Comparative safety of JAK inhibitors versus TNF inhibitors in psoriatic arthritis: a real-world propensity score-matched cohort study.

Background: Janus kinase inhibitors (JAKi) and tumor necrosis factor inhibitors (TNFi) demonstrate therapeutic efficacy in psoriatic arthritis (PsA), yet comparative real-world safety data remain limited. This study quantified adverse outcome risks between JAKi and TNFi in PsA patients. Methods: Retrospective cohort study utilized the TriNetX Global Collaborative Network electronic health records. Adults aged 18-99 years with PsA initiating JAKi or TNFi without prior exposure to the alternative class were identified. Cohorts underwent rigorous 1:1 propensity score matching on 42 baseline covariates, including inflammatory markers and indication-bias proxies. Incident adverse outcomes at 1-1825 days after treatment initiation were assessed using Kaplan-Meier analysis and absolute risk calculations. Results: Post-matching analysis included 2723 patients per cohort. Over a 5-year follow-up, JAKi initiation was associated with increased all-cause mortality [96 vs. 63 events; hazard ratio (HR) 2.012, 95% confidence interval 1.462-2.771, Conclusions: JAKi and TNFi exhibit distinct safety profiles in PsA. JAKi were associated with higher risks of mortality and severe or viral infections, whereas TNFi carried a higher skin and soft tissue infection risk. These findings emphasize the need for rigorous methodological adjustment in observational data and support individualized shared decision-making.