Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis.

Methods

In this phase 3, double-blindtrial, we randomly assigned patients with IPF to receive inhaled treprostinil or placebo (12 breaths four times daily) over a period of 52 weeks.

在这项为期52周的III期、双盲试验中，我们将IPF患者随机分配接受吸入曲前列环素或安慰剂（每天四次，每次12次呼吸）治疗。

The primary end point was the change from baseline in the absolute forced vital capacity (FVC) at week 52.

主要终点是基线至第52周时绝对用力肺活量（FVC）的变化。

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.

次要终点，按照预先设定的顺序进行分析以控制多重性，包括临床恶化和特发性肺纤维化（IPF）的急性加重（每项均通过时间至事件分析进行评估）、第52周时的死亡、基线至第52周时预测的FVC百分比变化、生活质量以及肺部对一氧化碳的扩散能力变化。

Safety was also assessed.

安全性也得到了评估。

Results

A total of 593 patients underwent randomization and received at least one dose of treprostinil (298 patients) or placebo (295 patients).

共有593名患者进行了随机分组，并至少接受了一剂曲前列环素（298名患者）或安慰剂（295名患者）。

Of these, 463 patients (224 in the treprostinil group and 239 in the placebo group) completed the trial assessments through week 52.

在这些患者中，共有463名患者（特雷普罗斯汀组224名和安慰剂组239名）完成了至第52周的试验评估。

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.

患者的平均年龄为71.7岁，80.1%为男性，基线时平均用力肺活量（FVC）为76.8%，75.4%的患者正在接受基础抗纤维化治疗。

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).

在第52周时，曲前列环素组的用力肺活量（FVC）中位数变化为-49.9毫升（95%置信区间[CI]，-79.2至-19.5），而安慰剂组为-136.4毫升（95% CI，-172.5至-104.0）；FVC变化的组间差异为95.6毫升（95% CI，52.2至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).

曲前列环素组中有81名患者（27.2%）出现临床恶化，而安慰剂组有115名患者（39.0%）出现临床恶化（风险比，0.71；95% CI，0.53至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.

观察到两组间IPF加重时间没有显著差异，因此没有进一步推断后续次要终点。

The most common adverse eventwas cough, reported in 48.3% of the patients in the treprostinil group and 24.1% of those in the placebo group.

最常见的不良事件是咳嗽，报告在48.3%的曲前列环素组患者和24.1%的安慰剂组患者中。

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.

33.6%的患者停止使用曲普司特，而24.7%的患者停止使用安慰剂，其中大约一半的患者将不良事件作为停止使用的主要原因。

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.

在特发性肺纤维化（IPF）患者中，吸入曲普司特与安慰剂相比，在52周的观察期内，用力肺活量（FVC）的下降幅度较小，临床恶化事件也较少。

(Funded by United Therapeutics; TETON-2 ClinicalTrials.gov number, NCT05255991.).

(由United Therapeutics资助; TETON-2临床试验注册号, NCT05255991.)