Analyses of efficacy end points in a controlled trial of interferon-gamma1b for idiopathic pulmonary fibrosis.


Journal Article

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating disease, yet validated, reliable criteria for evaluating patient response to therapies in clinical trials are lacking. METHODS: To optimize selection of end point criteria for the study of interferon (IFN)-gamma1b in patients with IPF, we retrospectively analyzed the components of the primary efficacy end point used in a large, controlled study of 330 patients for reliability, validity, and sensitivity to treatment effect. The primary end point components were death, disease progression defined as a > or = 5 mm Hg increase in resting alveolar-arterial oxygen pressure gradient (P[A-a]O2), and disease progression defined as a > or = 10% decrease in percentage of predicted FVC. RESULTS: We found that the P(A-a)O2 criterion was not reliable and was not associated with mortality. In contrast, the FVC criterion was reliable and was associated with a 2.4-fold increase in the risk of death. Of the three measures, only mortality was sensitive to a treatment effect of IFN-gamma1b. Additionally, the tendency for mortality benefit was observed in nearly all patient subgroups defined by baseline physiology. The effect of IFN-gamma1b on mortality was strongest in patients with baseline percentage of predicted FVC > or = 55% (p = 0.004) or percentage of predicted diffusing capacity of the lung for carbon monoxide > or = 30% (p = 0.008). CONCLUSION: We conclude that mortality is the most inclusive end point for future trials of IFN- gamma1b in patients with IPF, and that a > 10% decrement in the percentage of predicted FVC represents a valid measure of disease progression.

Full Text

Cited Authors

  • King, TE; Safrin, S; Starko, KM; Brown, KK; Noble, PW; Raghu, G; Schwartz, DA

Published Date

  • January 2005

Published In

Volume / Issue

  • 127 / 1

Start / End Page

  • 171 - 177

PubMed ID

  • 15653980

Pubmed Central ID

  • 15653980

Electronic International Standard Serial Number (EISSN)

  • 1931-3543

International Standard Serial Number (ISSN)

  • 0012-3692

Digital Object Identifier (DOI)

  • 10.1378/chest.127.1.171


  • eng