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Background: An improved understanding of how severe asthma heterogeneity affects response could inform treatment decisions., Objectives: Characterize heterogeneity and benralizumab responsiveness in patients grouped by predefined Severe Asthma Research Program clusters using a multivariate approach., Methods: In post-hoc analyses of the randomized, double-blind, placebo-controlled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies, patients with severe asthma who received benralizumab or placebo were assigned to clusters using an established discriminant function to analyze 11 clinical characteristics simultaneously. The annualized asthma exacerbation rate, exacerbation incidence, and lung function were analyzed across clusters., Results: Patients (n = 2,281) met criteria for four of five clusters: cluster 2 (early-onset moderate asthma, n = 393), cluster 4 (early-onset severe asthma, n = 386), cluster 3 (late-onset severe asthma, n = 641), and cluster 5 (late-onset severe, obstructed asthma, n = 861); no patients met cluster 1 criteria. Exacerbation rate reductions were significant in late-onset severe asthma (-48% [95% CI, -61% to -31%]; P < .0001) and late-onset severe, obstructed asthma (-50% [95% CI, -59% to -38%]; P < .0001), with nonsignificant reductions in early-onset clusters. These differences could not be fully explained by blood eosinophil count differences. Values for improvements in FEV 1 were significant in late-onset severe asthma (+133 mL [95% CI, 66-200]; P = .0001) and late-onset severe, obstructed asthma (+160 mL [95% CI, 85-235]; P < .0001) while maintaining acute bronchodilator responsiveness., Conclusions: Benralizumab reduced exacerbations and improved lung function, primarily in late-onset asthma clusters. This multivariate approach to identify subphenotypes, potentially reflecting pathobiological mechanisms, can guide therapy beyond univariate approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The stability and variability of blood eosinophil counts (BECs) to phenotype patients with severe asthma is not fully understood., Objective: 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., Methods: This analysis included patients from SIROCCO and CALIMA who received maintenance medium- to high-dosage inhaled corticosteroids plus long-acting β 2 -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)., Results: 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., Conclusions: 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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Benralizumab is an IL-5 receptor alpha-directed cytolytic mAb that depletes eosinophils, reducing exacerbations and oral corticosteroid (OCS) use, and improves asthma control for patients with severe eosinophilic asthma (SEA). Data on response in patients previously treated with other biologic therapies are limited., Objective: To describe real-world clinical outcomes with benralizumab for patients with and without prior biologic use for uncontrolled SEA., Methods: This retrospective study compared clinical outcomes before and after benralizumab initiation in adults with uncontrolled SEA with 3 or more asthma exacerbations in the previous 12 months or on maintenance OCS treatment. Outcomes included exacerbations, OCS use, patient-reported outcomes, and health care resource utilization, including emergency department visits and hospitalizations., Results: In all, 208 patients were enrolled, including 90 (43.3%) with previous experience with an alternate biologic for SEA. Benralizumab led to an 81% reduction in exacerbation rate, with 48% of patients with previous exacerbations experiencing none after 48 weeks. Overall, 67% of patients requiring baseline maintenance OCS achieved greater than or equal to 50% reduction in daily OCS dosage, and 53% eliminated maintenance OCS. Clinically meaningful improvements in patient-reported outcomes were seen, with response at 4 weeks predicting longer-term benefits. Health care resource utilization also decreased. Improvements were observed irrespective of previous biologic experience, fractional exhaled nitric oxide concentrations, atopic status, or other baseline characteristics., Conclusions: In a multicenter real-world setting, patients with uncontrolled SEA achieved substantial improvements in all clinical outcome measures with benralizumab irrespective of previous biologic use, atopic status, or baseline fractional exhaled nitric oxide concentration., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Greater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients with severe, uncontrolled asthma., Methods: Data were pooled from seven similarly designed phase II and III randomised controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualised asthma exacerbation rates (AAERs) for patients randomised to placebo were assessed by baseline clinical characteristics, and by biomarker concentrations at baseline and over the study duration., Results: The AAER for the 2016 patients in the combined placebo group was 0.91 (95% CI 0.84‒0.98). Baseline characteristics associated with greater AAER were frequent or severe exacerbations within the prior 12 months, nasal polyposis, maintenance oral corticosteroid use, Asian race and Asian or Western European region. AAER increased with baseline blood eosinophil counts and exhaled nitric oxide fraction ( F ENO ) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL -1 and F ENO ≥50 ppb. No relationship was observed between baseline serum IgE concentration and AAER. Combining type 2 inflammation criteria for eosinophils and F ENO had greater prognostic value than either biomarker alone. Persistent eosinophil and F ENO elevations throughout the study period were associated with greater AAER., Conclusions: Exacerbation history, maintenance corticosteroid use, nasal polyposis, Asian race, geographic region, and elevations in blood eosinophil counts and F concentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.ENO concentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma., Competing Interests: Conflict of interest: M. Kraft reports grants from the National Institutes of Health, grants and consulting fees from Sanofi, grants from ALA, grants from Chiesi Farmaceutici, personal fees from Elsevier, grants and consulting fees from AstraZeneca. Conflict of interest: G. Brusselle has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer and Teva; and is a member of advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi/Regeneron and Teva. Conflict of interest: J.M. FitzGerald is an advisory board member for AstraZeneca, Boehringer Ingelheim, Novartis, Sanofi-Regeneron and Teva, and has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Novartis. Conflict of interest: I.D. Pavord has received speaker's honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine AB, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini and GlaxoSmithKline, and payments for organising educational events from AstraZeneca, GlaxoSmithKline, Sanofi/Regeneron and Teva; he has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Teva, Merck, Circassia, Chiesi and Knopp, and payments to support FDA approval meetings from GlaxoSmithKline; he has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Teva and Chiesi; he has received a grant from Chiesi to support a phase II clinical trial in Oxford; he is co-patent holder of the rights to the Leicester Cough Questionnaire, and has received payments for its use in clinical trials from Merck, Bayer and Insmed; in 2014–2015 he was an expert witness for a patent dispute involving AstraZeneca and Teva. Conflict of interest: M. Keith is an employee of AstraZeneca. Conflict of interest: M. Fagerås is an employee of AstraZeneca. Conflict of interest: E. Garcia Gil is an employee of AstraZeneca. Conflict of interest: I. Hirsch is an employee of AstraZeneca. Conflict of interest: M. Goldman is a former employee of AstraZeneca. Conflict of interest: G. Colice is an employee of AstraZeneca., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Blood eosinophil count (BEC) measurements are a noninvasive, relatively reliable surrogate marker for eosinophilic airway inflammation. Single measurements of peripheral BEC greater than or equal to 150 cells/μL predict the response to anti-eosinophil therapies for patients with characteristics of severe eosinophilic asthma., Objective: To describe how BECs shift over time for patients with severe, uncontrolled asthma receiving placebo in 2 large, randomized, placebo-controlled clinical trials of benralizumab (SIROCCO and CALIMA)., Methods: Our analysis included all adult patients who were randomized to placebo in the SIROCCO and CALIMA phase III benralizumab studies. Patients were categorized into baseline BEC groups of less than 150 cells/μL, greater than or equal to 150 cells/μL but less than 300 cells/μL, and greater than or equal to 300 cells/μL. The timing of the initial shift from baseline to a different group was evaluated at weeks 4, 8, 24, and 40 and at the end of treatment. Baseline characteristics, including oral corticosteroid use, were described based on the presence or absence of a BEC group shift., Results: Of the 734 evaluable patients, 65% (n = 474) shifted BEC groups during the study, and most patients (86% [n = 410]) shifted by week 24. Patients who started in the less than 150 cells/μL group tended to shift groups earlier, with 59% shifting by week 4 compared with 38% to 55% for other groups in the same time frame. Patients who shifted BEC groups vs those who did not tend to have lower BECs, more oral corticosteroid use, and less incidence of nasal polyps or past polypectomy., Conclusion: A single BEC measurement, particularly when low, may be inadequate to help establish a phenotype of severe eosinophilic asthma., Trial Registration: ClinicalTrials.gov Identifiers NCT01928771 (SIROCCO trial) and NCT01914757 (CALIMA trial)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: For patients with eosinophilic asthma with allergic characteristics, understanding the key drivers of exacerbations is important to identify optimal treatment strategies. Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that significantly reduces exacerbation frequency for patients with severe, uncontrolled eosinophilic asthma. We evaluated the predictive value of baseline blood eosinophil counts vs. serum immunoglobulin E (IgE) concentrations on exacerbation risk and the association of these variables with benralizumab treatment effect., Methods: Analyses were performed with data pooled from the phase III SIROCCO and CALIMA benralizumab trials. Crude annual asthma exacerbation rates (AERs) were determined for placebo as a function of baseline blood eosinophil counts and serum IgE concentrations with prespecified blood eosinophil count categories (< 150, ≥ 150 to < 300, ≥ 300 to < 450, ≥ 450 cells/µL) and IgE concentration quartiles (< 62.0, ≥ 62.0 to < 176.2, ≥ 176.2 to < 453.4, and ≥ 453.4 kU/L). We compared AERs for patients receiving benralizumab 30 mg every 8 weeks (first three doses every 4 weeks) vs. placebo for overlapping baseline blood eosinophil count categories and serum IgE concentration quartiles via a regression approach and by continuously using locally weighted regression smoothing analysis., Results: Exacerbation risk for patients with severe asthma receiving placebo increased with increasing baseline blood eosinophil counts but not with increasing serum IgE concentrations. Addition of baseline atopy status did not influence the relationship between IgE concentrations and exacerbation risk for patients receiving placebo. Patients with blood eosinophil counts ≥ 300 cells/µL had consistent decreases in exacerbation risk with benralizumab relative to placebo across all serum IgE concentration quartiles., Conclusion: Baseline blood eosinophil counts, but not serum IgE concentrations, are an important predictor of exacerbation risk. Patients with severe eosinophilic asthma treated with benralizumab had consistent reductions in exacerbation risk, regardless of IgE concentrations., Clinical Trial Registration: ClinicalTrials.gov: SIROCCO, NCT01928771; CALIMA, NCT01914757.

Background: Fixed airflow obstruction (FAO) is associated with severe eosinophilic asthma. Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody for patients with severe, uncontrolled eosinophilic asthma., Objective: We evaluated FAO influence on benralizumab treatment response., Methods: We performed a post hoc analysis of pooled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) data for patients with severe, uncontrolled asthma with baseline blood eosinophil counts of 300 or more cells/μL who received benralizumab 30 mg every 8 weeks or placebo. Demographics, baseline clinical characteristics, and treatment responses were evaluated by FAO status. FAO+ and FAO- were defined as ratios of postbronchodilator forced expiratory volume in 1 second (FEV 1 ) to forced vital capacity of less than 70% and 70% or more, respectively, at baseline., Results: FAO+ prevalence was 63% (935/1493). With benralizumab, similar annual asthma exacerbation rate (AER) reductions vs placebo were achieved for FAO+ and FAO- patients (rate ratio [95% confidence interval (CI)] = 0.56 [0.44-0.71] and 0.58 [0.41-0.83], respectively), whereas annual AER reductions associated with emergency department visits or hospitalizations were greater for FAO+ vs FAO- patients (rate ratio [95% CI] = 0.55 [0.33-0.91] and 0.70 [0.33-1.48], respectively). Prebronchodilator FEV 1 (95% CI) increase from baseline to end of treatment was greater for FAO+ vs FAO- patients receiving benralizumab compared with placebo (0.159 L [0.082-0.236] vs 0.103 L [-0.008 to 0.215]). Other lung function measures, patient-reported outcomes, and symptom improvements were also numerically greater for FAO+ vs FAO- patients., Conclusion: Benralizumab improved asthma control across several measures for patients with severe, uncontrolled eosinophilic asthma and FAO., Trial Registration: SIROCCO trial: NCT01928771 (URL: https://clinicaltrials.gov/ct2/show/NCT01928771) CALIMA trial: NCT01914757 (URL: https://clinicaltrials.gov/ct2/show/NCT01914757)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Benralizumab is a unique eosinophil-depleting monoclonal antibody that significantly reduces asthma exacerbations, improves lung function and asthma symptoms, and permits the reduction of maintenance oral corticosteroid dosage for patients