LAUSR

Introduction: Benralizumab is an anti-eosinophil monoclonal antibody targeting human IL-5Rα. In the randomized, controlled Phase III SIROCCO ( Lancet . 2016;388:2115–27) and CALIMA ( Lancet . 2016;388:2128–41) trials, benralizumab 30 mg every 4 weeks and 30 mg every 8 weeks (Q8W) significantly improved asthma exacerbation rates (AER; primary endpoint) for patients with severe asthma receiving high-dosage ICS/LABA with baseline blood eosinophils ≥300 cells/µl. Aims and Objectives: We aimed to evaluate the relationship between benralizumab PK exposure and AER for all patients with severe asthma receiving high-dosage ICS/LABA. Methods: An empirical assessment was conducted to correlate steady-state trough PK quartiles with observed AER. A population PK exposure–response model was developed to characterize benralizumab treatment effect on AER. Results: In the empirical assessment, AER ratios in SIROCCO were similar across trough PK quartiles, whereas patients in CALIMA in the lowest trough PK quartile had a smaller AER response than those in other quartiles. In population modeling, the estimated benralizumab EC90 for AER was 927 ng/ml, which was lower than the typical steady-state average PK concentration (1,066 ng/ml) for the Q8W regimen. Number of exacerbations in the past 12 months, Central/Eastern Europe region, and OCS use were significant covariates for base AER. There was a positive trend toward improved benralizumab efficacy for patients with higher baseline eosinophil counts. Conclusions: Both empirical and population-based analyses of AER confirmed 30 mg Q8W as the optimal ED90 of benralizumab for patients with severe asthma.