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
胃肠道不良事件在nintedanib组比安慰剂组更常见。
原始出处：
来源：SCI天天读
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