To evaluate the real-world efficacy and safety of adalimumab (ADA) combined with conventional therapy in patients with chronic non-infectious anterior uveitis (NIAU). This retrospective cohort study included 114 patients with chronic NIAU treated at a single tertiary center between May 2022 and May 2025. Patients were divided into a study group receiving ADA plus conventional therapy (n = 58) and a control group receiving conventional therapy alone (n = 56). Anterior chamber (AC) cell count, best-corrected visual acuity (BCVA), treatment response, adjunctive therapy use, complications and adverse events were compared over 6months. Multivariate logistic regression was performed to identify factors associated with complete remission. At 3 and 6months, the ADA group showed significantly lower AC cell counts and greater BCVA improvement than controls (all P < 0.05). At 6months, complete remission was achieved in 84.5% of the ADA group versus 64.3% of controls, with lower relapse rates (13.8% vs. 28.6%, both P < 0.05). After adjustment, ADA use was independently associated with complete remission (adjusted OR = 2.85, 95% CI 1.15-7.05). The ADA group required less adjunctive corticosteroid and immunosuppressive therapy and had lower rates of cataract and ocular hypertension. Most adverse events were mild, with one serious infection leading to discontinuation. In real-world practice, adalimumab combined with conventional therapy is associated with improved inflammation control, visual outcomes and reduced relapse in chronic NIAU, with an acceptable safety profile.

Crohn's disease is associated with a high economic burden for the Spanish National Healthcare System, driven by pharmacological expenses. Following the recent incorporation of ustekinumab biosimilars into the market, this study aimed to evaluate the cost effectiveness of different treatment sequences, including biosimilar ustekinumab (bsUST), for moderate-to-severe Crohn's disease from the NHS perspective in Spain. Treatment sequences were defined according to clinical practice. A Markov model with 2-week cycles and a lifetime horizon was developed, including health states such as active disease, response, remission, surgery, and death. Funnel states simulated induction and treatment changes after loss of response, and surgery was considered only after four pharmacological lines. Efficacy data for biosimilar adalimumab (bsADA), biosimilar intravenous infliximab (bsIFX), biosimilar ustekinumab (bsUST) risankizumab (RIS), upadacitinib (UPA), vedolizumab (VDZ), and surgery (Q) were obtained through published literature, including network meta-analyses and clinical trials. Unitary costs were sourced from Spanish databases and literature. Pharmacological costs were ex-factory prices applying Royal Decree-Law (RDL) 8/2010 discount. For bsADA and bsIFX, average biosimilar market prices were used. A 30% discount was assumed for bsUST versus reference ustekinumab. Sequence 1 (bsADA-bsUST-UPA-RIS-Q) was set as the reference. Alternative strategies provided QALY gains ranging from 0.06 to 0.34 compared with the reference. However, due to varying incremental costs, Sequence 2 (bsUST, bsADA, UPA, RIS, Q) emerged as the only cost-effective strategy at a willingness-to-pay threshold of €27,000/QALY, with an incremental cost-effectiveness ratio (ICER) of €8672.6/QALY. Conversely, all other sequences exceeded the threshold, with ICERs starting at €42,594/QALY. Probabilistic sensitivity analysis confirmed the robustness of these findings, identifying Sequence 2 as the cost-effective option in 98.03% of simulations. Positioning bsUST as a first line of treatment appears to be cost effective and an efficient alternative from the NHS perspective in Spain. Additionally, none of the alternative sequences proved to be cost effective compared with the sequence starting with bsADA-bsUST. bsUST may significantly impact Crohn's disease management in Spain, improving patient access due to its lower drug acquisition costs.

BACKGROUNDBiologics are the preferred treatment for patients with moderate to severe Crohn’s disease (CD). Four biologics included in China’s National Reimbursement Drug List are available for CD treatment. Due to loss of response, patients need switching to another biologic, making it necessary to evaluate the cost-effectiveness of different biologic treatment sequences.AIMTo assess the cost-effectiveness of sequential treatment strategies with National Reimbursement Drug List-included biologics for moderate to severe CD in China.METHODSFrom a healthcare system perspective, a Markov model was constructed to evaluate the cost-effectiveness of four biologics [infliximab, adalimumab (ADA), ustekinumab (UST), and vedolizumab] applied in different treatment sequences for moderate to severe CD patients. Using one times the GDP per capita ($13444.68, 2024) in China as the willingness-to-pay threshold, the absolute net monetary benefit (NMB) and incremental cost-effectiveness ratio (ICER) were calculated. Both costs and utilities were discounted at an annual rate of 5%. Sensitivity analyses were conducted on key parameters.RESULTSWith $13444.68 as willingness-to-pay, among the 17 treatment sequences evaluated for biologic-naïve patients, sequence 3 (ADA-UST) yielded the highest absolute NMB of $35850.93. Compared with sequence 1 (vedolizumab-UST), sequence 3 had the most favorable ICER of $2285.38/quality-adjusted life year. For biologic-exposed patients, sequence 3 still demonstrated the optimal NMB and ICER results.CONCLUSIONAdding biologic treatment lines provides greater health benefits for patients with moderate to severe CD. Among the various sequential strategies, the treatment sequence combining ADA and UST is more likely to be the optimal cost-effective option in China.

