ustekinumab (Absimky / DMB 3115 / DA3115)

Correction: Pharmacokinetics, Safety, and Immunogenicity of DMB-3115, a Ustekinumab Biosimilar for Immune-Mediated Diseases, in Healthy Japanese Male Participants: A Randomized, Double-Blind, Single-Dose Study.

Konishi Hironori H, Kumagai Yuji Y, Shindo Takeyuki T, Yagi Michio M et al.

Prior Ustekinumab Exposure and Ulcerative Colitis Are Associated with Suboptimal Trough Levels in Patients Receiving Advanced-Line Vedolizumab or Ustekinumab for Inflammatory Bowel Disease: A Cross-Sectional Cohort Study.

Nagypál Petra P, Kovács Krisztián K, Vásárhelyi Barna B, Dezsőfi-Gottl Antal A et al.

Background: Ustekinumab (UST) and vedolizumab (VDZ) are established therapies for Crohn's disease (CD) and ulcerative colitis (UC), including in patients with prior tumour necrosis factor-alpha inhibitor (anti-TNF) failure. Trough levels (TRLs) and antidrug antibodies (ADAs) are among several factors associated with therapeutic response. The aim of this study was to retrospectively identify factors associated with suboptimal TRL and ADA presence in a large, multicentre, cross-sectional cohort. Methods: TRLs and ADAs for VDZ and UST were measured routinely during therapy. A Cox proportional hazards model was used to identify clinical and treatment-related factors associated with suboptimal TRLs. Results: A total of 184 patients (78 children and 106 adults) with inflammatory bowel disease (IBD) were included; 104 and 80 were treated with UST and VDZ, respectively. TRLs were measured as part of routine clinical care between 2022 and 2025. Of the 184 patients, 80 (43.48%) had previously received both infliximab and adalimumab. Overall, 103 patients (55.98%) had received at least two advanced therapies (infliximab, adalimumab, VDZ, UST or a small-molecule inhibitor (SMI)) before the current biologic therapy. In exploratory Cox analyses, prior UST exposure (HR = 4.13, 95% CI = 1.58-10.81, p = 0.004) and UC subtype (HR = 2.83, 95% CI = 1.39-5.76, p = 0.004) were associated with a higher hazard of suboptimal TRL, whereas longer duration of prior biologic therapy (HR = 0.89, 95% CI = 0.82-0.96, p = 0.003) and current VDZ treatment (HR = 0.36, 95% CI = 0.16-0.82, p = 0.014) were associated with a lower hazard. In a cross-sectional logistic model accounting for time on therapy, only longer duration of prior biologic therapy remained significantly associated with suboptimal TRL. Prior UST exposure was associated with ADA presence in the cross-sectional model, although the estimate was imprecise and sensitive to model specification. Conclusions: Prior UST exposure, UC subtype and current VDZ therapy were associated with suboptimal TRLs in exploratory Cox analyses; however, these associations were not reproduced in the cross-sectional logistic model and were sensitive to adjustment for inflammatory burden. Longer duration of prior biologic therapy remained associated with lower odds of suboptimal TRL in the cross-sectional analysis. The observed association between prior UST exposure and ADA presence was imprecise and model-dependent. Given the study's retrospective design and limited sample size, these findings should be considered preliminary and require validation in larger prospective cohorts.

Impact of Smoking on the Effectiveness of Advanced Therapies in Inflammatory Bowel Disease: Active Smoking Is Associated with Reduced Effectiveness of Anti-TNF Treatment.

Cinque Sofia S, Annunziata Maria Laura ML, Bianchi Antonella A, Bertoli Peter P et al.

Background and Objectives: Smoking is a well-established risk factor for Crohn's disease (CD), whereas patients with ulcerative colitis (UC) who smoke may exhibit a milder disease course. The impact of smoking on the efficacy of advanced therapies (AT) in patients with inflammatory bowel disease (IBD) remains largely unknown. Materials and Methods: Patients with IBD receiving AT and with a detailed smoking history were retrospectively identified from our electronic database. The primary outcome was the rate of clinical response and remission. Secondary outcomes included endoscopic improvement, the need for AT sequencing, and surgery. Results: A total of 346 patients (136 UC and 210 CD) were analyzed, with a mean age of 47.3 years and a mean disease duration of 14.1 years (range, 0.5-48 years). Overall, 614 treatment courses were evaluated: 382 anti-TNF, 92 vedolizumab, 84 ustekinumab, 36 JAK inhibitor, 16 IL-23 inhibitor, and 4 etrasimod treatment courses. The anti-TNF effectiveness analysis included 371 infliximab/adalimumab courses after exclusion of 11 golimumab courses. A total of 107 patients (30.9%) were active smokers and 76 (21.9%) were former smokers. Anti-TNF therapy was significantly more effective in never smokers than in active smokers in the adjusted analysis (OR 1.44, 95% CI 1.04-2.00; p = 0.03), and this association remained significant in the mixed-effects model accounting for repeated treatment courses within patients (OR 1.35, 95% CI 1.01-1.80; p = 0.04). The association for advanced therapies overall was significant in the adjusted model (OR 1.25, 95% CI 1.01-1.55; p = 0.04) but was attenuated after accounting for repeated courses (OR 1.10, 95% CI 0.99-1.22; p = 0.07). No statistically significant differences were demonstrated for vedolizumab or ustekinumab, although the smaller sample sizes preclude exclusion of a clinically relevant effect. Former smokers had outcomes comparable to never smokers. Active smokers also required significantly more treatment courses than never smokers in both UC and CD (p = 0.03). Conclusions: Smoking is associated with a negative impact on the effectiveness of anti-TNF therapy in both UC and CD, highlighting the need for systematic smoking cessation counseling and patient education as an integral component of IBD management.

Current management of Behçet syndrome.

Ozguler Yesim Y, Demir Busra B, Hatemi Gulen G

To summarize the most clinically relevant recent advances in the treatment of Behçet syndrome (BS), with emphasis on the updated 2025 EULAR recommendations and emerging evidence across different organ manifestations. The updated EULAR recommendations support earlier use of monoclonal TNF inhibitors (TNFi), particularly in severe ocular, vascular, and neurologic involvement, and favor their continued use for maintenance in selected major-organ disease. Recent randomized and comparative studies provide further support for TNFi in Behçet uveitis and vascular involvement. Newer agents, including PDE-4 inhibitors and JAK inhibitors (JAKi), have shown promising efficacy in mucocutaneous, gastrointestinal, ocular, vascular, and neurologic disease, although most evidence for JAKi remains derived from small uncontrolled studies. Ustekinumab has also shown encouraging results in refractory intestinal BS. The role of anticoagulation in vascular BS remains uncertain. Management of BS is increasingly organ- and risk-adapted, with earlier use of effective targeted therapies in patients at risk of irreversible damage. Despite encouraging results with several newer agents, comparative and high-quality evidence remains limited, highlighting the need for adequately powered studies with organ-specific outcomes.