BACKGROUND The two 52-week INPULSIS trials investigated nintedanib versus placebo in patients with IPF, FVC ≥50% predicted and DLco 30-79% predicted. The 24-week INSTAGE trial investigated nintedanib plus sildenafil versus nintedanib alone in patients with IPF and DLco ≤35% predicted. We used data from INPULSIS and INSTAGE to compare the effects of nintedanib in patients with IPF with less versus more severe impairment in gas exchange at baseline. METHODS Analyses were conducted in patients treated with nintedanib alone in the INPULSIS and INSTAGE trials and in patients treated with placebo in the INPULSIS trials. Outcomes included the rate of decline in FVC over 24 weeks, the proportions of patients who had a confirmed or suspected idiopathic acute exacerbation over 24 weeks, deaths over 24 weeks, and adverse events. Analyses were descriptive. RESULTS In total, 638 and 136 patients received nintedanib alone in the INPULSIS and INSTAGE trials, respectively, and 423 patients received placebo in the INPULSIS trials. Rates of FVC decline were - 52.3 and - 66.7 mL/24 weeks in patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and - 102.8 mL/24 weeks in patients treated with placebo in INPULSIS. Confirmed or suspected idiopathic acute exacerbations were reported in 0.6 and 3.7% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 2.1% of patients treated with placebo in INPULSIS. Deaths occurred in 2.0, 11.0 and 1.9% of patients in these groups, respectively. Diarrhoea adverse events were reported in 52.5 and 48.5% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 16.1% of patients treated with placebo in INPULSIS. CONCLUSIONS Based on data from the INSTAGE and INPULSIS trials, nintedanib had a similar effect on FVC decline over 24 weeks, and a similar safety and tolerability profile, in patients with IPF and more versus less severe impairment in gas exchange. These data support the use of nintedanib in patients with IPF who have advanced disease. TRIAL REGISTRATION INPULSIS (NCT01335464 and NCT01335477); INSTAGE (NCT02802345).

中文翻译：

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Nintedanib在晚期特发性肺纤维化患者中的疗效和安全性。

背景两项52周的INPULSIS试验研究了nintedanib与安慰剂治疗IPF，FVC≥50％预测和DLco 30-79％预测的患者。在为期24周的INSTAGE试验中，在IPF和DLco≤35％的预期患者中，研究了nintedanib加sildenafil与单独nintedanib的关系。我们使用来自INPULSIS和INSTAGE的数据来比较nintedanib对IPF患者基线基线气体交换较少或较严重的影响。方法在INPULSIS和INSTAGE试验中对仅使用nintedanib治疗的患者以及在INPULSIS试验中对使用安慰剂治疗的患者进行了分析。结果包括FVC在24周内下降的速度，在24周内确诊或怀疑为特发性急性加重的患者比例，在24周内死亡的患者以及不良事件。分析是描述性的。结果在INPULSIS和INSTAGE试验中，分别有638和136例患者单独接受了nintedanib治疗，在INPULSIS试验中，有423例患者接受了安慰剂治疗。在INPULSIS和INSTAGE中单独使用nintedanib治疗的患者FVC下降率分别为-52.3和-66.7 mL / 24周，在INPULSIS中用安慰剂治疗的患者FVC下降率分别为-102.8 mL / 24周。分别在INPULSIS和INSTAGE中单独或单独使用nintedanib治疗的患者中，已证实或怀疑的特发性急性加重发生率分别为0.6和3.7％，在INPULSIS中，安慰剂治疗的患者中分别占2.1％。这些组分别有2.0％，11.0％和1.9％的患者死亡。分别在INPULSIS和INSTAGE中分别有52.5％和48.5％的单独使用nintedanib治疗的患者出现腹泻不良事件，而在16名中。INPULSIS中有1％接受安慰剂治疗的患者。结论根据INSTAGE和INPULSIS试验的数据，对于IPF以及气体交换严重程度较轻的患者，nintedanib在24周内对FVC下降具有相似的作用，并且具有相似的安全性和耐受性。这些数据支持nintedanib在患有晚期疾病的IPF患者中的使用。试用注册（NCT01335464和NCT01335477）；安装（NCT02802345）。试用注册信息（NCT01335464和NCT01335477）；安装（NCT02802345）。试用注册（NCT01335464和NCT01335477）；安装（NCT02802345）。