This study developed a transdermal drug delivery system for Rheumatoid Arthritis (RA) using a dual-network hydrogel microneedle patch loaded with methotrexate nanocrystals (DHMN@MTX-NCs), and explored its synergistic therapy with Adalimumab (ADA) for a painless, long-acting, and targeted RA treatment. This study synthesized Methacrylated Hyaluronic Acid and Methacrylated Gelatin. MTX-NCs were prepared by solvent-antisolvent precipitation and incorporated into a dual-network hydrogel microneedle patch via centrifugal molding. Evaluations included pharmaceutical properties, mechanical strength, drug release, in vitro anti-inflammatory effects on RAW 264.7 cells, and therapeutic efficacy in a rat RA model. The experimental results show that the prepared MTX-NCs present a spherical shape, an average size of 325.72 nm, a PDI of 0.154, and a drug-loading capacity of 61.3%. The microneedle patch exhibited high puncture efficiency and suitable swelling. In vitro, DHMN@MTX-NCs combined with ADA most strongly inhibited macrophage migration, upregulated IL-10, and downregulated TNF-α, IL-1β, NO, iNOS, and COX-2. In vivo, both monotherapy and combination therapy reduced joint swelling, bone erosion, and histopathological damage. Ultimately, the study demonstrated the synergistic anti-inflammatory efficacy of DHMN@MTX-NCs combined with ADA, providing a novel, non-invasive, and targeted therapeutic strategy for RA.

Biological therapies have revolutionized the treatment of inflammatory bowel diseases enabling mucosal healing and sustained remission. However, their long-term effectiveness is substantially limited by immunogenicity, namely the development of anti-drug antibodies, which may lead to secondary loss of response. The aim of our study was to evaluate real-world immunogenicity data in Hungary among patients treated with tumor necrosis factor inhibitors infliximab (IFX) and adalimumab (ADA), as well as second-line biological agents vedolizumab (VDZ) and ustekinumab (UST). We performed a cross-sectional analysis of 153 inflammatory bowel disease patients receiving IFX or ADA and 183 patients treated with UST or VDZ, followed at Semmelweis University between 2020 and 2025. Both pediatric and adult patients were included. Immunogenicity data were assessed using modern immunoassay techniques, and results were analyzed according to treatment groups, disease characteristics, age, and sex. The overall prevalence of anti-drug antibodies was comparable between treatment groups (IFX/ADA: 21%, 32/153; UST/VDZ: 20%, 37/181; p = 0.98). In molecule-specific analyses, IFX was associated with significantly higher immunogenicity (33.0%) compared with ADA (12.0%; p = 0.001). Antibody positivity was low in patients treated with UST (15.0%), while a non-significantly higher rate was observed with VDZ (28.0%; p = 0.105). No significant differences in immunogenicity were detected according to inflammatory bowel diseases subtype, age, or sex. Although the overall immunogenicity of biological therapies may appear similar, substantial differences exist between individual agents. The higher immunogenicity of IFX compared with ADA supports the need for proactive therapeutic drug monitoring and, where appropriate, combination therapy. In the case of VDZ and UST, a more nuanced interpretation is required, considering the potential presence of transient antibodies. Our findings further emphasize the pivotal role of therapeutic drug monitoring in optimizing biological treatment strategies in inflammatory bowel diseases. Orv Hetil. 2026; 167(8): 291-299.

CVS Caremark changed their national commercial formularies in 2024 to prefer adalimumab-adaz over originator. We assessed the formulary change's effect on biosimilar adalimumab prescribing in U.S. community rheumatology practices. Data come from RISE, a registry of EHR data from participating community rheumatology practices nationwide. We used interrupted time series to analyze the effect of the CVS formulary change on the proportion of patients prescribed adalimumab-adaz or other adalimumab biosimilars each month between January 2023 and September 2024 stratified by payor and among new users. We included 22,079 patients. Among commercially insured, prescriptions for -adaz went from nearly 0% to more than 25% following the CVS formulary change. In the next month, prescriptions for -adaz dropped 12.3%. Prescriptions for other biosimilars increased slowly and linearly over the study period. Among patients with Medicare, we observed a similarly timed, but much smaller, increase in prescribing for both -adaz and other biosimilar molecules without a large subsequent decrease. Among new users, prescriptions for -adaz increased from 0% to 24% but was followed by a nearly 14% decrease in prescriptions in the first month after the formulary change. Other biosimilar prescriptions increased 0.6% per month throughout the period. While biosimilar adalimumab prescriptions rose sharply after a major national formulary change, the increase was not sustained. These findings highlight that persistent barriers, including the nocebo effect and the administrative burden of switching, may continue to limit biosimilar adoption and contribute to the loss of substantial cost savings in the US market.

Adalimumab (ADA) is an effective treatment for moderate to severe hidradenitis suppurativa (HS). However, nearly half of patients receiving the standard dose may lose response. To establish therapeutic thresholds for HS-specific ADA levels, leading to more personalized treatment. We conducted a single-center, prospective observational study of adults with HS treated with ADA (40 or 80mg/week, and 80mg/biweekly) at a specialized HS clinic (January 2023-May 2024). Serum samples were collected after ≥4 weeks of therapy to ensure steady state. Patients were stratified by physician-assessed response (low <50%, partial 50-75%, high >75% improvement). Associations of ADA concentration and clearance with response were tested using Spearman and Pearson correlations; discriminatory performance was evaluated with ROC analysis. Among 46 enrolled patients, the majority was female (60.9%) and White (54.3%), with a median age of 38 years (IQR: 30-45). ADA serum concentrations positively correlated with clinical response (r = 0.43, p = 0.002). Low responders had significantly lower concentrations than partial (p = 0.029) and high responders (p = 0.007). Clearance was inversely correlated with ADA levels (r = -0.65, p < 0.001). Receiver operating characteristic analysis identified optimal thresholds of 10.7 μg/mL for ADA concentration and 0.5 L/day for clearance. Higher ADA concentrations and lower drug clearance are associated with better clinical outcomes in HS. ROC analysis identified 10.7 μg/mL (ADA concentration) and 0.5 L/day (clearance) as optimal cut-off values to differentiate low from partial/high responders. These findings suggest that therapeutic drug monitoring may help optimize ADA therapy in HS.

