Persistence of IL-17 and TNF inhibitors following initial TNF inhibitor use in axial spondyloarthritis: a nationwide retrospective cohort study

Abstract

Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease primarily affecting the axial skeleton, with tumor necrosis factor inhibitors (TNFi) as the standard first-line biologic disease-modifying antirheumatic drugs since the early 2000s. Interleukin-17 inhibitors (IL-17i) have emerged as effective alternatives, but the optimal sequencing after first-line TNFi discontinuation remains uncertain.Objectives: To compare real-world treatment persistence of IL-17i and TNFi as second-line therapies following initial TNFi discontinuation in patients with axSpA.Design: A nationwide retrospective cohort study using the Korean National Health Insurance Service-National Health Information Database (2010-2023).Methods: We included patients with axSpA who initiated TNFi as first-line targeted therapy and received IL-17i or TNFi as second-line therapy. The primary outcome was discontinuation of the second-line drug within 1 year. Drug retention was analyzed using Kaplan-Meier curves, and discontinuation risk was estimated using Cox proportional hazards models with multivariable adjustment, inverse probability of treatment weighting (IPTW), and IPTW with covariate adjustment. Subgroup analyses were conducted by type of prior treatment failure (primary or secondary).Results: Among 1,660 patients (IL-17i: 375; TNFi: 1285), overall treatment persistence and discontinuation risk were similar between groups. However, patients with primary treatment failure had significantly higher discontinuation risk with TNFi versus IL-17i, with adjusted hazard ratios ranging from 1.54 (95% CI, 1.14-2.07) to 2.11 (95% CI, 1.13-3.94). Results remained consistent across all analytic approaches.Conclusion: While overall persistence was comparable, IL-17i showed greater retention than TNFi among patients with primary treatment failure to initial TNFi therapy.