Imatinib Treatment for Idiopathic Pulmonary Fibrosis Randomized Placebo-controlled Trial Results
Imatinib Treatment for Idiopathic Pulmonary Fibrosis Randomized Placebo-controlled Trial Results
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DOI：
10.1164/rccm.200906-0964oc
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发表时间：
2010-03-15
影响因子：
24.7
通讯作者：
Schroeder, Darrell R.
中科院分区：
文献类型：
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作者：
Daniels, Craig E.;Lasky, Joseph A.;Schroeder, Darrell R.
理论基础：特发性肺纤维化(IPF)是一种进行性肺部疾病，目前尚无有效的治疗方法。目的：研究伊马替尼治疗特发性肺纤维化的安全性和临床疗效。方法：我们研究了119名接受伊马替尼或安慰剂治疗96周的多中心、多国、双盲临床试验的患者。测量和主要结果：在超过96周的随访中，伊马替尼与安慰剂(对数等级P=0.89)的主要终点没有显著差异，主要终点定义为疾病进展时间(预计FVC较基线下降10%)或死亡时间。伊马替尼治疗对48周、72周和96周的FVC变化(所有时间点P>；=0.39)或48周、72周和96周的一氧化碳弥散量的变化(P>；=0.26)均无影响。48周时静息PaO2的变化有利于伊马替尼治疗(P=0.005)，而96周时不利于伊马替尼治疗(P=0.074)。在96周的试验中，伊马替尼组有8人死亡，安慰剂组有10人死亡(对数等级检验，P=0.64)。35名(29%)患者在没有达到主要终点的情况下停止了研究(伊马替尼32%；安慰剂27%；P=0.51)。严重不良事件(SAE)在伊马替尼组中并不常见(伊马替尼17例，18例；安慰剂，18例，19例)。结论：在一项对轻中度IPF患者随访96周的随机、安慰剂对照试验中，伊马替尼不影响生存或肺功能。
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.