[Efficacy and clinical remission in patients with severe asthma and blood eosinophil counts ≥150 cells/μl treated with benralizumab: a sub-analysis of the Phase 3 MIRACLE study].

Objective: To evaluate the efficacy of benralizumab in patients with baseline bEOS ≥150 cells/μl using data from the MIRACLE study in Asia. Methods: MIRACLE was a phase Ⅲ clinical trial. From September 7, 2017 to January 30, 2023, patients aged 12-75 years with eosinophilic severe asthma receiving medium- to high-dosage inhaled corticosteroids and long-acting β2 agonists were enrolled from 79 centres in Asia. They were randomized (1∶1) to receive either benralizumab 30 mg or placebo for 48 weeks. The endpoints included annual asthma exacerbation rate (AAER), pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1), total asthma symptom score (TASS), St George's Respiratory Questionnaire (SGRQ) score, and the proportion of patients achieving clinical remission (defined as no asthma exacerbations, FEV1 improvement ≥100 ml, and 6-item Asthma Control Questionnaire [ACQ-6 score;≤0.75 or <1.5]; at Weeks 24 and 48) in patients with no baseline oral corticosteroid (OCS) use. Results: Of 695 patients randomized, 598 patients had baseline bEOS ≥150 cells/μl [benralizumab n=301, placebo n=297; age: (50.9±12.1) years; 61.2% were women]. In this population, benralizumab reduced the AAER by 67% [rate ratio (RR)=0.33, 95%CI: 0.25-0.44, P<0.001) and improved lung function [least squares (LS) mean difference vs. placebo: 0.21 L, 95%CI: 0.14-0.29, P<0.001]. Benralizumab achieved greater reductions in TASS (LS mean difference:-0.29, 95%CI:-0.46--0.11, P=0.002) and ACQ-6 scores (LS mean difference:-0.33, 95%CI:-0.46--0.19, P<0.001), and improved SGRQ scores (LS mean difference:-8.07, 95%CI:-11.35--4.79], P<0.001). Among patients with no baseline OCS use (benralizumab n=277; placebo n=264), a higher proportion of benralizumab-treated patients achieved clinical remission at Weeks 24 and 48 compared to the placebo-treated patients. Conclusion: These results reinforce that benralizumab can improve clinical outcomes in patients with severe, uncontrolled asthma with bEOS ≥150 cells/μl in Asia.