Pitre Tyler, Lupas Daniel, Mah Jasmine, Stanbrook Matthew, Blazer Alina, Zeraatkar Dena, Ho Terence
Division of Respirology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
COPD. 2025 Dec;22(1):2449889. doi: 10.1080/15412555.2025.2449889. Epub 2025 Jan 29.
Despite limited breakthroughs in COPD pharmacotherapy, recent trials have shown promising results for biologics in COPD patients. However, robust evidence synthesis in this area is currently lacking.
We conducted a systematic review of MEDLINE, EMBASE, and Cochrane CENTRAL from inception to July 17, 2024, to identify randomized trials of biologic medications in patients with COPD. We performed a random effects frequentist network meta-analysis and present the results using relative risk (RR) and 95% confidence intervals (CI). We used the GRADE framework to rate the certainty of the evidence. Outcomes of interest included exacerbations, change in FEV1, change in quality of life, and serious adverse events.
Dupilumab reduced exacerbations as compared to placebo (RR 0.68 [95% CI 0.59 to 0.79]) (high certainty). Benralizumab (RR 0.89 [95% CI 0.78 to 1]), itepekimab (RR 0.81 [95% CI 0.61 to 1.07]) and tezepelumab (RR 0.83 [95% CI 0.61 to 1.12]) may reduce exacerbations as compared to placebo (all low certainty). Dupilumab probably reduced exacerbations more than mepolizumab (RR 0.74 [95% CI 0.62 to 0.89]) (moderate certainty). Dupilumab may reduce exacerbations more than tezepelumab (RR 0.82 [95% CI 1.14]) (low certainty). For all patients, no treatment improved FEV1 above the pre-specified minimal clinically important difference (MCID) of 0.1 L. Dupilumab probably has no meaningful effect on FEV1 compared to placebo (MD 0.07 [95% CI 0.02 to 0.13]) (moderate certainty). However, in the subgroup of patients with blood eosinophils ≥300/mcL, both tezepelumab (MD 0.15 [95% CI 0.05 to 0.26]) and dupilumab (MD 0.13 [95% CI 0.06 to 0.19]) probably improved FEV1 above the MCID.
Dupilumab is effective at improving patient-relevant outcomes in COPD with higher eosinophil levels. Other biological therapies, including tezepelumab, have no important effect on patient-relevant outcomes.
尽管慢性阻塞性肺疾病（COPD）药物治疗方面的突破有限，但近期试验显示生物制剂对COPD患者有良好效果。然而，该领域目前缺乏有力的证据综合分析。
我们对MEDLINE、EMBASE和Cochrane CENTRAL进行了系统回顾，涵盖从起始至2024年7月17日的内容，以确定生物制剂药物在COPD患者中的随机试验。我们进行了随机效应频率学派网络荟萃分析，并使用相对风险（RR）和95%置信区间（CI）呈现结果。我们使用GRADE框架对证据的确定性进行评级。感兴趣的结局包括急性加重、第一秒用力呼气容积（FEV1）变化、生活质量变化和严重不良事件。
与安慰剂相比，度普利尤单抗可降低急性加重风险（RR 0.68 [95% CI 0.59至0.79]）（高确定性）。与安慰剂相比，贝那利珠单抗（RR 0.89 [95% CI 0.78至1]）、依替膦单抗（RR 0.81 [95% CI 0.61至1.07]）和tezepelumab（RR 0.83 [95% CI 0.61至1.12]）可能降低急性加重风险（均为低确定性）。度普利尤单抗降低急性加重的效果可能优于美泊利珠单抗（RR 0.74 [95% CI 0.62至0.89]）（中等确定性）。度普利尤单抗降低急性加重的效果可能优于tezepelumab（RR 0.82 [95% CI 1.14]）（低确定性）。对于所有患者，没有治疗能使FEV1改善超过预先设定的最小临床重要差异（MCID）0.1 L。与安慰剂相比，度普利尤单抗对FEV1可能没有有意义的影响（MD 0.07 [95% CI 0.02至0.13]）（中等确定性）。然而，在血液嗜酸性粒细胞≥300/μL的患者亚组中，tezepelumab（MD 0.15 [95% CI 0.05至0.26]）和度普利尤单抗（MD 0.13 [95% CI 0.06至0.19]）可能使FEV1改善超过MCID。
度普利尤单抗可有效改善嗜酸性粒细胞水平较高的COPD患者与患者相关的结局。其他生物疗法，包括tezepelumab，对与患者相关的结局没有重要影响。
