). Sample size: In order to demonstrate 20% difference in endoscopic recurrence rate between groups is significant, we will need to study 42 children in each group to be able to reject the null hypothesis that the failure rates between the groups are equal with probability (power) of 80% and a type I error probability of 0.05."
The associations between female inflammatory bowel disease (IBD) patients and human papilloma virus (HPV) infection and cervical neoplasia (dysplasia or cancer) were unclear. Especially there was no data for Chinese IBD population. So we investigated the incidence and risk factors of HPV infection and cervical neoplasia (dysplasia or cancer) in female IBD patient.
"Rheumatoid arthritis (RA) is a frequent inflammatory arthritis that can lead to severe joint deformity and often requires orthopaedic surgical interventions. Anti-Tumor Necrosis Factor α (anti-TNFα) are biological disease-modifying antirheumatic drugs (DMARDs) increasingly used in the treatment of rheumatoid arthritis. An increased risk of opportunistic infection was demonstrated in patients treated with those drugs. This observation led many national committees to recommend anti-TNFα suspension in the perioperative period to avoid a raise in the postoperative infection risk in those patients. This approach is not supported by the data available in the current literature and it exposes patients to an increased risk of inflammatory flare ups of their disease during and after anti-TNFα suspension, which can compromise their postoperative rehabilitation and their quality of life.||The objective of this prospective randomized multicentric trial is to determine the effect of anti-TNFα suspension in the perioperative period on the postoperative infection risk. Overall, 660 rheumatoid arthritis patients requiring an elective foot or ankle surgery will be randomized into two groups. In the first group, anti-TNFα will be stopped 3 half-lives before the surgery while they will be continued in the second group. The postoperative infection rate will be compared between the two groups. Postoperative complication rates, flares and revision surgeries as well as the functional improvement will be compared.||The study hypothesis is that there is no significant difference in the risk of postoperative infection between the two groups.||Results from this study will help determine the optimal way to use anti-TNFα in the perioperative period and will therefore improve the quality of life of rheumatoid arthritis patients."
This will be a randomized placebo-controlled trial in inflammatory bowel disease patients before initiation of anti-tumor necrosis factor-α (anti-TNF) therapy that aims to test the effect of a pre-treatment short course of azithromycin therapy on immunogenicity
"The principal aim of this study is to fill a clear knowledge gap and provide guidance for rheumatologists and reassurance to the patient group on a management challenge faced daily in rheumatology practice. Specifically, it aims to provide robust evidence on the optimal management of patients with established RA that have failed an anti-TNF therapy (the first of the biological therapies to be introduced); in particular, the investigators wish to address whether the currently licensed but non NICE-approved treatment options, TNF-blocking drug or abatacept, are equivalent to the NICE-approved treatment, rituximab. If so, the intention is to broaden treatment options and target these specific therapies to disease sub-groups."
To show that prevalence of inflammation of the small bowel in patients with anorectal disease is under-diagnosed based on colonoscopy ileoscopy alone.
The purpose of the study is to compare the risk of dementia in participants diagnosed with rheumatoid arthritis (RA) exposed to anti-tumor necrosis factor (TNF) therapy versus those exposed to methotrexate.
"The objective of this study is to investigate the effect of different doses of intravenous immunoglobulin (IVIG) (1g/kg once, 1g/kg twice, 2g/kg once) for Kawasaki disease (KD) in a multicentre, prospective,randomised trial."
"The purpose of this study is to establish the safest doses of an investigational drug called MORAb-009 in subjects with pancreatic cancer, mesothelioma, or certain types of ovarian or lung cancer. MORAb-009 is a monoclonal antibody that is directed to an antigen on the surface of these cancers."
"The purpose of this study is to test the utility of PET/MRI in diagnosis and management of Inflammatory bowel disease (IBD) in children and adolescents, hereby||To test if PET/MRI scan is an accurate method to diagnose and differentiate Crohn's disease and Ulcerous Colitis in children and adolescents suspected of IBD.|To evaluate whether PET/MRI scan in children and adolescents with Crohn's disease is an accurate method to diagnose relapses and to monitor the effect of biological treatment with monoclonal antibodies directed towards Tumor Necrosis Factor-alpha."