with severe, uncontrolled eosinophilic asthma., Objective: To assess benralizumab's onset of action and efficacy by examining change in morning peak expiratory flow (PEF) after initiation of treatment in the phase 3 clinical trials SIROCCO, CALIMA, and ZONDA., Methods: Mixed-model repeated-measures analysis was used to calculate PEF using daily least squares mean changes from baseline in morning PEF as well as differences between the benralizumab every 8 weeks (first 3 doses every 4 weeks) and placebo groups. A Bayesian nonlinear mixed-effects approach with an exponential relationship was used to model trial data to determine time to clinically meaningful improvement in morning PEF (defined as ≥25 L/min)., Results: Least squares mean morning PEF improvement from baseline was numerically greater by Day 2 after initiation of benralizumab therapy in all 3 trials. The Bayesian nonlinear mixed-effects model indicated that PEF improvement reached the clinically meaningful threshold within 3 weeks in SIROCCO and CALIMA and 2 weeks in ZONDA., Conclusion: In 3 phase 3 randomized clinical trials, benralizumab provided notable improvement in morning PEF 2 days after initiation and clinically meaningful improvements within 3 weeks for patients with severe, uncontrolled eosinophilic asthma. The rapid improvement in PEF demonstrated in these trials suggests that benralizumab's unique mechanism of action rapidly improves lung function for patients with severe, eosinophilic asthma., Trial Registration: ClinicalTrials.gov Identifiers: NCT01928771 (SIROCCO), NCT01914757 (CALIMA), and NCT02075255 (ZONDA)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Benralizumab is an anti-eosinophilic monoclonal antibody that reduces exacerbations and improves lung function for patients with severe, uncontrolled asthma with eosinophilic inflammation. We evaluated the impact of baseline factors on benralizumab efficacy for patients with severe asthma.This analysis used pooled data from the SIROCCO (ClinicalTrials.gov identifier NCT01928771) and CALIMA (ClinicalTrials.gov identifier NCT01914757) Phase III studies. Patients aged 12-75 years with severe, uncontrolled asthma receiving high-dosage inhaled corticosteroids plus long-acting β 2 -agonists received benralizumab 30 mg subcutaneously every 8 weeks (Q8W, first three doses every 4 weeks (Q4W)), Q4W or placebo. Baseline factors that influenced benralizumab efficacy were evaluated, including oral corticosteroid (OCS) use, nasal polyposis, pre-bronchodilator forced vital capacity (FVC), prior year exacerbations and age at diagnosis. Efficacy outcomes included annual exacerbation rate and change in pre-bronchodilator forced expiratory volume in 1 s at treatment end relative to placebo.Benralizumab Q8W treatment effect was enhanced with each baseline factor for all patients and those with ≥300 eosinophils·μL -1 relative to the overall population. OCS use, nasal polyposis and FVC <65% of predicted were associated with greater benralizumab Q8W responsiveness for reduced exacerbation rate for patients with <300 eosinophils·μL -1 Baseline clinical factors and blood eosinophil counts can help identify patients potentially responsive to benralizumab., Competing Interests: Conflict of interest: E.R. Bleecker has performed clinical trials through his former employer, the Wake Forest School of Medicine, and his current employer, the University of Arizona; and has served as a paid consultant for AstraZeneca/MedImmune, Boehringer Ingelheim, GSK, Novartis, Regeneron and Sanofi-Genzyme. Conflict of interest: M.E. Wechsler received consulting honoraria from AstraZeneca, Boehringer Ingelheim, Genentech, GSK, Novartis, Regeneron, Sanofi and Teva. Conflict of interest: J.M. FitzGerald is an advisory board member for ALK, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Sanofi-Regeneron and Teva, and has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Cephalon/Teva, Forest, Genentech, GSK, Johnson and Johnson (Janssen), MedImmune, Novartis, Pfizer and Sanofi. Conflict of interest: A. Menzies-Gow has consultancy agreements with AstraZeneca and Vectura, was an advisory board member for AstraZeneca, Boehringer Ingelheim, GSK, Novartis and Teva, received speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Teva, and Vectura; has participated in research that his institution has been renumerated from Boehringer Ingelheim, GSK and Hoffman La Roche, and has attended international conferences sponsored by AstraZeneca and Boehringer Ingelheim. Conflict of interest: Y. Wu is an employee of AstraZeneca. Conflict of interest: I. Hirsch is an employee of AstraZeneca. Conflict of interest: M. Goldman is an employee of AstraZeneca. Conflict of interest: P. Newbold is an employee of MedImmune LLC. Conflict of interest: J.G. Zangrilli is an employee of AstraZeneca., (Copyright ©ERS 2018.)

