Background: Medications used in the treatment of dermatologic conditions have been associated with squamous cell carcinoma (SCC), basal cell carcinoma (BCC), melanoma, and Merkel cell carcinoma (MCC). Objective: The objective of the study was to examine the relationship between systemic dermatologic medications and skin cancer in the FDA Adverse Event Reporting System (FAERS). Methods: Case-control analyses were performed in FAERS from 1968 to 2021 to examine the reporting odds ratios (RORs) for SCC, BCC, melanoma, and MCC. Results: The oral immunosuppressants were all associated with increased ROR of SCC, BCC, melanoma, and MCC. Azathioprine had the highest ROR for SCC (34.13, 95% CI 29.07–40.08), BCC (21.15, 95% CI 20.63–25.98), and MCC (44.76, 95% CI 31.52–63.55), while quinacrine and guselkumab had the highest ROR for melanoma (13.14, 95% CI 1.84–93.89 vs. 12.73, 95% CI 10.60–15.30, respectively). The TNF-α inhibitors were associated with an increased ROR for all skin cancers investigated. Conclusions: The oral immunosuppressants and many biologic medications were associated with an increased ROR of skin cancers including TNF-α inhibitors (etanercept, adalimumab, infliximab), IL-23 or IL-12/23 inhibitors (ustekinumab, risankizumab), and the CD-20 inhibitor rituximab but not dupilumab or IL-17 inhibitors.

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