Herman Derrick, Ghazipura Marya, Barnes Hayley, Macrea Madalina, Knight Shandra L, Silver Richard M, Montesi Sydney B, Raghu Ganesh, Hossain Tanzib
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, The Ohio State Wexner Medical Center, Columbus, Ohio.
ZS Associates, Global Health Economics and Outcomes Research, New York, New York.
Ann Am Thorac Soc. 2024 Mar;21(3):474-485. doi: 10.1513/AnnalsATS.202301-081OC.
The American Thoracic Society convened an international multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with nintedanib alone or with the combination of nintedanib plus mycophenolate. Literature searches were conducted across MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using nintedanib or nintedanib plus mycophenolate to treat patients with SSc-ILD. Mortality, disease progression, quality of life, and adverse event data were extracted, and meta-analysis was performed when possible. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group method was used to assess the quality of evidence. For nintedanib therapy alone, the systematic review included three total studies and revealed that disease progression was less in the nintedanib arm (the annual rate of decline in forced vital capacity [FVC] was 44.5 ml less, the absolute change from baseline was 46.4 ml less, and FVC% predicted was 1.2% less in the nintedanib arm) compared with placebo. However, gastrointestinal side effects and treatment discontinuation were double in the nintedanib arm compared with placebo. For combination therapy, the systematic review also included three total studies and revealed that changes in the annual rate of decline in FVC favored combination therapy over placebo (mean difference, 79.1 ml). Combination therapy was, however, associated with increased gastrointestinal adverse effects compared with placebo. The quality of evidence for all outcomes was very low as per GRADE. The use of nintedanib alone and in combination with mycophenolate in patients with SSc-ILD is associated with a significant reduction in disease progression compared with placebo but at the cost of increased gastrointestinal side effects and treatment discontinuation. The quality of evidence is very low.
美国胸科学会召集了一个国际多学科小组，以制定系统性硬化症相关间质性肺病（SSc-ILD）的治疗临床实践指南。进行系统评价并评估文献，以确定SSc-ILD患者应单独使用尼达尼布治疗还是采用尼达尼布联合霉酚酸酯治疗。通过检索MEDLINE、EMBASE和Cochrane对照试验中央注册库数据库，检索截至2022年6月使用尼达尼布或尼达尼布联合霉酚酸酯治疗SSc-ILD患者的研究。提取死亡率、疾病进展、生活质量和不良事件数据，并在可能的情况下进行荟萃分析。采用推荐分级、评估、制定和评价（GRADE）工作组方法评估证据质量。对于单独使用尼达尼布治疗，系统评价共纳入三项研究，结果显示与安慰剂相比，尼达尼布组的疾病进展较少（用力肺活量[FVC]的年下降率少44.5ml，与基线相比的绝对变化少46.4ml，尼达尼布组预测的FVC%少1.2%）。然而，与安慰剂相比，尼达尼布组的胃肠道副作用和治疗中断率增加了一倍。对于联合治疗，系统评价也共纳入三项研究，结果显示FVC年下降率的变化表明联合治疗优于安慰剂（平均差异为79.1ml）。然而，与安慰剂相比，联合治疗与胃肠道不良反应增加有关。根据GRADE，所有结局的证据质量都非常低。与安慰剂相比，在SSc-ILD患者中单独使用尼达尼布以及与霉酚酸酯联合使用均与疾病进展显著减少相关，但代价是胃肠道副作用增加和治疗中断。证据质量非常低。