Abstract BACKGROUND Although biologics are widely used in pediatric inflammatory bowel disease (IBD), the long-term durability of the biologics in children remains incompletely understood. METHODS Using the Korean Health Insurance Review and Assessment Service database (2007-2023), we identified patients aged 6-17 years with Crohn’s disease (CD) or ulcerative colitis (UC) who initiated infliximab (IFX) or adalimumab (ADA) as first biologic therapy. Persistence was evaluated using Kaplan-Meier analysis at 6 months, 1 year, and 5 years. Subgroup analyses assessed concomitant immunomodulator (IM) use and duration. RESULTS Among 2542 CD patients, 1895 initiated IFX and 647 ADA; 581 UC started IFX. Among CD, IFX persistence was 97.47%. 88.0%, and 78.64%, while ADA showed 95.58%, 87.17%, and 72.79%. In UC, IFX persistence was 76.21%, 40.35% and 24.66%. In CD, IFX with IM improved durability compared with monotherapy (HR 0.67, 95% CI 0.52-0.85, p = 0.0003 at 1 year; HR 0.77, 95% CI 0.63-0.95, p = 0.0078 at 5 years), mainly when IM was continued ≥6 months, while ADA showed no clear durability benefit from the combination therapy. In UC, IFX durability improved with IM ≥ 6months at 1 year (HR 0.65, 95% CI 0.44-0.96, p = 0.023), while the effect was attenuated over time. CONCLUSION In this nationwide, real-world study, IFX and ADA demonstrated comparable persistence in CD, while IFX durability in UC declined substantially. Sustained IM use for ≥6 months enhanced IFX durability, whereas short-term use offered limited benefit. These findings underscore the importance of IM duration in optimizing anti-TNF therapy in pediatric IBD and provide robust evidence from a nationwide population-based cohort.

Abstract BACKGROUND Crohn’s disease (CD) reduces quality of life (QOL), which burdens society. Studies have identified clinical, psychological, and productivity determinants of QOL associated with CD, including increases in disease activity, relapse rate, mental illness, and workplace disability. Biologic treatments are effective and can improve patient QOL by reducing the disease severity, but high costs can limit access. Biosimilars provide similar efficacy and safety as reference products at a more cost-effective price, which can provide considerable savings. Biosimilars may generate societal benefits by allowing a greater number of patients to access similar treatment for the same cost compared to reference products. The objective of this study was to assess the current and expected savings from biosimilar use in North America (NA). METHODS A literature search was conducted using MEDLINE and grey literature from January 2020 to January 2025. Keywords included “projection*”, “economic”, “ex ante analysis”, “budget impact model”, and “biosimilar*”. Peer-reviewed publications and economic reports from industry, accredited associations, and state/provinces were included. RESULTS Twenty-seven peer-reviewed publications (18 from the US, 9 from Canada) and four reports were deemed relevant to the search question. Economic benefit was reported or forecasted by 94% (n = 30) studies. Across Medicare and US commercial plans, biosimilar use has been estimated to provide $12.4 billion in savings in 2023 alone. A projection report examining the US healthcare system estimated that cumulative use of over 20 biosimilars (including CD treatments such as infliximab, adalimumab, and ustekinumab) could yield savings of $125 to $237 billion from 2022 to 2027. Non-medical switching policies have been implemented in Canada to drive biosimilar uptake. The pilot adopter (British Columbia) reported $731 million in savings between 2019-2024 from use of eight biosimilars. While no NA studies were available, a study of cost-saving and patient access opportunities in Europe found €10.5 to €187 million in savings associated with biosimilar adalimumab uptake, which translates to an additional 1,096 to 19,454 patients able to access adalimumab for the same cost. Biosimilar introduction may create economic benefit through the direct reduction of treatment costs, as well as potential improvements in workplace function for patients without previous biologic access. CONCLUSION Increased access to effective CD treatment can improve patient QOL by reducing disease severity, psychological impact, and workplace disability. A growing body of literature demonstrates the potential economic benefits associated with the introduction or increased use of biosimilars for the US and Canada. Health economic decision makers should consider policies that favor biosimilar use as a tool to control costs.

Tumor necrosis factor-alpha (TNF-α) inhibitors, particularly adalimumab (ADA), are widely used for ocular inflammatory diseases but may increase the risk of tuberculosis reactivation. Data on latent tuberculosis infection (LTBI) screening and outcomes are limited. This study aimed to describe LTBI screening outcomes in ADA-treated uveitis and identify patterns of missed cases. A total of 188 patients evaluated for ADA eligibility between December 2021 and April 2025 were retrospectively analyzed. LTBI screening included medical history, tuberculin skin test (TST), interferon-gamma release assay (IGRA), or both. Isoniazid prophylaxis was given when indicated, and tuberculosis occurrence during ADA was assessed. Among 188 patients (mean age 40.3 ± 14.2 years), Behçet's uveitis (39.7%) and sarcoidosis (23.9%) were the most common. TST alone was used in 60.2%, IGRA in 13.4%, and both in 26.3% among those with baseline testing. TST and IGRA results were significantly associated (p = 0.001). INH prophylaxis rates varied by screening method (p = 0.003). Tuberculosis occurred in 1.6% (n = 3), including two despite prophylaxis. LTBI screening and prophylaxis reduce but do not eliminate TB risk under ADA. Combined TST/IGRA and periodic re-evaluation may reduce missed cases in BCG-vaccinated populations.

