Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma

Background: Patients with severe asthma can have eosinophilic inflammation and/or allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody indicated for add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. Objective: To investigate the efficacy of benralizumab by atopic status and serum immunoglobulin E (IgE) concentrations. Methods: We analyzed pooled results from the SIROCCO (NCT01928771) and CALIMA (NCT01914757) phase III studies. Patients 12 to 75 years old with severe, uncontrolled asthma on high-dosage inhaled corticosteroids plus long-acting beta(2)-agonists received 30 mg of subcutaneous benralizumab every 4 weeks or every 8 weeks (first 3 doses every 4 weeks) or placebo every 4 weeks. The analysis stratified patients who did and did not meet similar omalizumab-qualifying criteria of atopy and serum IgE levels 30 to 700 kU/L. Patients also categorized as having high serum IgE (>= 150 kU/L) or low serum IgE (<150 kU/L) and as having atopy or no atopy. Efficacy outcomes were for all patients and by blood eosinophil counts and included annual exacerbation rate ratio and pre-bronchodilator forced expiratory volume in 1 second change at treatment end vs placebo. Results: Benralizumab every 8 weeks decreased exacerbations by 46% (95% confidence interval 26-61, P=.0002) and increased forced expiratory volume in 1 second by 0.125 L (95% confidence interval 0.018-0.232, P=.0218) vs placebo for patients with at least 300 eosinophils/mu L who met the atopy and IgE criteria. For patients with eosinophilia and high or low IgE, treatment with benralizumab every 8 weeks resulted in 42% and 43% decreases in exacerbation rate (P <=.0004) and 0.123- and 0.138-L increases in forced expiratory volume in 1 second (P <=.0041) vs placebo, respectively. Conclusion: Benralizumab treatment decreased exacerbations and improved lung function for patients with severe, uncontrolled eosinophilic asthma regardless of serum IgE concentrations and atopy status. (c) 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc.