NEJM:Nintedanib系统性硬化相关的肺间质疾病的效果

2019-06-17 佚名 SCI天天读

间质性肺疾病(ILD)是系统性硬化症(SS)的常见表现,是导致SS死亡的主要原因。Nintedanib是一种酪氨酸激酶抑制剂(TKI),在SS和ILD的临床前研究中已被证明具有抗纤维化和抗炎作用。

BACKGROUND 背景

Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis–related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD.

间质性肺疾病(ILD)是系统性硬化症(SS)的常见表现,是导致SS死亡的主要原因。Nintedanib是一种酪氨酸激酶抑制剂(TKI),在SS和ILD的临床前研究中已被证明具有抗纤维化和抗炎作用。

METHODS 方法

We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud’s symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. 

我们进行了一项随机、双盲、安慰剂对照试验,来研究nintedanib在SS相关的ILD患者中的疗效和安全性。我们将过去7年内首次出现雷诺综合征以外症状且HR-CT显示至少有10%肺野纤维化的患者纳入研究,并按照1:1的比例随机分配口服nintedanib每天两次,每次150mg或接受安慰剂。

The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire (SGRQ) at week 52.

主要终点是52周时间内,评估用力肺活量(FVC)年下降率。次要终点主要是第52周改良的Rodnan皮肤评分和St. George’s呼吸问卷 (SGRQ)的总分与基线相比的绝对变化。

RESULTS 结果

A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was−52.4 ml per year in the nintedanib group and −93.3 ml per year in the placebo group difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P = 0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. 

本研究共入组576例患者,每例患者至少接受一剂nintedanib或安慰剂治疗;51.9%患者有弥漫性皮肤表现,48.4%接受基线吗替麦考酚酯(MMF)治疗。对主要终点进行统计分析发现:nintedanib组和安慰剂组调整后FVC年下降总量分别是-52.4ml、-93.3ml(相差 41.0ml;95%置信区间[CI],2.9—79.0;P=0.04)。使用多重插补分析缺失病例的影响,发现病例缺失对于主要终点指标FVC的变化并无影响,P值在0.06到0.10之间。

The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of −0.21 (95% CI, −0.94 to 0.53; P = 0.58) and 1.69 (95% CI, −0.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group.

在第52周,改良后的Rodnan皮肤评分与SGRQ总得分与基线相比变化无显著性差异,分别为- 0.21 (95% CI, - 0.94 - 0.53;P = 0.58)和1.69 (95% CI, - 0.73至4.12[未行多重比较来调整])。腹泻是最常见的不良事件,nintedanib组75.7%的患者出现腹泻,安慰剂组31.6%的患者出现腹泻。

CONCLUSIONS 结论

Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo. 

SS相关ILD患者中,nintedanib组的FVC年下降率低于安慰剂组;nintedanib对其他SS的临床表现没有任何益处。本试验中nintedanib的不良事件分布与特发性肺纤维化患者相似;包括腹泻在内的肠道不良事件在nintedanib组比安慰剂组更常见。

原始出处:

作者:佚名



版权声明:
本网站所有注明“来源:梅斯医学”或“来源:MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明“来源:梅斯医学”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (6)
#插入话题
  1. 2020-01-18 aliceclz
  2. 2019-06-18 旺医

    顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息

    0

相关资讯

PLoS One:间质性肺炎患者服用他汀可降低死亡率

本研究旨在评估间质性肺炎患者服用他汀是否能降低患者死亡率。 研究人员对从从1995到2009年间服用他汀药物的间质性肺炎患者和未服用他汀类药物进行1:2配对研究,被诊断为间质性肺炎的患者来自丹麦。 间质性肺病(n = 1786 + 1786)和先天性非纤维化患者(n = 261 + 261)功能随访累积生存率,服用他汀药物的间质性肺炎患者的生存率比非他汀使用组要高(log-rank:P =

CHEST:与自身抗体相关的特发性间质性肺炎

一些具有自身免疫特征和特发性间质性肺炎(IIP),特别是常见的间质性肺炎(UIP)的患者不适合归入结缔组织疾病相关性间质性肺病(CTD-ILD)、特发性肺纤维化(IPF)或最近提议的有自身免疫特征的间质性肺炎(IPAF)中。这些患者的临床结果仍然未知。近期,一项发表在杂志CHEST上的回顾性单中心研究,使用 ANOVA分析了124个定义明确患者的1年内用力肺活量(FVC)和弥散能力(DLCO)(2

Lancet Respir Med:肺纤维化诊断全新方法

本文基于对Fleischner学会成员的医学文献和专家意见所作的系统性研究,提供了一种诊断特发性肺纤维化(IPF)的最新方法,为疑似普通性间质性肺炎(UIP)患者的临床评估提供了标准。

普通型间质性肺炎病理诊断中国专家共识(草案)

普通型间质性肺炎,也称寻常型间质性肺炎(usual interstitial pneumonia, UIP),是间质性肺炎主要的病理类型,1968年Liebow和Carrington首次在间质性肺炎分类中将UIP列为一种基本类型。50年来,随着对间质性肺炎认识的不断深入,其分类历经多次修改和完善,但UIP作为间质性肺炎的基本类型始终没有改变。由于UIP病变标本不太常见,加之其标本处理、病理诊断思维

发热、皮疹伴快速进展型间质性肺炎,小心这类疾病!

患者2周前受凉后出现咳嗽,干咳为主,偶少量白稀痰,伴发热(体温不详),曾于外院就诊,诊断“社区获得性肺炎”,予以抗感染治疗,症状无改善。1周前出现活动后气促,并呈进行性加重。遂转至当地人民医院住院治疗,胸部CT示“双肺间质病变并感染”,予“比阿培南+利奈唑胺”抗感染,症状无改善,现为求进一步诊治收住我科。起病以来,患者精神稍差,食纳及睡眠可,大小便正常,体重无明显变化。