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.
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Longitudinal Blood Eosinophil Counts and Eosinophilic Immune Dysfunction Among Placebo Patients with Severe Asthma from Phase 3 Benralizumab Studies
Session Title
TP10 - TP010 CLINICAL AND POPULATION-LEVEL STUDIES OF ASTHMA
Abstract
A1469 - Longitudinal Blood Eosinophil Counts and Eosinophilic Immune Dysfunction Among Placebo Patients with Severe Asthma from Phase 3 Benralizumab Studies
Author Block: E. Bleecker1, X. Li1, D. A. Meyers1, H. Li1, P. Newbold2, J. Kwiatek2, I. Hirsch2, R. Katial3, D. Billheimer4; 1University of Arizona College of Medicine, Tucson, AZ, United States, 2Global Medical Respiratory, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States, 3Global Medical Respiratory, BioPharmaceuticals R&D, AstraZeneca, Denver, CO, United States, 4University of Arizona College of Public Health, Tucson, AZ, United States.
Rationale: Activated eosinophils contribute to asthma pathobiology, and eosinophilic immune dysfunction (EID) can play a crucial role in persistent inflammatory disease mechanisms. Blood eosinophil count (BEC) variability and EID among patients with severe asthma are not well understood. We conducted a post-hoc, longitudinal, pooled analysis of phase 3 benralizumab clinical studies to assess the variability of BEC and EID for patients with severe asthma. Methods: Data from placebo patients in the randomized, double-blind, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies, which included patients with severe asthma who were supplied standardized high-dosage inhaled corticosteroids plus long-acting β2-agonists (ICS/LABA) (2/3 had BEC>300 at baseline), were analyzed for BEC variability over 56 weeks. Eosinophils (EOS) were measured up to six times throughout the study (baseline [Week 0], and Weeks 4, 8, 24, 40, and 56) in a centralized clinical laboratory. Longitudinal analysis of EOS variability was conducted using multiple BEC measurements over 1 year for all placebo patients on standardized ICS/LABA therapy not seen or treated during an acute asthma exacerbation. BEC variability was assessed based on consistent-low (<300 cells/μL), consistent-high (≥300 cells/μL), and variable BEC (<80% similar BEC measurements). Results: Of the 718 placebo patients, the highest percentage had consistent-high BEC (42.2% [n=303]), followed by consistent-low BEC (30.9% [n=222]) and variable BEC (26.9% [n=193]). Baseline demographics were similar between groups (Table). Age of asthma onset was lowest in the variable group. History of nasal polyposis was more common in the consistent-high (28%) and variable (18%) compared with the consistent-low BEC (9%) group. Annual prospective exacerbation rates were significantly lower in the consistent-low BEC group (1.05) compared with the variable BEC group (1.41) or the consistent-high BEC group (1.39). Change from baseline in lung function and ACQ-6 was similar between the consistent-high and variable groups compared with the consistent-low group. Conclusions: Patients with severe asthma were over-recruited across baseline BEC in the benralizumab phase 3 clinical trials. In those receiving placebo, 42% had consistent-high BEC of ≥300 cells/μL with 27% with variable BEC and 31% with consistent-low BEC. Thus, 73% of patients had relatively stable BEC measures over time. Patients in the consistent-high and variable BEC groups had significantly more asthma exacerbations compared with the consistent-low BEC group, although all patients were on standardized ICS/LABA. Thus, patients with asthma with intermittently elevated BEC levels had similar exacerbation frequencies over time as those with persistently elevated BEC levels.
Author Block: E. Bleecker1, X. Li1, D. A. Meyers1, H. Li1, P. Newbold2, J. Kwiatek2, I. Hirsch2, R. Katial3, D. Billheimer4; 1University of Arizona College of Medicine, Tucson, AZ, United States, 2Global Medical Respiratory, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States, 3Global Medical Respiratory, BioPharmaceuticals R&D, AstraZeneca, Denver, CO, United States, 4University of Arizona College of Public Health, Tucson, AZ, United States.
Rationale: Activated eosinophils contribute to asthma pathobiology, and eosinophilic immune dysfunction (EID) can play a crucial role in persistent inflammatory disease mechanisms. Blood eosinophil count (BEC) variability and EID among patients with severe asthma are not well understood. We conducted a post-hoc, longitudinal, pooled analysis of phase 3 benralizumab clinical studies to assess the variability of BEC and EID for patients with severe asthma. Methods: Data from placebo patients in the randomized, double-blind, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies, which included patients with severe asthma who were supplied standardized high-dosage inhaled corticosteroids plus long-acting β2-agonists (ICS/LABA) (2/3 had BEC>300 at baseline), were analyzed for BEC variability over 56 weeks. Eosinophils (EOS) were measured up to six times throughout the study (baseline [Week 0], and Weeks 4, 8, 24, 40, and 56) in a centralized clinical laboratory. Longitudinal analysis of EOS variability was conducted using multiple BEC measurements over 1 year for all placebo patients on standardized ICS/LABA therapy not seen or treated during an acute asthma exacerbation. BEC variability was assessed based on consistent-low (<300 cells/μL), consistent-high (≥300 cells/μL), and variable BEC (<80% similar BEC measurements). Results: Of the 718 placebo patients, the highest percentage had consistent-high BEC (42.2% [n=303]), followed by consistent-low BEC (30.9% [n=222]) and variable BEC (26.9% [n=193]). Baseline demographics were similar between groups (Table). Age of asthma onset was lowest in the variable group. History of nasal polyposis was more common in the consistent-high (28%) and variable (18%) compared with the consistent-low BEC (9%) group. Annual prospective exacerbation rates were significantly lower in the consistent-low BEC group (1.05) compared with the variable BEC group (1.41) or the consistent-high BEC group (1.39). Change from baseline in lung function and ACQ-6 was similar between the consistent-high and variable groups compared with the consistent-low group. Conclusions: Patients with severe asthma were over-recruited across baseline BEC in the benralizumab phase 3 clinical trials. In those receiving placebo, 42% had consistent-high BEC of ≥300 cells/μL with 27% with variable BEC and 31% with consistent-low BEC. Thus, 73% of patients had relatively stable BEC measures over time. Patients in the consistent-high and variable BEC groups had significantly more asthma exacerbations compared with the consistent-low BEC group, although all patients were on standardized ICS/LABA. Thus, patients with asthma with intermittently elevated BEC levels had similar exacerbation frequencies over time as those with persistently elevated BEC levels.
