背景:美国胸科学会,欧洲呼吸学会,日本呼吸学会,和拉丁美洲协会召开会议,以更新间质性肺病(ILD)的临床实践指南。目的:进行系统评价以评估现有的ILD文献,以确定是否应使用抗纤维化尼达尼布治疗进行性肺纤维化(PPF)患者。数据来源:在MEDLINE进行了文献检索,EMBASE,以及2020年12月之前的Cochrane数据库,用于使用尼达尼布治疗PPF患者的研究。数据提取:死亡率,疾病进展,并提取不良事件数据,并在可能的情况下进行荟萃分析。建议的分级,评估,使用开发和评估(GRADE)工作组方法来评估证据质量。合成:选择两个相关研究。在整个研究人群中,nintedanib臂的强迫肺活量的年度下降较少(平均差[MD],107毫升/年;95%置信区间[CI],65.4至148.5毫升/年),在患有肺纤维化的常见间质性肺炎(UIP)模式的亚组中(MD,128.2毫升/年;95%CI,70.8至185.6毫升/年),肺纤维化的非UIP模式(MD,75.3毫升/年;95%CI,15.5至135.0毫升/年),纤维化结缔组织疾病相关ILD(MD,106.2毫升/年;95%CI,10.6至201.9毫升/年),纤维化特发性非特异性间质性肺炎(MD,141.7毫升/年;95%CI,46.0至237.4毫升/年),和纤维化职业性ILD(MD,252.8毫升/年;95%CI,79.2至426.5毫升/年),但不是纤维化过敏性肺炎(MD,72.9毫升/年;95%CI,-8.9至154.7毫升/年),纤维化结节病(MD,-20.5毫升/年;95%CI,-337.1至296.1毫升/年),或未分类的纤维化ILD(MD,68.5毫升/年;与安慰剂相比,95%CI,-31.3至168.4毫升/年)。胃肠道副作用很常见。结果的证据质量从非常低到中等等级不等。结论:在PPF患者中使用Nintedanib与疾病进展的统计学显着降低相关,但胃肠道副作用增加,而与肺纤维化的影像学模式无关。然而,现有证据的局限性导致这些效应估计的确定性较低,并且难以确定ILD亚型的差异效应的确切结论。主要资金来源:由美国胸科学会资助,欧洲呼吸学会,日本呼吸学会,和拉丁美洲社会协会。
Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic
review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the
antifibrotic nintedanib. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using nintedanib to treat patients with PPF. Data Extraction: Mortality, disease progression, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Synthesis: Two relevant studies were selected. The annual decline in forced vital capacity was less in the nintedanib arm in the overall study population (mean difference [MD], 107 ml/yr; 95% confidence interval [CI], 65.4 to 148.5 ml/yr) and in the subgroups with usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis (MD, 128.2 ml/yr; 95% CI, 70.8 to 185.6 ml/yr), non-UIP patterns of pulmonary fibrosis (MD, 75.3 ml/yr; 95% CI, 15.5 to 135.0 ml/yr), fibrotic connective tissue disease-related ILD (MD, 106.2 ml/yr; 95% CI, 10.6 to 201.9 ml/yr), fibrotic idiopathic nonspecific interstitial pneumonia (MD, 141.7 ml/yr; 95% CI, 46.0 to 237.4 ml/yr), and fibrotic occupational ILD (MD, 252.8 ml/yr; 95% CI, 79.2 to 426.5 ml/yr), but not fibrotic hypersensitivity pneumonitis (MD, 72.9 ml/yr; 95% CI, -8.9 to 154.7 ml/yr), fibrotic sarcoidosis (MD, -20.5 ml/yr; 95% CI, -337.1 to 296.1 ml/yr), or unclassified fibrotic ILD (MD, 68.5 ml/yr; 95% CI, -31.3 to 168.4 ml/yr) when compared with placebo. Gastrointestinal side effects were common. Quality of evidence for the outcomes ranged from very low to moderate GRADE. Conclusions: Nintedanib use in patients with PPF is associated with a statistically significant decrease in disease progression but increase in gastrointestinal side effects regardless of the radiographic pattern of pulmonary fibrosis. However, limitations in the available evidence lead to low certainty in these effect estimates and make definitive conclusions about the differential effects by subtype of ILD difficult to determine. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.