Incidence of interstitial lung disease in seropositive rheumatoid arthritis patients receiving biologics, Janus kinase inhibitors, or methotrexate

Abstract

Background: The relationship between biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and the incidence of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) remains unclear. Objective: To investigate the influence of b/tsDMARDs on the development of ILD in patients with RA, particularly in Asian patients. Design: Retrospective cohort study. Methods: We examined data from patients with seropositive RA who had no prior ILD between January 1, 2010, and October 31, 2022, utilizing the Nationwide Korean Health Insurance Review and Assessment database. Cohort A consisted of individuals initiating b/tsDMARDs, while Cohort B included those starting conventional DMARDs, including individuals who subsequently began b/tsDMARDs. Patients were observed from the medication index date until the onset of ILD, death, or the conclusion of the study. In Cohort A, multivariate Cox proportional hazards analysis was conducted, followed by propensity score matching (PSM) analysis. In Cohort B, a time-dependent Cox proportional hazards analysis was performed, accounting for methotrexate (MTX) pretreatment period. Results: In Cohort A (13,908 patients), the crude incidence rate (IR) of ILD was 3.05 per 1000 person-years. After multivariable adjustment and PSM, no statistically significant differences in ILD development were observed among the biologics classes, with hazard ratios (HRs) ranging from 0.81 to 1.19 when compared to tumor necrosis factor (TNF) inhibitors as a reference. In Cohort B (75,013 patients), the overall IR was 2.8 per 1000 person-years. Time-dependent multivariable Cox analysis, adjusting for baseline characteristics and MTX pretreatment duration, showed no statistically significant differences between biologic users and MTX maintainers (adjusted HR range: 0.74-1.29, all p > 0.05). Conclusion: No specific b/tsDMARDs consistently showed significant differences in ILD incidence compared to other b/tsDMARDs. Biologics showed no significant increase in the risk of ILD compared to MTX maintainers. TNF inhibitors performed similarly to non-TNF biologics and Janus kinase inhibitors in terms of ILD incidence.