Mohamed Mohamed M G, Kamel Ghassan, Charbek Edward
Division of Pulmonary, Critical Care, and Sleep Medicine, Saint Louis University School of Medicine, St. Louis, Missouri.
Ann Am Thorac Soc. 2025 May;22(5):768-775. doi: 10.1513/AnnalsATS.202406-597OC.
Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide. Acute exacerbations are associated with progressive decline in lung function and quality of life. After recognition of the role of type 2 inflammation in the pathogenesis of eosinophilic COPD, there was increased interest in studying monoclonal antibodies as a therapeutic agent. Multiple randomized controlled trials showed promising results, yet no consensus exists. Our study aims to summarize the current evidence regarding the role of monoclonal antibodies in the management of patients with eosinophilic COPD. We systematically searched multiple databases using prespecified search terms. We included only randomized controlled trials that compared monoclonal antibodies versus placebo in patients with objective evidence of eosinophilic COPD receiving standard-of-care therapy. The primary outcome of interest was the annualized rate of COPD exacerbation. Absolute changes in forced expiratory volume in 1 second and St. George's Respiratory Questionnaire scores were secondary outcomes. We also reported serious adverse effects and all-cause mortality. Statistical analysis was conducted via random effects model using RevMan software. We identified and included eight double blinded, placebo-controlled trials with a total of 4,512 patients and a median follow up of 52 weeks. The patients' mean age was 65 ± 8 years, with 85% male. Seventy percent of patients were former smokers, with a mean of 43 ± 25 pack-years of smoking history. The majority of patients were receiving triple inhaled therapy. The mean serum eosinophil count at enrollment was 398 ± 297 cells/μl. The monoclonal antibodies studied were dupilumab, mepolizumab, benralizumab, astegolimab, and itepekimab. Compared with placebo, patients who received monoclonal antibodies had a significantly decreased annualized COPD exacerbation rate (rate ratio, 0.79; 95% confidence interval [CI], 0.73-0.86; < 0.001). The serious adverse effect rate was significantly lower in the monoclonal antibody arm compared with placebo (odds ratio, 0.80; 95% CI, 0.69-0.93; = 0.004). The all-cause mortality rates were not statistically different between the groups (odds ratio, 0.91; 95% CI, 0.63-1.3; = 0.6). Dupilumab showed a trend of improved efficacy over mepolizumab and benralizumab. In patients with eosinophilic COPD receiving standard-of-care therapy, the use of monoclonal antibodies led to a significant reduction in annualized COPD exacerbation rate compared with placebo. Monoclonal antibodies have an acceptable tolerability and safety profile.
慢性阻塞性肺疾病（COPD）仍然是全球发病和死亡的主要原因。急性加重与肺功能和生活质量的逐渐下降相关。在认识到2型炎症在嗜酸性粒细胞性COPD发病机制中的作用后，人们对研究单克隆抗体作为治疗药物的兴趣增加。多项随机对照试验显示了有前景的结果，但尚未达成共识。我们的研究旨在总结关于单克隆抗体在嗜酸性粒细胞性COPD患者管理中作用的现有证据。我们使用预先指定的检索词系统地检索了多个数据库。我们仅纳入了在接受标准治疗的有嗜酸性粒细胞性COPD客观证据的患者中比较单克隆抗体与安慰剂的随机对照试验。感兴趣的主要结局是COPD急性加重的年化率。1秒用力呼气量和圣乔治呼吸问卷评分的绝对变化是次要结局。我们还报告了严重不良反应和全因死亡率。使用RevMan软件通过随机效应模型进行统计分析。我们识别并纳入了8项双盲、安慰剂对照试验，共4512例患者，中位随访时间为52周。患者的平均年龄为65±8岁，男性占85%。70%的患者为既往吸烟者，平均吸烟史为43±25包年。大多数患者接受三联吸入治疗。入组时的平均血清嗜酸性粒细胞计数为398±297个细胞/μl。研究的单克隆抗体有度普利尤单抗、美泊利单抗、贝那利珠单抗、阿斯特利单抗和依替西单抗。与安慰剂相比，接受单克隆抗体治疗的患者COPD急性加重年化率显著降低（率比，0.79；95%置信区间[CI]，0.73 - 0.86；P<0.001）。与安慰剂相比，单克隆抗体组的严重不良反应率显著更低（比值比，0.80；95% CI，0.69 - 0.93；P = 0.004）。两组间的全因死亡率无统计学差异（比值比，0.91；95% CI，0.63 - 1.3；P = 0.6）。度普利尤单抗显示出比美泊利单抗和贝那利珠单抗疗效更好的趋势。在接受标准治疗的嗜酸性粒细胞性COPD患者中，与安慰剂相比，使用单克隆抗体可使COPD急性加重年化率显著降低。单克隆抗体具有可接受的耐受性和安全性。
