Nicotinamide for Skin Cancer Chemoprevention.

Importance: Nicotinamide supplementation has been studied as a chemopreventive medication for reducing skin cancer risk, but large-scale data are limited. Objective: To determine the clinical efficacy of nicotinamide supplementation for skin cancer prevention in the general population and among solid organ transplant recipients. Design, Setting, and Participants: A retrospective cohort study was conducted using electronic health record data (October 1, 1999, to December 31, 2024) from the Veterans Affairs Corporate Data Warehouse (CDW) of 33 822 patients. Analyses were conducted from January 17, 2025, to May 9, 2025. Patients who were exposed to nicotinamide were propensity score matched based on the number and year of skin cancers after which treatment with nicotinamide was initiated, age, sex, self-reported race, exposure to acitretin, exposure to field therapy, history of chronic lymphocytic leukemia, and history of solid organ transplant. The index date was the first prescription of nicotinamide filled within the VA system. Stratified Cox models were used to investigate the association of nicotinamide with skin cancer development. Exposures: Nicotinamide, 500 mg, twice daily for longer than 30 days as documented in the electronic health record. Main Outcomes and Measures: Time to the next skin cancer after baseline. Results: There were 12 287 patients (mean [SD] age, 77.2 [8.9] years; 241 women [2.0%]; 31 [0.3%] American Indian or Alaska Native, 3 [<0.1%] Asian, 13 [0.1%] Black or African American, 59 [0.5%] Native Hawaiian or other Pacific Islander, and 11 662 [94.9%] White individuals) exposed to oral nicotinamide, 500 mg, twice daily for longer than 30 days who were matched to 21 479 unexposed patients (mean [SD] age, 76.9 [8.7] years; 374 women [2.0%]; 49 [0.2%] American Indian or Alaska Native, 3 [<0.1%] Asian, 16 [0.1%] Black or African American, 88 [0.4%] Native Hawaiian or other Pacific Islander, and 20 517 [95.3%] White individuals). Within the matched dataset, there were 10 994 instances of basal cell carcinoma after nicotinamide exposure and 12 551 cutaneous squamous cell carcinoma (cSCC). A total of 1334 (3.9%) in the matched cohort were solid organ transplant recipients. Overall, there was a significant 14% reduction in skin cancer risk. When nicotinamide was initiated after a first skin cancer, the risk reduction rose to 54%, although this benefit declined with initiation following subsequent skin cancers. This risk reduction was seen for skin cancers overall, basal cell carcinoma, and cSCC, with the greatest risk reduction seen for cSCC. Among solid organ transplant recipients, no overall significant risk reduction was observed, although early nicotinamide use was associated with reduced cSCC incidence. Conclusions and Relevance: The results of this cohort study suggest that there is a decreased risk of skin cancer among patients treated with nicotinamide, with the greatest effect seen when initiated after the first skin cancer.