Imatinib treatment for idiopathic pulmonary fibrosis: Randomized placebo-controlled trial results

Craig E. Daniels, Joseph A. Lasky, Andrew H. Limper, Kathleen Mieras, Edith Gabor, Darrell R. Schroeder, Jeffrey Chapman, Steven Nathan, Moises Selman, Charles Alex, Augustine Lee, Leo Ginns, Joaode De Andrade, Imre Noth, Marilyn Glassberg, Janice Lieber, Lisa Lancaster, Paul Nobel, Stephen Pascoe, Jo Ann Duffy

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Abstract

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 PaO2 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).

Original languageEnglish (US)
Pages (from-to)604-610
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume181
Issue number6
DOIs
StatePublished - Mar 15 2010

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Keywords

  • Idiopathic pulmonary fibrosis
  • Imatinib
  • Pulmonary function testing
  • Tryosine kinase inhibitor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Daniels, C. E., Lasky, J. A., Limper, A. H., Mieras, K., Gabor, E., Schroeder, D. R., Chapman, J., Nathan, S., Selman, M., Alex, C., Lee, A., Ginns, L., De Andrade, J., Noth, I., Glassberg, M., Lieber, J., Lancaster, L., Nobel, P., Pascoe, S., & Duffy, J. A. (2010). Imatinib treatment for idiopathic pulmonary fibrosis: Randomized placebo-controlled trial results. American journal of respiratory and critical care medicine, 181(6), 604-610. https://doi.org/10.1164/rccm.200906-0964OC