Mortality and Lung Function Decline of Idiopathic Pulmonary Fibrosis Patient with Ezetimibe and Pirfenidone

Abstract

Introduction: Recently inhibition of autophagy has been identified as one of the primary pathogenesis in idiopathic pulmonary fibrosis (IPF). Our previous study identified that Ezetimibe, an FDA-approved lipid-lowering agent, activates autophagy in nonalcoholic steatohepatitis preclinical models, but its effect on fibrotic lung disease has not been evaluated yet. We investigated the efficacy of Ezetimibe in improving survival and reducing lung function decline in patients with IPF.

Methods: Electronic medical records of IPF patients diagnosed from 2013 to 2021 were retrospectively collected in Yonsei University Health System. Patients were classified by Ezetimibe and/or Pirfenidone treatment group if they were prescribed each drug for at least 180 days. We compared all-cause mortality and the rate of lung function decline according to their medication.

Results: The 5-year survival rate of all IPF patients was 51.2%. Overall survival and transplant-free survival rates were lower in the group without Ezetimibe or Pirfenidone. After adjusting gender, age, GAP score, hospital factor, year of diagnosis, and comorbidities by multivariate cox regression analysis, the survival rate is higher in Ezetimibe and/or Pirfenidone treatment group. We analyze lung function decline in IPF patients with Ezetimibe. After adjusting with age, sex, lung cancer history, and initial FVC by mixed model, Forced Vital Capacity and Diffusion Capacity for CO declined slowly in the group with Ezetimibe.

Conclusions: Ezetimibe may decrease the mortality and lung function decline in IPF patients. But furthur prospective validation clinical study is required.