TNF-α inhibitors (TNFis) are effective biologic drugs for rheumatoid arthritis (RA), but their comparative efficacy is unclear due to limited direct comparisons. The objective of this work was to compare the efficacy of infliximab (INX), certolizumab pegol (CZP), etanercept (ETN), golimumab (GOM) and adalimumab (ADM) in achieving remission at 3 months in bio-naïve RA patients. Using data from the NOR-DMARD study of adult RA patients in Norway starting a TNFi as their first biologic treatment, we employed a target trial emulation approach. TNFi selection is mainly determined by drug prices in annual national tenders, allowing us to use drug cost as an instrumental variable (IV). Applying a novel IV method, causal effects were estimated with remission at 3 months as the end point. Results were compared with standard regression analysis adjusted for baseline variables. The IV analysis suggested potential differences in efficacy among TNFis, with INX showing higher remission rates compared with CZP, and ETN performing better than GOM. However, confidence intervals were wide, and many comparisons were not statistically significant. Sensitivity analyses confirmed the overall direction of results. Regression analysis adjusting for observed confounders showed no substantial differences, underscoring the importance of addressing unobserved confounding effects. This hypothesis-generating study provides evidence that TNFis may not be equally effective. The uncertainty in the estimates highlights the need for a pragmatic randomized controlled trial to validate the findings. With decreasing costs of TNFis, such studies are increasingly feasible and critical to guide clinical decision-making.

Behçet's disease (BD) is characterized by relapsing mucocutaneous and major organ involvement. Although conventional immunosuppressants and CSs remain the mainstay of therapy, severe or refractory cases often require biologics. TNF-α inhibitors, particularly infliximab (IFX) and adalimumab (ADA), have become central to BD management. We compared the efficacy, safety, and drug retention of IFX and ADA in a real-world single-centre cohort. Eighty-seven BD patients receiving IFX (n = 45) or ADA (n = 42) as their first anti-TNF therapy between April 2020 and 2025 were retrospectively reviewed. Baseline demographics, organ involvement, laboratory parameters, treatment regimens, and outcomes were recorded. Except for a tendency of male predominance in the IFX group, baseline demographics were comparable. Vascular (51.1% vs 26.2%) and neurological (15.6% vs 2.4%) involvement were more frequent in the IFX group, while ocular disease predominated in the ADA group (45.2% vs 28.9%). Complete remission was achieved in 75.6% (IFX) and 78.6% (ADA) initially, increasing to 88.9% and 76.5%, respectively, at the last visit. Concomitant AZA use exceeded 60% in both groups, while pulse glucocorticoids, CYC, and anticoagulants were more common with IFX. Relapses occurred more often and earlier with IFX (37.8% vs 16.7%, median 8 vs 13 months). Drug retention and adverse event rates were comparable (IFX 80% vs ADA 85.7%; ∼16% adverse events). No severe events occurred. Both IFX and ADA were highly effective and well tolerated in severe or refractory BD. ADA provided durable control in mucocutaneous and ocular phenotypes, whereas IFX offered rapid remission in vascular and neurological disease. Phenotype-oriented and individualized treatment strategies may optimize anti-TNF use in BD.

BackgroundBiosimilars represent a significant opportunity in the treatment of inflammatory bowel disease (IBD). Our aim is to assess the effectiveness and safety of the five approved adalimumab (ADA) biosimilars in IBD patients naive to biologics.MethodsIBD patients naive to biologics from eight Spanish hospitals were enrolled. We included patients who started ADA biosimilars between November 2018 and January 2022. The study endpoints included (1) induction of remission at week 8; (2) drug persistence at the conclusion of the follow-up period; and (3) safety of the five ADA biosimilars.ResultsIn total, 383 patients were included. After induction, 63.8% of patients were in clinical remission. In total, 114 (29.8%) patients discontinued treatment during follow-up. Clinical remission was maintained in 78.4% of patients after a median follow-up of 18 (12-24) months. Dose intensification was performed in 35 (9.1%) patients during follow-up. There was no significant difference in effectiveness for the 5-ADA biosimilars. Additionally, drug persistence was significantly higher in Crohn’s disease (CD) patients (P = .012), in the group of patients co-treated with immunomodulators (IMM) (P = .001) and in patients with post-induction (at week 8) ADA levels ≥ 7 μg/mL (P = .002). Adverse events were reported in 30 (7.8%) patients with no significant difference between ADA biosimilars.ConclusionADA biosimilars are safe and effective in inducing and maintaining remission in a real-life population of bio-naive IBD patients. Furthermore, there is no significant difference between the 5-ADA biosimilars. Drug persistence was significantly higher in patients with CD treated with IMM and with post-induction ADA levels ≥7 μg/mL.

