Serious Infection Risk With <scp>TNF</scp> Inhibitors vs. <scp>JAK</scp> Inhibitors in Rheumatoid Arthritis: A Nationwide Claims‐Based Cohort Study

Tumor necrosis factor-α inhibitors (TNFαi) and Janus kinase inhibitors (JAKi) are widely used biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatoid arthritis. We aimed to compare the risk of serious infections between TNFαi and JAKi in patients with rheumatoid arthritis. We conducted a retrospective cohort study using a nationwide Japanese claims database covering over 19 million individuals. Patients were identified using the International Classification of Diseases, 10th Revision (ICD-10) codes (M05 or M06), and new users of bDMARDs or JAKi were included. We applied overlap weighting based on propensity scores. The primary outcome was serious infection, defined as a hospitalization-associated infection accompanied by diagnostic testing or anti-infective treatment. Among 5,018 eligible rheumatoid arthritis patients (TNFαi: 4042; JAKi: 976), TNFαi use was associated with a significantly lower risk of serious infections (HR: 0.55; 95% confidence interval: 0.39-0.77). The E-value for the observed HR was 2.39, suggesting that unmeasured confounding would need to be strongly associated with both treatment assignment and infection risk to fully explain the result. Site-specific analyses showed significantly lower risks of respiratory tract infections, urogenital infections, and sepsis in the TNFαi group. Drug-specific analyses indicated an elevated infection risk with baricitinib and infliximab. In this study, TNFαi use was associated with a lower risk of serious infections than JAKi in patients with rheumatoid arthritis. These findings support the preferential use of TNFαi in infection-prone populations and highlight the importance of individualized risk assessment in rheumatoid arthritis treatment decisions.