Low body weight as a risk factor for serious azathioprine-related adverse events in patients with rheumatic diseases

Serious azathioprine (AZA)-related adverse events (AEs) contribute to treatment discontinuation in patients with rheumatic diseases, although real-world data on patient-related risk factors in Japanese patients remain limited. This study investigated predictive factors for serious AEs and their associations with patient characteristics in Japanese patients with rheumatic diseases. We previously conducted a nationwide questionnaire survey collecting clinical data from patients who initiated AZA treatment between November 2000 and September 2023, and performed a secondary analysis of these data. The incidence of serious AEs after AZA initiation and associations with patient characteristics were evaluated using univariable and multivariable analyses. Among 1,943 previously registered patients, body weight data were available for 1,824. AEs occurred in 618 patients (33.9%), including 47 (2.6%) with serious AEs. Multivariable analysis showed that older age (>66.5 years; odds ratio [OR] 1.98, 95% confidence interval [CI] 1.004-3.91) and lower body weight (BW) (<47.35 kg; OR 2.82, 95% CI 1.55-5.15) were significantly associated with serious AZA-related AEs. In subgroup analysis, low BW was significantly associated with serious AEs only in patients without NUDT15 codon 139 risk alleles. Older age and lower BW may help identify high-risk patients and support safer AZA use in Japanese patients with rheumatic diseases.