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Imatinib Treatment for Idiopathic Pulmonary Fibrosis

Randomized Placebo-controlled Trial Results

¹ Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota; and ² Division of Pulmonary and Critical Care Medicine, Tulane University, New Orleans, Louisiana

Correspondence and requests for reprints should be addressed to Joseph Lasky, M.D., Division of Pulmonary and Critical Care Medicine, 1430 Tulane Avenue, New Orleans, LA 70112. E-mail: jlasky{at}tulane.edu

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no known efficacious therapy. Imatinib is a tyrosine kinase inhibitor with potential efficacy to treat fibrotic lung disease.

Objectives: To investigate the safety and clinical effects of imatinib in patients with IPF.

Methods: We studied 119 patients in an investigator-initiated, multicenter, multinational, double-blind clinical trial to receive imatinib or placebo for 96 weeks.

Measurements and Main Results: Over 96 weeks of follow-up, imatinib did not differ significantly from placebo (log rank P = 0.89) for the primary endpoint defined as time to disease progression (10% decline in percent predicted FVC from baseline) or time to death. There was no effect of imatinib therapy on change in FVC at 48, 72, or 96 weeks (P 0.39 at all time points) or change in diffusing capacity of carbon monoxide at 48, 72, or 96 weeks (P 0.26 at all time points). Change in resting Pa_O2 favored imatinib therapy at 48 weeks (P = 0.005) but not at 96 weeks (P = 0.074). During the 96-week trial there were 8 deaths in the imatinib group and 10 deaths in the placebo group (log rank test P = 0.64). Thirty-five (29%) patients discontinued the study without reaching the primary endpoint (imatinib, 32%; placebo, 27%; P = 0.51). Serious adverse events (SAEs) were not more common in the imatinib group (imatinib, 18 SAEs in 17 patients; placebo, 19 SAEs in 18 patients).

Conclusions: In a randomized, placebo-controlled trial of patients with mild to moderate IPF followed for 96 weeks, imatinib did not affect survival or lung function.

Clinical trial registered with www.clinicaltrials.gov (NCT00131274).

Key Words: idiopathic pulmonary fibrosis • imatinib • tryosine kinase inhibitor • pulmonary function testing

AT A GLANCE COMMENTARY Current Scientific Knowledge on the Subject Idiopathic pulmonary fibrosis is a relentlessly progressive interstitial lung disease with a median survival of only 3 years from diagnosis. Despite multiple recent high-quality clinical trials, no definitive therapy is known to alter survival. What This Study Adds to the Field This study is the first to investigate the safety and feasibility of tyrosine kinase inhibitors for fibrotic lung disease. It adds to a growing body of literature demonstrating the potential for this class of drugs in treatment of fibrotic and inflammatory diseases.

 

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