Tumor necrosis alpha inhibitor therapy is associated with increased long-term risk of nonmelanoma skin cancer and melanoma: A retrospective cohort study.

Abstract

TNF-α inhibitors (TNF-I) are widely used to treat chronic inflammatory diseases, although there may be an associated risk of nonmelanoma skin cancer (NMSC) and melanoma. To evaluate if TNF-I exposure is associated with an increased risk or severity of NMSC or melanoma. A retrospective cohort study of adults with chronic inflammatory disease from 1996 to 2020. Primary outcome was basal cell carcinoma, squamous cell carcinoma, or melanoma diagnosis. Skin cancer diagnosis identified via International Classification of Diseases code and TNF-I exposure were manually reviewed for accuracy. Differential malignancy risk was analyzed by multivariable Cox proportional hazards to determine adjusted hazard ratios with disease severity stratification. Of 56,209 patients with chronic inflammatory conditions, 13,377 had TNF-I exposure. TNF-I exposure was significantly associated with increased risk of any cutaneous malignancy, melanoma, squamous cell carcinoma, and basal cell carcinoma. No significant differences in NMSC histopathological severity or melanoma clinical stage were found between TNF-I exposed and unexposed patients. Retrospective design, variability in patient-level risk factor documentation. TNF-I therapy in patients with inflammatory disease is associated with increased risk of NMSC and melanoma diagnosis but not severity. Prescribers of TNF-I should be aware of this increased risk, which may impact skin cancer screening patterns.