Seasonal variability of exacerbations of severe, uncontrolled eosinophilic asthma and clinical benefits of benralizumab
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.
This study evaluated the effect of benralizumab treatment on seasonal asthma exacerbation rates for patients with severe, uncontrolled asthma.
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.
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).
Benralizumab significantly and consistently reduced asthma exacerbations across all seasons versus placebo for patients with severe, uncontrolled eosinophilic asthma.
Document Type: Research Article
Affiliations: 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
Publication date: September 1, 2018
This article was made available online on August 4, 2018 as a Fast Track article with title: "Seasonal variability of exacerbations of severe, uncontrolled eosinophilic asthma and clinical benefits of benralizumab ".
- Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.
The goal of the Proceedings is to publish articles with a predominantly clinical focus which directly impact quality of care for patients with allergic disease and asthma and by having the potential to directly impact the quality of patient care. AAP welcomes the submission of original works including peer-reviewed original research and clinical trial results. Additionally, as the official journal of the Eastern Allergy Conference (EAC), AAP will publish content from EAC poster sessions as well as review articles derived from EAC lectures.
Featured topics include asthma, rhinitis, sinusitis, food allergies, allergic skin diseases, diagnostic techniques, allergens, and treatment modalities. Published material includes peer-reviewed original research, clinical trials and review articles.
Articles marked "F" offer free full text for personal noncommercial use only.
The journal is indexed in Thomson Reuters Web of Science and Science Citation Index Expanded, plus the National Library of Medicine's PubMed service.
- Editorial Board
- Information for Authors
- Submit a Paper
- Information for Advertisers
- Reprint Requests
- Commercial level: Permission to use content
- Ingenta Connect is not responsible for the content or availability of external websites