UNASSIGNED: Despite infliximab biosimilars becoming widely used in inflammatory bowel disease (IBD) patients, real-world non-medical switching is sparse. A biosimilar non-medical switch was launched in British Columbia in 2019, the first Canadian province to do so, from Remicade to an approved biosimilar (CT-P13 or SB2).
UNASSIGNED: This study aims to obtain real-world evidence evaluating the clinical outcomes of non-medical switching from Remicade to the infliximab biosimilars.
UNASSIGNED: This is a retrospective observational study of stable IBD patients from the IBD Centre of BC who underwent the non-medical infliximab switch. The primary outcome is treatment continuation at 12 ± 2 months post-switch. Secondary outcomes include frequency of loss of response, adverse events, and immunogenicity within the first 12 months post-switch. A control group of patients maintained on the originator served as a comparison.
UNASSIGNED: Patients in the biosimilar switch group (n = 264) and originator group (n = 99), show similar demographics and disease characteristics. There was no difference in infliximab continuation between the biosimilar group (94.9%) and the originator group (90.1%) (P = 0.18). Reasons for discontinuation of infliximab included loss of response (4.04% vs 4.91%), immunogenicity (1.01% vs 0.75%), or adverse effect (1.01% vs 2.3%) in the infliximab originator vs biosimilar switch group, respectively. Similarly, no differences in safety or efficacy were observed between patients switched to CT-P13 or SB2.
UNASSIGNED: Non-medical biosimilar switch of infliximab demonstrates similar clinical outcomes compared to originator molecule continuation for therapy of IBD. These data support the safety and efficacy of non-medical infliximab switching in IBD patients.

UNASSIGNED: Children with very early onset inflammatory bowel disease (VEO-IBD) are uniquely at risk of inadequate infliximab (IFX) exposure. We studied the association between standard body weight (BW)-based and body surface area (BSA)-based dosing strategies and outcomes.
UNASSIGNED: We identified VEO-IBD patients treated with IFX before 9 years at a single center. Patients were separated into those that received a BSA-based dose (200 mg/m2) and standard BW dosing (5 mg/kg). IFX drug levels, dose intensification, time on steroids, and long-term outcomes were compared. Receiver operator characteristic curves determined the optimal BW- and BSA-based dose to achieve a trough ≥10 μg/ml at dose 4 (IFX#4).
UNASSIGNED: Forty-three children with VEO-IBD were identified. Receiver operator characteristic curves demonstrated optimal BW- and BSA-based doses to achieve IFX trough ≥10 μg/ml at IFX#4 were 7.5 mg/kg and 180mg/m2. Children were classified to standard BW dosing (22/43) and BSA dosing (10/43). IFX#4 trough was significantly higher in those who received BSA dosing (BSA 18.6 μg/ml [interquartile range 10.8-28.1] vs BW 5.1 μg/ml [interquartile range 2.6-10.7], P = .04). BSA dosing was more likely to achieve a target drug level >10 μg/ml at IFX#4 (BSA 70% vs BW 18%, P = .02). BW dosing was associated with a greater likelihood of dose escalation (BW 82% vs BSA 30%, P < .01) and a shorter time to first escalation. BSA dosing was associated with shorter time spent on steroids (P = .02).
UNASSIGNED: Young children require higher IFX dosing to achieve adequate drug exposure. Our data support the use of a BSA-based dose of 200 mg/m2 or, if a BW-based approach is used, 7.5 mg/kg. BSA dosing allows the use of a consistent dose over the age and weight spectrum.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune disease that affects desmoglein-1 and desmoglein-3, leading to intraepithelial vesiculobullous lesions. In the oral mucosa, PV lesions can mimic other diseases such as mucous membrane pemphigoid, other forms of pemphigus, recurrent aphthous stomatitis, erythema multiforme, Stevens-Johnson syndrome, and virus-induced ulcers like herpes simplex virus (HSV), making diagnosis challenging. The co-occurrence of PV with Crohn\'s disease is rare and predominantly seen in younger patients. The therapeutic mainstay for both PV and Crohn\'s disease usually involves systemic corticosteroids combined with immunosuppressants and immunobiological drugs. Literature indicates that the use of these drugs, particularly TNF-alpha inhibitors, for managing autoimmune diseases like Crohn\'s can potentially induce other autoimmune diseases known as autoimmune-like syndromes, which include episodes of lupus-like syndrome and inflammatory neuropathies. There are few cases in the literature reporting the development of PV in individuals with CD undergoing infliximab therapy.
METHODS: A young female with severe Crohn\'s disease, treated with the TNF-alpha inhibitor infliximab, developed friable pseudomembranous oral ulcerations. Histopathological and immunofluorescence analyses confirmed these as PV. The treatment included clobetasol propionate and low-level photobiomodulation, which resulted in partial improvement. The patient later experienced severe intestinal bleeding, requiring intravenous hydrocortisone therapy, which improved both her systemic condition and oral lesions. Weeks later, new ulcerations caused by herpes virus and candidiasis were identified, leading to treatment with oral acyclovir, a 21-day regimen of oral nystatin rinse, and photodynamic therapy, ultimately healing the oral infections. To manage her condition, the gastroenterologists included methotrexate (25 mg) in her regimen to reduce the immunogenicity of infliximab and minimize corticosteroid use, as the patient was in remission for Crohn\'s disease, and the oral PV lesions were under control.
CONCLUSIONS: Young patients with Crohn\'s disease should be referred to an oral medicine specialist for comorbidity investigation, as oral PV and opportunistic infections can arise during immunosuppressive therapy. The use of TNF-alpha inhibitors in patients treated for inflammatory bowel disease, such as Crohn\'s, should be carefully evaluated for potential side effects, including oral PV.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by continuous inflammation of the colonic mucosa. Autoimmune hepatitis (AIH) is a chronic liver disease characterized by hypergammaglobulinemia, circulating autoantibodies, interface hepatitis, and favorable response to immunosuppression. An association between IBD and AIH is uncommon, and experts have suggested that in patients with overlapping IBD and AIH, the anti-tumor necrosis factor agents can be used. Therefore, this study reports a rare case of a patient with liver cirrhosis due to AIH and UC refractory to conventional treatment and discusses the risks and benefits of using anti-tumor necrosis factor in both conditions.
METHODS: A 28-year-old female presented with symptoms of diarrhea, abdominal pain, asthenia, and inappetence, accompanied by abdominal collateral circulation, anemia, alteration of liver enzymes, and elevation of C-reactive protein levels.
METHODS: The patient underwent a liver biopsy, which was consistent with liver cirrhosis due to AIH. Colonoscopy showed an inflammatory process throughout the colon, compatible with moderately active UC.
METHODS: The patient received mesalazine, azathioprine, and corticotherapy, with no control of the inflammatory process. Faced with refractoriness to drug treatment and side effects of corticosteroids with an increased risk of severe infection due to cirrhosis, we opted to use infliximab for the treatment of UC. The patient presented with a clinical response and infliximab therapy was maintained.
RESULTS: Eight months after starting infliximab therapy, the patient developed pneumonia with complications from disseminated intravascular coagulation and died.
UNASSIGNED: AIH is a rare cause of elevated transaminase levels in patients with UC. The best treatment to control the 2 conditions should be evaluated with vigilance for the side effects of medications, mainly infections, especially in patients with cirrhosis.

