Dual effects of JAK vs TNF inhibitors on osteoporosis, fractures and mortality in rheumatoid arthritis: a real-world cohort study.

Purpose: This real-world study compared the effects of JAK inhibitors (JAKi) versus TNF inhibitors (TNFi) on bone health and survival in rheumatoid arthritis (RA) patients. Methods: We conducted a retrospective cohort study using the collaborative electronic health records (EHR) database network (2016-2024). After 1:1 propensity score matching, 16, 572 JAKi and 16, 572 TNFi users were included, with follow-up for up to 5 years. Primary outcomes were a composite of "any fracture or osteoporosis, " individual fracture and osteoporosis events, and all-cause mortality. Results: In the propensity score-matched cohort, JAKi use was associated with a lower risk of the composite outcome (HR = 0.930) and osteoporosis (HR = 0.906) compared with TNFi. However, a reduction in fracture risk was not clearly observed. JAKi use was also associated with higher all-cause mortality (HR = 1.582). Subgroup estimates suggested potential heterogeneity, but these findings were exploratory. Conclusion: In this large EHR-based cohort, JAKi initiation was associated with lower rates of osteoporosis-related outcomes but higher all-cause mortality compared with TNFi. Given the observational design, potential residual confounding, and limited follow-up for many patients, these findings should be interpreted as associations and warrant confirmation in other datasets and prospective studies. Rationale: To compare real-world associations of JAKi vs TNFi with bone outcomes and all-cause mortality in RA. Main result: In a propensity score-matched cohort, JAKi use was associated with lower osteoporosis-related outcomes but higher all-cause mortality compared with TNFi. Significance: These observational findings suggest a potential trade-off and highlight the need for individualized risk-benefit discussions and confirmation in other datasets/prospective studies.