Risk of gastrointestinal perforation in patients with rheumatic diseases exposed to janus kinase inhibitors versus adalimumab: nationwide cohort study.

Abstract

To compare the risk of gastrointestinal perforation (GIP), a rare but serious adverse event, in patients initiating a Janus kinase inhibitor (JAKi; tofacitinib, baricitinib, upadacitinib or filgotinib) versus adalimumab (tumor necrosis factor inhibitor) among a comprehensive real-world population of patients with rheumatic diseases. We conducted a nationwide population-based cohort study of the French national health data system, the exposed group initiating a JAKi and the comparison group adalimumab. We included all individuals with a rheumatic disease who had their first dispensation of these treatments from July 2017 to December 2021. The primary endpoint was the occurrence of GIP (end of follow-up May 2022). Weighted hazard ratios (wHRs) were estimated with the inverse probability of treatment weighting method to account for confounding factors. Concomitant administration of systemic corticosteroids, non-steroidal anti-inflammatory drugs and proton pump inhibitors were time-varying variables. The cohort included 39,758 patients: 12,335 and 27,423 in the JAKi and adalimumab groups (mean age 58.2 and 47.3 years; female 76% and 58%; rheumatoid arthritis 85.3% and 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% and 72.7%). During follow-up, 38 and 42 GIPs occurred in the JAKi and adalimumab groups, incidence rates were 2.1 (95% CI 1.5-2.8) and 1.1 (0.8-1.5) per 1000 person-years respectively. Rates of GIP did not differ between JAKi and adalimumab groups : wHR 1.1 (95% CI 0.7-1.9) (p=0.65). Despite lack of power in some subgroup analyses, results were consistent whatever the JAKi or rheumatic disease subgroup. In this nationwide cohort study, the rates of GIP did not differ between groups of patients initiating JAKi and adalimumab treatment. These results need to be confirmed in other observational studies.