Abstract Background Mepolizumab and Benralizumab, monoclonal antibodies targeting the interleukin-5 pathway, reduce eosinophil-driven airway inflammation in severe eosinophilic asthma. Although both are recommended for biologic-eligible patients, comparative real-world evidence on their long-term effectiveness remains limited. Methods We conducted a retrospective, propensity-matched cohort study using the TriNetX Global Collaborative Network, which aggregates de-identified electronic medical records from 162 healthcare organisations worldwide. Adults (≥18 years) with severe eosinophilic asthma, identified by ICD-10 codes J45.5, J82, or J82.83 and blood eosinophil count ≥0.15 × 10³/µL, were included. Cohort 1 comprised patients who initiated Mepolizumab (n = 2,081), and Cohort 2 included those treated with Benralizumab (n = 1,664). Patients with overlapping biologic exposure (Dupilumab, Omalizumab, Reslizumab) were excluded. The index date was defined as the first administration of the biologic, with a 5-year follow-up after treatment initiation. Propensity score matching (1:1) was performed across baseline demographics and comorbidities. Time-to-event outcomes were evaluated for asthma exacerbations, hospitalisations, emergency department (ED) visits, all-cause healthcare utilisation, composite adverse events (headache, fatigue, dyspnea), and all-cause mortality. Adjusted hazard ratios (HRs) were obtained using Cox proportional hazards models. Results After matching, 3,270 patients (1,635 per cohort) were included, with a mean age of 51±17 years, 69% female, and 65% White. The median follow-up duration was 4.9 (IQR 4.1-5.0)years. Baseline comorbidities were well-balanced (standardised mean differences 0.1). Over the 5-year follow-up period, Mepolizumab and Benralizumab users had similar event rates across our endpoints: asthma exacerbation (HR 0.99, 95% CI 0.90-1.11, p = 0.29), ED visits (HR 1.12, 95% CI 0.98-1.27, p = 0.09), hospitalization (HR 1.12, 95% CI 0.95-1.31, p = 0.18), all-cause healthcare utilization (HR 1.09, 95% CI 0.97-1.21, p = 0.14), composite adverse events (HR 1.06, 95% CI 0.95-1.18, p = 0.36), and all-cause mortality (HR 1.22, 95% CI 0.63-2.36, p = 0.56). Composite adverse events (headache, fatigue, dyspnea) were similar (HR 1.06 95% CI 0.95-1.18; p = 0.36) Conclusions In this large, real-world comparative effectiveness study, Mepolizumab and Benralizumab exhibited comparable hazards for exacerbations, hospitalisation, and mortality among adults with severe eosinophilic asthma. These findings suggest equivalent 5-year clinical performance and safety of IL-5-pathway-targeting biologics in routine care. Figure 1. Forest plot of hazard ratios for major clinical outcomes comparing Benralizumab versus Mepolizumab in severe eosinophilic asthma. The plot displays hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Hazard ratios were estimated using Cox proportional hazards models after 1:1 propensity score matching on baseline characteristics. This abstract is funded by: No funding
Ikwu et al. (Fri,) studied this question.