Questionnaire-based nationwide survey on the safety of azathioprine in Japanese patients with rheumatic diseases: a cross-sectional study

Azathioprine (AZA) is an established treatment for rheumatic diseases, but real-world safety data in Japanese patients remain limited. This study aimed to evaluate the real-world use and safety of AZA in Japan. A nationwide questionnaire survey was conducted, distributing forms to 1163 facilities, including university hospitals and Japan College of Rheumatology-certified institutions. Of these, 170 facilities (14.6%) responded. A total of 1943 patients with rheumatic diseases who initiated AZA between November 2000 and September 2023 were enrolled. Among them, 33.9% experienced adverse events (AEs), including hepatobiliary disorders (13.9%), gastrointestinal disorders (10.4%), blood and lymphatic system disorders (9.3%), infections (5.1%), and skin/subcutaneous disorders (2.4%). AZA therapy was discontinued in 468 (71.6%) of the 660 patients with AEs. The incidence of serious AEs (grade ≥3) was 2.7% and varied by rheumatic disease. Multivariate analysis identified older age (odds ratio [OR] 2.47, 95% confidence interval [CI]: 1.32-4.59) and systemic lupus erythematosus (OR 2.31, 95% CI: 1.09-4.87) as risk factors for serious AEs. This nationwide survey provides evidence of AZA-related AEs in Japanese patients with rheumatic diseases. AE incidence was relatively high, and serious AEs (grade ≥3) occurred more frequently in patients aged over 65 years and those with systemic lupus erythematosus.