Clinical Factors and Cumulative Smoking Burden Associated with Anti-TNF Switching in Radiographic Axial Spondyloarthritis: A Real-World Cohort Study

Background/Objectives: Anti-tumor necrosis factor (anti-TNF) switching remains common in radiographic axial spondyloarthritis (r-axSpA). We aimed to evaluate cumulative smoking burden and clinical factors associated with anti-TNF switching. Methods: This retrospective single-center cohort included 212 patients with r-axSpA. Clinical data were collected from medical records. Bivariate comparisons, Kaplan–Meier analysis and multivariable Cox regression assessed switching, with a cause-specific sensitivity analysis for lack-of-response switching. Results: Eighty patients (37.7%) switched initial anti-TNF agent, including 70 (87.5%) for lack of response. While the global comparison of smoking status was nonsignificant (p = 0.105), exploratory unadjusted comparisons of current smokers versus former and never-smokers combined showed associations with all-cause (p = 0.035) and lack-of-response switching (p = 0.012). In adjusted Cox analysis, cumulative smoking burden was associated with increased switching hazard (HR 1.025 per pack-year, 95% CI 1.011–1.039; p < 0.001), alongside peripheral articular involvement (HR: 2.0, 95% CI 1.216–3.296, p = 0.006), higher BASDAI at anti-TNF initiation (HR: 1.02, 95% CI 1.004–1.029, p = 0.007) and later calendar year of treatment initiation (HR: 1.24, 95% CI 1.107–1.394, p < 0.001). Smoking burden >20 pack-years was associated with a higher adjusted switching hazard compared with never-smokers (HR 3.54, 95% CI 2.081–6.033; p < 0.001). Among ever-smokers, Kaplan–Meier comparisons showed shorter drug survival with >20 versus ≤10 and >10–20 pack-years (both p < 0.001). Conclusions: Cumulative smoking burden was associated with an increased hazard of anti-TNF switching, particularly among patients with >20 pack-years. Quantifying smoking exposure may provide additional information beyond smoking status alone.