Cardiovascular risk associated with first-line Janus kinase inhibitors versus TNF inhibitors in patients with RA: a nationwide cohort study

OBJECTIVE: To compare the risk of major adverse cardiovascular events (MACE) between tumor necrosis factor inhibitors (TNFi) and Janus kinase inhibitors (JAKi) when initiated as first-line advanced therapy in patients with rheumatoid arthritis (RA). METHODS: Using the Korean nationwide claims database, we identified patients newly diagnosed with RA between 2010 and 2015. Patients who initiated TNFi or JAKi as first-line advanced therapy were selected for analysis. Patients were followed from initiation of TNFi or JAKi through June 2024. The primary outcome was incident MACE, defined as myocardial infarction, ischemic stroke, or coronary revascularization. Multivariable Cox proportional hazards models were applied in the total cohort. We additionally performed propensity score (PS)-matched analyses to address confounding by indication. Prespecified subgroup analyses were conducted according to baseline cardiovascular risk factors. RESULTS: The study included 6,174 patients (TNFi = 5,152; JAKi = 1,022). The incidence rates of MACE were 4.1 and 3.6 per 1,000 person-years in the TNFi and JAKi groups, respectively. MACE risk did not differ significantly between JAKi and TNFi in the total study cohort (adjusted hazard ratio [HR] 0.636, 95% confidence interval [CI] 0.283 to 1.429) or in the PS-matched population (adjusted HR 0.715, 95% CI 0.187 to 2.739). Results were consistent across all prespecified subgroups, including patients with baseline cardiovascular risk factors. CONCLUSION: First-line use of JAKi was not associated with an increased risk of MACE compared with TNFi. These findings provide real-world evidence supporting the cardiovascular safety of JAKi as first-line advanced therapy in patients with RA.