Efficacy and Safety of Dupilumab in COPD with Type 2 Inflammation Guided by Blood Eosinophils: The BOREAS Study

Surya Bhatt, Claus Rabe, Nicolas Hanania, Claus Vogelmeier, Jeremy Cole, Mona Bafadhel, Stephanie Christenson, Alberto Papi, Dave Singh, Elizabeth Laws, Leda Mannent, Naimish Patel , Heribert Staudinger, George Yancopoulos, Eric Mortensen, Bolanle Akinlade, Jennifer Maloney, Xin Lu, Deborah Bauer, Ashish BansalLacey Robinson, Raolat Abdulai

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Abstract

Background: Chronic obstructive pulmonary disease (COPD) is often associated with markedly reduced lung function and frequent exacerbations despite optimized inhaled treatment. Type 2 inflammation is hypothesized to play a role in a subset of patients with COPD and drive exacerbation risk. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation. Methods: BOREAS was a phase 3, 52-week, multi-center, randomized, double-blind trial of dupilumab (300mg) versus placebo administered subcutaneously once every two weeks in COPD participants with type 2 inflammation (blood eosinophils ≥300 cells/μL), who have high exacerbation risk despite standard-of-care triple inhaled medications. Primary endpoint: annualized rate of moderate or severe exacerbations. Additional endpoints: pre-bronchodilator (BD) FEV1 and St. George's Respiratory Questionnaire (SGRQ) and Evaluating Respiratory Symptoms in COPD (E-RS) scores. Results: 939 participants (468 dupilumab, 471 placebo) were randomized. The annualized rate of moderate or severe exacerbations was 30% lower with dupilumab (0.776; 95% confidence interval [CI], 0.645–0.934) than with placebo (1.101; 95% CI 0.931–1.301; rate ratio: 0.705; 95% CI, 0.581–0.857; p=0.0005). Dupilumab significantly increased pre-BD FEV1 at Week 12 vs placebo (least squares mean [LSM] 160mL vs 77mL, respectively; LSM difference: 83mL; p
Original languageEnglish
JournalThe New England Journal of Medicine
DOIs
Publication statusPublished - 1 Mar 2024

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