Risk of Cancer According to Duration of Targeted Therapy Exposure in Spondyloarthritis: A Nationwide Cohort Study From the French Health Insurance Database

OBJECTIVE: To assess the association between duration of targeted therapy exposure and cancer risk in patients with spondyloarthritis (SpA), including those with psoriatic arthritis, axial SpA, and other subtypes. METHODS: This nationwide cohort study used the French health insurance database to identify adults with SpA initiating a targeted therapy (tumor necrosis factor inhibitors [TNFi], interleukin-17 inhibitors [IL-17i], IL-12/23i, IL-23i, JAK inhibitors [JAKi]) from January 2014 to September 2022. Patients with prior cancer, HIV infection, or organ transplantation were excluded. Follow-up began after a three-month delay and continued until December 2024. Exposure was assessed annually and classified as ≤6 or >6 months per year. Incident cancer was the primary outcome. Weighted Cox marginal structural models with inverse probability of treatment and censoring weights were used. A post hoc sensitivity analysis evaluated cumulative exposure trajectories over time. RESULTS: We included 56,591 patients (53.9% women; mean ± SD age 44 ± 13 years; median follow-up 5.0 years). During follow-up, 1,224 cancers occurred (1,029 solid, 116 hematological, 79 unclassified). Exposure >6 months versus ≤6 months was associated with a lower risk of overall cancer (weighted hazard ratio [wHR] 0.86, 95% confidence interval [CI] 0.75-0.99). In subgroup analyses, this association was observed for hematological malignancies (wHR 0.65, 95% CI 0.42-0.99) but not for solid cancers (wHR 0.92, 95% CI 0.79-1.07). Cumulative exposure history was not associated with cancer risk. CONCLUSION: In this nationwide study, prolonged exposure to targeted therapies was not associated with an increased cancer risk. Exposure >6 months per year was associated with a lower cancer risk, mainly for hematological malignancies, whereas cumulative exposure over multiple years was not associated with cancer risk.