Emeritus Professor of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Director of Respiratory Services, Valley Regional Hospital, Claremont, NH, USA.
Expert Rev Respir Med. 2024 Aug;18(8):645-654. doi: 10.1080/17476348.2024.2389960. Epub 2024 Aug 8.
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.
The pooled population (ensifentrine, = 975; placebo, = 574) included patients aged 40-80 years with post-bronchodilator FEV/FVC <0.7, FEV 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.
After 24 weeks, ensifentrine significantly improved TDI scores (least-squares mean difference, 0.97; 95% CI, 0.64, 1.30; < 0.001) and across all TDI subdomains. Ensifentrine-treated patients were more likely to be TDI responders at week 24 ( < 0.001), which was consistent across clinically relevant subgroups. Ensifentrine-treated patients had improved E-RS breathlessness subdomain scores ( = 0.053) and reduced rescue medication use ( = 0.002).
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.
www.clinicaltrials.gov identifiers are ENHANCE-1: NCT04535986; ENHANCE-2: NCT04542057.
呼吸困难是慢性阻塞性肺疾病（COPD）的一个关键组成部分。我们报告了新型 PDE3/PDE4 抑制剂恩斯福林对呼吸困难的影响，这是基于 3 期 ENHANCE-1/2 试验的汇总数据。
汇总人群（恩斯福林，n=975；安慰剂，n=574）包括年龄在 40-80 岁之间的患者，他们在支气管扩张剂后 FEV/FVC<0.7，FEV 占预计值的 30-70%，mMRC 呼吸困难量表评分≥2，且有吸烟史≥10 包年。排除正在服用双长效抗胆碱能药物/长效β2 受体激动剂（LABA）或 LABA/LABA/ICS 三联疗法的患者。呼吸困难评估包括过渡呼吸困难指数（TDI）、呼吸症状评估（E-RS）和急救药物使用情况。
在 24 周后，恩斯福林显著改善了 TDI 评分（最小二乘均数差值，0.97；95%置信区间，0.64，1.30；<0.001）和所有 TDI 亚域。在第 24 周，恩斯福林治疗的患者更有可能成为 TDI 应答者（<0.001），在各个具有临床意义的亚组中均如此。恩斯福林治疗的患者 E-RS 呼吸困难亚域评分得到改善（=0.053），急救药物使用减少（=0.002）。
在有症状的中重度 COPD 患者中，恩斯福林在多项呼吸困难评估中产生了有临床意义的改善。本研究的一个局限性是排除了正在服用双 LAMA/LABA 和 LAMA/LABA/ICS 三联疗法的患者。
www.clinicaltrials.gov 标识符是 ENHANCE-1：NCT04535986；ENHANCE-2：NCT04542057。
