Mepolizumab for eosinophilic COPD with frequent exacerbations: single-centre real-world experience in a phenotype-directed approach

Background: Chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype is linked to frequent exacerbations and increased oral corticosteroid (OCS) use. Mepolizumab, an anti–IL-5 monoclonal antibody, has shown efficacy in eosinophilic airway disease. This study assessed its real-life effectiveness in COPD patients with frequent OCS-requiring exacerbations. Objectives: To evaluate the effectiveness of mepolizumab in reducing exacerbations and corticosteroid use in eosinophilic COPD patients in a real-world setting. Design: Retrospective, single-centre cohort study with two-year follow-up. Methods: The study included 13 consecutive COPD patients treated with mepolizumab (100 mg SC every 4 weeks) from 2020 to 2022 and followed for two years. Inclusion required ⩾2 OCS-treated exacerbations or maintenance OCS use in the prior year and blood eosinophils > 300 cells/µL. Response was defined as a ⩾50% reduction in annual OCS-requiring exacerbations. Results: At one year, 9 of 13 patients (69%) were responders. Median annual moderate-to-severe exacerbations decreased from 4.0 (IQR: 1.5–10.0) to 1.0 (IQR: 0.0–2.0; p = 0.007). COPD-related hospitalizations declined from 2.0 (IQR: 0.0–4.0) to 0.0 (IQR: 0.0–0.0; p = 0.007). Among the eight patients who continued therapy into the second year, moderate-to-severe exacerbations declined from a median of 5.0 (IQR: 3.0–12.0) at baseline to 2.0 (IQR: 1.0–2.8) in year one and 0.5 (IQR: 0.0–2.8) in year two ( p = 0.018), representing 60% and 90% reductions, respectively. Hospitalisations dropped from 2.0 (IQR: 0.3–4.0) to 0.0 (IQR: 0.0–0.0) in both years ( p = 0.008). Maintenance OCS was discontinued in 2 of 4 patients (50%) after one year. Responders did not differ from non-responders in type 2 markers, but tended to have a higher baseline frequency of exacerbations. Conclusion: Mepolizumab significantly reduced exacerbations and hospitalizations in eosinophilic COPD patients with frequent OCS use. A 69% response rate at one year and sustained benefit in the second year support its role in this difficult-to-treat population.