Treatment of Idiopathic Pulmonary Fibrosis with Etanercept: An Exploratory, Placebo-controlled Trial

作者：Ganesh Raghu, Kevin M. Brown, Ulrich Costabel, Vincent Cottin, Roland M. du Bois, Joseph A. Lasky, Michiel Thomeer, James P. Utz, Rezaul Karim Khandker, Lawrence McDermott, Saeed Fatenejad · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2008 · DOI：10.1164/rccm.200709-1446oc · 被引用次数：379 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Systemic Sclerosis and Related Diseases、Chronic Obstructive Pulmonary Disease (COPD) Research

RATIONALE: An efficacious medical therapy for idiopathic pulmonary fibrosis (IPF) remains elusive. OBJECTIVES: To explore the efficacy and safety of etanercept in the treatment of IPF. METHODS: This was a randomized, prospective, double-blind, placebo-controlled, multicenter exploratory trial in subjects with clinically progressive IPF. Primary endpoints included changes in the percentage of predicted FVC and lung diffusing capacity for carbon monoxide corrected for hemoglobin (Dl(CO(Hb))) and change in the alveolar to arterial oxygen pressure difference P(a-a)(O(2)) at rest from baseline over 48 weeks. MEASUREMENTS AND MAIN RESULTS: Eighty-eight subjects received subcutaneous etanercept (25 mg) or placebo twice weekly as their sole treatment for IPF. No differences in baseline demographics and disease status were detected between treatment groups; the mean time from first diagnosis was 13.6 months and mean FVC was 63.9% of predicted. At 48 weeks, no significant differences in efficacy endpoints were observed between the groups. A nonsignificant reduction in disease progression was seen in several physiologic, functional, and quality-of-life endpoints among subjects receiving etanercept. There was no difference in adverse events between treatment groups. CONCLUSIONS: In this exploratory study in patients with clinically progressive IPF, etanercept was well tolerated. Although there were no differences in the predefined endpoints, a decreased rate of disease progression was ob...