Benralizumab efficacy for patients with fixed airflow obstruction and severe, uncontrolled eosinophilic asthma

Ann Allergy Asthma Immunol. 2020 Jan;124(1):79-86. doi: 10.1016/j.anai.2019.10.006. Epub 2019 Oct 15.


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.

Trial registration: SIROCCO trial: NCT01928771 (URL: CALIMA trial: NCT01914757 (URL:

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Asthmatic Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / pathology
  • Double-Blind Method
  • Eosinophils / cytology
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Interleukin-5 Receptor alpha Subunit / antagonists & inhibitors
  • Leukocyte Count
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Pulmonary Eosinophilia / drug therapy*
  • Pulmonary Eosinophilia / pathology
  • Quality of Life / psychology
  • Vital Capacity / drug effects


  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal, Humanized
  • Interleukin-5 Receptor alpha Subunit
  • Placebos
  • benralizumab

Associated data