Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis
Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis
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DOI：
10.1056/nejmoa1811737
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发表时间：
2018-11-01
影响因子：
158.5
通讯作者：
Martinez, Fernando J.
中科院分区：
文献类型：
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作者：
Kolb, Martin;Raghu, Ganesh;Martinez, Fernando J.
背景尼达尼布是一种批准的治疗特发性肺纤维化（IPF）的药物。先前发表的一项试验的亚组分析表明，西地那非可能在氧合、气体交换（通过肺部一氧化碳 (DLCO) 扩散能力测量）、IPF 和 DLCO 严重下降患者的症状和生活质量方面带来益处。这个想法在这项试验中得到了检验。方法我们以 1:1 的比例随机分配患有 IPF 且 DLCO 为预测值 35% 或更低的患者接受尼达尼布 150 mg 每日两次加西地那非 20 mg 每日 3 次（尼达尼布加西地那非组）或尼达尼布 150 mg 每日两次加安慰剂每日 3 次（尼达尼布组）24周。主要终点是第 12 周圣乔治呼吸问卷 (SGRQ) 总分相对于基线的变化（总分范围从 0 到 100，分数越高表明健康相关生活质量越差）。次要终点包括呼吸困难和安全性的测量。结果共有 274 名患者接受了随机分组。第 12 周时，尼达尼布加西地那非组和尼达尼布组的 SGRQ 总分相对于基线的调整后平均变化没有显着差异（分别为 -1.28 分和 -0.77 分；P = 0.72）。使用加州大学圣地亚哥分校的呼吸急促问卷测量，没有观察到西地那非治疗对呼吸困难有益处。与之前的试验相比，没有观察到新的安全信号。结论对于 IPF 且 DLCO 为预测值 35% 或更低的患者，尼达尼布加西地那非与单用尼达尼布相比并没有提供显着的益处。在这组患者中，两种治疗方案均未发现新的安全信号。 （由勃林格殷格翰资助；INSTAGE ClinicalTrials.gov 编号，NCT02802345。）
BACKGROUNDNintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF). A subgroup analysis of a previously published trial suggested that sildenafil may provide benefits regarding oxygenation, gas exchange as measured by the diffusion capacity of the lungs for carbon monoxide (DLCO), symptoms, and quality of life in patients with IPF and severely decreased DLCO. That idea was tested in this trial.METHODSWe randomly assigned, in a 1: 1 ratio, patients with IPF and a DLCO of 35% or less of the predicted value to receive nintedanib at a dose of 150 mg twice daily plus sildenafil at a dose of 20 mg three times daily (nintedanib-plus-sildenafil group) or nintedanib at a dose of 150 mg twice daily plus placebo three times daily (nintedanib group) for 24 weeks. The primary end point was the change from baseline in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 12 (the total score ranges from 0 to 100, with higher scores indicating worse health-related quality of life). Secondary end points included measures of dyspnea and safety.RESULTSA total of 274 patients underwent randomization. There was no significant difference in the adjusted mean change from baseline in the SGRQ total score at week 12 between the nintedanib-plus-sildenafil group and the nintedanib group (-1.28 points and -0.77 points, respectively; P = 0.72). A benefit from sildenafil treatment was not observed with regard to dyspnea as measured with the use of the University of California, San Diego, Shortness of Breath Questionnaire. No new safety signals were observed, as compared with previous trials.CONCLUSIONSIn patients with IPF and a DLCO of 35% or less of the predicted value, nintedanib plus sildenafil did not provide a significant benefit as compared with nintedanib alone. No new safety signals were identified with either treatment regimen in this population of patients. (Funded by Boehringer Ingelheim; INSTAGE ClinicalTrials.gov number, NCT02802345.)