Comparative Safety of Janus Kinase Inhibitors vs Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases.
BACKGROUND & AIMS: We conducted a retrospective cohort study comparing the safety of Janus kinase (JAK) inhibitors vs tumor necrosis factor-a (TNF) antagonists in patients with inflammatory bowel diseases (IBDs). METHODS: Using an administrative claims database, we identified patients with IBD who were new users of either JAK inhibitors or TNF antagonists between 2016 and 2023 and had insurance coverage for at least 1 year before and after treatment initiation. We compared the risk of infections (overall and serious infections requiring hospitalization), venous thromboembolism (VTE), and major adverse cardiovascular events (MACE) through stabilized inverse probability of treatment weighted Cox proportional hazards model accounting for disease characteristics, health care utilization, comorbidities, prior and concomitant medications, and competing risk of mortality. RESULTS: We included 856 patients treated with JAK inhibitors (age, 47 ± 17 years; 82% with ulcerative colitis [UC]) and 9422 patients treated with TNF antagonists (age, 45 ± 18 years; 44% with UC). JAK inhibitors were associated with higher risk of overall infections (incidence rate, 62.4 per 100 person-years [PY] vs 37.4 per 100 PY; hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.33-1.93), but not serious infections (4.9 vs 5.4; HR, 0.97; 95% CI, 0.66-1.44) compared with TNF antagonists. There was no difference in the risk of VTE (1.3 vs 1.2; HR, 0.66; 95% CI, 0.28-1.57) and MACE (0.4 vs 0.7; HR, 0.50; 95% CI, 0.19-1.30). Findings were largely stable on subgroup analyses based on type of IBD, type of JAK inhibitors, age, prior biologic exposure, concomitant use of corticosteroids, and baseline risk of adverse events. CONCLUSIONS: In an observational study of patients with IBD, JAK inhibitors were not associated with an increased risk of serious infections, VTE, or MACE compared with TNF antagonists, although the overall risk of infections was higher.