Comparative efficacy of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis.

BACKGROUND: The comparative safety and efficacy of the biologics currently approved for asthma is unclear. OBJECTIVE: To compare the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma. METHODS: Systematic review of peer-reviewed literature from 2000 through 2021, and Bayesian network meta-analyses of exacerbation rates, prebronchodilator FEV1, the Asthma Control Questionnaire (ACQ) and serious adverse events (SAE) in individuals with eosinophilic asthma. RESULTS: Eight randomized clinical trials (n=6,461) were identified. In individuals with ≥300 eosinophils per microliter (eosin/mcl), in reducing exacerbation rates in comparison to placebo: dupilumab (risk ratio [RR] 0.32; 95% credible interval [CI], 0.23-0.45), mepolizumab (RR, 0.37; 95%CI, 0.30-0.45), and benralizumab (RR, 0.49; 95%CI, 0.43-0.55). In improving FEV1: dupilumab (mean difference in milliliters [MD] 230; [CI], 160-300), benralizumab (MD 150; 95%CI, 100-200), and mepolizumab (MD 150; 95%CI, 66-220); and in reducing ACQ: mepolizumab (MD -0.63; [CI], -0.81 to -0.45), dupilumab (MD -0.48; 95%CI, -0.83 to -0.14), and benralizumab (MD -0.32; 95%CI, -0.43 to -0.21). In individuals with eosinophil counts of 150-299 eosin/mcl, benralizumab (RR, 0.62; 95%CI, 0.52-0.73) and dupilumab (RR, 0.60; 95%CI, 0.38-0.95) were associated with lower exacerbation rates; and only benralizumab (MD 81; 95% CI, 8-150) significantly improved FEV1. These differences were minimal in comparison to clinically important thresholds. For SAE in the overall population, mepolizumab (odds ratio, 0.67; 95% CI, 0.48-0.92) and benralizumab (0.74; 95% CI, 0.59-0.93) were associated with lower odds of a SAE, while dupilumab was not different from placebo (1.0; 95% CI, 0.74-1.4). CONCLUSIONS: There are minimal differences in the efficacy and safety of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma. CLINICAL IMPLICATION: In individuals with eosinophilic asthma, mepolizumab, benralizumab, and dupilumab are similar in their effect on exacerbations, FEV1, or ACQ.