Abstract
Background Pirfenidone (PFD) is widely used in patients with idiopathic pulmonary fibrosis (IPF), and its adverse effects, such as nausea and photosensitivity, are well known. Many patients with IPF have reduced doses or even cessation of PFD because of its side effects. No solutions have been found for these side effects because the current mechanistic insights are insufficient.
Methods Using the results of real-world data analysis from the Food and Drug Administration Adverse Events Reporting System, we hypothesised that PFD-related symptoms may be similar to pellagra. Reverse translational experiments using female Balb/c mice were performed to validate and estimate this hypothesis. Niacin and its metabolite responses were compared between patients with IPF treated by PFD and those treated without PFD.
Results The pellagra hypothesis was translated from real-world data analysis. Pharmacological and comprehensive genetic investigations showed that PFD caused pellagra-related nausea and photosensitivity in a mouse model, which may have been mediated by the actions of nicotinamide N-methyltransferase. Higher nicotinamide N-methyltransferase substrate responses were observed in urine from patients and mice with PFD than in those without PFD.
Conclusions PFD may cause pellagra or pellagra-like symptoms such as photosensitivity. Further studies are required to investigate whether niacin prevents pellagra-like symptoms caused by PFD in patients with IPF.
Footnotes
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Conflict of interest: Tomohiro Kuroita, Natsumi Susai, and Takeshi Yoshioka are employees of Shionogi & Co., Ltd. Other authors declare no competing interests.
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- Received May 18, 2022.
- Accepted July 20, 2022.
- Copyright ©The authors 2022
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