Effect of depemokimab on asthma control and clinical outcomes: a systematic review and meta-analysis of randomized controlled trials

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 I2 statistic.Results Four RCTs (n = 954) were included. Depemokimab did not significantly improve ACQ-5 (MD -0.30; 95% CI -0.92 to 0.32; I2 = 73.6%; p = 0.23), but reduced exacerbation rates (IRR 0.47; 95% CI 0.36 to 0.59; I2 = 0%; p < 0.001) and modestly improved SGRQ scores without reaching the MCID (MD -2.80; 95% CI -5.38 to -0.23; I2 = 0.0%; p = 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).