Bhatt Surya P, Freemantle Nick, Soliman Mena, Heble Jigna, Cabon Yann, Mayen Herrera Ernesto, Yang Joe, Xu Yingxin
Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Institute of Clinical Trials and Methodology, University College London, London, UK.
Pulm Ther. 2025 Sep 26. doi: 10.1007/s41030-025-00322-1.
Up to 40% of patients with chronic obstructive pulmonary disease (COPD) exhibit elevated blood eosinophils, reflective of type 2 inflammation. Dupilumab and mepolizumab versus standard of care have demonstrated moderate-to-severe exacerbation reductions of 30-34% and 15-18%, respectively, over 52 weeks. This study compared their relative efficacy using indirect treatment comparison (ITC).
A Bucher ITC was performed on 52-week phase 3 trials of dupilumab (BOREAS/NOTUS) and mepolizumab (MATINEE/METREX/METREO). The primary ITC endpoint was annualized moderate-to-severe exacerbation rates in patients from BOREAS + NOTUS versus MATINEE + METREX (modified intention-to-treat high stratum cohort, representing an eosinophilic phenotype); sensitivity analyses were performed using different combinations of mepolizumab data including MATINEE + METREX + METREO (100-mg arm). Other 52-week endpoints included mean difference in pre-bronchodilator forced expiratory volume in 1 s (FEV), proportion of St. George's Respiratory Questionnaire (SGRQ) improvement ≥ 4 points, proportion of Evaluating Respiratory Symptoms in COPD (E-RS:COPD) improvement ≥ 2 points, and annualized severe exacerbation rate. Rate ratios (RRs)/odds ratios (ORs) with 95% confidence intervals (CIs) are reported.
The primary ITC resulted in an RR of 0.82 (95% CI 0.66, 1.01), showing a numerical advantage for dupilumab versus mepolizumab in reducing moderate-to-severe exacerbation. Sensitivity analyses confirmed findings from the primary ITC (BOREAS + NOTUS vs. MATINEE + METREX + METREO: RR 0.83 [95% CI 0.68, 1.01]). Dupilumab demonstrated significantly greater FEV improvement (mean difference 83.4 mL [95% CI 36.1, 130.7]) and proportion of E-RS:COPD improvement ≥ 2 points (OR 1.71; [95% CI 1.18, 2.48]), with a numerical difference favoring dupilumab for the proportion of SGRQ improvement ≥ 4 points (OR 1.16; [95% CI 0.86, 1.56]) and for annualized severe exacerbation rate (RR 0.61 [95% CI 0.33, 1.13]) versus mepolizumab.
This ITC suggests potential clinical benefits of dupilumab over mepolizumab in reducing exacerbations and improving lung function, respiratory symptoms, and quality of life in patients with COPD and type 2 inflammation. Direct head-to-head trials are necessary to confirm these results and better guide treatment choices.
高达40%的慢性阻塞性肺疾病（COPD）患者血液嗜酸性粒细胞升高，这反映了2型炎症。度普利尤单抗和美泊利单抗与标准治疗相比，在52周内分别使中重度急性加重减少了30%-34%和15%-18%。本研究使用间接治疗比较（ITC）来比较它们的相对疗效。
对度普利尤单抗（BOREAS/NOTUS）和美泊利单抗（MATINEE/METREX/METREO）的52周3期试验进行Bucher ITC。ITC的主要终点是BOREAS + NOTUS组与MATINEE + METREX组（改良意向性治疗高分层队列，代表嗜酸性粒细胞表型）患者的年化中重度急性加重率；使用美泊利单抗数据的不同组合进行敏感性分析，包括MATINEE + METREX + METREO（100 mg剂量组）。其他52周终点包括支气管扩张剂前1秒用力呼气容积（FEV）的平均差异、圣乔治呼吸问卷（SGRQ）改善≥4分的比例、慢性阻塞性肺疾病呼吸症状评估（E-RS:COPD）改善≥2分的比例以及年化重度急性加重率。报告了具有95%置信区间（CI）的率比（RRs）/比值比（ORs）。
主要ITC得出RR为0.82（95% CI 0.66, 1.01），表明在减少中重度急性加重方面，度普利尤单抗相对于美泊利单抗在数值上具有优势。敏感性分析证实了主要ITC的结果（BOREAS + NOTUS vs. MATINEE + METREX + METREO：RR 0.83 [95% CI 0.68, 1.01]）。度普利尤单抗在FEV改善方面显著更大（平均差异83.4 mL [95% CI 36.1, 130.7]）以及E-RS:COPD改善≥2分的比例方面（OR 1.71；[95% CI 1.18, 2.48]），在SGRQ改善≥4分的比例方面（OR 1.16；[95% CI 0.86, 1.56]）以及年化重度急性加重率方面（RR 0.61 [95% CI 0.33, 1.13]）相对于美泊利单抗在数值上更具优势。
该ITC表明，在减少COPD和2型炎症患者的急性加重以及改善肺功能、呼吸症状和生活质量方面，度普利尤单抗相对于美泊利单抗具有潜在的临床益处。需要直接的头对头试验来证实这些结果并更好地指导治疗选择。
