Comparative risk of serious infection in patients with ulcerative colitis treated with JAK inhibitors

INTRODUCTION: While Janus kinase inhibitors (JAKi) have been associated with an increased risk of serious infections compared with biologics in patients with ulcerative colitis (UC), data comparing the risk of infection across individual JAKi remain limited. We aimed to compare the risk of serious infections among patients with UC treated with tofacitinib, upadacitinib, or filgotinib. METHODS: We conducted a nationwide cohort study using the French National Health Data System, including UC patients aged >15 years who initiated tofacitinib, upadacitinib, or filgotinib between 2019 and 2025. We assessed the risk of serious infection (defined as requiring hospitalization) according to treatment exposure. Propensity score weighting accounted for indication bias. RESULTS: Overall, 237 serious infections occurred among 6449 JAKi initiations: 2735 used upadacitinib, 2825 tofacitinib, and 889 filgotinib. Median age was 39 years, 49.5% were women, and median time since UC diagnosis was 7.1 years. Incidence rates per 1000 patient-years were 38.8 for upadacitinib, 30.6 for tofacitinib, and 28.4 for filgotinib. Compared with upadacitinib, adjusted hazard ratios for serious infection were 0.93 (95% CI: 0.70-1.24) for tofacitinib and 0.88 (95% CI: 0.56-1.39) for filgotinib. No differences were observed across infection sites or pathogen types. Higher doses of upadacitinib and tofacitinib were associated with increased infection risk. The risk of non-severe infections, particularly against herpes simplex virus and varicella zoster virus, was highest with upadacitinib and lowest with filgotinib. CONCLUSION: Tofacitinib, upadacitinib, and filgotinib were associated with similar risks of serious infection in patients with UC. Infection risk appeared to be driven primarily by dose rather than by type of JAKi.