Safety and efficacy of mepolizumab in eosinophilic chronic obstructive pulmonary disease: a systematic review and meta-analysis

Introduction: Up to 40% of patients with COPD have an eosinophilic phenotype, which increases the risk of acute exacerbations. Mepolizumab, an anti–IL-5 monoclonal antibody, has shown mixed results. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of mepolizumab 100 mg in eosinophilic COPD. Methods: Following PRISMA and Cochrane guidelines, we searched PubMed, Embase, and Cochrane Central through 18 May 2025. Randomized controlled trials comparing mepolizumab 100 mg versus placebo in eosinophilic COPD were included. The primary outcome was the annualized rate of moderate or severe exacerbations. Data were pooled using random-effects models. Results: Four RCTs (1,953 patients) were included. Mepolizumab reduced annualized rate of moderate or severe exacerbations (Rate Ratio 0.80; 95% CI: 0.73–0.89; p < 0.00001) and prolonged time to first exacerbation (HR 0.78; 95% CI: 0.69–0.88; p < 0.0001). Sensitivity analysis excluding METREX showed fewer exacerbations requiring ED visits or hospitalization (Rate Ratio 0.63; 95% CI: 0.46–0.86; p = 0.004). Patient-reported outcomes did not improve. Safety was favorable, with reduced serious adverse events, including deaths (RR 0.84; 95% CI: 0.73–0.98; p = 0.03). Conclusions: Mepolizumab reduces exacerbations with good safety in eosinophilic COPD, though without improvement in quality-of-life outcomes.