Very-early-onset inflammatory bowel disease (VEO-IBD), representing cases diagnosed before age 6years, is increasing in prevalence. Although VEO-IBD often presents as severe, treatment-resistant disease requiring biologic agents, studies showing the effectiveness of biologics, such as ustekinumab (UST) and vedolizumab (VDZ), remain limited. We retrospectively analyzed patients with VEO-IBD treated for at least a year from 13 institutions in Japan, evaluating clinical course including effectiveness of biologics, such as infliximab (IFX), adalimumab (ADL), UST, and VDZ. Patients with monogenic IBD were excluded. Steroid-free clinical remission (SFCR) and treatment persistence were assessed separately for first-line and for second-line or subsequent biologic therapies. We studied 101 VEO-IBD patients (56% male; median age, 3.6years), including 40 with Crohn's disease, 52 with ulcerative colitis, and 9 with unclassified IBD. Biologics were used in 67 patients, most commonly infliximab (IFX; n = 52), followed by UST (n = 38), adalimumab (ADL; n = 23), and VDZ (n = 21). As first-line therapy, IFX and ADL achieved 1-year SFCR rates of 19% and 46%, with persistence rates of 36% and 48%. Despite being used mainly as second-line or subsequent therapies, UST and VDZ showed 1-year SFCR rates of about 45% and 36%, and maintained persistence of 79% and 46%, respectively, with UST demonstrating higher persistence than TNF-α inhibitors (P < 0.01). No discontinuations due to infusion reactions or other adverse events occurred with UST or VDZ. UST and VDZ were effective and well tolerated even when used as second-line or subsequent therapies for VEO-IBD.

Abstract Background Biologics are used to induce clinical remission in individuals with active Crohn’s disease (CD), but around 50-60% of patients achieve clinical remission. Exclusive enteral nutrition is also an effective induction treatment, but tolerability limits its use, especially in adults. This study aimed to assess the efficacy of partial enteral nutrition (PEN) in combination with adalimumab (ADA) compared to ADA monotherapy. Methods Adults with active CD (CDAI&amp;gt;150) starting ADA were randomised to replace half of their diet with Modulen-IBD (ADA+PEN) for six weeks or to continue their habitual diet (ADA). The primary outcome was to compare response (CDAI decrease≥70) and remission rates (CDAI&amp;lt;150) between ADA+PEN and ADA at week-12. PEN adherence was assessed with three approaches. Calprotectin (FCAL), CRP, SIBDQ, drug levels and antibodies were measured at baseline, week-6 and week-12. In a subset of patients ileocolonoscopy (SES-CD scoring) was performed at baseline and week-12. Data presented as intention-to-treat analysis. Results 101 patients recruited (51 ADA+PEN, 50 ADA). PEN adherence was high (81%). Clinical response and remission rates at week 12 were similar between the two groups (response; ADA+PEN 67%, vs ADA 65%, p = 0.86, remission; ADA+PEN 51% vs ADA 54%, p = 0.79). FCAL, CRP, and SIBDQ improved but did not differ between groups. At week-12, a higher volume of PEN consumed was associated with a lower CDAI at week-12 (CDAI; rho=-0.35, p = 0.02). ADA+PEN patients with FCAL≥100mg/kg and CRP≥5mg/L, at baseline, had a higher rate of clinical response at week-6 (ADA+PEN, 96% vs ADA, 65%, p = 0.01) but not at week-12 (p = 0.08). In patients with ileal disease, ADA+PEN had a lower median CDAI at week-6 (ADA+PEN, 71 vs ADA, 149, p = 0.039). Sixteen patients had endoscopies; 86% in ADA+PEN achieved a &amp;gt; 50% SES-CD decrease compared with 33% in ADA (p = 0.03, Figure 1A). Drug levels were similar in the two groups at week-6 and 12. More patients developed drug antibodies in ADA (ADA+PEN vs ADA; week-6: 0%, vs 3%, week-12: 7% vs 16%; p = 0.123 across all timepoints, Figure 1B). Conclusion Addition of PEN to ADA is beneficial in those with a greater inflammatory burden and with ileal disease. It is also associated with increased rates of mucosal endoscopic response and with fewer patients forming anti-drug antibodies during induction treatment. Conflict of interest: White, Bernadette: Studentship paid for by Nestle Health Science and the University of Glasgow. Previous travel support also from Nestle Health Science. Campbell, Iona: No conflict of interest Fandinga, Catarina: Previous travel support also from Nestle Health Science Kerbiriou, Caroline: No conflict of interest Clowe, Jennifer: No conflict of interest Jatkowska, Aleksandra: Studentship paid for by Nestle Health Science and the University of Glasgow. Previous travel support also from Nestle Health Science. Brownson, Emily: No conflict of interest Milling, Simon: No conflict of interest Ho, Gwo-Tzer: None Mowat, Craig: No conflict of interest Robertson, Elaine: No conflict of interest Gaya, Daniel: No conflict of interest Kefayat, Amirhosein: No conflict of interest Din, Shahida: No conflict of interest Seenan, John Paul: No conflict of interest Macdonald, Jonathan: None to declare Gerasimidis, Konstantinos: Grant: Nestle Health Science, Nutricia-Danone, Mylan Personal Fees: Abbott, Baxter, Nestle Health Science, Nutricia-Danone, Servier, Janssen

