A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis

作者：Talmadge E. King, Williamson Z. Bradford, Socorro Castro-Bernardini, Elizabeth A. Fagan, Ian Glaspole, Marilyn K. Glassberg, Eduard Gorina, Peter Hopkins, David Kardatzke, Lisa Lancaster, David J. Lederer, Steven D. Nathan, Carlos A. Pereira, Steven A. Sahn, Robert Sussman, Jeffrey J. Swigris, Paul W. Noble · 发表于：New England Journal of Medicine · 年份：2014 · DOI：10.1056/nejmoa1402582 · 被引用次数：4027 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Systemic Sclerosis and Related Diseases、Respiratory and Cough-Related Research

BACKGROUND: In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients. METHODS: In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis. RESULTS: In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P=0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P=0.16) or in rates of death from any cause (P=0.10) or from idiopathic pulmonary fibrosis (P=0.23). However, in a prespecified pooled analysis incorporating...