Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis.
Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis.
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DOI：
10.1056/nejmoa1113354
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发表时间：
2012-05-24
期刊：
影响因子：
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通讯作者：
Martinez FJ
中科院分区：
文献类型：
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作者：
Idiopathic Pulmonary Fibrosis Clinical Research Network;Raghu G;Anstrom KJ;King TE Jr;Lasky JA;Martinez FJ
泼尼松、硫唑嘌呤和N-乙酰半胱氨酸（NAC）的组合已被广泛用作特发性肺纤维化的治疗。这种三种药物方案的安全性和有效性尚不清楚。在这项随机、双盲、安慰剂对照试验中，我们将患有轻至中度肺功能损害的特发性肺纤维化患者按1：1：1的比例分配到三组之一-接受泼尼松、硫唑嘌呤和NAC联合治疗（联合治疗），单独使用NAC或安慰剂。主要结果是60周治疗期间用力肺活量纵向测量值的变化。当收集到大约50%的数据时（联合治疗组77名患者，安慰剂组78名患者），计划的中期分析显示，与安慰剂组相比，联合治疗组患者的死亡率（8比1，P = 0.01）和住院率（23比7，P<0.001）增加。这些观察结果，加上没有证据表明联合治疗具有生理或临床益处，促使独立数据和安全监测委员会建议在平均随访32周时终止联合治疗组。此处未报告仅NAC组和安慰剂组正在进行的比较数据。与安慰剂相比，在接受泼尼松、硫唑嘌呤和NAC联合治疗的特发性肺纤维化患者中观察到死亡和住院风险增加。这些发现提供了反对在此类患者中使用该组合的证据。（由国家心肺血液研究所和考林家庭基金资助; ClinicalTrials.gov编号，NCT 00650091。
A combination of prednisone, azathioprine, and N-acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety and efficacy of this three-drug regimen is unknown. In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups — receiving a combination of prednisone, azathioprine, and NAC (combination therapy), NAC alone, or placebo — in a 1:1:1 ratio. The primary outcome was the change in longitudinal measurements of forced vital capacity during a 60-week treatment period. When approximately 50% of data had been collected (with 77 patients in the combination-therapy group and 78 in the placebo group), a planned interim analysis revealed that patients in the combination-therapy group, as compared with the placebo group, had an increased rate of death (8 vs. 1, P = 0.01) and hospitalization (23 vs. 7, P<0.001). These observations, coupled with no evidence of physiological or clinical benefit for combination therapy, prompted the independent data and safety monitoring board to recommend termination of the combination-therapy group at a mean follow-up of 32 weeks. Data from the ongoing comparison of the NAC-only group and the placebo group are not reported here. Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo. These findings provide evidence against the use of this combination in such patients. (Funded by the National Heart, Lung, and Blood Institute and the Cowlin Family Fund; ClinicalTrials.gov number, NCT00650091.)