Long-term comparative analysis of secukinumab versus TNFα inhibitors in patients with spondyloarthritis: treatment persistence is differentially affected by disease phenotype, obesity and sex.

BACKGROUND: The anti-interleukin 17A agent secukinumab has been approved for the treatment of spondyloarthritis (SpA) patients as an alternative to tumor necrosis factor inhibitors (TNFis). Our aim was to compare long-term treatment persistence and relevant effect modifiers, as well as 6-month clinical responses, in SpA patients starting secukinumab versus TNFis in routine clinical care. METHODS: This was a prospective single-center cohort study of consecutive axial SpA (axSpA) or peripheral SpA (perSpA) patients, including psoriatic arthritis (PsA) patients, who started or switched to either secukinumab or TNFis from 2016-2022. Drug persistence and low/minimal disease activity rates were assessed via Kaplan‒Meier curves and multivariable and propensity score-adjusted regression analyses. Confounding and effect modification were tested for several baseline demographic, clinical and laboratory characteristics. RESULTS: A total of 644 patients (secukinumab: 214, TNFis: 430) were analyzed. Unadjusted 4-year treatment persistence was greater with secukinumab than with TNFis in the total SpA cohort (38.7% versus 30.5%, respectively, log-rank p = 0.004); including the axSpA (37% versus 34.5%, p = 0.044) and perSpA (40% versus 18.2%, p = 0.011) cohorts. Multivariable analysis confirmed a greater risk for discontinuation of TNFis [HR (95% CI): 1.62 (1.23-2.14), p < 0.001] both for inefficacy [1.38 (1.01-1.90)] and safety reasons [2.95 (1.22-7.14)]. Psoriatic arthritis, obesity and female sex significantly modified the differential efficacy-related persistence. The 2-year persistence in obese female psoriatic arthritis patients was 76% with secukinumab versus 39% with TNFis, whereas in nonobese axSpA males, it was 48% versus 78%, respectively. Six-month treatment target achievement rates were comparable between the two agents in axSpA, perSpA, and PsA patients. CONCLUSIONS: The differential persistence of biologic agents commonly used in SpA has been shown in this real-life prospective study. Should the distinct effects of obesity, sex and specific SpA diagnosis on persistence be confirmed in other cohorts, it could optimize clinical decision-making and improve patient outcomes.