Cardiovascular, cancer, and infection risks of Janus kinase inhibitors in rheumatoid arthritis and ulcerative colitis: A nationwide cohort study

Background: Evolving evidence suggests that patients undergoing treatment with Janus kinase inhibitors (JAKi) may face an increased risk of cardiovascular events, malignancies, and serious infections. Objectives: We assessed cardiovascular, malignancy, and serious infection risks associated with JAKi use compared to tumor necrosis factor inhibitor (TNFi) use, which served as the active comparator, in patients with rheumatoid arthritis (RA) or ulcerative colitis (UC). Methods: This study emulated a target trial using South Korea's nationwide claims database (2013–2023). We constructed two separate cohorts comprising new users of JAKi or TNFi with either RA or UC and performed overlap weighting to control for confounders. Outcomes included three-point-major adverse cardiovascular events (3P-MACE) (cardiovascular death, myocardial infarction, and stroke), malignancy, and serious infection. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: The RA cohort included 14,972 patients, with 4759 initiating JAKi. The UC cohort included 2085 patients, with 347 initiating JAKi. In the overall RA cohort, the weighted HR was 0.92 (95% CI 0.59–1.42) for 3P-MACE, 1.61 (1.08–2.41) for malignancy, and 1.08 (0.94–1.23) for serious infection. In the overall UC cohort, the weighted HR was 0.98 (0.11–8.42) and 0.45 (0.26–0.78) for malignancy and serious infection, respectively. No 3P-MACE cases were observed in JAKi users. Conclusions: JAKis were associated with an elevated risk of malignancy but no significant difference in the risk of 3P-MACE and serious infection among all patients with RA. Further data are needed regarding the risk of malignancy and 3P-MACE in patients with UC.