Introduction: For patients with eosinophilic asthma with allergic characteristics, understanding the key drivers of exacerbations is important to identify optimal treatment strategies. Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that significantly reduces exacerbation frequency for patients with severe, uncontrolled eosinophilic asthma. We evaluated the predictive value of baseline blood eosinophil counts vs. serum immunoglobulin E (IgE) concentrations on exacerbation risk and the association of these variables with benralizumab treatment effect.
Methods: Analyses were performed with data pooled from the phase III SIROCCO and CALIMA benralizumab trials. Crude annual asthma exacerbation rates (AERs) were determined for placebo as a function of baseline blood eosinophil counts and serum IgE concentrations with prespecified blood eosinophil count categories (< 150, ≥ 150 to < 300, ≥ 300 to < 450, ≥ 450 cells/µL) and IgE concentration quartiles (< 62.0, ≥ 62.0 to < 176.2, ≥ 176.2 to < 453.4, and ≥ 453.4 kU/L). We compared AERs for patients receiving benralizumab 30 mg every 8 weeks (first three doses every 4 weeks) vs. placebo for overlapping baseline blood eosinophil count categories and serum IgE concentration quartiles via a regression approach and by continuously using locally weighted regression smoothing analysis.
Results: Exacerbation risk for patients with severe asthma receiving placebo increased with increasing baseline blood eosinophil counts but not with increasing serum IgE concentrations. Addition of baseline atopy status did not influence the relationship between IgE concentrations and exacerbation risk for patients receiving placebo. Patients with blood eosinophil counts ≥ 300 cells/µL had consistent decreases in exacerbation risk with benralizumab relative to placebo across all serum IgE concentration quartiles.
Conclusion: Baseline blood eosinophil counts, but not serum IgE concentrations, are an important predictor of exacerbation risk. Patients with severe eosinophilic asthma treated with benralizumab had consistent reductions in exacerbation risk, regardless of IgE concentrations.
Clinical trial registration: ClinicalTrials.gov: SIROCCO, NCT01928771; CALIMA, NCT01914757.
Keywords: Asthma; Benralizumab; CALIMA; Eosinophils; Exacerbations; Immunoglobulin E; Interleukin-5 receptor; SIROCCO.
Many patients with severe asthma have elevated numbers of eosinophils (a subset of white blood cells) and raised serum concentrations of immunoglobulin E (IgE; antibodies). Elevated eosinophil counts together with IgE concentrations are associated with more frequent asthma attacks. Benralizumab is a drug that almost completely depletes eosinophils and significantly reduces asthma attacks for patients with severe, uncontrolled asthma and elevated blood eosinophil counts. The individual influence of eosinophils and IgE on benralizumab efficacy has been published. In this study, we further extend the analyses to evaluate the interrelationship of eosinophil counts and IgE concentrations with asthma attack frequency and benralizumab efficacy for patients with severe, uncontrolled asthma. We evaluated the association of blood eosinophil counts and IgE concentrations with asthma attack frequency for patients with severe asthma who received high-dosage inhaled corticosteroids plus additional controller medications but did not receive benralizumab in the benralizumab clinical trials. We observed that increased blood eosinophil counts were associated with greater asthma attack frequency, while serum IgE concentrations had no influence on asthma attack frequency. We also evaluated patients who received benralizumab and determined that benralizumab can reduce the occurrence of these attacks for patients with elevated blood eosinophil counts regardless of their serum IgE concentrations. Frequency of asthma attacks also decreased with benralizumab for patients with elevated serum IgE concentrations, but serum IgE concentrations did not influence benralizumab efficacy. Benralizumab is an efficacious treatment for patients with uncontrolled eosinophilic asthma, regardless of their IgE concentrations.