Biosimilars offer the potential for cost savings and expanded access to biologic products; however, there are concerns regarding the rate of biosimilar uptake. We assessed the relationship between biosimilar and originator pricing, coverage, and market share by describing four case studies that fall into two categories: (1) sole preferred coverage strategy (ie, aim is to have originator product preferred; biosimilar(s) non-preferred), defined as steep average sales price (ASP) reductions for originator products (decline in net prices by at least 50% following the introduction of biosimilar competition by 2022) and (2) non-sole preferred coverage strategy (ie, aim is to have originator product preferred alongside biosimilar products), defined as moderate ASP reductions for originator products with (net prices did not decline by at least 50% of its pre-biosimilar competition value). We found that originators with sole preferred coverage strategies maintained formulary preference and market share relative to originators with non-sole preferred coverage strategies. Regardless of strategy, the market-weighted ASP for all four product families (originator and biosimilars) declined significantly in the years following the introduction of biosimilars, suggesting that biosimilar uptake alone may not be a complete measure of whether the biosimilar market is facilitating competition and lowering prices.

Treatment for pregnant women with psoriasis is limited by the lack of information typically related to clinical trials. While anti-tumor necrosis factor (TNF) drugs offer therapeutic benefits, their safety during pregnancy is a concern. Notably, certolizumab is comparatively safer than adalimumab, etanercept, infliximab, and golimumab according to the current recommendations. Thus, this study aimed to conduct a pharmacovigilance comparative analysis of maternal and neonatal outcomes associated with certolizumab versus other anti-TNF drugs by using data from EudraVigilance. A descriptive analysis was performed of Individual Case Safety Reports (ICSRs) associated with an anti-TNF drug and related to the pregnant patients with psoriasis from 2009 and 2023, focusing our analysis on the specific pregnancy outcomes and fetal/neonatal disorders. The most common pregnancy-related adverse event was spontaneous abortion, predominantly related to adalimumab and certolizumab. Certolizumab was also reported in cases of caesarean section, gestational diabetes, abortion, fetal death, fetal distress syndrome, pre-eclampsia, and premature separation of placenta. Generally, the findings from our study depicted a safety profile that overlapped for each anti-TNF drug, both in maternal/neonatal outcomes and other adverse events, suggesting no substantial differences between treatments. We advocate for further investigations before making concrete recommendations.

