Lawrence DuBuske1, Paul Newbold2, Yanping Wu3, Frank Trudo4. 1. From the Division of Allergy and Immunology, Department of Internal Medicine, George Washington University School of Medicine and Health Sciences, George Washington University Medical Faculty Associates, Washington, D.C. 2. Translational Medicine, MedImmune LLC, Gaithersburg, Maryl. 3. Department of Statistics, AstraZeneca, Gaithersburg, Maryland. 4. Department of Medical Affairs, AstraZeneca, Wilmington, Delaware.
Abstract
BACKGROUND:Benralizumab is a humanized, afucosylated, monoclonal antibody that targets interleukin-5 receptor alpha and induces direct, rapid, and nearly complete depletion of eosinophils via enhanced antibody-dependent cell-mediated cytotoxicity. In the United States, benralizumab is indicated for add-on maintenance treatment of patients ≥12 years old with severe asthma and an eosinophilic phenotype. OBJECTIVE: This study evaluated the effect of benralizumab treatment on seasonal asthma exacerbation rates for patients with severe, uncontrolled asthma. METHODS: This was a post hoc analysis of pooled data from the phase III SIROCCO (ClinicalTrials.gov identifier: NCT01928771) and CALIMA (NCT01914757) trials. The primary analysis population was patients ages 12-75 years treated with high-dosage inhaled corticosteroids and long-acting beta-2 agonists who had baseline blood eosinophil counts of ≥300 cells/μL. Patients received benralizumab 30 mg subcutaneously every 4 weeks or every 8 weeks (the first three doses every 4 weeks) or placebo every 4 weeks. Crude exacerbation rates (asthma exacerbations per patient-year) were determined for each month and season. Marginal asthma exacerbation rates and exacerbation rate ratios were estimated by season or month by using a negative binomial model that included covariates for study code, treatment, region, use of maintenance oral corticosteroids, and number of exacerbations in the previous year. Hemispheric seasons were accounted for by normalizing the study site locations. RESULTS: Observed crude exacerbation rates were higher in the fall and winter than in the spring and summer for all the patients. For the patients who received placebo, benralizumab every 4 weeks, and benralizumab every 8 weeks, crude exacerbation rates were the following: fall, 1.52, 0.86, and 0.81, respectively; winter, 1.44, 0.91, and 0.82, respectively; spring, 1.11, 0.66, and 0.52, respectively; and summer, 1.02, 0.55, and 0.51, respectively. Rate reductions in seasonal marginal annual exacerbation rates were 37-50% versus placebo at each season (p < 0.001). CONCLUSION:Benralizumab significantly and consistently reduced asthma exacerbations across all seasons versus placebo for patients with severe, uncontrolled eosinophilic asthma.
RCT Entities:
BACKGROUND:Benralizumab is a humanized, afucosylated, monoclonal antibody that targets interleukin-5 receptor alpha and induces direct, rapid, and nearly complete depletion of eosinophils via enhanced antibody-dependent cell-mediated cytotoxicity. In the United States, benralizumab is indicated for add-on maintenance treatment of patients ≥12 years old with severe asthma and an eosinophilic phenotype. OBJECTIVE: This study evaluated the effect of benralizumab treatment on seasonal asthma exacerbation rates for patients with severe, uncontrolled asthma. METHODS: This was a post hoc analysis of pooled data from the phase III SIROCCO (ClinicalTrials.gov identifier: NCT01928771) and CALIMA (NCT01914757) trials. The primary analysis population was patients ages 12-75 years treated with high-dosage inhaled corticosteroids and long-acting beta-2 agonists who had baseline blood eosinophil counts of ≥300 cells/μL. Patients received benralizumab 30 mg subcutaneously every 4 weeks or every 8 weeks (the first three doses every 4 weeks) or placebo every 4 weeks. Crude exacerbation rates (asthma exacerbations per patient-year) were determined for each month and season. Marginal asthma exacerbation rates and exacerbation rate ratios were estimated by season or month by using a negative binomial model that included covariates for study code, treatment, region, use of maintenance oral corticosteroids, and number of exacerbations in the previous year. Hemispheric seasons were accounted for by normalizing the study site locations. RESULTS: Observed crude exacerbation rates were higher in the fall and winter than in the spring and summer for all the patients. For the patients who received placebo, benralizumab every 4 weeks, and benralizumab every 8 weeks, crude exacerbation rates were the following: fall, 1.52, 0.86, and 0.81, respectively; winter, 1.44, 0.91, and 0.82, respectively; spring, 1.11, 0.66, and 0.52, respectively; and summer, 1.02, 0.55, and 0.51, respectively. Rate reductions in seasonal marginal annual exacerbation rates were 37-50% versus placebo at each season (p < 0.001). CONCLUSION:Benralizumab significantly and consistently reduced asthma exacerbations across all seasons versus placebo for patients with severe, uncontrolled eosinophilic asthma.
Authors: Jean-Pierre Llanos; Hector Ortega; Michael Bogart; Elizabeth R Packnett; Janna Manjelievskaia; Christopher F Bell; Beth Hahn Journal: J Asthma Allergy Date: 2020-01-29