Dupilumab reduces exacerbations and improves lung function in patients with chronic obstructive pulmonary disease and emphysema: Phase 3 randomized trial (BOREAS)
- PMID: 39481660
- DOI: 10.1016/j.rmed.2024.107846
Dupilumab reduces exacerbations and improves lung function in patients with chronic obstructive pulmonary disease and emphysema: Phase 3 randomized trial (BOREAS)
Abstract
Background: Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, reduced exacerbations and improved lung function in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation in the phase 3 BOREAS trial.
Objective: To assess clinical outcomes in patients from BOREAS by emphysema status.
Methods: Patients with COPD and type 2 inflammation (screening blood eosinophils ≥300 cells/μL) on maximal inhaled therapy were randomized to add-on dupilumab 300 mg or placebo every 2 weeks for 52 weeks. We assessed the annualized moderate/severe COPD exacerbation rates over 52 weeks and change from baseline to Week 12 in prebronchodilator forced expiratory volume in 1 s (FEV1) in patients with and without investigator-reported emphysema.
Results: Investigator-reported emphysema was present in 306/939 patients (32.6 %) at baseline. Dupilumab reduced exacerbation rates vs placebo by 29 % (relative risk [RR] 0.71 [95 % CI 0.53-0.95]) and 31 % (RR 0.69 [95 % CI 0.53-0.89]) in patients with and without emphysema, respectively. Prebronchodilator FEV1 least squares mean difference from baseline to Week 12 for dupilumab vs placebo was 0.07 L ([95 % CI 0.002-0.14]) and 0.09 L ([95 % CI 0.04-0.14]) in patients with and without emphysema, respectively. No treatment by emphysema interaction effect was observed for the annualized rate of exacerbations (P value for interaction = 0.8296) or change in prebronchodilator FEV1 (P value for interaction = 0.6438).
Conclusion: Dupilumab efficacy was similar in patients with COPD and type 2 inflammation, with or without investigator-reported emphysema.
Trial registration: ClinicalTrials.gov NCT03930732.
Keywords: BMI body mass index; COPD; Dupilumab; Emphysema; Eosinophils; Exacerbations; Type 2 inflammation.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of competing interest Bhatt SP: Apreo, Boehringer Ingelheim, Chiesi, Genentech, Medscape, Sanofi, Verona Pharma – consultant; Genentech, Nuvaira, Sanofi – grants (to institution); GSK, Regeneron Pharmaceuticals Inc. – advisory board; Horizon CME, Integrity CME – honoraria. Rabe KF: AstraZeneca, Chiesi Farmaceutici, CSL Behring, Sanofi – consultant; AstraZeneca, Boehringer Ingelheim – travel fees; Boehringer Ingelheim, Sanofi, Novartis – grants. Hanania NA: Amgen, AstraZeneca, Boehringer Ingelheim, Genentech USA, GSK – consultant; AstraZeneca, Genentech, GSK, Sanofi, Teva Pharmaceuticals – grants (to institution); Sanofi, Teva Pharmaceuticals – advisory board; Elsevier Publishing – Editor in Chief, Respiratory Medicine. Vogelmeier CF: AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, CSL Behring, GSK, Grifols, Insmed, Novartis, Roche, Sanofi – advisory board and speaking engagements; AstraZeneca – data and safety monitoring board. Bafadhel M: AstraZeneca, Roche – grant funding to institution; AstraZeneca, Chiesi, GSK – consultancy and speaker honoraria; Albus Health, ProAxsis – scientific advisor. Christenson SA: Amgen, Apogee Therapeutics, Atheneum Consulting, Axon Advisors, Genentech, Verona Pharma – consultant; AstraZeneca, GSK, Regeneron Pharmaceuticals Inc., Sanofi – advisory boards/non-branded medical teaching; BMJ Publishing Group – Associate Editor for Thorax; CME Consultants, Horizon CME, Medscape, MJH Life Sciences – non-branded medical teaching; Glenmark Pharmaceuticals – advisory boards; UpToDate – compensation for authorship. Papi A: AstraZeneca, Avillion, Chiesi Farmaceutici, Edmond Pharma, GSK, Mundipharma, Roche, Sanofi – consultant/advisory boards; IQVIA – advisory board; Mundipharma – speaker; Sandoz, Zambon – lecture fees. Singh D: Aerogen, AstraZeneca, BIAL, Boehringer Ingelheim, Chiesi Farmaceutici, Cipla USA, CSL Behring, EpiEndo, Glenmark, GSK, Kinaset, Menarini, Novartis Pharma, Orion Corporation, Pulmatrix, Sanofi, Therevance, Verona Pharma – consultant; NIHR Manchester Biomedical Research Centre – research grants (to institution). Laws E, Lu X, Bauer D, Robinson LB: Sanofi – employees, may hold stock and/or stock options in the company. Dakin P, Maloney J, Bansal A: Regeneron Pharmaceuticals Inc. – employees and shareholders. Abdulai RM: Sanofi – former employee.
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