Mepolizumab in COPD with Eosinophilic Bronchitis: A Randomized Clinical Trial

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with eosinophilic bronchitis in 10–20% of patients. Mepolizumab, an anti-interleukin-5 antibody, depletes blood eosinophils, sputum eosinophils and reduces exacerbations. We investigated if it had similar effects in COPD with airway eosinophilia.

Methods: This was a double-blind, placebo-controlled, randomized single-centre study. Patients (40 – 80 years) with current moderate-to-severe COPD (post-bronchodilator FEV₁/VC<70%; post-bronchodilator FEV₁<60% predicted) and current/ex-smokers (>10 pack-years) with sputum eosinophilia (≥3%) received monthly IV injections of mepolizumab 750 mg or placebo for 6 months.

Results: A total of 18 patients were recruited (8 in active-arm; 10 in placebo).1 patient in the placebo group withdrew after randomization. Mepolizumab reduced sputum eosinophils (baseline 11% to 0.3% at 6 months in active arm vs 9.4% to 1.7% in placebo arm, p<0.05) and blood eosinophils (0.69 at baseline to 0.02 at 6 months in active-arm vs 0.36 to 0.28 in placebo-arm, p<0.05). There were no significant changes in the secondary outcome measures: lung function (FEV₁, FVC, SVC, FEV₁/SVC, FEV₁/FVC, TLC, RV, RV/TLC and DLCO), exacerbation rates and Quality of life scores; no significant treatment effects on airway-wall area %, lumen area, parametric response maps or relative areas of the CT density-histogram.  However, the CRQ mean dyspnea domain score change was clinically meaningful (>0.5 units).

Conclusions: Mepolizumab does not improve lung function and exacerbation rates in COPD with eosinophilia. This suggests that although eosinophils are a predictor of response to treatment with corticosteroids, unlike in asthma, they may not directly contribute to luminal obstruction in COPD.