Efficacy and safety of mepolizumab in severe eosinophilic asthma: a systematic review and meta-analysis.

Background: Asthma remains a global health challenge, with eosinophilic asthma constituting over half of all cases. This refractory phenotype is characterized by persistent type 2 inflammation, where interleukin-5 (IL-5)-mediated eosinophil activity drives disease progression. Although current therapies including high-dose corticosteroids provide partial relief, many severe patients still suffer from uncontrolled symptoms and frequent exacerbations. Mepolizumab, an anti-IL-5 monoclonal antibody, offers targeted intervention, yet its therapeutic effects on lung function remain inconsistently reported across studies. This systematic review aims to clarify mepolizumab's clinical efficacy by analyzing its impact on forced expiratory volume in 1 second (FEV1) improvement, exacerbation reduction, and symptom control [Asthma Control Questionnaire-5 (ACQ-5)], while evaluating safety profiles and potential biomarkers for treatment optimization in severe eosinophilic asthma. Methods: A systematic literature search was conducted across PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) evaluating mepolizumab in patients ≥12 years with severe eosinophilic asthma (baseline blood eosinophils ≥150 cells/µL). Included RCTs reported FEV1, exacerbation rates, ACQ-5 scores, or adverse events (AEs). Two investigators independently performed data extraction and quality assessment. Statistical analyses used RevMan 5.4 and Stata 16.0, with subgroup analyses examining baseline eosinophil counts and dosing regimens. Publication bias was assessed using Begg's funnel plots with rank correlation tests. Results: Ten RCTs (n=4,471) met inclusion criteria. Compared to placebo, mepolizumab significantly improved FEV1 [mean difference (MD) =0.06 L, 95% confidence interval (CI): 0.02 to 0.10; P=0.008], reduced exacerbation rates by 42% [risk ratio (RR) =0.58, 95% CI: 0.51 to 0.67; P<0.001], and improved ACQ-5 scores (MD =-0.29, 95% CI: -0.40 to -0.17; P<0.001). Subgroup analyses demonstrated enhanced treatment effects for both FEV1 and exacerbation outcomes in patients with baseline eosinophils ≤300 cells/µL and those administered mepolizumab 75-100 mg. The overall safety profile of mepolizumab was comparable to placebo, with the 75-100 mg regimen associated with significantly reduced incidence of serious adverse events (SAEs). Conclusions: This meta-analysis demonstrates the efficacy and safety of mepolizumab in severe eosinophilic asthma, showing improvements in lung function, exacerbation reduction, and asthma control. The 75-100 mg dosing schedule exhibits a favorable benefit-risk ratio. Baseline blood eosinophil count serves as a predictive biomarker for therapeutic response, supporting individualized treatment approaches. Further research is required to establish optimal dosing and evaluate long-term safety.