Hu Khai-Chi, Chuang Min-Hsiang, Lai Chih-Cheng, Liao Kuang-Ming
Division of Pulmonary Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Clin Ther. 2025 Mar;47(3):226-234. doi: 10.1016/j.clinthera.2024.12.001. Epub 2025 Jan 4.
Anti-interleukin-5 (IL-5), anti-IL-5 receptor and anti-interleukin-4 (IL-4) have emerged as potential treatments for severe eosinophilic asthma, yet their role in treating chronic obstructive pulmonary disease (COPD) is unclear. A literature review was conducted up to May 31, 2024. Only randomized controlled trials (RCTs) assessing the clinical efficacy and adverse effects of biological treatment (anti-IL-5/ anti-IL-5 receptor /anti-IL-4) in COPD patients were included in this meta-analysis. Primary outcomes focused on COPD exacerbation risk, with secondary outcomes examining lung function, quality of life, and adverse events. Four articles comprising 6 RCTs were analyzed. Among 2837 patients receiving anti-IL-5/anti-IL-5 receptor therapies, 468 receiving anti-IL-4 therapies, and 1913 receiving placebo. Overall, biological treatment therapies collectively demonstrated a reduced risk of COPD exacerbation compared to placebo (rate ratio, 0.88; 95% CI, 0.80-0.97, I = 53%). Specifically, dupilumab statistically significant reduction in exacerbation risk (rate ratio 0.70, 95% CI 0.58-0.84). Benralizumab showed a borderline reduction in exacerbation risk (rate ratio, 0.92; 95% CI, 0.85-1.00, I = 0%, while Mepolizumab exhibited a trend towards lower exacerbation risk that did not reach statistical significance (rate ratio 0.90, 95% CI 0.77-1.06, I = 62%). Subgroup analysis showed that patients with COPD and eosinophils ≥300 per cubic millimeter who received biological treatment may experience a reduced risk of acute exacerbation. Changes in lung function from baseline did not significantly differ between biological therapies and placebo. Analysis of St. George's Respiratory Questionnaire (SGRQ) scores indicated significant improvements with biological therapies compared to placebo (mean difference -1.30, 95% CI -2.46 to -0.14, I = 28%). Biological therapies showed comparable risks of adverse events compared to placebo. This meta-analysis suggests that biological therapies may reduce the risk of acute exacerbations and improve quality of life in COPD patients compared to placebo. However, these therapies did not demonstrate significant improvements in pulmonary function. Future studies are needed to delineate the role of these biologic therapies in managing COPD exacerbations.
抗白细胞介素-5（IL-5）、抗IL-5受体及抗白细胞介素-4（IL-4）已成为重度嗜酸性粒细胞性哮喘的潜在治疗方法，但其在慢性阻塞性肺疾病（COPD）治疗中的作用尚不清楚。截至2024年5月31日进行了一项文献综述。本荟萃分析仅纳入评估生物治疗（抗IL-5/抗IL-5受体/抗IL-4）对COPD患者临床疗效和不良反应的随机对照试验（RCT）。主要结局聚焦于COPD急性加重风险，次要结局则考察肺功能、生活质量和不良事件。分析了包含6项RCT的4篇文章。在接受抗IL-5/抗IL-5受体治疗的2837例患者中，468例接受抗IL-4治疗，1913例接受安慰剂治疗。总体而言，与安慰剂相比，生物治疗总体上显示出COPD急性加重风险降低（率比，0.88；95%CI，0.80 - 0.97，I² = 53%）。具体而言，度普利尤单抗使急性加重风险有统计学意义的降低（率比0.70，95%CI 0.58 - 0.84）。贝那利珠单抗使急性加重风险有临界降低（率比，0.92；95%CI，0.85 - 1.00，I² = 0%），而美泊利珠单抗显示出急性加重风险降低的趋势但未达到统计学意义（率比0.90，95%CI 0.77 - 1.06，I² = 62%）。亚组分析表明，COPD且每立方毫米嗜酸性粒细胞≥300的患者接受生物治疗可能会降低急性加重风险。生物治疗与安慰剂相比，肺功能自基线的变化无显著差异。圣乔治呼吸问卷（SGRQ）评分分析表明，与安慰剂相比，生物治疗有显著改善（平均差值 -1.30，95%CI -2.46至 -0.14，I² = 28%）。与安慰剂相比，生物治疗显示出相当的不良事件风险。本荟萃分析表明，与安慰剂相比，生物治疗可能降低COPD患者急性加重风险并改善生活质量。然而，这些治疗在肺功能方面未显示出显著改善。未来需要开展研究以明确这些生物治疗在管理COPD急性加重中的作用。