"To develop a cost-effective, individualised anti-TNF treatment strategy for patients with Crohn's disease which maximizes benefit and minimises harm.||The primary objective of this study is to investigate the mechanisms that underlie primary non-response (PNR), loss of response (LOR) and adverse drug reactions (ADRs) to anti-TNF drugs in patients with active luminal Crohn's disease."
"This study is to assess the efficacy of Neihulizumab versus ""conventional therapy"" and to evaluate safety, pharmacokinetics and immunogenicity in treating steroid-refractory acute Graft-vs-Host Disease"
"An Observational, Prospective Cohort Study to Evaluate Safety and Efficacy of RemsimaTM in Patients with Rheumatoid Arthritis."
This study is designed to establish the prevalence of anal squamous intraepithelial lesion (ASIL) in patients with inflammatory bowel disease (IBD) and healthy controls.
"The purpose of this study is to summarize the safety and tolerability of abatacept during 6 months of combined treatment with one or more of the background non-biologic disease modifying anti-rheumatic drugs (DMARDs) approved for rheumatoid arthritis (RA) in subjects with active RA. Secondary objectives assessed the clinical efficacy of combination treatment, including disease activity, physical function, and quality of life outcomes."
Observe in real life adherence therapy and time to switch in ankylosing spondylitis patients with predominant assial involvement with 4 anti-TNF.
"Background The risk for hospitalized infection (i.e. infection leading to hospitalization) in patients with inflammatory arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) treated with biological drugs is known to be increased compared to the background population. In daily clinical practice, there is a need for a simple way to assess the absolute risk for hospitalized infection in individual patients based on easily available information such as age, diagnosis, functional status, comorbidities and medication. This risk estimate will be useful in clinical decision making e.g. when advising patients on whether or not to initiate biologic therapy or when advising patients on influenza or pneumococcal vaccination.||Objectives The objectives are 1) to assess the risk for hospitalized infection (infection leading to hospitalization) in patients with inflammatory arthritis during 12 months of follow-up after initiating treatment with their first biological drug (bDMARD) with the risk in the general population, and 2) to develop a simple, clinically useful algorithm that allows prediction of the risk of hospitalized infection in individual patients.||Methods Observational cohort study based on existing data in: The Danish Rheumatology Register (DANBIO), The Danish National Patient Register, The Danish National Prescription Register and The Danish Register of Causes of Death. All patients registered in DANBIO with RA, PsA or axSpA who initiated treatment with their first biological drug between January 1, 2006 and December 31, 2016 will be identified. Baseline predictors and outcomes (hospitalized infection or death) during 12 months of follow-up are obtained. Logistic regression analysis and 10-fold cross-validation will be used to develop and internally validate the prediction model."
"This study is health economic analysis of medicinal treatment options for moderate-to-severe psoriasis vulgaris from the societal perspective. Efficacy data and other clinical outcomes will be derived from an up-to-date meta-analysis of randomized clinical trials (RCTs) for moderate-to-severe psoriasis. Direct and indirect costs will be extracted from various different sources, including summary of product characteristics (SPCs) and the German S3 guideline on psoriasis care, health care utilization data and official statistics.||The study aims to investigate the comparative cost-effectiveness of biologic and conventional systemic treatments currently (as of June 1st, 2012) approved for moderate-to-severe plaque-type psoriasis in Germany. Effectiveness will be measured by means of the pooled (Psoriasis Area and Severity Index) PASI-75 response rates as reported in RCTs Direct cost as well as indirect cost will be considered."
The purpose of this study is to assess the efficacy of ruxolitinib against best available therapy in participants with steroid-refractory chronic graft-versus-host disease (SR cGvHD).
