恩司氟烷对中重度慢性阻塞性肺疾病患者呼吸困难的影响：ENHANCE 试验的汇总分析。
Effect of ensifentrine on dyspnea in patients with moderate-to-severe chronic obstructive pulmonary disease: pooled analysis of the ENHANCE trials.
机构信息
Emeritus Professor of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Director of Respiratory Services, Valley Regional Hospital, Claremont, NH, USA.
出版信息
Expert Rev Respir Med. 2024 Aug;18(8):645-654. doi: 10.1080/17476348.2024.2389960. Epub 2024 Aug 8.
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, = 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.
RESULTS
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).
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.
背景
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。
方法
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。
结果
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）。
结论
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。
临床试验注册
www.clinicaltrials.gov 标识符是 ENHANCE-1：NCT04535986；ENHANCE-2：NCT04542057。
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