Efficacy of dupilumab and mepolizumab in eosinophilic COPD: insights from phase 3 trials

TY - JOUR

T1 - Efficacy of dupilumab and mepolizumab in eosinophilic COPD

T2 - insights from phase 3 trials

AU - Suter, Philipp

AU - Greig, Robert

AU - Chan, Rory

AU - Lipworth, Brian

N1 - © 2025 The Authors

PY - 2025/11

Y1 - 2025/11

N2 - Background Eosinophilic chronic obstructive pulmonary disease (eCOPD), characterized by type 2 inflammation, is an emerging target for biologic therapies. Objective To indirectly compare the efficacy of dupilumab and mepolizumab in eCOPD, defined as blood eosinophil counts ≥300 cells/μL, by synthesizing data from phase 3 randomized controlled trials: BOREAS and NOTUS for dupilumab, MATINEE for mepolizumab. Methods We performed an indirect comparison of trial primary and secondary outcomes including annual exacerbation rates (AER), quality of life (St. George's Respiratory Questionnaire, SGRQ), symptoms (E-RS–COPD), and lung function (FEV1). Rate ratios and mean differences with crude 95 % CI were evaluated using forest plots. Results Both dupilumab and mepolizumab significantly reduced AER versus placebo, with comparable magnitude based on overlapping 95 % CI. The time needed to prevent one exacerbation was shorter for dupilumab (2.3–3.1 years) compared to mepolizumab (4.8 years). However, dupilumab but not meplizumab showed significant improvements in quality of life, symptoms, and FEV1, along with enhanced effects in patients with elevated fractional exhaled nitric oxide (FeNO ≥20 ppb). None of the secondary outcomes reached the minimal clinical important difference. Conclusion While both biologics reduced AER in eCOPD, dupilumab demonstrated statistically but not clinically relevant improvements on quality of life, symptoms, and lung function. Especially in patients with elevated FeNO, dupilumab demonstrated an improvement. Further direct comparisons and biomarker-driven studies are warranted.

AB - Background Eosinophilic chronic obstructive pulmonary disease (eCOPD), characterized by type 2 inflammation, is an emerging target for biologic therapies. Objective To indirectly compare the efficacy of dupilumab and mepolizumab in eCOPD, defined as blood eosinophil counts ≥300 cells/μL, by synthesizing data from phase 3 randomized controlled trials: BOREAS and NOTUS for dupilumab, MATINEE for mepolizumab. Methods We performed an indirect comparison of trial primary and secondary outcomes including annual exacerbation rates (AER), quality of life (St. George's Respiratory Questionnaire, SGRQ), symptoms (E-RS–COPD), and lung function (FEV1). Rate ratios and mean differences with crude 95 % CI were evaluated using forest plots. Results Both dupilumab and mepolizumab significantly reduced AER versus placebo, with comparable magnitude based on overlapping 95 % CI. The time needed to prevent one exacerbation was shorter for dupilumab (2.3–3.1 years) compared to mepolizumab (4.8 years). However, dupilumab but not meplizumab showed significant improvements in quality of life, symptoms, and FEV1, along with enhanced effects in patients with elevated fractional exhaled nitric oxide (FeNO ≥20 ppb). None of the secondary outcomes reached the minimal clinical important difference. Conclusion While both biologics reduced AER in eCOPD, dupilumab demonstrated statistically but not clinically relevant improvements on quality of life, symptoms, and lung function. Especially in patients with elevated FeNO, dupilumab demonstrated an improvement. Further direct comparisons and biomarker-driven studies are warranted.

KW - Chronic obstructive pulmonary disease

KW - Eosinophil

KW - Biologics

KW - Dupilumab

KW - Mepolizumab

UR - https://www.scopus.com/pages/publications/105014945156

U2 - 10.1016/j.rmed.2025.108343

DO - 10.1016/j.rmed.2025.108343

M3 - Review article

C2 - 40915326

SN - 0954-6111

VL - 248

JO - Respiratory Medicine

JF - Respiratory Medicine

M1 - 108343

ER -