The objective of the study is to establish a prospective disease registry for chronic recurrent multifocal osteomyelitis (CRMO)/chronic nonbacterial osteomyelitis (CNO) in order to investigate the natural history of the disease and the responses of patients to different clinical managements over 5 years.
"Patients with ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), have been shown to be at increased risk of developing certain infections, such as shingles from the Herpes Zoster (HZ) virus, as a result of their underlying disease. Patients with UC are also often treated with immunosuppressants, and research has shown that IBD patients on immunosuppressants have an impaired immune response to vaccination in comparison to immunocompetent controls. Because UC patients are often treated with immunosuppressants, the live HZ vaccine was not recommended in these patients. Shingrix, however, is a new inactivated vaccine recently approved by the FDA for prevention of HZ in adults age 50 and older, and Shingrix should be safe to administer in IBD patients because it does not contain live HZ virus. Data on efficacy of the Shingrix vaccine also appears promising in immunocompromised patients.||Tofacitinib citrate (Xeljanz), an immunosuppressant that works by inhibiting the Janus kinase pathway, is currently approved for treatment of certain inflammatory diseases such as rheumatoid arthritis and psoriasis. The drug is currently awaiting FDA-approval for use in moderate-to-severe UC but has been used off-label in various settings. Notably, tofacitinib was associated with an increased risk of HZ in patients with rheumatoid arthritis and psoriasis.||The research hypothesis is that UC patients on tofacitinib will mount an adequate response and that the response will be slightly diminished compared to non-immunosuppressed IBD patients, comparable to those on anti-tumor necrosis alpha (anti-TNF) monotherapy, and superior to those on anti-TNF therapy in combination with a thiopurine. Strong cell mediated immunity is shown to prevent reactivation of HZ, and demonstrating a robust immune response to Shingrix may serve as a surrogate for a reduced risk of developing shingles and might alleviate prescribers' concerns regarding the use of tofacitinib. The results will also serve as pilot data to inform larger future studies evaluating the actual risk of developing shingles in patients on tofacitinib who receive Shingrix."
This is a study of visual outcomes in retinal disease that seeks to identify the causes of visual loss. This data will be used to predict which patients are at risk of losing vision and how they can be better treated.
"The purpose of this study is to learn about the safety of islet transplantation for Type 1 diabetes mellitus, which may provide more normal control of blood sugar without the need for insulin shots. Islets are special clusters of cells within the pancreas that produce insulin. These cells will be obtained from cadaver (non-living) donors and given to subjects by vein."
"For aim 1, the proposed studies will be performed in 150 patients with RA and 25 subjects without RA (healthy volunteers) who will function as controls.||For aim 2, 25 of the patients enrolled in aim 1 (who are in need for further treatment due to increased RA activity despite their current treatment) will be recruited to continue in the study for an additional 24 (+/- 2) weeks (or 6 months). These patient will receive a TNF inhibitor in addition to their current treatment in an open label protocol for increased disease activity and in the context of standard of care.||The investigators hypothesize that anti-TNF agents in RA patients without heart disease will not adversely affect the heart (will not cause a detrimental change in heart structure or its function)."
The purpose of this study is to evaluate the efficacy and safety of TA-650 in comparison with a control drug Polyethylene Glycol-treated Human Immunoglobulin (VGIH) in patients with Kawasaki disease refractory to initial therapy with Intravenous Immunoglobulin (IVIG). The pharmacokinetics of TA-650 is also examined.
This randomized pragmatic trial will generate knowledge about strategies used to de-escalate tumor necrosis factor inhibitor (TNFi) therapy in patients with juvenile spondyloarthritis with sustained inactive disease and are treated at one of the 21 participating pediatric healthcare systems. This open label study will be conducted in the setting of routine clinical care and will compare the risk and timing of flare (Aim 1) and patients' lived experiences (Aim 2) across three arms.
"The primary aim of this study is allow the patients suffering from Crohn's disease , who both completed the therapeutic confirmatory study C87055 of certolizumab pegol and benefited from the treatment, to receive treatment with certolizumab pegol until the drug is available for the Crohn's disease indication in Greece."
