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

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.