尼达尼布治疗晚期特发性肺纤维化患者的疗效和安全性。
Efficacy and safety of nintedanib in patients with advanced idiopathic pulmonary fibrosis.
机构信息
Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
McMaster University and St. Joseph's Healthcare, Hamilton, Ontario, Canada.
出版信息
BMC Pulm Med. 2020 Jan 8;20(1):3. doi: 10.1186/s12890-019-1030-4.
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).
背景
两项为期 52 周的 INPULSIS 试验研究了尼达尼布与安慰剂在特发性肺纤维化（IPF）患者中的疗效，这些患者用力肺活量（FVC）≥预测值的 50%，且一氧化碳弥散量（DLco）≥预测值的 30%-79%。为期 24 周的 INSTAGE 试验研究了尼达尼布联合西地那非与尼达尼布单药治疗一氧化碳弥散量（DLco）≤预测值的 35%的 IPF 患者的疗效。我们使用 INPULSIS 和 INSTAGE 试验的数据，比较了尼达尼布在基线时气体交换受损程度较轻和较重的 IPF 患者中的疗效。
方法
分析纳入了 INPULSIS 和 INSTAGE 试验中接受尼达尼布单药治疗的患者，以及 INPULSIS 试验中接受安慰剂治疗的患者。主要结局指标包括 24 周时 FVC 的下降率、24 周时确诊或疑似特发性急性加重的患者比例、24 周时的死亡病例数和不良事件。分析为描述性分析。
结果
INPULSIS 和 INSTAGE 试验中分别有 638 例和 136 例患者接受尼达尼布单药治疗，INPULSIS 试验中有 423 例患者接受安慰剂治疗。在 INPULSIS 和 INSTAGE 试验中，接受尼达尼布单药治疗的患者的 FVC 下降率分别为-52.3 和-66.7mL/24 周，而接受安慰剂治疗的患者的 FVC 下降率为-102.8mL/24 周。在 INPULSIS 试验中，接受尼达尼布单药治疗的患者中分别有 0.6%和 3.7%发生确诊或疑似特发性急性加重，接受安慰剂治疗的患者中则有 2.1%发生该事件。在这些组中，分别有 2.0%、11.0%和 1.9%的患者死亡。在 INPULSIS 和 INSTAGE 试验中，分别有 52.5%和 48.5%的接受尼达尼布单药治疗的患者和 16.1%的接受安慰剂治疗的患者出现腹泻不良事件。
结论
基于 INSTAGE 和 INPULSIS 试验的数据，尼达尼布在 24 周时对 FVC 下降的影响、安全性和耐受性在气体交换受损程度更严重和更轻的 IPF 患者中相似。这些数据支持在气体交换受损程度更严重的 IPF 患者中使用尼达尼布。
试验注册
INPULSIS（NCT01335464 和 NCT01335477）；INSTAGE（NCT02802345）。
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