Clinical efficacy and safety evaluation of drug therapies for the treatment of progressive fibrotic-interstitial lung diseases (PF-ILDs): a network meta-analysis of randomized controlled trials

This network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of pharmacotherapies for progressive fibrotic-interstitial lung diseases (PF-ILDs) to identify optimal treatments. We searched for RCTs on PF-ILD [idiopathic pulmonary fibrosis (IPF), connective tissue disease-ILD (CTD-ILD), chronic hypersensitivity pneumonitis (CHP), and pulmonary sarcoidosis] pharmacotherapies until 5 June 2025. NMA assessed efficacy [forced vital capacity, diffusing capacity of lungs for carbon monoxide, 6-minute-walk distance] and safety [serious adverse events (SAEs) and all-cause mortality] (PROSPERO: CRD42024554475). We included 65 studies (13,521 participants) for 48 drugs in IPF, 10 studies (1,508 participants) for eight drugs in CTD-ILD, four studies (259 participants) for three drugs in CHP, and nine studies (525 participants) for nine drugs in pulmonary sarcoidosis. In IPF, pirfenidone, nintedanib, and IFNγ-1b slowed lung function decline and reduced mortality. In CTD-ILD, pirfenidone, nintedanib, tocilizumab, and cyclophosphamide improved lung function and reduced mortality, with higher SAEs for nintedanib and cyclophosphamide. Pirfenidone and prednisolone benefited CHP, while budesonide improved lung function in pulmonary sarcoidosis. Anti-fibrotic drugs – Pirfenidone and nintedanib effectively slow disease progression and reduce mortality in PF-ILDs. Emerging therapies like IFNγ-1b warrant further research, underscoring the need for large, high-quality RCTs.本研究针对进行性纤维化性间质性肺疾病（progressive fibrotic-interstitial lung diseases, PF-ILDs）的随机对照试验（randomized controlled trials, RCTs）开展网络Meta分析（network meta-analysis, NMA），旨在评估药物治疗的有效性与安全性，以筛选最优治疗方案。我们检索了截至2025年6月5日发表的、针对PF-ILDs[包括特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）、结缔组织病相关间质性肺疾病（connective tissue disease-ILD, CTD-ILD）、慢性过敏性肺炎（chronic hypersensitivity pneumonitis, CHP）及肺结节病]的药物治疗随机对照试验。本网络Meta分析的评估指标涵盖有效性指标[用力肺活量、肺一氧化碳弥散量、6分钟步行距离]与安全性指标[严重不良事件（serious adverse events, SAEs）及全因死亡率]，本研究已在PROSPERO国际系统评价注册平台注册（注册号：CRD42024554475）。 最终共纳入65项研究（合计13521名受试者），涉及IPF患者的48种药物；10项研究（1508名受试者），涉及CTD-ILD患者的8种药物；4项研究（259名受试者），涉及CHP患者的3种药物；以及9项研究（525名受试者），涉及肺结节病患者的9种药物。 在IPF患者中，吡非尼酮、尼达尼布及干扰素γ-1b（IFNγ-1b）可延缓肺功能下降并降低死亡率。在CTD-ILD患者中，吡非尼酮、尼达尼布、托珠单抗及环磷酰胺可改善肺功能并降低死亡率，但尼达尼布与环磷酰胺的严重不良事件发生率更高。吡非尼酮与泼尼松对CHP患者具有临床获益，而布地奈德可改善肺结节病患者的肺功能。抗纤维化药物——吡非尼酮与尼达尼布可有效延缓PF-ILDs的疾病进展并降低死亡率。新兴治疗手段如IFNγ-1b仍需开展进一步研究，这也凸显了开展大样本、高质量随机对照试验的必要性。