Clinical Implications of Longitudinal Blood Eosinophil Counts in Patients With Severe Asthma

BackgroundThe stability and variability of blood eosinophil counts (BECs) to phenotype patients with severe asthma is not fully understood.ObjectiveThis post hoc, longitudinal, pooled analysis of placebo-arm patients from 2 phase 3 studies evaluated the clinical implications of BEC stability and variability in moderate-to-severe asthma.MethodsThis analysis included patients from SIROCCO and CALIMA who received maintenance medium- to high-dosage inhaled corticosteroids plus long-acting β2-agonists; 2:1 patients with BECs of 300 cells/μL or higher and less than 300 cells/μL were enrolled. The BECs were measured 6 times over 1 year in a centralized laboratory. Exacerbations, lung function, and Asthma Control Questionnaire 6 scores were documented across patients grouped by BEC (<300 cells/μL or ≥300 cells/μL) and variability (<80% or ≥80% BECs less than or greater than 300 cells/μL).ResultsAmong 718 patients, 42.2% (n = 303) had predominantly high, 30.9% (n = 222) had predominantly low, and 26.9% (n = 193) had variable BECs. Prospective exacerbation rates (mean ± SD) were significantly greater in patients with predominantly high (1.39 ± 2.20) and variable (1.41 ± 2.09) BECs versus predominantly low (1.05 ± 1.66) BECs. Similar results were observed for the number of exacerbations while on placebo.ConclusionsAlthough patients with variable BECs had intermittently high and low BECs, they experienced similar exacerbation rates to the predominantly high group, which were greater than those in the predominantly low group. A high BEC supports an eosinophilic phenotype in clinical settings without additional measurements, whereas a low BEC requires repeated measurements because it could reflect intermittently high or predominantly low BECs. The stability and variability of blood eosinophil counts (BECs) to phenotype patients with severe asthma is not fully understood. This post hoc, longitudinal, pooled analysis of placebo-arm patients from 2 phase 3 studies evaluated the clinical implications of BEC stability and variability in moderate-to-severe asthma. This analysis included patients from SIROCCO and CALIMA who received maintenance medium- to high-dosage inhaled corticosteroids plus long-acting β2-agonists; 2:1 patients with BECs of 300 cells/μL or higher and less than 300 cells/μL were enrolled. The BECs were measured 6 times over 1 year in a centralized laboratory. Exacerbations, lung function, and Asthma Control Questionnaire 6 scores were documented across patients grouped by BEC (<300 cells/μL or ≥300 cells/μL) and variability (<80% or ≥80% BECs less than or greater than 300 cells/μL). Among 718 patients, 42.2% (n = 303) had predominantly high, 30.9% (n = 222) had predominantly low, and 26.9% (n = 193) had variable BECs. Prospective exacerbation rates (mean ± SD) were significantly greater in patients with predominantly high (1.39 ± 2.20) and variable (1.41 ± 2.09) BECs versus predominantly low (1.05 ± 1.66) BECs. Similar results were observed for the number of exacerbations while on placebo. Although patients with variable BECs had intermittently high and low BECs, they experienced similar exacerbation rates to the predominantly high group, which were greater than those in the predominantly low group. A high BEC supports an eosinophilic phenotype in clinical settings without additional measurements, whereas a low BEC requires repeated measurements because it could reflect intermittently high or predominantly low BECs.