近日，美国伊诺瓦费尔法克斯医院Steven D. Nathan团队研究了吸入曲前列地尼治疗特发性肺纤维化的疗效与安全性。这一研究成果发表在2026年3月11日出版的《新英格兰医学杂志》上。

临床前研究数据显示，吸入性曲前列尼尔可能通过抗纤维化机制对特发性肺纤维化（IPF）具有治疗价值，这一假设得到了临床观察的支持。

在这项为期52周的3期双盲试验中，研究组将IPF患者随机分配接受吸入性曲前列尼尔或安慰剂治疗（每日四次，每次12吸）。主要终点是第52周时用力肺活量较基线的绝对变化值。为控制多重性问题，按预设顺序分析的次要终点包括：临床恶化事件、IPF急性加重（两者均采用事件发生时间分析）、52周内死亡率、以及第52周时FVC占预计值百分比、生活质量和一氧化碳弥散量较基线的变化值。同时进行安全性评估。

共有593例患者接受随机分组并至少接受一次试验药物（曲前列尼尔组298例，安慰剂组295例），其中463例患者（曲前列尼尔组224例，安慰剂组239例）完成了52周试验评估。患者平均年龄71.7岁，男性占80.1%，基线FVC占预计值百分比平均为76.8%，75.4%的患者正在接受背景抗纤维化治疗。第52周时FVC变化中位数：曲前列尼尔组为-49.9 ml（95%置信区间：-79.2至-19.5），安慰剂组为-136.4 ml（95% CI：-172.5至-104.0）；两组FVC变化差异为95.6 ml（95% CI：52.2至139.0；P<0.001）。临床恶化事件发生率：曲前列尼尔组81例（27.2%），安慰剂组115例（39.0%）（风险比：0.71；95% CI：0.53至0.95；P=0.02）。两组IPF急性加重时间未见显著差异，因此未对后续次要终点进行进一步推断。最常见不良事件为咳嗽，曲前列尼尔组报告率为48.3%，安慰剂组为24.1%。曲前列尼尔组和安慰剂组分别有33.6%和24.7%的患者中止治疗，其中约半数将不良事件作为中止主因。

研究结果表明，在IPF患者中，与安慰剂相比，为期52周的吸入性曲前列尼尔治疗与FVC下降减缓及临床恶化事件减少相关。

附：英文原文

Title: Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis

Author: Steven D. Nathan, Peter Smith, Chunqin Deng, Maria De Salvo, Wim Wuyts, Juana Pavie-Gallegos, Jin Woo Song, Mordechai R. Kramer, Christopher S. King, John A. Mackintosh, Daniel Chambers, Georgina Viviana Miranda, Natalie Breytenbach, Leigh Peterson, Heidi Bell, Kevin R. Flaherty, Juergen Behr, Vincent Cottin

Issue&Volume: 2026-03-11

Abstract:

Background

Preclinical data indicate that inhaled treprostinil may be useful for the treatment of idiopathic pulmonary fibrosis (IPF) through an antifibrotic mechanism, a premise that is supported by clinical observation.

Methods

In this phase 3, double-blind trial, we randomly assigned patients with IPF to receive inhaled treprostinil or placebo (12 breaths four times daily) over a period of 52 weeks. The primary end point was the change from baseline in the absolute forced vital capacity (FVC) at week 52. Secondary end points, which were analyzed in a prespecified order to control for multiplicity, were clinical worsening and acute exacerbation of IPF (each assessed in a time-to-event analysis), death by week 52, and the change from baseline in the percentage of predicted FVC, quality of life, and the diffusing capacity of the lungs for carbon monoxide by week 52. Safety was also assessed.

Results

A total of 593 patients underwent randomization and received at least one dose of treprostinil (298 patients) or placebo (295 patients). Of these, 463 patients (224 in the treprostinil group and 239 in the placebo group) completed the trial assessments through week 52. The mean age of the patients was 71.7 years, 80.1% were men, the mean FVC at baseline was 76.8%, and 75.4% of the patients were receiving background antifibrotic therapy. The median change in FVC at week 52 was 49.9 ml (95% confidence interval [CI], 79.2 to 19.5) in the treprostinil group and 136.4 ml (95% CI, 172.5 to 104.0) in the placebo group; the between-group difference in the change in FVC was 95.6 ml (95% CI, 52.2 to 139.0; P<0.001). Clinical worsening occurred in 81 patients (27.2%) in the treprostinil group and 115 patients (39.0%) in the placebo group (hazard ratio, 0.71; 95% CI, 0.53 to 0.95; P=0.02). No substantial between-group difference in the time to IPF exacerbation was observed, and so no further inferences with regard to subsequent secondary end points were made. The most common adverse event was cough, reported in 48.3% of the patients in the treprostinil group and 24.1% of those in the placebo group. Discontinuation of treprostinil or placebo occurred in 33.6% and 24.7%, respectively, with approximately half these patients citing adverse events as the primary reason for discontinuation.

Conclusions

In patients with IPF, inhaled treprostinil was associated with a smaller decline in FVC and fewer clinical-worsening events than placebo over a period of 52 weeks.

DOI: NJ202603110000001

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2512911