Mortality and risk factors in Japanese patients with rheumatoid arthritis: a 14-year observation of the IORRA cohort

Objectives To investigate standardized mortality ratio (SMR), causes of death, and mortality risk factors in Japanese patients with rheumatoid arthritis (RA) between 2007 and 2021, representing the biological disease-modifying antirheumatic drug (bDMARD) era. Methods We analyzed Japanese patients in the Institute of Rheumatology, Rheumatoid Arthritis cohort. The SMR was calculated using the Japanese General Population Life Table. Multiple imputation methods were used for sensitivity analysis of lost to follow-up cases. Risk factors were analyzed using time-dependent Cox proportional hazards model. Results Among 10,613 patients with RA, 915 deaths occurred for 99,364.8 patient-years. Major causes of death were malignancy (27.8%), respiratory disease (22.3%), and cardiovascular disease (16.3%). The SMR varied based on lost to follow-up assumptions: 0.92 (95% confidence interval (CI): 0.86 to 0.98) assuming all survived, 1.57 (95% CI: 1.47 to 1.68) assuming lost cases had equal mortality to followed cases, and 1.68 (95% CI: 1.58 to 1.79) assuming 1.65-times higher mortality than followed cases, respectively. Time-dependent analysis revealed protective associations with methotrexate (MTX) and bDMARDs, while even low-dose glucocorticoids showed increased mortality risk. Conclusion Japanese patients with RA show excess mortality despite bDMARD-era treatments. MTX and bDMARDs were protective, while glucocorticoids increased mortality risk.