Improving asthma remission with benralizumab in real-world asthma patients in the US: Results from the ZEPHYR-4 study

08 May 2024


The anti-interleukin-5 receptor α (anti-IL-5α) monoclonal antibody (mAb), benralizumab, had been approved for the treatment of severe eosinophilic asthma offering significant improvements in exacerbation rates, maintenance oral corticosteroid (mOCS) use, and other asthma outcomes in phase 3 clinical trials.1 Although benralizumab has achieved asthma remission in clinical trials and non-United States (US) populations, real-world data within the US assessing similar outcomes remained limited.1

The ZEPHYR-4 study was a retrospective observational study using data from the US federated electronic health record (EHR) describing the clinical outcomes in patients with benralizumab in real-world US practice.1 The study included 2,895 patients aged ≥12 years who had received ≥2 benralizumab prescriptions and had ≥1 healthcare encounter in the previous 12 months.1 A subgroup of patients who have had ≥2 exacerbations (n=1,275) within the 12-month baseline period was also defined and analyzed separately.1

The primary outcome was the proportion of patients achieving the components of remission 12 months after initiating benralizumab.1 The components were established by an expert consensus, and represent a more comprehensive treatment goal for patients with severe asthma.1 Only 3 of the 4 components were assessed in this study as Asthma Control Tests results were unavailable in this dataset.1 The other components included no exacerbations during the 12-month follow-up period, defined as no asthma-related inpatient hospitalization, emergency department visit, or oral corticosteroids (OCS) prescription within 5 days before or after an asthma-related outpatient visit; no mOCS use, defined as ≤4 OCS prescriptions during the 12-month follow-up period; and stabilization of lung function, defined as a ≤10% forced expiratory volume in the first second (FEV1) reduction from baseline.1 Secondary outcomes were blood eosinophil count and lung function changes in the pre- and post-initiation periods.1


Primary outcome:
  • The primary outcome was the proportion of patients with 3 components of remission within 12 months after benralizumab treatment1
  • In the full study population, 41.8% of patients achieved no exacerbations, 87.7% achieved no mOCS use, and 83.9% achieved lung function stabilization1
  • Among the patients with ≥2 baseline exacerbations, 17.9% of patients achieved no exacerbations, 79.7% of patients achieved no mOCS use, and 87.2% of patients achieved stabilized lung function1
  • Furthermore, all 3 criteria were met in 14.5% and 10.3% of patients in the full study population and the population with ≥2 baseline exacerbations respectively1
Secondary outcomes: 
  • The secondary outcomes were blood eosinophils, FEV1, and FEV1/forced vital capacity (FVC) measures in the pre- and post-initiation periods1
  • Compared with pre-initiation, mean blood eosinophils decreased post-initiation from 417 cells/μL to 110 cells/μL in the full study population and 448 cells/μL to 118 cells/μL in the ≥2 baseline asthma exacerbations population (p<0.01 for both)1
  • Mean FEV1 also decreased from 64.0% to 63.4% in the full study population and from 65.7% to 63.0% in the population with ≥2 baseline asthma exacerbations, neither of which achieved statistical significance1
  • Similarly, mean FEV1/FVC was reduced in both populations, but the reduction was not statistically significant1
  • Subgroup analysis of patients stratified by duration of benralizumab use, baseline blood eosinophil count, and serum immunoglobulin E (IgE) revealed similar outcomes as the full study population but higher responses were noted in those with blood eosinophils ≥150 cells/μL than those with <150 cells/μL1


“This study elucidates real-world benralizumab outcomes  by describing key components of asthma remission,  an increasingly important asthma endpoint”

Dr. Donna D. Carstens
 Wilmington, Delaware, United State

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