Bhatt, Surya P;
Freemantle, Nick;
Soliman, Mena;
Heble, Jigna;
Cabon, Yann;
Mayen Herrera, Ernesto;
Yang, Joe;
(2025)
Dupilumab Versus Mepolizumab for COPD: Evaluating Efficacy Outcomes Using Placebo-Adjusted Indirect Treatment Comparison.
Pulmonary Therapy
10.1007/s41030-025-00322-1.
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Abstract
INTRODUCTION: 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). METHODS: 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 (FEV1), 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. RESULTS: 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 FEV1 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. CONCLUSION: 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.
| Type: | Article |
|---|---|
| Title: | Dupilumab Versus Mepolizumab for COPD: Evaluating Efficacy Outcomes Using Placebo-Adjusted Indirect Treatment Comparison |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s41030-025-00322-1 |
| Publisher version: | https://doi.org/10.1007/s41030-025-00322-1 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. |
| Keywords: | COPD; Dupilumab; Exacerbations; FEV1; Indirect treatment comparison; Mepolizumab; Quality of life |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > Comprehensive CTU at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215320 |
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