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SCI 6 July 2019 Nintedanib for Systemic Sclerosis– Associated Interstitial Lung Disease
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. 間質性肺?。↖LD）是系統(tǒng)性硬化癥的常見表現(xiàn)，也是系統(tǒng)性硬化相關死亡的主要原因。Nintedanib是一種酪氨酸激酶抑制劑，已被證明在系統(tǒng)性硬化癥和ILD的臨床前模型中具有抗纖維化和抗炎作用。 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. 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. 我們進行了一項隨機、雙盲、安慰劑對照試驗，以研究nintedanib對ILD合并系統(tǒng)性硬化癥患者的療效和安全性?；加邢到y(tǒng)性硬化癥且在過去7年內出現(xiàn)第一次非雷諾氏癥狀的患者和高分辨率計算機斷層掃描顯示，纖維化影響至少10％的肺部的患者被隨機分配，比例為1：1，接受150毫克的nintedanib，每日口服兩次，或安慰劑。主要終點是在52周內評估強迫肺活量（FVC）的年下降率。關鍵的次要終點是第52周改良的Rodnan皮膚評分和圣喬治呼吸問卷（SGRQ）總分與基線相比的絕對變化。 RESULTS 結果 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. 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. 共有576名患者接受了至少一劑nintedanib或安慰劑; 51.9％的患者患有彌漫性皮膚系統(tǒng)性硬化癥，48.4％的患者在基線時接受了霉酚酸酯治療。在主要終點分析中，nintedanib組的FVC調整后年變化率為-52.4 ml /年，安慰劑組為-93.3 ml（差異，每年41.0 ml; 95％置信區(qū)間[CI] ]，2.9至79.0; P = 0.04）。基于對缺失數(shù)據(jù)的多重插補的靈敏度分析產(chǎn)生主要終點的P值范圍在0.06到0.10質檢。在第52周時，改良Rodnan皮膚評分與基線的變化以及SGRQ的總評分在試驗組之間沒有顯著差異，差異為-0.21（95％CI，-0.94至0.53; P = 0.58）和1.69 （95％CI，-0.73至4.12 [未進行多重比較調整]）。在nintedanib組中75.7％的患者和安慰劑組中31.6％的患者報告了腹瀉，這是最常見的不良事件。 CONCLUSIONS 結論 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. 在ILD伴系統(tǒng)性硬化癥患者中，使用nintedanib的FVC年降低率低于安慰劑組; 對于系統(tǒng)性硬化癥的其他表現(xiàn)，沒有觀察到nintedanib的臨床益處。在本試驗中觀察到的nintedanib的不良事件特征與在特發(fā)性肺纖維化患者中相似; 包括腹瀉在內的胃腸道不良事件nintedanib比安慰劑更常見。 喜歡SCI天天讀的理由 陪您一起學習SCI醫(yī)學論文 每天5分鐘，讓自己的英語牛逼起來 特殊福利讓您驚喜連連 |
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來自： 生物_醫(yī)藥_科研 > 《待分類》