To evaluate pharmacokinetic drug interaction by comparing the steady-state pharmacokinetic characteristics of each arms after repeated administrating Lipilfen cap. 160mg and Livalo tab. 2mg through 3 period by separately or combinedly.
"The investigators aim to prospectively study the feasibility and clinical impact of hyperbaric oxygen therapy in acute hospitalized moderate to severe ulcerative colitis flares as an adjunct to standard medical treatment. Specifically, we will investigate the impact of hyperbaric oxygen therapy on clinical response/remission and serum and mucosal inflammatory markers. The investigators expect that hyperbaric oxygen therapy will improve patient responsiveness to steroids and avoid progression to second line therapy during hospitalization."
The investigators' preliminary study indicates that MSC is effective therapy in treating IBD. But the standard treatment is still lacking and the effect is not stable in IBD patients. This study is to explore the efficacy and standard strategy when using MSC in refractory IBD.
"The purpose of this study is to compare the effectiveness of standardized systemic therapy versus fluocinolone acetonide implant therapy for the treatment of severe cases of non-infectious intermediate uveitis, posterior uveitis, or panuveitis."
"Treatment of moderate to severe Psoriasis (Pso) and Psoriasis-Arthritis (PsA) is largely confined to systemic therapy in Germany. Systemic therapy includes conventional systemic therapy (e.g. fumaric acids, methotrexate, ciclosporin A) and biological treatment (e.g. adalimumab, etanercept). While short- and middle-term efficacy of most systemic treatments has been shown in clinical studies (and is incorporated in international guidelines), knowledge about long-term outcomes, optimal treatment and effectiveness under real-world conditions is still missing. PsoBest, the German registry on the treatment of moderate to severe Pso and PsA started in 2008 and documents the long-term course of patients being administered any biologic or conventional systemic antipsoriatic drug authorized in Germany for the first time. The registry evaluates the long-term course of 3,500 patients with Pso and PsA treated with systemic antipsoriatics."
"A growing number of patients with Crohn's disease are treated with immunosuppressive agents, such as anti-tumor necrosis factor blockers and immunomodulators. Several recent studies have indicated that immunosuppressive treatment may impair the immunological response to pneumococcal vaccination in patients with inflammatory bowel disease (Crohn's disease and Ulcerative colitis). One of weaknesses in the previous studies did not focus on specific disease, such as Crohn's disease. In addition, predictive factors affecting impaired response following pneumococcal vaccination have not clearly evaluated in patients with Crohn's disease. In this study, patients with Crohn's disease will be assessed for serological response to pneumococcal vaccination. Further, potential predictive factors that impact on vaccination outcomes and adverse events related to vaccination will be evaluated."
The purpose of this clinical research study is to learn if abatacept can improve signs and symptoms of active ulcerative colitis in patients who have not had an adequate response to other therapies. The safety of this treatment will also be studied
"The investigators proposed study is the first of its kind. The investigators will measure measles, mumps, rubella, tetanus, diphtheria and pertussis antibodies in patients on the current IBD treatment modalities and compare the vaccine antibody concentrations and correlate them with time since immunization."
The aim of this study is to determine the impact of systemic immunosuppression on sustained antibody COVID-19 concentrations in patients with IBD who received a COVID-19 vaccine.
The efficacy and safety of Cyclosporine A as rescue therapy for acute severe ulcerative colitis in long-term follow-up.
The aim of this study is to evaluate the ideal dose of PEG and timing of bowel preparation in patients referred for CE examination.
This study is a multi-center randomized non-inferiority study that aims to observe the short-term (3 months) efficacy and safety of adalimumab plus medium-dose glucocorticosteroid (30mg/d prednisone or equivalent) with slow tapering for recurrent Behçet's uveitis (BU) attack compared with adalimumab plus high-dose glucocorticosteroid (60mg/d prednisone or equivalent) with slow tapering.
