特发性肺纤维化中3期抗纤维化导向治疗结局：超越FVC下降。
完整摘要 · 中文译文
背景：针对特发性肺纤维化（IPF）抗纤维化定向治疗的3期证据已有所扩展，但缺乏直接头对头试验。用力肺活量（FVC）下降仍是主要试验结局，尽管它可能无法完全反映各疗法之间具有临床相关性的差异。 方法：我们系统综述了IPF抗纤维化定向治疗的3期随机安慰剂对照试验。采用标准化的48-52周估计值对FVC相较于安慰剂的效果进行描述性总结。全因治疗中止和全因死亡率采用安慰剂对照比值比进行分析。敏感性分析评估了随访持续时间、背景抗纤维化治疗和试验层面的一致性。 结果：共纳入10项试验，包括5，386名随机化参与者。吡非尼酮和尼达尼布显示相较于安慰剂一致减少FVC下降。吸入曲前列尼尔在TETON-1/2合并证据中显示出有利的FVC信号，主要作为背景抗纤维化治疗基础上的附加治疗。在无背景抗纤维化治疗的情况下，若干疗法显示出方向有利但不精确的FVC效应，无等效性证据。尼达尼布和吸入曲前列尼尔相较于安慰剂与更高的全因治疗中止几率相关：OR分别为1.39（95% CI，1.02-1.88）和OR 1.39（95% CI，1.08-1.78）。吡非尼酮是唯一与较低全因死亡几率相关的疗法（OR，0.50；95% CI，0.31-0.83），基于已发表的汇总ASCEND/CAPACITY死亡率数据a 以及日本3期试验。 结论：FVC下降仍是关键指标，但可能无法完全区分IPF中针对抗纤维化的治疗。整合FVC效应、背景治疗、治疗持续性和死亡率，可为解读不断扩展的3期证据提供一个谨慎、依赖背景的框架。
完整摘要 · 英文原文
BACKGROUND: Phase 3 evidence for antifibrotic-directed therapies in idiopathic pulmonary fibrosis (IPF) has expanded, but direct head-to-head trials are lacking. Forced vital capacity (FVC) decline remains the principal trial outcome, although it may not fully capture clinically relevant differences among therapies. METHODS: We systematically reviewed phase 3 randomized placebo-controlled trials of antifibrotic-directed therapies in IPF. FVC effects versus placebo were descriptively summarized using standardized 48-52-week estimates. All-cause treatment discontinuation and all-cause mortality were analyzed using placebo-controlled odds ratios. Sensitivity analyses assessed follow-up duration, background antifibrotic therapy, and trial-level consistency. RESULTS: Ten trials including 5,386 randomized participants were included. Pirfenidone and nintedanib showed consistent reductions in FVC decline versus placebo. Inhaled treprostinil showed a favorable FVC signal in the combined TETON-1/2 evidence, largely as add-on therapy with background antifibrotic treatment. Without background antifibrotic therapy, several therapies showed directionally favorable but imprecise FVC effects, without evidence of equivalence. Nintedanib and inhaled treprostinil were associated with higher odds of all-cause treatment discontinuation versus placebo: OR 1.39 (95% CI, 1.02-1.88) and OR 1.39 (95% CI, 1.08-1.78), respectively. Pirfenidone was the only therapy associated with lower odds of all-cause mortality (OR, 0.50; 95% CI, 0.31-0.83), based on published pooled ASCEND/CAPACITY mortality data and the Japanese phase 3 trial. CONCLUSIONS: FVC decline remains essential but may not fully distinguish antifibrotic-directed therapies in IPF. Integrating FVC effects, background therapy, treatment continuation, and mortality provides a cautious, context-dependent framework for interpreting expanding phase 3 evidence.