哮喘联盟

    摘要
    背景：美泊利珠单抗是一种人源化单克隆抗体，可靶向白细胞介素-5（IL-5），后者是一种在嗜酸性粒细胞性炎症中起核心作用的细胞因子，20%-40%的慢性阻塞性肺疾病（COPD）患者存在嗜酸粒细胞炎症表型。
    目的：探讨在筛查时外周血嗜酸性粒细胞计数≥300 个/μL 且有急性加重风险的 COPD 患者中，美泊利单抗对比安慰剂的疗效和安全性。
    方法： 本研究是一项3期、双盲、随机、安慰剂对照试验。纳入有急性加重病史且外周血嗜酸性粒细胞计数≥300 个/μL的COPD患者，在继续三联吸入治疗的基础上，按1:1的比例被分配接受每4周一次、连续52-104周的皮下注射美泊利珠单抗（剂量为100mg）或安慰剂。主要终点是中度或重度加重的年发生率。通过分层检验控制多重性的次要终点包括：首次中重度急性加重时间分析、健康相关生活质量和症状评估指标，以及导致急诊就诊/住院的急性加重年化发生率。
    结果： 在随机分组的804名患者中，403名被分配接受美泊利珠单抗治疗，401名被分配接受安慰剂治疗。美泊利珠单抗组的中度或重度急性加重年发生率显著低于安慰剂组（0.80 次/人年 vs 1.01 次/人年；率比 0.79；95% CI 0.66–0.94；P=0.01）。美泊利珠单抗组首次出现中度或重度急性加重的时间比安慰剂组长（419 天 vs 321 天；风险比 0.77；95% CI 0.64–0.93；P=0.009）。两组在健康相关生活质量和症状指标上无显著差异，因此未对统计检验层次中的后续次要终点进行统计推断。两组不良事件发生率相似。
    结论： 对于具有嗜酸性粒细胞表型的COPD患者，在三联吸入治疗基础上联合美泊利单抗治疗可降低中-重度急性加重的年发生率。
    关键词：美泊利单抗；慢性阻塞性肺疾病（COPD）

（南方医科大学南方医院 欧阳文珊 龚钊乾 赵文驱）

（Sciurba FC, Criner GJ, Christenson SA, Martinez FJ, Papi A, Roche N, Bourbeau J, Korn S, Bafadhel M, Han MK, Kolterer S, Miller K, Mouneimne D, Fletcher J, Mayer B, Min J, Pavord ID; MATINEE Study Investigators. Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype. N Engl J Med. 2025 May 1;392(17):1710-1720. doi: 10.1056/NEJMoa2413181）

Abstract
Background:  Mepolizumab is a humanized monoclonal antibody that targets interleukin-5, a cytokine that plays a central role in eosinophilic inflammation, which is present in 20 to 40% of patients with chronic obstructive pulmonary disease (COPD).
Objective: Investigating the efficacy and safety of mepolizumab as compared with placebo in patients with COPD and a risk of exacerbations who had a blood eosinophil count of at least 300 cells per microliter at screening.
Methods: In a phase 3, double-blind, randomized, placebo-controlled trial, patients with COPD, a history of exacerbations, and a blood eosinophil count of at least 300 cells per microliter who were receiving triple inhaled therapy were assigned, in a 1:1 ratio, to receive mepolizumab (at a dose of 100 mg) or placebo subcutaneously every 4 weeks for 52 to 104 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Secondary end points, tested hierarchically to control for multiplicity, were moderate or severe exacerbation as assessed in a time-to-first-event analysis, measures of health-related quality of life and symptoms, and the annualized rate of exacerbations leading to an emergency department visit, hospitalization, or both.
Results:Of the 804 patients who underwent randomization, 403 were assigned to receive mepolizumab and 401 to receive placebo. The annualized rate of moderate or severe exacerbations was significantly lower with mepolizumab than with placebo (0.80 vs. 1.01 events per year; rate ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.01). The time to the first moderate or severe exacerbation was longer with mepolizumab than with placebo (Kaplan-Meier median time to the first moderate or severe exacerbation, 419 vs. 321 days; hazard ratio, 0.77; 95% CI, 0.64 to 0.93; P = 0.009). Between-group differences in measures of health-related quality of life and symptoms were not significant; thus, no statistical inferences regarding subsequent secondary end points in the statistical testing hierarchy were made. The incidence of adverse events was similar in the mepolizumab and placebo groups.
Conclusions:Treatment with mepolizumab led to a lower annualized rate of moderate or severe exacerbations when added to background triple inhaled therapy among patients with COPD and an eosinophilic phenotype.
Keywords: mepolizumab;chronic obstructive pulmonary disease（COPD） ;