OP16Serious infection in Inflammatory Bowel Diseases patients treated with vedolizumab, ustekinumab, JAK inhibitors, anti-TNF or aminosalicylates

Background JAK inhibitors and biologics are increasingly used to treat inflammatory bowel diseases (IBD). Serious infections are among the most important adverse events. Randomized trials are underpowered to detect relatively rare outcomes. We aimed to compare the risk of serious infections across IBD therapies in real-world practice. Methods We conducted a nationwide cohort study using French health data system (SNDS). All IBD patients aged aged more than 15 years, who intiated vedolizumab, ustekinumab, JAK inhibitors, anti-TNF, or aminosalicylates between 2014 and June 2024, were included. Patients with primary immunodeficiency, HIV, or organ transplantation were excluded. Follow-up ended at serious infection (hospitalization), treatment discontinuation, switch, or December 2024. Propensity score weighting accounted for indication bias, and weighted Cox models were adjusted for time-dependent corticosteroid and thiopurine/methotrexate use. Results We identified 309,025 treatment initiations in 219,229 patients (median age 41 years [IQR 29–55], 52% women, 45% Crohn’s disease). Over a median follow-up of 1.0 year (IQR 0.5–2.6), 15,081 serious infections occurred (incidence rate [IR] 26.1/1000 patient-years; 95%CI, 25.7–26.5). IRs were 21.9 (95%CI: 21.3-22.5) for aminosalicylates, 26.6 (95%CI: 25.2-27.9) for ustekinumab, 27.8 (95%CI: 27.1-28.4) for anti-TNF, 33.0 (95%CI: 31.4-34.6) for vedolizumab, and 38.9 (95%CI: 34.3-43.5) for JAK inhibitors. Compared with aminosalicylates, adjusted hazard ratios (aHR) for serious infection were 1.05 (95% CI, 0.98–1.11) for ustekinumab, 1.29 (95% CI, 1.42–1.54) for anti-TNF, 1.38 (95% CI, 1.30–1.46) for vedolizumab, and 1.63 (95% CI, 1.45–1.84) for JAK inhibitors. Patterns were consistent across Crohn’s disease and ulcerative colitis. Particular associations were seen between anti-TNF and vedolizumab and skin, upper respiratory, and neurologic infections; JAK inhibitors were associated with herpesvirus infections; anti-TNF were associated with mycobacterial infections. Concomitant corticosteroids and thiopurine/methotrexate further increased infection risk (aHR 2.06 [95% CI, 1.98–2.14] and 1.11 [95% CI, 1.06–1.16], respectively). Conclusion In this nationwide study, JAK inhibitors carried the highest risk of serious infection, ustekinumab the lowest, and anti-TNF and vedolizumab an intermediate risk. These findings may guide therapeutic choices in IBD patients at high risk of infection. Conflict of interest: Bertrand, Anaïs: No conflict of interest Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Martin, Antoine: Personnel fees : Abbvie, Janssen Carbonnel, Franck: Grant: Alpha Wassermann, Nestlé, Mayoly Spindler Personal Fees: Abbvie, Arena, Biogen, Celltrion, Enterome, Ferring, Janssen, MaaT Pharma, Nestlé, Nordic Pharma, Pierre Fabre, Pharmacosmos, Roche, Takeda, Tillotts, Viatris Meyer, Antoine: No conflict of interest