Wang Yuxin, Luo Jinmei, Huang Rong, Xiao Yi
Department of Pulmonary and Critical Care Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
Lung. 2025 Mar 14;203(1):46. doi: 10.1007/s00408-025-00795-6.
Monoclonal antibody therapies targeting specific inflammatory pathways have shown potential in treating chronic obstructive pulmonary disease (COPD). However, the efficacy and safety of these treatments across different patient phenotypes remain uncertain.
This meta-analysis included 15 registered randomized controlled trials (RCTs) evaluating monoclonal antibodies targeting type 2 and non-type 2 inflammatory pathways in COPD. The primary outcomes assessed were rates of moderate to severe exacerbations, rates of severe exacerbations, lung function (pre- and post-bronchodilator FEV), St. George's Respiratory Questionnaire (SGRQ) scores, and safety-related events. Subgroup analyses were performed based on inflammatory phenotype, exacerbation frequency, and smoking status. Meta-regression was used to examine the influence of covariates, such as baseline FEV%pred and other demographic factors.
Monoclonal antibody therapies significantly reduced the rates of moderate to severe exacerbations (RR 0.88, 95% CI 0.83-0.93) and severe exacerbations (RR 0.82, 95% CI 0.72-0.94). Subgroup analyses revealed more pronounced benefits in eosinophilic and frequent exacerbator phenotypes. Non-eosinophilic patients demonstrated a better response to IL-33-targeting therapies. Lung function and quality of life showed modest improvements across most therapies. Smoking status and baseline FEV were significant modifiers of treatment efficacy. No significant increase in serious adverse events was noted.
Monoclonal antibody therapies, particularly those targeting type 2 inflammation, effectively reduce exacerbation rates in COPD, with greater benefits observed in patients with eosinophilic phenotypes and frequent exacerbations. Baseline lung function also influences treatment response. These findings underscore the importance of personalized, phenotype-driven treatment approaches and support the continued development of biologics for COPD management.
针对特定炎症途径的单克隆抗体疗法在治疗慢性阻塞性肺疾病（COPD）方面已显示出潜力。然而，这些治疗方法在不同患者表型中的疗效和安全性仍不确定。
这项荟萃分析纳入了15项注册的随机对照试验（RCT），评估了针对COPD中2型和非2型炎症途径的单克隆抗体。评估的主要结局为中重度急性加重率、重度急性加重率、肺功能（支气管扩张剂使用前后的第一秒用力呼气容积[FEV]）、圣乔治呼吸问卷（SGRQ）评分以及与安全性相关的事件。基于炎症表型、急性加重频率和吸烟状态进行亚组分析。采用Meta回归分析来检验协变量的影响，如基线FEV%预计值和其他人口统计学因素。
单克隆抗体疗法显著降低了中重度急性加重率（风险比[RR]0.88，95%置信区间[CI]0.83 - 0.93）和重度急性加重率（RR 0.82，95% CI 0.72 - 0.94）。亚组分析显示，在嗜酸性粒细胞增多型和频繁急性加重型表型中获益更为明显。非嗜酸性粒细胞增多型患者对靶向IL - 33的疗法反应更佳。大多数治疗方法在肺功能和生活质量方面有适度改善。吸烟状态和基线FEV是治疗疗效的显著调节因素。未观察到严重不良事件有显著增加。
单克隆抗体疗法，尤其是那些靶向2型炎症的疗法，可有效降低COPD的急性加重率，在嗜酸性粒细胞增多型表型和频繁急性加重的患者中观察到更大益处。基线肺功能也会影响治疗反应。这些发现强调了个性化、表型驱动的治疗方法的重要性，并支持继续研发用于COPD管理的生物制剂。
