Comparative Safety of JAK versus TNF Inhibitors in Older Adults with Rheumatoid Arthritis: A Propensity Score-Matched Cohort Study

Objective This study evaluated the comparative safety of Janus kinase inhibitors (JAKi) vs tumor necrosis factor inhibitors (TNFi) among older adults aged ≥65 years with rheumatoid arthritis (RA), including a prespecified subgroup of patients aged ≥75 years. Methods A retrospective cohort study was conducted using the TriNetX U.S. Collaborative Network. Adults aged ≥65 years with RA who initiated JAKi or TNFi between 2016 and 2023 were included. Propensity score matching (1:1) was used to balance demographics, comorbidities, medications, and healthcare utilization. Patients were followed for up to 3 years. Primary outcomes were venous thromboembolism (VTE) and major adverse cardiovascular events (MACE). Secondary outcomes included malignancy and all-cause mortality. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses using an as-treated (AT) design and a prespecified subgroup analysis of adults aged ≥75 years were performed. Results After matching, 1,304 patients remained in each group. Over 3 years, JAKi vs TNFi was not associated with increased risk of VTE (50 vs 43 events; HR 1.18, 95% CI 0.79-1.78), MACE (164 vs 148; HR 1.13, 95% CI 0.91-1.41), malignancy (63 vs 68; HR 0.94, 95% CI 0.66-1.32), or mortality (71 vs 66; HR 1.10, 95% CI 0.79-1.54). Findings were consistent in the ≥75-year subgroup and as-treated analyses. Conclusion In this real-world cohort of older adults with RA, initiation of JAK inhibitors was not associated with higher risks of MACE, VTE, malignancy, or mortality compared with TNF inhibitors.