"This non-interventional, retrospective, cross sectional chart review study will evaluate the management of rheumatoid arthritis patients with a biologic in monotherapy. Data from eligible patients will be collected from the patient's last visit on the prior rheumatoid arthritis treatment and from the most recent visit for the biological monotherapy."
"This study will generate safety data on Nivolumab given by itself in treatment of advanced Renal Cell Carcinoma (RCC). The primary objective of this study is to assess immune related side effects, also known as immune-mediated adverse events (IMAEs), in patients treated with Nivolumab."
This observational study will describe the treatment patterns of usage of biological DMARDs in routine clinical practice and the demographics and RA disease characteristics in patients suffering from rheumatoid arthritis. Patients will be recruited and examined the same day when recruited. There will be no follow up visit or treatment period only one visit in this study.
The purpose of Biobadaderm is a to study the safety of systemic therapy in psoriasis.
"This observational, prospective, multicenter study will evaluate the efficacy and safety of MabThera/Rituxan in participants with active rheumatoid arthritis and an inadequate response or intolerance to one anti-TNF therapy. Participants who receive MabThera/Rituxan according to the current standard and in line with the summary of product characteristics at a dose of 1000 milligram (mg) intravenously on Days 1 and 15 will be followed for 20 weeks."
"To address the objectives, a retrospective cohort design will be employed to evaluate patient characteristics, treatment patterns, medication effectiveness, and health care cost and utilization in RA patients newly initiating tofacitinib in combination with oral methotrexate (MTX)"
"This is a Phase 4, retrospective chart review of subjects that participated in the ATTRACT study. Site investigators will conduct a chart review and complete a data collection form. The purpose of this study is to describe the treatment used and clinical outcomes of these subjects following completion of the ATTRACT trial up until their most recent assessment by the treating physicians."
"This multi-center, observational study will evaluate the clinical practice patterns, efficacy and safety of RoActemra/Actemra in patients with rheumatoid arthritis who have had an inadequate response (or were intolerant to) treatment with non-biological DMARDs or with one biological agent. Data will be collected from each eligible patient initiated on RoActemra/Actemra treatment by their treating physician according to approved label for 6 months from start of treatment."
"The purpose of this study is to evaluate the efficacy and safety of switching rheumatoid arthritis (RA) participants who have an inadequate response to their current treatment with either etanercept + methotrexate or adalimumab + methotrexate to treatment with golimumab 50 milligram (mg) subcutaneous (SC) injection (a needle inserted under the skin in the back of upper arm, upper thigh or stomach area) every 4 weeks + methotrexate. This study is also designed to evaluate the benefit and safety of switching participants from treatment with golimumab 50 mg subcutaneous injection every 4 weeks + methotrexate to golimumab 2 milligram per kilogram (mg/kg) intravenous every 8 weeks + methotrexate, for those who do not achieve a marked improvement of their RA at Week 16."
"This was a retrospective cohort study utilizing data from Modernizing Medicine Data Services' (MMDS) electronic medical records (EMR)-based dermatology database to evaluate secukinumab patient characteristics, treatment patterns, and outcomes."
This observational multicenter study will evaluate the management of disease and safety in clinical practice in patients with moderate to severe rheumatoid arthritis receiving any biological therapies in monotherapy.
The study is planned as a randomised control trial to study the adjuvant use of antibiotics (ceftriaxone and metronidazole) to achieve a clinical response in hospitalised patients with acute severe ulcerative colitis
"The purpose of this study is to gather information regarding the population with moderate to severe inflammatory bowel disease (IBD), the burden of the disease, and understand their treatment patterns, particularly on the use of available biologic therapies."
"This multicenter, prospective, observational study will assess the efficacy of MabThera/Rituxan (rituximab) and alternative TNF-inhibitors in patients with rheumatoid arthritis who are non-responders or intolerant to a single previous TNF-inhibitor. Data will be collected from each patient from the time of change in biologic therapy for 12 months."
