ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
Search Tips:
- Use the keyword search to search by keyword or author's name.
- Filter your search results by selecting the checkboxes that apply.
- Click on "Clear" to clear the form and start a new search. .
Search results will display below the form.
Eosinophil as a Biomarker of Severity and Clinically Important Asthma Outcomes in Benralizumab Phase III Studies
Session Title
TP10 - TP010 CLINICAL AND POPULATION-LEVEL STUDIES OF ASTHMA
Abstract
A1468 - Eosinophil as a Biomarker of Severity and Clinically Important Asthma Outcomes in Benralizumab Phase III Studies
Author Block: R. Katial1, I. Hirsch2, P. Barker3, E. Garcia Gil4, F. Hoyte5; 1BioPharmaceuticals, Medical, Respiratory & Immunology, AstraZeneca, Denver, CO, United States, 2BioPharmaceuticals, Medical, Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, United States, 3BioPharmaceuticals, Medical, Respiratory & Immunology, AstraZeneca, Cambridge, United Kingdom, 4BioPharmaceuticals Medical, Respiratory & Immunology, Astrazeneca, Barcelona, Spain, 5Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO, United States.
Rationale: A post-hoc, pooled analysis of Phase III clinical studies on benralizumab, an interleukin (IL)-5 receptor alpha-directed cytolytic monoclonal antibody, was conducted to describe baseline characteristics of subjects with treatment responses in different asthma outcome criteria. Methods: Data from randomized, double-blind, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) clinical studies were analyzed for overall treatment response for 48 and 56 weeks, respectively, relating to baseline patient demographics and characteristics. In the studies, patients aged 12-75 years with severe asthma and prescribed high-dosage inhaled corticosteroids plus long-acting β2-agonists (ICS/LABA) received benralizumab or placebo. A post-hoc analysis of overall asthmatic-treatment response based on predetermined response criteria was conducted on the pooled group taking benralizumab 30 mg Q8W, receiving high-dosage ICS, having ≥2 asthma exacerbations in the past year, and a blood eosinophil count (BEC) ≥300 cells/µL (n=506). Post-hoc response criteria included: asthma exacerbation risk (reduced by ≥50%); change from baseline in Asthma Control Questionnaire-6 ([ACQ-6] ≤-0.5), FEV1 (≥100 mL), Standardized Asthma Quality of Life Questionnaire (≥0.5), and Total Asthma Symptom score (≤-0.5); and proportion of nights with awakenings requiring asthma rescue medication (≥50% reduction from baseline). Baseline demographics and characteristics were assessed for patients meeting the 3 key response criteria (exacerbation + ACQ-6 and/or FEV1). Results: BEC (726.5 cells/µL) was substantially higher in the 35.1% (n=178) of individuals meeting all 3 key response criteria (exacerbations, FEV1, ACQ-6) than in the 7.5% (n=38) of patients responding to exacerbation criteria only (466.5 cells/µL). A greater percentage of patients meeting all 3 key response criteria reported ≥3 exacerbations (50.6% vs. 18.4%), OCS use (19.7% vs. 10.5%), and nasal polyps (29.2% vs. 15.8%) compared with patients responding to exacerbation criteria only (29.2% vs. 15.8%). Other baseline measures, including IgE, BMI, and ACQ-6, were similar for key criteria groups (Table). When considering additional PROs as response criteria, 56.9% (n=288) responded on 4 or more criteria. Conclusions: In this post-hoc analysis of patients treated with benralizumab, those with characteristics of more severe disease and demonstrating response on 3 criteria (exacerbations, FEV1, ACQ-6) had substantially higher BEC, suggesting that BEC is an effective biomarker reflecting baseline severity and a marker associated with responses on multiple outcomes. Additionally, a large percentage of patients demonstrated improvement in outcomes beyond traditional measures of exacerbations, lung function, and ACQ, but included other symptom-based PROs, indicating that treatment with benralizumab improves asthma in multiple clinically important elements of the disease.
Author Block: R. Katial1, I. Hirsch2, P. Barker3, E. Garcia Gil4, F. Hoyte5; 1BioPharmaceuticals, Medical, Respiratory & Immunology, AstraZeneca, Denver, CO, United States, 2BioPharmaceuticals, Medical, Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, United States, 3BioPharmaceuticals, Medical, Respiratory & Immunology, AstraZeneca, Cambridge, United Kingdom, 4BioPharmaceuticals Medical, Respiratory & Immunology, Astrazeneca, Barcelona, Spain, 5Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO, United States.
Rationale: A post-hoc, pooled analysis of Phase III clinical studies on benralizumab, an interleukin (IL)-5 receptor alpha-directed cytolytic monoclonal antibody, was conducted to describe baseline characteristics of subjects with treatment responses in different asthma outcome criteria. Methods: Data from randomized, double-blind, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) clinical studies were analyzed for overall treatment response for 48 and 56 weeks, respectively, relating to baseline patient demographics and characteristics. In the studies, patients aged 12-75 years with severe asthma and prescribed high-dosage inhaled corticosteroids plus long-acting β2-agonists (ICS/LABA) received benralizumab or placebo. A post-hoc analysis of overall asthmatic-treatment response based on predetermined response criteria was conducted on the pooled group taking benralizumab 30 mg Q8W, receiving high-dosage ICS, having ≥2 asthma exacerbations in the past year, and a blood eosinophil count (BEC) ≥300 cells/µL (n=506). Post-hoc response criteria included: asthma exacerbation risk (reduced by ≥50%); change from baseline in Asthma Control Questionnaire-6 ([ACQ-6] ≤-0.5), FEV1 (≥100 mL), Standardized Asthma Quality of Life Questionnaire (≥0.5), and Total Asthma Symptom score (≤-0.5); and proportion of nights with awakenings requiring asthma rescue medication (≥50% reduction from baseline). Baseline demographics and characteristics were assessed for patients meeting the 3 key response criteria (exacerbation + ACQ-6 and/or FEV1). Results: BEC (726.5 cells/µL) was substantially higher in the 35.1% (n=178) of individuals meeting all 3 key response criteria (exacerbations, FEV1, ACQ-6) than in the 7.5% (n=38) of patients responding to exacerbation criteria only (466.5 cells/µL). A greater percentage of patients meeting all 3 key response criteria reported ≥3 exacerbations (50.6% vs. 18.4%), OCS use (19.7% vs. 10.5%), and nasal polyps (29.2% vs. 15.8%) compared with patients responding to exacerbation criteria only (29.2% vs. 15.8%). Other baseline measures, including IgE, BMI, and ACQ-6, were similar for key criteria groups (Table). When considering additional PROs as response criteria, 56.9% (n=288) responded on 4 or more criteria. Conclusions: In this post-hoc analysis of patients treated with benralizumab, those with characteristics of more severe disease and demonstrating response on 3 criteria (exacerbations, FEV1, ACQ-6) had substantially higher BEC, suggesting that BEC is an effective biomarker reflecting baseline severity and a marker associated with responses on multiple outcomes. Additionally, a large percentage of patients demonstrated improvement in outcomes beyond traditional measures of exacerbations, lung function, and ACQ, but included other symptom-based PROs, indicating that treatment with benralizumab improves asthma in multiple clinically important elements of the disease.
