Psoriasis Therapies and the Risk of Cutaneous Malignancy

Abstract

AbstractBackground: Systemic therapies for moderate to severe psoriasis target the dysregulated inflammatory response. However, their immunomodulatory properties may also contribute to carcinogenesis, leading to increased risk of cutaneous malignancy in patients exposed to systemic agents.Objective: A review of the literature was performed to evaluate the risk of cutaneous malignancy associated with the following therapies for moderate to severe psoriasis: PUVA, UVB, cyclosporine, methotrexate, retinoids, TNF-a inhibitors, IL-12/23 inhibitors, and IL-17 inhibitors.Results: Rates of NMSC, most notably SCC, increase linearly with number of PUVA exposures. UVB radiation, both narrowband and broadband, has no clear association with skin cancer. There is a well-characterized association between cyclosporine and NMSC, particularly SCCs, although it is less clear whether cyclosporine predisposes to malignant melanoma. Methotrexate appears to increase the risk of melanoma and NMSC in a dose-dependent fashion. Retinoids, on the other hand, have chemopreventative properties and may decrease risk of NMSC in patients with psoriasis. A large body of evidence supports an increased risk of NMSC, particularly SCC, in TNF-a inhibitors, but an association with melanoma is less clear. The newly-developed agents, IL-12/23 and IL-17 inhibitors, do not clearly show increased carcinogenic risk, but their long-term safety profiles are still under investigation.Conclusions: Many systemic psoriasis therapies, including PUVA, cyclosporine, methotrexate, and TNF-a inhibitors, appear to increase the risk of cutaneous malignancy. When prescribing these agents, physicians must weigh the benefit of treatment with their carcinogenic potential. Additional post-marketing surveillance is required to better understand the long-term risks of the newer biologic agents.