The purpose of this study is to evaluate the efficacy of the addition of GMA apheresis to steroid conventional treatment for achieving and maintaining remission in Active steroid dependant Ulcerative Colitis patients
To estimate the efficacy of treatment with TNFi as monotherapy or combination therapy with MTX and compare and contrast efficacy with Tofacitinib as monotherapy and combination therapy in a real world setting.
"This is a prospective unblinded, randomized trial for the use of Fecal Microbiota Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or without antibiotic pretreatment."
Inflammatory bowel disease (IBD) patients under the age of 50 can have a greater risk than the general population above age 50. IBD patient are commonly treated with immunosuppression that increases the risk for Herpes Zoster. A new HZ vaccine is available that could decrease the risk of HZ in IBD patients.
"The investigators have recently developed a paediatric adaptation of the INTERMED tool to address the unique developmental and social contexts of children and youth. The Pediatric INTERMED adopts a life-chart methodology to structure and organize complex case material in time, colour-coding domains to facilitate identification of areas of high need and risk for each patient. The focus of the present study is to examine the characteristics and usefulness of the tool in identifying psychosocial stress in children/youth diagnosed with Inflammatory Bowel Disease (IBD), as well as identifying overall case complexity. Children and parents will participate in a semi-structured structured interview with a clinical nurse who will then rate the 34-PIM items. To examine the construct validity of each of the Pediatric INTERMED domains (biological, psychological, social, caregiver/family, health care system) participants will complete questionnaires assessing social and psychological functioning, parent and family stress, quality of life and adaptive functioning. Information about disease status, and health care utilization will be obtained from medical chart review. It is hypothesized that greater case complexity will be predictive of more complex disease course/treatment, poorer quality of life, and increased health care utilization."
The purpose of this study is to evaluate the percentage of moderate to severe IBD participants with active disease at Day 1.
The primary objective of this study is to evaluate the incidence of high-grade (i.e. Grade 3-4 and Grade 5 of CTCAE v4.0) adverse reactions of interest in patients with metastatic RCC who have progressed during or after receiving at least one prior systemic anti-angiogenic treatment and who are eligible for nivolumab monotherapy.
The main aim of this study is to check the disease activity in people with moderate to severe ulcerative colitis and Crohn's disease.||Participants will complete questionnaires about their disease and quality of life on Day 1 clinic visit. They will do this during a standard scheduled appointment with their doctor. Some of this study will also involve collecting information about participants from their medical records.
"The aim of the proposed project is to compare the effectiveness of two strategies designed to enhance patient understanding of medication risks/benefits: (1) Medication Guides, mandated for many medications by the Food and Drug Administration and (2) Drug Facts Boxes, developed by Woloshin and Schwartz to enhance the usability of consumer medication information. The investigators will also assess whether the effectiveness of these communication strategies can be increased by Gist Reasoning Training, which is designed to enhance patients' ability to extract meaningful gist from complex information.The investigators anticipate enrolling 300 individuals with rheumatoid arthritis. The study will use a randomized controlled trial design with four study arms. Data will be collected primarily via self-administered, Internet-based surveys using REDCap. All participants will be followed for 6 months after the completion of baseline data collection."
"Inflammatory bowel disease is a condition caused by gastrointestinal immune system dysregulation and affected by both genetic and environmental factors. Differences in intestinal bacteria exist between IBD patients and healthy controls, but the role of intestinal bacteria in the development and treatment of IBD remains largely unknown. Fecal microbiota transplantation (FMT) is the transfer of gastrointestinal bacteria from a healthy donor to a patient with altered microbial diversity with the intent of restoring a normal bacterial balance. Most studies focus on its use in treating Clostridium difficile (CDI), an infection characterized by dysbiosis. Given the role of dysbiosis in IBD, the investigators hypothesize that FMT may be beneficial in IBD. The purpose of this study is to prospectively examine the safety of FMT in the management of ulcerative colitis (UC)."
"This study was a non-interventional, retrospective study collecting data from hospital medical records. Approximately 200 adult patients with moderate to severe plaque psoriasis who were treated with secukinumab from hospitals in Thailand that participated in this study were expected for data collection."