Real world data analysis indicates that pirfenidone may cause pellagra-like photosensitivity

Introduction: Pirfenidone is widely used in patients with idiopathic pulmonary fibrosis, although they sometimes cause side effects such as photosensitivity. However, the current mechanistic insights are insufficient. Real world data (RWD) from databases, such as the Food and Drug Administration Adverse Events Reporting System (FAERS), support the hypothesis that pirfenidone-related photosensitivity may be pellagra-like. Aims and objectives: We conducted an in vivo study to investigate whether pirfenidone-related photosensitivity is pellagra-like or not. Methods: RWD from FAERS was analyzed to test this hypothesis. Mice maintained on normal or niacin-deficient diets were administered pirfenidone (1.0 and 3.0 mg/mg/animal, twice daily, 5 days), and photosensitivity was analyzed using skin erythema score. Results: RWD from FAERS indicated that pirfenidone plays a role in the development of photosensitivity, and vitamins such as niacin showed a tendency to reduce the incidence of pirfenidone-induced photosensitivity. Pharmacologically, a greater dermal response to ultraviolet radiation was observed in the mice with pirfenidone placed on niacin-deficient diets compared to those on normal diets. Furthermore, urinary and hepatic metabolites were significantly reduced in mice treated with pirfenidone than in those treated without pirfenidone. Conclusions: Pirfenidone-induced photosensitivity is pellagra-like, and niacin treatment may improve the adverse effects in patients with pirfenidone.