Tyler Pitre, Daniel Lupas, Jasmine Mah, Matthew Stanbrook, Alina Blazer, Dena Zeraatkar, Terence Ho
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Outcomes of interest included exacerbations, change in FEV1, change in quality of life, and serious adverse events.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Dupilumab is effective at improving patient-relevant outcomes in COPD with higher eosinophil levels. 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引用次数: 0
摘要
背景：尽管COPD药物治疗方面的突破有限，但最近的试验显示生物制剂治疗COPD患者的结果很有希望。然而，目前在这一领域缺乏强有力的证据综合。方法：我们对MEDLINE、EMBASE和Cochrane CENTRAL从启动到2024年7月17日进行了系统回顾，以确定生物药物治疗COPD患者的随机试验。我们进行了随机效应频率网络荟萃分析，并使用相对风险（RR）和95%置信区间（CI）呈现结果。我们使用GRADE框架来评估证据的确定性。关注的结局包括急性加重、FEV1改变、生活质量改变和严重不良事件。结果：与安慰剂相比，Dupilumab减少了恶化（RR 0.68 [95% CI 0.59至0.79]）（高确定性）。与安慰剂相比，Benralizumab （RR 0.89 [95% CI 0.78至1]）、itepekimab （RR 0.81 [95% CI 0.61至1.07]）和tezepelumab （RR 0.83 [95% CI 0.61至1.12]）可能减少恶化（均为低确定性）。Dupilumab可能比mepolizumab更能减少恶化（RR 0.74 [95% CI 0.62至0.89]）（中等确定性）。Dupilumab可能比tezepelumab更能减少恶化（RR 0.82 [95% CI 1.14]）（低确定性）。对于所有患者，没有任何治疗方法使FEV1的改善高于预先规定的最小临床重要差异（MCID） 0.1 L。与安慰剂相比，Dupilumab可能对FEV1没有显著影响（MD为0.07 [95% CI为0.02至0.13]）（中度确定性）。然而，在血嗜酸性粒细胞≥300/mcL的患者亚组中，tezepelumab （MD 0.15 [95% CI 0.05至0.26]）和dupilumab （MD 0.13 [95% CI 0.06至0.19]）可能改善MCID以上的FEV1。结论：Dupilumab可有效改善嗜酸性粒细胞水平较高的COPD患者相关结局。其他生物疗法，包括tezepelumab，对患者相关结果没有重要影响。
Biologic Therapies for Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍：
From pathophysiology and cell biology to pharmacology and psychosocial impact, COPD: Journal Of Chronic Obstructive Pulmonary Disease publishes a wide range of original research, reviews, case studies, and conference proceedings to promote advances in the pathophysiology, diagnosis, management, and control of lung and airway disease and inflammation - providing a unique forum for the discussion, design, and evaluation of more efficient and effective strategies in patient care.
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