POSB21 Monoclonal Antibodies in the Treatment of Persistent, Uncontrolled Eosinophilic Asthma: Systematic Review, Meta-Analysis and Indirect Comparison

Eosinophilic asthma is a phenotype of severe asthma, characterized by elevated blood eosinophils. Monoclonal antibody therapies targeting interleukin (IL)-4/IL-13 and IL-5 cytokine pathways, seem to reduce asthma exacerbations, improve lung function and asthma symptoms. The scope of the present research was to explore the efficacy and safety of monoclonal antibodies that target IL-5 (mepolizumab and reslizumab) or its receptor (benralizumab) and the IL-4 and IL-13 receptor (dupilumab) compared to placebo, in adults with severe eosinophilic asthma. A literature search was performed using the databases PubMed/Medline and CENTRAL. The selected studies were all randomized, double-blind, phase III, placebo-controlled trials. A standard meta-analysis and an indirect comparison were performed. The literature search identified 1511 studies, nine of which fulfilled the inclusion criteria. Meta-analysis findings suggested that all treatments were more effective than placebo, based on reduced rates of clinically significant asthma exacerbations (Rate Ratios(RRs) 95% CI 0.46-0.52–high to moderate certainty), a small improvement in FEV1 (Mean Difference(MD) 95% CI 0.11L-0.14L-moderate certainty), and were generally well tolerated, with the exception of benralizumab and dupilumab (moderate to low certainty).The indirect comparison did not show any statistically significant difference in exacerbation rates, FEV1 and serious adverse events (low to very low certainty). Based on ACQ-scores, mepolizumab was found to be more effective than reslizumab (MD 95% CI -0.17[-0.34,-0.04]) and benralizumab (MD 95% CI -0.17[-0.33,-0,01]), while based on adverse events that led to drug discontinuation, mepolizumab appeared to be safer than benralizumab (RR95% CI 0.20[0.05,0.87]) and reslizumab (RR 95% CI 0.33[0.13,0.82]) (low to very low certainty). Results suggest that the monoclonal antibodies are more effective than placebo. The indirect comparison did not show significant differences between the treatments, in terms of efficacy and safety. Head to head clinical trials should be conducted to confirm these findings.