Abstract
IMPORTANCE: Rheumatoid arthritis (RA), a chronic autoimmune disease linked to higher mortality, benefits from physical activity (PA), which has been shown to reduce disease activity and improve physical function. However, PA’s association with all-cause mortality in RA patients remains unclear. OBJECTIVE: To investigate the relationship between various levels of PA and all-cause mortality among patients with RA. DESIGN, SETTING, AND PARTICIPANTS: This dual-cohort observational study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 and the UK Biobank database. PA was assessed using self-reported questionnaires in NHANES and 7-day wrist-worn accelerometers in the UK Biobank. MAIN OUTCOMES AND MEASURES: Cox proportional-hazards models and restricted cubic spline (RCS) analysis were employed to evaluate the association between PA and all-cause mortality. Subgroup and interaction analyses were conducted to examine the robustness of the findings. Stratified analyses were performed using polygenic risk scores for RA in the UK Biobank cohort. An analysis combining results from both cohorts was conducted using random-effects models to estimate pooled associations and assess heterogeneity. RESULTS: A total of 1493 patients with RA from the NHANES cohort and 1724 from the UK Biobank cohort were included. Across both cohorts, PA was significantly associated with a lower risk of all-cause mortality. In fully adjusted models, active and highly active groups showed reduced mortality risks compared with the inactive group [NHANES: hazard ratio (HR): active = 0.381, highly active = 0.675; UK Biobank: HR: active = 0.557, highly active = 0.491]. RCS analysis revealed a U-shaped association between PA and mortality in the NHANES cohort, with moderate PA levels showing the greatest protective effect. However, an L-shaped pattern was observed in the UK Biobank cohort, where the highly active group had the lowest mortality risk. A joint analysis in NHANES revealed that active work-related PA combined with inactive recreational PA yielded the greatest mortality reduction. In the UK Biobank, moderate-to-vigorous PA remained protective even among patients with high genetic risk. A pooled analysis combining both cohorts confirmed a robust inverse association between PA and all-cause mortality (HR: active = 0.48, highly active = 0.61), with low heterogeneity across studies. CONCLUSIONS AND RELEVANCE: PA is associated with reduced all-cause mortality in patients with RA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-026-03748-3.