Treatment of Idiopathic Pulmonary Fibrosis With Etanercept: An Exploratory, Placebo-Controlled Trial

Am J Respir Crit Care Med. 2008 Nov 1;178(9):948-55. doi: 10.1164/rccm.200709-1446OC. Epub 2008 Jul 31.

Abstract

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 observed on several measures. Further evaluation of TNF antagonists in the treatment of IPF may be warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 00063869).

Trial registration: ClinicalTrials.gov NCT00063869.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Carbon Monoxide / blood
  • Disease Progression
  • Double-Blind Method
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects
  • Immunoglobulin G / therapeutic use*
  • Lung / drug effects
  • Lung / physiopathology
  • Male
  • Oxygen / blood
  • Predictive Value of Tests
  • Prospective Studies
  • Pulmonary Fibrosis / drug therapy*
  • Quality of Life
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Research Design
  • Severity of Illness Index
  • Treatment Outcome
  • Vital Capacity / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Carbon Monoxide
  • Etanercept
  • Oxygen

Associated data

  • ClinicalTrials.gov/NCT00063869