Phase 3 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis.

TETON-2 was completed first, and results were published; the results of TETON-1 and of both trials combined are reported here.

TETON-2试验首先完成，并已发表结果；TETON-1试验的结果以及两项试验的综合结果在此报告。

Methods

In the double-blindTETON-1 trial, we randomly assigned patients with IPF to receive inhaled treprostinil or placebo (12 breaths four times daily).

在双盲的TETON-1试验中，我们随机将特发性肺纤维化(IPF)患者分配接受吸入曲前列环素或安慰剂治疗（每日四次，每次12次呼吸）。

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

主要终点是第52周时用力肺活量(FVC)的变化。

Secondary end points, which were analyzed in a prespecified order to control for multiplicity, were clinical worsening (the first occurrence of death from any cause, hospitalization for a respiratory cause, or a relative decline of ≥10% in the percentage of predicted FVC) and acute exacerbation of IPF (each assessed in a time-to-event analysis), survival, change in percentage of predicted FVC, quality of life, and change in diffusion capacity of the lungs for carbon monoxide at week 52.

次要终点事件，按照预定顺序进行分析以控制多重性，包括临床恶化（首次发生任何原因的死亡、因呼吸原因住院或预测用力肺活量（FVC）百分比相对下降≥10%）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）、生存期、预测用力肺活量百分比的变化、生活质量以及第52周时一氧化碳肺扩散能力的变化。

Results

A total of 598 patients underwent randomization and received at least one dose of treprostinil (299 patients) or placebo (299 patients).

共有598名患者进行了随机分组，并至少接受了曲普司坦（299名患者）或安慰剂（299名患者）的至少一次剂量治疗。

Of these, 434 completed the assessments through week 52 (218 in the treprostinil group and 216 in the placebo group).

在这些患者中，434名完成了至第52周的评估（其中218名在曲前列环素组，216名在安慰剂组）。

The mean age of the patients was 73.0 years, 77.3% were men, and 77.6% were receiving background antifibrotic therapy; the percentage of predicted FVC at baseline was 74.6%.

患者的平均年龄为73.0岁，77.3%为男性，77.6%正在接受基础抗纤维化治疗；基线时预测的用力肺活量（FVC）百分比为74.6%。

The median change in FVC at week 52 was -43.3 ml (95% confidence interval[CI], -92.1 to -9.1) with treprostinil and -196.2 ml (95% CI, -227.1 to -155.6) with placebo (difference, 130.1 ml; 95% CI, 82.2 to 178.1; P<0.001).

在第52周时，使用曲普斯特的患者中位用力肺活量(FVC)变化为-43.3毫升（95%置信区间[CI]，-92.1至-9.1），而使用安慰剂的患者为-196.2毫升（95% CI，-227.1至-155.6）（差异，130.1毫升；95% CI，82.2至178.1；P<0.001）。

Clinical worsening occurred in 95 patients (31.8%) with treprostinil and in 133 patients (44.5%) with placebo (hazard ratio, 0.67; 95% CI, 0.52 to 0.88; P = 0.003).

使用曲普斯特的患者中有95人（31.8%）出现临床恶化，而使用安慰剂的患者中有133人（44.5%）出现临床恶化（风险比，0.67；95% CI，0.52至0.88；P=0.003）。

No significant difference was observed in the time to an IPF exacerbation, and no further inferences regarding secondary end points were made.

未观察到间质性肺病加重时间的显著差异，且未对次要终点进行进一步推断。

The most frequent adverse eventwas cough (reported in 54.8% of the patients in the treprostinil group and 33.1% patients in the placebo group).

最常见的不良事件是咳嗽（在曲前列环素组的患者中有54.8%报告，而在安慰剂组的患者中有33.1%报告）。

Discontinuation of treprostinil or placebo occurred in 40.5% and 32.8% of the patients, respectively, with adverse eventbeing the primary reason (20.7% and 14.7%).

分别有40.5%和32.8%的患者停用了曲前列环素或安慰剂，其中不良事件是主要停药原因（分别为20.7%和14.7%）。

Efficacy and safety outcomes were similar in analyses of the combined trial data.

在联合试验数据的分析中，疗效和安全性结果相似。

Conclusions

In patients with IPF, treatment with inhaled treprostinil led to a smaller decline in FVC and fewer clinical-worsening events than placebo over the course of 52 weeks.

在特发性肺纤维化(IPF)患者中，吸入曲前列环素治疗在52周内导致用力肺活量(FVC)下降幅度较小，临床恶化事件也比安慰剂组少。

(Funded by United Therapeutics; TETON-1 ClinicalTrials.gov number, NCT04708782.).

(该研究由联合治疗公司资助；TETON-1临床试验注册号为NCT04708782。)