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

Abstract

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. This nationwide cohort study used the French health insurance database to identify adults with SpA initiating a targeted therapy (TNFi, IL17i, IL12/23i, IL23i, JAKi) from January 2014 to September 2022. Patients with prior cancer, HIV infection, or organ transplantation were excluded. Follow-up began after a 3-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. We included 56,591 patients (53.9% women; mean 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 versus ≤6 months was associated with a lower risk of overall cancer (weighted HR 0.86, 95%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. 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.