Benralizumab Efficacy for Patients with Fixed Airflow Obstruction and Severe, Uncontrolled Eosinophilic Asthma

Abstract Background Fixed airflow obstruction (FAO) is associated with severe eosinophilic asthma. Benralizumab is an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody for patients with severe, uncontrolled eosinophilic asthma. Objective We evaluated FAO influence on benralizumab treatment response. Methods We performed a post hoc analysis of pooled phase III SIROCCO ( NCT01928771 ) and CALIMA ( NCT01914757 ) data for patients with severe, uncontrolled asthma with baseline blood eosinophil counts of 300 or more cells/μL who received benralizumab 30 mg every 8 weeks or placebo. Demographics, baseline clinical characteristics, and treatment responses were evaluated by FAO status. FAO+ and FAO− were defined as ratios of postbronchodilator forced expiratory volume in 1 second (FEV1) to forced vital capacity of less than 70% and 70% or more, respectively, at baseline. Results FAO+ prevalence was 63% (935/1493). With benralizumab, similar annual asthma exacerbation rate (AER) reductions vs placebo were achieved for FAO+ and FAO− patients (rate ratio [95% confidence interval (CI)] = 0.56 [0.44-0.71] and 0.58 [0.41-0.83], respectively), whereas annual AER reductions associated with emergency department visits or hospitalizations were greater for FAO+ vs FAO− patients (rate ratio [95% CI] = 0.55 [0.33-0.91] and 0.70 [0.33-1.48], respectively). Prebronchodilator FEV1 (95% CI) increase from baseline to end of treatment was greater for FAO+ vs FAO− patients receiving benralizumab compared with placebo (0.159 L [0.082-0.236] vs 0.103 L [−0.008 to 0.215]). Other lung function measures, patient-reported outcomes, and symptom improvements were also numerically greater for FAO+ vs FAO− patients. Conclusion Benralizumab improved asthma control across several measures for patients with severe, uncontrolled eosinophilic asthma and FAO. SIROCCO trial: NCT01928771 (URL: https://clinicaltrials.gov/ct2/show/NCT01928771 ) CALIMA trial: NCT01914757 (URL: https://clinicaltrials.gov/ct2/show/NCT01914757 )