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


OBJECTIVE
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.


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 > or = 0.39 at all time points) or change in diffusing capacity of carbon monoxide at 48, 72, or 96 weeks (P > or = 0.26 at all time points). Change in resting Pa(O(2)) 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).
Daniels
Craig E
CE
Mayo Clinic, Rochester, Minnesota, USA.
Lasky
Joseph A
JA
Limper
Andrew H
AH
Mieras
Kathleen
K
Gabor
Edith
E
Schroeder
Darrell R
DR
D000368:Aged; D000740:Anemia / Q000139:chemically induced; D001549:Benzamides; D018450:Disease Progression; D004311:Double-Blind Method; D004417:Dyspnea / Q000139:chemically induced; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006408:Hematoma, Subdural / Q000139:chemically induced; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy*; D000068877:Imatinib Mesylate; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012129:Respiratory Function Tests / Q000379:methods / Q000706:statistics & numerical data; D016019:Survival Analysis; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate