Effect of ensifentrine on dyspnea in patients with moderate-to-severe chronic obstructive pulmonary disease: pooled analysis of the ENHANCE trials.

Expert review of respiratory medicine Pub Date : 2024-08-01 Epub Date: 2024-08-08 DOI:10.1080/17476348.2024.2389960

Donald A Mahler, Surya P Bhatt, Tara Rheault, Daniel Reyner, Thomas Bengtsson, Amy Dixon, Kathleen Rickard, Dave Singh

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Abstract

Background: Dyspnea is a critical component of chronic obstructive pulmonary disease (COPD). We report the effect of ensifentrine, a novel PDE3/PDE4 inhibitor, on dyspnea using pooled data from the Phase 3 ENHANCE-1/2 trials.

Methods: The pooled population (ensifentrine, n = 975; placebo, n = 574) included patients aged 40-80 years with post-bronchodilator FEV₁/FVC <0.7, FEV₁ 30-70% predicted, mMRC Dyspnea Scale score ≥2, and a smoking history ≥10 pack-years. Patients taking dual LAMA/LABA or LAMA/LABA/ICS triple therapy were excluded. Dyspnea measures included the Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms (E-RS), and rescue medication use.

Results: After 24 weeks, ensifentrine significantly improved TDI scores (least-squares mean difference, 0.97; 95% CI, 0.64, 1.30; p < 0.001) and across all TDI subdomains. Ensifentrine-treated patients were more likely to be TDI responders at week 24 (p < 0.001), which was consistent across clinically relevant subgroups. Ensifentrine-treated patients had improved E-RS breathlessness subdomain scores (p = 0.053) and reduced rescue medication use (p = 0.002).

Conclusion: Ensifentrine produced clinically meaningful improvements in multiple dyspnea measures in patients with symptomatic, moderate-to-severe COPD. A limitation of this study was the exclusion of patients taking dual LAMA/LABA and LAMA/LABA/ICS triple therapy.

Clinical trial registration: www.clinicaltrials.gov identifiers are ENHANCE-1: NCT04535986; ENHANCE-2: NCT04542057.

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安思芬特林对中重度慢性阻塞性肺病患者呼吸困难的影响：ENHANCE 试验的汇总分析。

背景：呼吸困难是慢性阻塞性肺病（COPD）的一个重要组成部分。Ensifentrine 是一种新型 PDE3/PDE4 抑制剂，在 ENHANCE-1/2 3 期临床试验中进行了评估。在此，我们利用ENHANCE试验的汇总数据报告了安思芬特林对呼吸困难的影响：汇总人群（依西芬太尼，n = 975；安慰剂，n = 574）包括年龄在 40-80 岁、支气管扩张后 FEV1/FVC 1 预测值在 30%-70% 之间、mMRC 呼吸困难量表评分≥ 2 分、吸烟史≥ 10 包年的患者。服用 LAMA/LABA 双联疗法或 LAMA/LABA/ICS 三联疗法的患者除外。测量呼吸困难的指标包括过渡性呼吸困难指数（TDI）、呼吸道症状评估（E-RS）和抢救药物的使用：24周后，安思芬特林可显著改善TDI评分（最小二乘平均差，0.97；95% CI，0.64，1.30；p p = 0.053），并减少抢救用药（p = 0.002）。最常见的不良反应是背痛（安赛芬特林，1.8% vs 安慰剂，1.0%）、高血压（1.7% vs 0.9%）、尿路感染（1.3% vs 1.0%）、腹泻（1.0% vs 0.7%）：结论：对于有症状的中度至重度慢性阻塞性肺疾病患者，安非他酮能改善多种呼吸困难指标，具有临床意义。本研究的局限性在于排除了服用LAMA/LABA双重疗法和LAMA/LABA/ICS三联疗法的患者。临床试验注册：www.clinicaltrials.gov identifiers are ENHANCE-1: NCT04535986; ENHANCE-2: NCT04542057.

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Expert review of respiratory medicine

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