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1b for Idiopathic Pulmonary Fibrosis*
* From the Department of Medicine (Dr. King), San Francisco General Hospital, University of California at San Francisco, San Francisco, CA; InterMune, Inc. (Drs. Safrin and Starko), Brisbane, CA; National Jewish Medical and Research Center (Dr. Brown), Denver, CO; Yale University School of Medicine (Dr. Noble), New Haven, CT; Division of Pulmonary Disease (Dr. Raghu), University of Washington Medical Center, Seattle, WA; and Duke University Medical Center (Dr. Schwartz), Durham, NC.
Correspondence to: Talmadge E. King, Jr, MD, FCCP, San Francisco General Hospital, Department of Medicine, 1001 Potrero Ave, San Francisco, CA 94110; e-mail: tking{at}medsfgh.ucsf.edu
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)-
1b 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 
5 mm Hg increase in resting alveolar-arterial oxygen pressure gradient (P[A-a]O2), and disease progression defined as a 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-1b. Additionally, the tendency for mortality benefit was observed in nearly all patient subgroups defined by baseline physiology. The effect of IFN-1b on mortality was strongest in patients with baseline percentage of predicted FVC 55% (p = 0.004) or percentage of predicted diffusing capacity of the lung for carbon monoxide 30% (p = 0.008).
Conclusion: We conclude that mortality is the most inclusive end point for future trials of IFN- 1b in patients with IPF, and that a > 10% decrement in the percentage of predicted FVC represents a valid measure of disease progression.
Key Words: arterial-alveolar pressure gradient • efficacy end points • idiopathic pulmonary fibrosis • mortality • percentage of predicted FVC
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