Abstract Background Treatment efficacy may vary by disease location in Crohn’s disease (CD). We assessed the maintenance efficacy of biological and small molecule therapies in moderate-to-severe luminal CD, stratified by disease location. Methods A systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs) in adults (≥ 18 years) with CD (CDAI 220-450) were conducted per PRISMA, Cochrane, and NICE-DSU guidelines (PubMed/Embase to 12/08-2025). Outcomes included clinical and endoscopic remission and response at week 52, stratified by Montreal location (L1 ileal, L2 colonic, L3 ileocolonic), and randomization design. Results Twenty RCTs were included evaluating adalimumab (ADA), infliximab (IFX), vedolizumab (VDZ), ustekinumab(UST), mirikizumab (MIRI), risankizumab (RZB), guselkumab (GUS) and upadacitinib (UPA). In re-randomization trials, IFX ranked highest in L1 (SUCRA 93.7) compared to VDZ (RR 2.83 [95% CI 1.10–10.53]), RZB (3.35 [1.09–14.49]), and UPA 15 mg (7.68 [1.81–51.40]). In L2, UPA 30 mg (SUCRA 94.5) showed greatest efficacy compared toVDZ (2.39 [1.06–5.61]), RZB (3.23 [1.53–7.55]), and IFX (3.35 [1.58–7.34]). In L3, UPA 30 mg (3.40 [1.79–7.27]; SUCRA 90.2) and ADA (3.20 [1.52–7.75]; SUCRA 84.6) ranked highest, while IFX (2.23 [1.51–3.54]) and VDZ (1.57 [1.25–2.03]) also proved beneficial. GUS 100/200 mg outperformed placebo across all locations in treat-through trials. In pairwise meta-analysis, only GUS (treat-through) significantly improved clinical remission rates vs. placebo in L1. In L2, IFX, UPA15 mg/30 mg, RZB, MIRI, and UST were superior to placebo. In L3, ADA, IFX, VDZ, RZB, MIRI, and UPA but not UST were significantly more effective compared to placebo. In network meta-regression, UPA 15 mg was 12.3 × (95% CI 3.15–47.8) more effective in maintaining clinical remissionat week 52 in L2 and 8.08 × (2.04–32.0) higher in L3 vs. L1; for UPA 30 mg, 4.60 × (1.68–12.6) and 3.45 × (1.23–9.64), respectively. VDZ showed similar patterns (Figure 1), whereas IFX efficacy ratios were lower (0.52 [0.16–1.65]; 0.84 [0.26–2.75]). UST, RZB, GUS and MIRI showed no significant location effect in terms of clinical remission (Figure 1). Conclusion A location-dependent efficacy gradient was observed with reduced responsiveness in isolated ileal disease and greater efficacy in colonic and ileocolonic involvement, and superiority of specific drug classes in ileal and colonic disease location, emphasizing the importance of considering CD location in treatment algorithms and personalized CD management. Conflict of interest: Ms. Dalsgarð, Sóley Poulsen: No conflict of interest Kalinga Bandara Pkb, Kavini: No conflict of interest Seidelin, Jakob Benedict: has received research grants from Takeda, Janssen, the Danish Research Council, and the Capital Region Denmark, and is national coordinator of studies from AbbVie, Arena Pharmaceuticals, Ely Lilly, and Boehringer Ingelheim. Wium Bjerrum, Jacob Tveiten: reports personal fees from Johnson and Johnson, Tillotts, and Pfizer. Attauabi, Mohamed: Research grants from Novo Nordisk Fonden and Lundbeck Foundation. Personal fees from Eli Lilly, Celltrion, and Lundcbeck foundation, outside the submitted work.

