临床前数据表明,尼达尼布是一种酪氨酸激酶的细胞内抑制剂,可抑制肺纤维化的进展过程。目前已证实尼达尼布可用于治疗特发性肺纤维化,但它在多种纤维化肺病中的疗效尚未明确。
研究组在15个国家进行了这项双盲、安慰剂对照的临床3期试验,研究组共招募了663例肺纤维化患者,经高分辨率CT检查,肺纤维化的体积均占10%及以上,过去24个月内符合间质性肺病进展的标准,强迫肺活量(FVC)至少为预测值的45%,CO的肺扩散能力为预测值的30-80%。将患者随机分为两组,分别接受尼达尼布或安慰剂进行治疗。
在总体人群中,尼达尼布组和安慰剂组的校正FVC下降率分别为-80.8mL/年和-187.8mL/年,差异显著。在普通型间质性肺炎(UIP)纤维化的患者中,尼达尼布组的校正FVC下降率为-82.9mL/年,安慰剂组为-211.1mL/年,差异显著。腹泻是最常见的不良反应,其中尼达尼布组发生率为66.9%,安慰剂组为23.9%。与安慰剂相比,尼达尼布更容易导致肝功能异常。
总之,对于进展性肺间质纤维化的患者,尼达尼布治疗的FVC年下降率明显低于安慰剂,但容易发生腹泻。
附:英文原文
Title: Nintedanib in Progressive Fibrosing Interstitial Lung Diseases
Author: Kevin R. Flaherty, Athol U. Wells, Vincent Cottin, Anand Devaraj, Simon L.F. Walsh, Yoshikazu Inoue, Luca Richeldi, Martin Kolb, Kay Tetzlaff, Susanne Stowasser, Carl Coeck, Emmanuelle Clerisme-Beaty, Bernd Rosenstock, Manuel Quaresma, Thomas Haeufel, Rainer-Georg Goeldner, Rozsa Schlenker-Herceg, Kevin K. Brown
Issue&Volume: 2019-09-29
Abstract:
BACKGROUND
Preclinical data have suggested that nintedanib, an intracellular inhibitor of tyrosine kinases, inhibits processes involved in the progression of lung fibrosis. Although the efficacy of nintedanib has been shown in idiopathic pulmonary fibrosis, its efficacy across a broad range of fibrosing lung diseases is unknown.
METHODS
In this double-blind, placebo-controlled, phase 3 trial conducted in 15 countries, we randomly assigned patients with fibrosing lung disease affecting more than 10% of lung volume on high-resolution computed tomography (CT) to receive nintedanib at a dose of 150 mg twice daily or placebo. All the patients met criteria for progression of interstitial lung disease in the past 24 months despite treatment and had a forced vital capacity (FVC) of at least 45% of the predicted value and a diffusing capacity of the lung for carbon monoxide ranging from 30 to less than 80% of the predicted value. Randomization was stratified according to the fibrotic pattern (a pattern of usual interstitial pneumonia [UIP] or other fibrotic patterns) on high-resolution CT. The primary end point was the annual rate of decline in the FVC, as assessed over a 52-week period. The two primary populations for analysis were the overall population and patients with a UIP-like fibrotic pattern.
RESULTS
A total of 663 patients were treated. In the overall population, the adjusted rate of decline in the FVC was −80.8 ml per year with nintedanib and −187.8 ml per year with placebo, for a between-group difference of 107.0 ml per year (95% confidence interval [CI], 65.4 to 148.5; P<0.001). In patients with a UIP-like fibrotic pattern, the adjusted rate of decline in the FVC was −82.9 ml per year with nintedanib and −211.1 ml per year with placebo, for a difference of 128.2 ml (95% CI, 70.8 to 185.6; P<0.001). Diarrhea was the most common adverse event, as reported in 66.9% and 23.9% of patients treated with nintedanib and placebo, respectively. Abnormalities on liver-function testing were more common in the nintedanib group than in the placebo group.
CONCLUSIONS
In patients with progressive fibrosing interstitial lung diseases, the annual rate of decline in the FVC was significantly lower among patients who received nintedanib than among those who received placebo. Diarrhea was a common adverse event.
DOI: 10.1056/NEJMoa1908681
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1908681
The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home