UNASSIGNED: The combination of TNF-α inhibitors and vitamin D in colitis remains to be elucidated. In the present study, we revealed the benefit of infliximab (IFX) and vitamin D in a mouse model of Ulcerative colitis (UC).
UNASSIGNED: A dextran sulfate sodium-induced colitis model was used. The therapeutic effect of the combination was evaluated by symptom and histopathology analysis. The synergistic mechanism was explored by detecting the regulatory effect of the combined therapy on Regulatory T cell (Treg) differentiation.
UNASSIGNED: IFX and 1,25-dihydroxyvitamin D3 (VitD3) synergistically prevented the development of colitis by improving clinical signs, pathological and hematological manifestation, and inhibiting intestinal inflammation (decreasing TNF-α, IL-1β, and IL-6). Co-administration of IFX (2.5 mg/kg) with VitD3 or IFX (5.0 mg/kg) with VitD3 was more effective than administration of IFX (2.5 mg/kg, 5.0 mg/kg). There was no difference in therapeutic effect between IFX (5.0 mg/kg) and VitD3+ IFX (2.5 mg/kg) groups or between the VitD3+IFX (5.0 mg/kg) and VitD3+ Azathioprine (AZA) groups. VitD3 or combination therapy showed more powerful regulation of splenetic Treg differentiation and IL-10 production than IFX alone. Moreover, VitD3 alone or in combination induced higher levels of Foxp3 and IL-10 than IFX in colon tissue. In ulcerative colitis patients, serum VitD3 levels positively correlated with Treg levels.
UNASSIGNED: VitD3 and IFX synergistically inhibit colitis based on their powerful regulation of Treg differentiation. VitD3 combined with IFX is an alternative therapy for patients who are intolerant to standard doses of IFX or combination of IFX and AZA.

UNASSIGNED: The efficacy of anti-TNF therapy in Crohn\'s disease (CD), such as infliximab, is often compromised by the development of anti-drug antibodies (ADAs). The genetic variation HLA-DQA1*05 has been linked to the immunogenicity of biologics, influencing ADA formation. This study investigates the correlation between HLA-DQA1*05 and ADA formation in CD patients treated with infliximab in a Chinese Han population and assesses clinical outcomes.
UNASSIGNED: In this retrospective cohort study, 345 infliximab-exposed CD patients were genotyped for HLADQ A1*05A > G (rs2097432). We evaluated the risk of ADA development, loss of infliximab response, adverse events, and treatment discontinuation among variant and wild-type allele individuals.
UNASSIGNED: A higher percentage of patients with ADAs formation was observed in HLA-DQA1*05 G variant carriers compared with HLA-DQA1*05 wild-type carriers (58.5% vs 42.9%, P = 0.004). HLA-DQA1*05 carriage significantly increased the risk of ADAs development (adjusted hazard ratio = 1.65, 95% CI 1.18-2.30, P = 0.003) and was associated with a greater likelihood of infliximab response loss (adjusted HR = 2.55, 95% CI 1.78-3.68, P < 0.0001) and treatment discontinuation (adjusted HR = 2.21, 95% CI 1.59-3.06, P < 0.0001). Interestingly, combined therapy with immunomodulators increased the risk of response loss in HLA-DQA1*05 variant carriers.
UNASSIGNED: HLA-DQA1*05 significantly predicts ADAs formation and impacts treatment outcomes in infliximab-treated CD patients. Pre-treatment screening for this genetic factor could therefore be instrumental in personalizing anti-TNF therapy strategies for these patients.

BACKGROUND: A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring.
METHODS: The DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants.
BACKGROUND: Multisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment.
BACKGROUND: ACTRN12622001458729.

UNASSIGNED: Since adalimumab approval in childhood chronic non-infectious uveitis (cNIU), the prognosis has been dramatically changed, but the 25 % failed to achieve inactivity. There is not accordance if it is better to switch to another anti-TNF or to swap to another category of biologic. Thus, we aim to summarize evidence regarding the best treatment of cNIU refractory to the first anti-TNF.
UNASSIGNED: A systematic literature review and meta-analysis, according to PRISMA Guidelines, was performed(Jan2000-Aug2023). Studies investigating the efficacy of treatment in cNIU refractory to the first anti-TNF were considered for inclusion. The primary outcome was the improvement of intraocular inflammation according to SUN. A combined estimation of the proportion of children responding to switch or swap and for each drug was performed.
UNASSIGNED: 23 articles were eligible, reporting 150 children of whom 109 switched anti-TNF (45 adalimumab, 49 infliximab, 9 golimumab) and 41 swapped to another biologics (31 abatacept, 8 tocilizumab and 1 rituximab). The proportion of responding children was 46 %(95 % CI 23-70) for switch and 38 %(95 % CI 8-73) for swap (χ20.02, p = 0.86). Instead analysing for each drug, the proportion of responding children was the 24 %(95 % CI 2-55) for adalimumab, 43 %(95 % CI 2-80) for abatacept, 79 %(95 % CI 61-93) for infliximab, 56 %(95 % CI 14-95) for golimumab and 96 %(95 % CI 58-100) for tocilizumab. We evaluated a superiority of tocilizumab and infliximab compared to the other drugs(χ2 27.5 p < 0.0001).
UNASSIGNED: Although non-conclusive, this meta-analysis suggests that, after the first anti-TNF failure, tocilizumab and infliximab are the best available treatment for the management of cNIU.