dupilumab和mepolizumab治疗嗜酸性COPD的疗效：来自3期试验的见解

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Respiratory medicine Pub Date : 2025-09-05 DOI:10.1016/j.rmed.2025.108343

Philipp Suter, Robert Greig, Rory Chan, Brian Lipworth

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引用次数: 0

摘要

背景嗜氧粒细胞性慢性阻塞性肺疾病（eCOPD）以2型炎症为特征，是生物治疗的新兴靶点。目的通过综合3期随机对照试验的数据，间接比较dupilumab和mepolizumab在eCOPD（定义为血液嗜酸性粒细胞计数≥300个细胞/μL）中的疗效：dupilumab用于BOREAS和NOTUS， mepolizumab用于MATINEE。方法对试验主要和次要结局进行间接比较，包括年加重率（AER）、生活质量（圣乔治呼吸问卷，SGRQ）、症状（E-RS-COPD）和肺功能（FEV1）。使用森林样地评估比率和粗95% CI的平均差异。与安慰剂相比，dupilumab和mepolizumab均可显著降低AER，基于重叠95% CI的幅度相当。dupilumab预防一次恶化所需的时间（2.3-3.1年）比mepolizumab（4.8年）短。然而，dupilumab而不是meplizumab在生活质量、症状和FEV1方面表现出显着改善，同时在分数呼出一氧化氮（FeNO≥20 ppb）升高的患者中效果增强。次要结果均未达到最小的临床重要差异。结论：虽然这两种生物制剂都能降低eCOPD患者的AER，但dupilumab在改善生活质量、症状和肺功能方面表现出统计学意义上的改善，但与临床无关。特别是在FeNO升高的患者中，dupilumab表现出改善。进一步的直接比较和生物标志物驱动的研究是必要的。

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Efficacy of dupilumab and mepolizumab in eosinophilic COPD: insights from phase 3 trials

Background

Eosinophilic chronic obstructive pulmonary disease (eCOPD), characterized by type 2 inflammation, is an emerging target for biologic therapies.

Objective

To indirectly compare the efficacy of dupilumab and mepolizumab in eCOPD, defined as blood eosinophil counts ≥300 cells/μL, by synthesizing data from phase 3 randomized controlled trials: BOREAS and NOTUS for dupilumab, MATINEE for mepolizumab.

Methods

We performed an indirect comparison of trial primary and secondary outcomes including annual exacerbation rates (AER), quality of life (St. George's Respiratory Questionnaire, SGRQ), symptoms (E-RS–COPD), and lung function (FEV₁). Rate ratios and mean differences with crude 95 % CI were evaluated using forest plots.

Results

Both dupilumab and mepolizumab significantly reduced AER versus placebo, with comparable magnitude based on overlapping 95 % CI. The time needed to prevent one exacerbation was shorter for dupilumab (2.3–3.1 years) compared to mepolizumab (4.8 years). However, dupilumab but not meplizumab showed significant improvements in quality of life, symptoms, and FEV₁, along with enhanced effects in patients with elevated fractional exhaled nitric oxide (FeNO ≥20 ppb). None of the secondary outcomes reached the minimal clinical important difference.

Conclusion

While both biologics reduced AER in eCOPD, dupilumab demonstrated statistically but not clinically relevant improvements on quality of life, symptoms, and lung function. Especially in patients with elevated FeNO, dupilumab demonstrated an improvement. Further direct comparisons and biomarker-driven studies are warranted.

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来源期刊

Respiratory medicine 医学-呼吸系统

CiteScore

7.50

自引率

0.00%

发文量

199

审稿时长

38 days

期刊介绍： Respiratory Medicine is an internationally-renowned journal devoted to the rapid publication of clinically-relevant respiratory medicine research. It combines cutting-edge original research with state-of-the-art reviews dealing with all aspects of respiratory diseases and therapeutic interventions. Topics include adult and paediatric medicine, epidemiology, immunology and cell biology, physiology, occupational disorders, and the role of allergens and pollutants. Respiratory Medicine is increasingly the journal of choice for publication of phased trial work, commenting on effectiveness, dosage and methods of action.