Sciurba Frank C, Christenson Stephanie A, Rheault Tara, Bengtsson Thomas, Rickard Kathleen, Barjaktarevic Igor Z
Division of Pulmonary and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA.
Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, San Francisco.
Chest. 2025 Feb;167(2):425-435. doi: 10.1016/j.chest.2024.07.168. Epub 2024 Aug 27.
Exacerbations in COPD can be life-threatening and can lead to irreversible declines in lung function and quality of life. Medications that reduce exacerbation burden are an unmet need, because exacerbations put patients at risk of more exacerbations and decrease quality of life. Ensifentrine is a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 with demonstrated nonsteroidal antiinflammatory activity and bronchodilatory effects.
Does ensifentrine reduce the rate or risk of COPD exacerbations?
A prespecified, pooled analysis of the phase 3 clinical trials Ensifentrine as a Novel Inhaled Nebulized COPD Therapy (ENHANCE)-1 (ClinicalTrials.gov Identifier: NCT04535986) and ENHANCE-2 (ClinicalTrials.gov Identifier: NCT04542057) was conducted to assess the effect of ensifentrine on exacerbation rate and risk (time to first exacerbation). The trials included symptomatic patients aged 40 to 80 years with moderate to severe COPD who received 3 mg twice-daily ensifentrine over 24 weeks or placebo. Subgroup analyses and frequent exacerbator transition risk assessment were conducted post hoc.
In total, 975 patients treated with ensifentrine and 574 patients who received placebo were included in the pooled analysis, including 62% of patients receiving concomitant long-acting muscarinic antagonist or long-acting β-agonist therapy and 18% receiving concomitant inhaled corticosteroid therapy. Ensifentrine was associated with significant reductions in the rate (rate ratio, 0.59; 95% CI, 0.43-0.80; P < .001) and risk (hazard ratio, 0.59; 95% CI, 0.44-0.81; P < .001) of moderate to severe exacerbations compared with placebo. Reductions in the rate and risk of exacerbations generally were consistent across patient subgroups, including age, sex, race, background maintenance medication use, chronic bronchitis, eosinophil count, COPD severity, and exacerbation history. Ensifentrine was associated with a numerical delay in transitioning from an infrequent exacerbator (Global Initiative for Chronic Obstructive Lung Disease group B) to a frequent exacerbator (Global Initiative for Chronic Obstructive Lung Disease group E) compared with placebo.
Ensifentrine reduced the rate of exacerbations and increased the time to first exacerbation among patients with COPD across a broad range of clinically relevant subgroups.
慢性阻塞性肺疾病（COPD）急性加重可能危及生命，并可导致肺功能和生活质量不可逆转的下降。减轻急性加重负担的药物是一种未满足的需求，因为急性加重会使患者面临更多急性加重的风险并降低生活质量。恩昔芬净是首个磷酸二酯酶3和4的选择性双重抑制剂，具有非甾体抗炎活性和支气管扩张作用。
恩昔芬净是否能降低COPD急性加重的发生率或风险？
对3期临床试验“恩昔芬净作为新型吸入雾化COPD治疗药物（ENHANCE）-1（ClinicalTrials.gov标识符：NCT04535986）”和“ENHANCE-2（ClinicalTrials.gov标识符：NCT04542057）”进行预先设定的汇总分析，以评估恩昔芬净对急性加重发生率和风险（首次急性加重时间）的影响。试验纳入了40至80岁有症状的中重度COPD患者，他们在24周内每日两次接受3mg恩昔芬净或安慰剂治疗。事后进行了亚组分析和频繁急性加重者转变风险评估。
汇总分析共纳入975例接受恩昔芬净治疗的患者和574例接受安慰剂治疗的患者，其中62%的患者同时接受长效毒蕈碱拮抗剂或长效β受体激动剂治疗，18%的患者同时接受吸入性糖皮质激素治疗。与安慰剂相比，恩昔芬净使中重度急性加重的发生率（发生率比，0.59；95%CI，0.43 - 0.80；P <.001）和风险（风险比，0.59；95%CI，0.44 - 0.81；P <.001）显著降低。急性加重发生率和风险的降低在各患者亚组中总体一致，包括年龄、性别、种族、背景维持药物使用情况、慢性支气管炎、嗜酸性粒细胞计数、COPD严重程度和急性加重病史。与安慰剂相比，恩昔芬净使从不频繁急性加重者（慢性阻塞性肺疾病全球倡议组织B组）转变为频繁急性加重者（慢性阻塞性肺疾病全球倡议组织E组）的时间出现数值上的延迟。
恩昔芬净降低了COPD患者在广泛的临床相关亚组中的急性加重发生率，并延长了首次急性加重的时间。
