Role of Monoclonal Antibodies in the Management of Eosinophilic COPD: A Meta-analysis of Randomized Controlled Trials.

Background: COPD remains a leading cause of morbidity and mortality worldwide. Acute exacerbations are associated with progressive decline in lung function and quality of life. After recognition of the role of type 2 inflammation in the pathogenesis of eosinophilic COPD, there was increased interest in studying monoclonal antibodies as a therapeutic agent. Multiple randomized control trials (RCTs) showed promising results, yet no consensus exist. Our study aims to summarize the current evidence regarding the role of monoclonal antibodies in the management of patients with eosinophilic COPD.

Methodology: We systematically searched multiple databases using pre-specified search terms. We included only RCTs comparing monoclonal antibodies to placebo in patients with objective evidence of eosinophilic COPD receiving standard of care. The primary outcome of interest was annualized rate of COPD exacerbation. Absolute changes in FEV1, and SGRQ scores were secondary outcomes. We also reported serious adverse effects and all-cause mortality. Statistical analysis was conducted via random effects model, using RevMan software.

Results: We identified and included 8 double blinded, placebo-controlled trials with a total of 4,512 patients, and a median follow up of 52 weeks. The patients mean age was 65±8 years, with 85% male majority. 70% of patients were former smokers, with a mean of 43±25 pack-years. The majority of patients were on triple inhaled therapy. The mean serum eosinophil count on enrollment was 398±297 cell/µL. Monoclonal antibodies were Dupilumab, Mepolizumab, Benralizumab, Astegolimab, and Itepekimab. Compared to placebo, patients who received monoclonal antibody had a significantly decreased annualized COPD exacerbation rate [RR 0.79; 95% CI (0.73, 0.86), P<0.001]. The serious adverse effect rate was significantly lower in monoclonal antibody arm compared to placebo, [OR 0.80, 95% CI (0.69, 0.93, P=0.004)]. All-cause mortality rate was not statistically different between the groups, [OR of 0.91, 95% CI (0.63, 1.3, P=0.6)]. Dupilumab showed a trend of efficacy over Mepolizumab and Benralizumab.

Conclusion: In patients with eosinophilic COPD receiving standard of care therapy, the use of monoclonal antibodies led to a significant reduction in annualized COPD exacerbation rate compared to placebo. Monoclonal antibodies have an acceptable tolerability and safety profile.