Objective A post-hoc analysis of the INCREASE trial and its open-label extension (OLE) was performed to evaluate whether inhaled treprostinil has a long-term survival benefit in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). Methods Two different models of survival were employed; the inverse probability of censoring weighting (IPCW) and the rank-preserving structural failure time (RPSFT) models both allow construction of a pseudo-placebo group, thereby allowing for long-term survival evaluation of patients with PH-ILD receiving inhaled treprostinil. Time-varying stabilised weights were calculated by fitting Cox proportional hazards models based on the baseline and time-varying prognostic factors to generate weighted Cox regression models with associated adjusted HRs. Results In the INCREASE trial, there were 10 and 12 deaths in the inhaled treprostinil and placebo arms, respectively, during the 16-week randomised trial. During the OLE, all patients received inhaled treprostinil and there were 29 and 33 deaths in the prior inhaled treprostinil arm and prior placebo arm, respectively. With a conventional analysis, the HR for death was 0.71 (95% CI 0.46 to 1.10; p=0.1227). Both models demonstrated significant reductions in death associated with inhaled treprostinil treatment with HRs of 0.62 (95% CI 0.39 to 0.99; p=0.0483) and 0.26 (95% CI 0.07 to 0.98; p=0.0473) for the IPCW and RPSFT methods, respectively. Conclusion Two independent modelling techniques that have been employed in the oncology literature both suggest a long-term survival benefit associated with inhaled treprostinil treatment in patients with PH-ILD. Data are available upon reasonable request.

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PH-ILD INCREASE 研究的生存分析：评估交叉治疗对总体死亡率的影响

目的 对 INCREASE 试验及其开放标签扩展 (OLE) 进行事后分析，以评估吸入曲前列环素是否对伴有间质性肺疾病 (PH-ILD) 的肺动脉高压患者具有长期生存获益。方法采用两种不同的生存模型；截尾加权逆概率 (IPCW) 和保留等级的结构失效时间 (RPSFT) 模型都允许构建伪安慰剂组，从而允许对接受吸入曲前列环素的 PH-ILD 患者进行长期生存评估。通过基于基线和时变预后因素拟合 Cox 比例风险模型来计算时变稳定权重，以生成具有相关调整 HR 的加权 Cox 回归模型。结果 在 INCREASE 试验中，在为期 16 周的随机试验中，吸入曲前列环素组和安慰剂组分别有 10 例和 12 例死亡。在 OLE 期间，所有患者均接受了吸入曲前列环素治疗，之前吸入曲前列环素组和安慰剂组分别有 29 例和 33 例死亡。通过常规分析，死亡的 HR 为 0.71（95% CI 0.46 至 1.10；p=0.1227）。两种模型均显示，吸入曲前列环素治疗相关的死亡显着减少，IPCW 和 RPSFT 方法的 HR 分别为 0.62（95% CI 0.39 至 0.99；p=0.0483）和 0.26（95% CI 0.07 至 0.98；p=0.0473）。 。结论 肿瘤学文献中采用的两种独立建模技术均表明 PH-ILD 患者吸入曲前列环素治疗具有长期生存获益。数据可根据合理要求提供。