Abstract Background As therapeutic options for ulcerative colitis (UC) expand, real-world data are needed to understand durability of different advanced therapies (ADV) beyond initial treatment lines. Longer-term outcomes in bio-experienced individuals remain poorly characterised. We evaluated persistence—a pragmatic measure of ongoing effectiveness across six ADVs—in bio experienced people with UC and assessed predictors of persistence. Methods Prospectively collected routine-care data from the Crohn’s Colitis Care (CCCare) registry were analysed. Adults with UC and prior ADV exposure who commenced a subsequent maintenance course (standard or dose-escalated) of adalimumab (ADA), infliximab (IFX), ustekinumab (UST), vedolizumab (VDZ), upadacitinib (UPA) or tofacitinib (TOF) were included. All courses up to 30 October 2025 were eligible. The primary outcome was treatment persistence, assessed with Kaplan–Meier curves; predictors of persistence were evaluated using univariate and multivariable Cox models. Results A total of 402 maintenance courses were analysed in 280 individuals. Median age at course commencement was 35.5 years; 52.0% were in males. Median disease duration was 7.7 years and follow-up 4.9 years. Most had left-sided or extensive colitis. Courses were predominantly second-line (66.4%), and 41.8% were dose-escalated from initiation, most commonly with UPA (61.2%, p &amp;lt; 0.001). UPA and UST were the most common second-line agents (22.8% and 23.2%) while later lines were increasingly dominated by UPA (47.4% third-line; 37.5% fourth-line). Concomitant 5-ASA use in UPA (24%) was significantly lower than IFX (45%), VDZ (47.7%) and ADA (55.6%; p &amp;lt; 0.001). Concomitant IMS use in UPA (4.1%) was the lowest across therapies, though not significantly different from TOF (12.0%). In the bio-experienced cohort, 24-month persistence ranged from 43.6% (ADA) to 69.7% (VDZ), without a significant difference between therapies (p = 0.16). In pairwise Cox analyses, subsequent therapy with VDZ showed a consistent trend toward lower discontinuation risk versus other ADVs (HRs 0.51–0.61), although none reached statistical significance. In multivariable modelling, independent predictors of discontinuation were dose escalation (HR 1.84, 95% CI 1.10–3.11) and concomitant systemic steroid use (HR 1.71, 1.14–2.55). Conclusion In this large, multicentre real-world UC cohort, no ADV as second or subsequent choice demonstrated superior persistence, although VDZ had a non-significant trend toward greater persistence. Dose escalation at initiation and systemic steroid use were strong predictors of shorter persistence, identifying individuals with more severe or higher-risk disease who may benefit from proactive monitoring and treatment optimisation. Conflict of interest: Wu, Rodger: No conflicts Ghali, Mark: No conflicts. Wilson, William: No conflict of interest Caquilpan, Victor: No conflict of interest Rivas, Consuelo: No conflict of interest Lynch, Kate: Kate Lynch has received speaker honoraria, advisory board fees, and/or conferencetravel/registration support from AbbVie, Bristol-Myers Squibb (BMS), Chiesi, Dr. Falk, Ferring, Gilead, Guidepoint, Intercept Pharmaceuticals, Janssen-Cilag, Merck Sharp &amp; Dohme (MSD), Norgine, Pfizer, Pliant, Sandoz, Takeda, and the Royal Adelaide Hospital (RAH) Research Fund. Haifer, Craig: Grant: Grants from St Vincent’s Clinic Foundation, Gastroenterological Society of Australia, Gutsy Group, Royal Australasian College of Physicians and Ferring. Personal Fees: CH has received speaker fees and educational support from Janssen, Pfizer, Takeda, Ferring and Abbvie. Walker, Gareth: In the last 24 months, Dr Walker has received investigator grants or served as a speaker, a consultant or an advisory board member for: Janssen AbbVie Takeda Ferring Dr Falk Pharma Georgiamune Radford-Smith, Graham Lindsay: No conflict of interest Lawrance, Ian Craig: No conflict of interest Begun, Jakob: I have received honoraria or consulting fees from Abbvie, Janssen, Takeda, Pfizer, Ferring, Bristol Myers Squibb, Gilead, Tillott’s, Sandoz, Celltrion, Chiesi, Dr Falk, Microba, Glaxo Smith Klein, Antara, Suono, Therpeutic Guidelines, Research Review,Grants: NHMRC, US Department of Defence, The Gutsy Foundation, The Gastroenterological Society of Australia, The University of Queensland, The Viertel Foundation, and The Mater Foundation Wark, Gabrielle: Conference travel/registration support from Dr Falk Verdon, Christine: No conflict of interest Andrews, Jane Mary: Grant: The work I will present was funded svia CCCure. CCCure’s funding sources include grants for research and payments for data reports from Pharma including AbbVie, J &amp; J, Takeda, Celltrion, Falk, Ferring, BMS, Janssen, Pfizer, Sandoz Ghaly, Simon: Speaker fees, research grants and travel grants from Dr. Falk pharma, Janssen, Pfizer, AbbVie, Sandoz and Ferring and served on advisory boards for Pfizer and AbbVie. Connor, Susan Jane: Grant: Research Support: Abbvie, Agency for Clinical Innovation, Amgen, BMS, Chiesi, Celltrion, Dr Falk, Ferring, Janssen, Medical Research Future Fund, Pfizer, South Western Sydney Local Health District, Sydney Partnership for Health, Research and Enterprise, Takeda and The Leona M and Harry B Helmsley Charitable Trust Personal Fees: Ad Boards: Abbvie, Amgen, BMS, Celltrion, Eli Lilly, Ferring, GSK, Janssen, Organon, Pfizer, Takeda Speaker Fees: Abbvie, Cornerstones Health, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Sydney IBD School, Takeda Educational Support: DrFalk, Sandoz, Takeda

Abstract Background Biologic therapies have transformed the management of inflammatory bowel disease (IBD), but their high cost has prompted the introduction of biosimilars (1). Although switching from originator biologics to biosimilars is increasingly common, real-world evidence remains limited (2). We aimed to explore the safety and efficacy of switching between biologics originator and biosimilars. Methods We conducted retrospective chart review of patients with IBD between 2015 and 2025. Adult patients receiving adalimumab-adaz, or adalimumab-atto were included. Patients who were non-medically switched once from adalimumab originator (Humira) to any biosimilar were classified as group A. Patients who also switched back to originator (multiple switches) were classified as group B. Primary outcome was safety of biosimilar including any adverse events (AEs) and serious AEs. Secondary outcome was efficacy including sustained clinical remission and sustained normalization ofinflammatory markers. Logistic regression identified predictors of biosimilar switching. Results A total of 237 patients were included in the study. The number of patients in group A and group B was 208 and 58 patients, respectively. Sustained clinical remission was achieved in 198 (95.4%) of Group A and 54 (93.6%) of Group B participants. Sustained normalization of inflammatory markers was also comparable, occurring in 190 (91.5%) of Group A and 54 (92.3%) of Group B (figure 1). No treatment-emergent adverse events (AEs), infections, or treatment discontinuations were reported in either group (0%). Local or mild AEs were rare, occurring in 3 (1.2%) of Group A and 1 (2%) of Group B, with no other AEs reported (0% in both groups). Regression analysis identified older age and prior immunomodulator use as significant predictors of switching. Conclusion Multiple switches of adalimumab biosimilars can be safely undertaken without increasing the risk of adverse reactions, or treatment failure. Our study provides meaningful evidence to guide policy, resource allocation, and clinician confidence in biosimilar interchangeability as a sustainable therapeutic strategy in IBD mansagement.

