Abstract
INTRODUCTION: Asthma is a complex and heterogeneous disease that significantly impacts quality of life. Eosinophilic asthma, characterized by elevated eosinophil levels, leads to inflammation and hypersensitivity. Many patients remain inadequately managed, resulting in frequent exacerbations and hospitalizations despite standard treatment options. Depemokimab, a long-acting monoclonal antibody that targets IL-5, could offer a novel approach for managing severe eosinophilic asthma. METHODS: A systematic search was conducted across the PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and Scopus databases up to January 2025. Dichotomous outcomes were pooled as risk ratios (RR), and continuous outcomes were represented as mean differences (MD) from baselines, with 95% confidence intervals (CIs), using a random-effects model. Statistical analysis was performed using RevMan (version 5.4). RESULTS: Two randomized controlled trials (n = 762) were included. Depemokimab significantly reduced the annualized rate of exacerbations (MD -0.59, 95% CI [-0.76 to -0.42], P < 0.00001) and improved the St. George's Respiratory Questionnaire (SGRQ) score (MD -2.93, 95% CI [-5.48 to -0.38], P = 0.02). It also significantly decreased the annualized rate of exacerbations requiring hospitalization or emergency department visits (RR 0.33, 95% CI [0.15 to 0.75], P = 0.008). No significant differences were observed in changes to the Asthma Control Questionnaire (ACQ-5) score, pre-bronchodilator FEV1, or asthma-related diaries. Safety outcomes indicated significantly lower risks for pneumonia, nasopharyngitis, rhinitis, and back pain in the Depemokimab group. However, an increased risk of allergic rhinitis was noted (RR 2.71, 95% CI [1.22 to 6.02], P = 0.01). No significant differences were observed in serious adverse events or other adverse events. CONCLUSION: Depemokimab demonstrates promising efficacy in reducing clinically significant exacerbations and improving quality of life measures in patients with severe eosinophilic asthma, with a generally favorable safety profile. However, the current evidence is limited to two trials with relatively short follow-up periods. Further research with larger, more diverse patient populations and extended long-term follow-up is needed to establish the drug's definitive place in therapeutic algorithms and to comprehensively evaluate potential long-term safety concerns before widespread clinical implementation can be recommended.