Association between non-melanoma skin cancer, psoriasis, and immunomodulatory therapy: a national epidemiologic study

The association between psoriasis and non-melanoma skin cancer (NMSC) remains inconsistent despite biologic plausibility. Immunosuppressive effects of systemic psoriasis treatments have also been hypothesized to contribute to the development of NMSC as well. However, data assessing the risk of NMSC associated with immunomodulatory psoriasis medications, particularly newer biologic therapies, are limited.Our objective was to quantify the association between psoriasis, systemic psoriasis therapy, and NMSC accounting for other relevant factors such as smoking status and ultraviolet (UV) light exposure.We performed a cross-sectional, case-control study of 413,457 adults containing 7,478 psoriasis and 9,756 NMSC cases taken from the National Institutes of Health All of Us Research Program database (queried July 2024). NMSC, psoriasis, UV-light exposure, and drug exposures were defined using disease or drug classification codes. Smoking exposure was defined using survey data. Multivariable logistic regression models were used to assess relationships, providing adjusted odds ratios with 95% confidence intervals (aOR with 95% CI).After adjustment for UV-light exposure, coal tar exposure, smoking status, race, ethnicity, gender, age, income, and insurance status, psoriasis history was a significant predictor for NMSC (aOR 1.37 95% CI 1.22-1.52). Psoriasis patients exposed to immunomodulatory medications were also at higher odds of NMSC compared to psoriasis patients who were never exposed (aOR 1.26 95% CI 1.01-1.57). Of these drugs, IL-23 inhibitors (aOR 2.47 95% CI 1.17-5.18), Janus kinase inhibitors (aOR 2.32 95% CI 1.09-4.92), and azathioprine (aOR 2.16 95% CI 1.18-3.96) were the only classes that significantly contributed to increased NMSC risk in psoriasis patients.Psoriasis is independently associated with NMSC. While treatment with some classes of systemic medications is also associated with increased NMSC risk, therapeutic benefits are significant and should be weighed against this risk. NMSC is treatable and high-risk patients may benefit from increased surveillance or preventative counseling. Further prospective studies that assess medication dose and length of exposure should validate our findings.