Depemokimab reduces exacerbation rates in patients with eosinophilic asthma without improving symptom scoresDepemokimab Reduces Asthma Exacerbations in Eosinophilic Asthma Patients

INTRODUCTION: Patients with eosinophilic asthma are at increased risk of poor asthma control despite optimized standard therapy. Depemokimab, a novel long-acting anti-interleukin-5 monoclonal antibody, has shown efficacy in reducing exacerbations; however, its effects across clinical outcomes have not been comprehensively synthesized. METHODS: PubMed, Embase, Cochrane databases, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) comparing depemokimab with placebo. Outcomes included Asthma Control Questionnaire-5 (ACQ-5), asthma exacerbation rate, quality of life assessed by St. George's Respiratory Questionnaire (SGRQ), and adverse events. Results were reported as mean differences (MDs) or incidence rate ratios (IRRs) with 95% confidence intervals (CIs), and heterogeneity was assessed using the I statistic. RESULTS: Four RCTs ( = 954) were included. Depemokimab did not significantly improve ACQ-5 (MD -0.30; 95% CI -0.92 to 0.32; I = 73.6%;  = 0.23), but reduced exacerbation rates (IRR 0.47; 95% CI 0.36 to 0.59; I = 0%;  < 0.001) and modestly improved SGRQ scores without reaching the MCID (MD -2.80; 95% CI -5.38 to -0.23; I = 0.0%;  = 0.033). Safety was comparable to placebo. CONCLUSIONS: Depemokimab reduced exacerbations and had a comparable safety profile, but did not improve symptom control or achieve the MCID for health-related quality-of-life. REGISTRATION: The study protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD420261282685).