Abstract Background Gut microbial dysbiosis in ulcerative colitis (UC) exhibits substantial inter-individual heterogeneity, yet the delineation of patterns and their clinical implications remain poorly understood. We hypothesized that understanding distinct dysbiotic pathotypes and their longitudinal variability may help elucidate microbiome–disease interactions and improve patient stratification. Methods Fecal microbiome data from a previously reported longitudinal cohort of UC patients treated with adalimumab (ADA) and healthy controls [1] were analyzed, with dysbiosis defined by the median beta-diversity distance to controls. Microbial communities were clustered into ecotypes based on network analysis to identify distinct dysbiotic pathotypes contributing to dysbiosis. Gut microbial variability was assessed through intra-individual beta-diversity. Subgroup of samples have been processed with shotgun metagenomics for functional profiling. Results Substantial heterogeneity in gut dysbiosis was observed among UC patients, separating them into dysbiotic and less dysbiotic groups. Ecotype-based analysis using baseline samples revealed five distinguishable dysbiotic pathotypes characterized by enrichment of facultative anaerobes, including a cluster dominated by Gammaproteobacteria (e.g., Escherichia and Pantoea spp.) and another by Enterococcaceae (e.g., Enterococcus spp.), as well as clusters enriched with oral-origin bacteria (e.g., Actinomyces spp. and Rothia), environmental taxa (e.g., Ralstonia spp.), and lactate-producing bacteria (e.g., Lactobacillus spp.). Patients who achieved long-term clinical remission at week 56 exhibited a significant decrease in specific dysbiotic pathotypes, whereas the non-remission group did not. Microbiome variability was significantly associated with disease duration, with long-standing UC patients exhibiting lower overall compositional change and enrichment of genes associated with response to stress environment in metagenomic functional profiles. Conclusion This study identifies several distinct dysbiotic pathotypes in UC patients, where specific ecotypes showing characteristic microbial signatures. The change of these pathotypes over time was linked to treatment outcomes. Long-term disease duration shaped less variability of microbiome and functional genes enriched in stress environment. Together, these findings indicate that UC-associated dysbiosis and its association with clinical outcomes are not uniform but vary by pathotypes and longitudinal dynamics. Reference: 1. Oh HN, Shin SY, Kim JH, et al. Dynamic changes in the gut microbiota composition during adalimumab therapy in patients with ulcerative colitis: implications for treatment response prediction and therapeutic targets. Gut Pathog. 2024;16(1):44. Published 2024 Aug 26. doi:10.1186/s13099-024-00637-5 Conflict of interest: Prof. Shin, Seungyong: N/A Jung, Yeonjae: Yeonjae Jung is employees of CJ Bioscience, Inc. Oh, Hyun-Seok: Hyun-Seok Oh is employees of CJ Bioscience, Inc Choi, Chang Hwan: N/A

Abstract Background Cytomegalovirus (CMV) colitis mimics acute IBD flares, making it a critical differential diagnosis in acute severe colitis (ACS). Therefore, it’s an important differential diagnosis in patients with ACS. Prevalence ranges from 10 to 30% in steroid-refractory ulcerative colitis (UC).1,2 Corticosteroids are identified as risk factors for CMV colitis. Evidence for biologics and small molecules remains conflicting or absent.1 This study aimed to evaluate demographic data of CMV colitis in a central European inflammatory bowel disease (IBD) cohort. Methods We conducted a retrospective analysis of 110 colon biopsy samples of IBD patients with clinical suspicion of CMV colitis at our IBD center between 2020 and 2024. All biopsies were obtained from the most inflamed colonic segments during diagnostic colonoscopy. CMV testing including immunohistochemistry (IHC) and quantitative tissue PCR (qPCR) was performed at the affiliated pathology and virology departments. CMV positivity was defined as IHC+/qPCR-, IHC-/qPCR+ or IHC+/qPCR+.3 Results A total of 110 IBD patients with clinical suspicion of CMV colitis were included. The median age was 43.5 years [IQR 36-57]. Gender distribution was nearly equal: 50.9% male (56/110) and 49.1% female (54/110). The majority had UC 75.5% (83/110), followed by Crohn’s colitis (CC) 23.6% (26/110), and colitis indeterminata (1/110). The overall prevalence of CMV colitis was 16.4% (18/110). Among CMV-positive cases 94.4% (17/18) had UC and 5.6% (1/18) had CC. Among the 18 CMV-positive patients, current immunosuppressive therapy included systemic glucocorticoids (GC) 33.3% (6/18), VDZ 27.8% (5/18), Updadacitinib (UPA) 22.2% (4/18), Ustekinumab (UST) 11.1% (2/18), Adalimumab (ADA) 5.6% (1/18), Filgotinib (FILGO) 5.6% (1/18), and topical GCs 5.6% (1/18). 94.4% (17/18) of CMV positive patients had a history of prior systemic immunosuppressive therapy. Of those, 6 never received a biologic, 5 received 1 biologic, 3 received 2 biologics, and 4 received ≥3 biologics. 61.1% (11/18) CMV-positive patients had a documented prior episode of CMV colitis. Conclusion The prevalence of CMV-colitis was 16.4% among IBD patients with clinical suspicion, predominantly affecting those with UC (94.4%). Nearly all positive cases had prior or current immunosuppressive exposure, mostly systemic GCs (33.3%), VDZ (27.8%) or JAK inhibitors (UPA/FILGO 27.8%). Notably, 61.1% had a documented prior episode of CMV colitis. These findings highlight, that immunosuppressed patients – particularly those with UC are at elevated risk of a CMV colitis. Further studies are needed to identify IBD patients and immunosuppressive therapies associated with the highest risk of CMV colitis.