Mepolizumab Prophylaxis in Eosinophilic COPD: A Meta-Analysis

Introduction: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Recent advances have identified a distinct eosinophilic COPD. Mepolizumab, an IL-5 monoclonal antibody effective in eosinophilic asthma, has been studied in eosinophilic COPD primarily through four randomized controlled trials (RCTs)–METREX, METREO, F.C Sciurba, and C.Flynn trial. Given their shared protocols, this meta-analysis enhances statistical power and provides a more precise estimate of its efficacy.


Methods: A comprehensive search of PubMed, Cochrane Library, and ClinicalTrials.gov was performed from inception through June 2025 in accordance with PRISMA guidelines to identify RCTs evaluating the efficacy of mepolizumab (100 mg subcutaneously every 4 weeks) in patients with eosinophilic COPD. Eligible studies reported outcomes including moderate to severe exacerbation rates, ED visits, time to first exacerbation. Risk of bias was assessed using the Cochrane Collaboration’s Risk of Bias Tool. A random-effects meta-analysis was performed to calculate pooled rate ratios for exacerbations, with statistical heterogeneity assessed using the I² statistic. Forest plots were generated using RevMan software to visually summarize effects.


Results: Four RCTs (n = 2553, 2014–2025) showed that mepolizumab reduced moderate/severe COPD exacerbations (RR 0.80; 95% CI: 0.73–0.89; p < 0.00001; I² = 0%). Exacerbations requiring hospitalization and ED visits showed heterogeneity (I² = 45%) due to the METREX trial (RR = 0.78); this trial included a lower-risk population (a mix of eosinophilic and non-eosinophilic patients). Sensitivity analysis excluding METREX showed a significant effect (RR 0.68; 95% CI: 0.52–0.87; p < 0.003; I² = 0%). Time to first moderate or severe exacerbation was also reduced (HR 0.78; 95% CI: 0.69–0.88; p < 0.0001; I² = 0%). The C. Flynn trial lacked hazard ratio data and was excluded from this outcome analysis.


Conclusions: Prophylaxis with mepolizumab in eosinophilic COPD, significantly reduced the annualized rate of moderate-to-severe exacerbations, lowered the hospitalization rates, and delayed the onset of exacerbations. These findings reinforce mepolizumab’s role as a targeted therapy to improve patient outcomes and underscore its importance in informing future treatment guidelines.