Background: Patients with severe asthma can have eosinophilic inflammation and/or allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody indicated for add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype., Objective: To investigate the efficacy of benralizumab by atopic status and serum immunoglobulin E (IgE) concentrations., Methods: We analyzed pooled results from the SIROCCO (NCT01928771) and CALIMA (NCT01914757) phase III studies. Patients 12 to 75 years old with severe, uncontrolled asthma on high-dosage inhaled corticosteroids plus long-acting β 2 -agonists received 30 mg of subcutaneous benralizumab every 4 weeks or every 8 weeks (first 3 doses every 4 weeks) or placebo every 4 weeks. The analysis stratified patients who did and did not meet similar omalizumab-qualifying criteria of atopy and serum IgE levels 30 to 700 kU/L. Patients also categorized as having high serum IgE (≥150 kU/L) or low serum IgE (<150 kU/L) and as having atopy or no atopy. Efficacy outcomes were for all patients and by blood eosinophil counts and included annual exacerbation rate ratio and pre-bronchodilator forced expiratory volume in 1 second change at treatment end vs placebo., Results: Benralizumab every 8 weeks decreased exacerbations by 46% (95% confidence interval 26-61, P = .0002) and increased forced expiratory volume in 1 second by 0.125 L (95% confidence interval 0.018-0.232, P = .0218) vs placebo for patients with at least 300 eosinophils/μL who met the atopy and IgE criteria. For patients with eosinophilia and high or low IgE, treatment with benralizumab every 8 weeks resulted in 42% and 43% decreases in exacerbation rate (P ≤ .0004) and 0.123- and 0.138-L increases in forced expiratory volume in 1 second (P ≤ .0041) vs placebo, respectively., Conclusion: Benralizumab treatment decreased exacerbations and improved lung function for patients with severe, uncontrolled eosinophilic asthma regardless of serum IgE concentrations and atopy status., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Benralizumab is an anti-eosinophilic, anti-interleukin-5 receptor α monoclonal antibody that has been shown to significantly reduce asthma exacerbations and improve lung function for patients with severe, uncontrolled asthma. We further explored the efficacy of benralizumab for patients with different baseline blood eosinophil thresholds and exacerbation histories., Methods: This study is a pooled analysis of the results from the randomised, double-blind, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) phase 3 studies. In these studies, patients with severe, uncontrolled asthma were randomly assigned (1:1:1) to receive subcutaneous benralizumab 30 mg, either every 4 weeks or every 8 weeks (with first three doses given every 4 weeks), or placebo every 4 weeks. The primary endpoint was annual exacerbation rate (AER) ratio versus placebo, analysed by baseline eosinophil counts (≥0, ≥150, ≥300, or ≥450 cells per μL) and by number of exacerbations (two vs three or more) during the year before enrolment. The analyses were done in accordance with the intention-to-treat principle., Findings: Of 2295 patients, 756 received benralizumab every 4 weeks, 762 received benralizumab every 8 weeks, and 777 patients received placebo. AER among patients with baseline blood eosinophil counts of at least 0 cells per μL was 1·16 (95% CI 1·05-1·28) in patients who received placebo versus 0·75 (0·66-0·84) in patients who received benralizumab every 8 weeks (rate ratio 0·64, 0·55-0·75; p<0·0001). In patients who received benralizumab every 4 weeks who had eosinophil counts of 0 or more cells per μL, AER was 0·73 (0·65-0·82); rate ratio versus placebo was 0·63 (0·54-0·74; p<0·0001). The extent to which exacerbation rates were reduced increased with increasing blood eosinophil thresholds and with greater exacerbation history in patients in the 4-weekly and 8-weekly benralizumab groups. Greater improvements in AER were seen with benralizumab compared with placebo for patients with a combination of high blood eosinophil thresholds and a history of more frequent exacerbations., Interpretation: These results will help to guide clinicians when they are deciding whether to use benralizumab to treat patients with severe, uncontrolled, eosinophilic asthma., Funding: AstraZeneca., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Benralizumab, an anti-eosinophilic monoclonal antibody, in combination with high-dosage inhaled corticosteroids and long-acting β 2 -agonists (ICS/LABA), significantly reduced asthma exacerbations, improved lung function, and reduced symptoms for patients with severe, uncontrolled asthma with blood eosinophil counts ≥300 cells/μL in the Phase III SIROCCO and CALIMA studies. To understand the efficacy and safety of benralizumab for patients with eosinophil-driven disease with blood eosinophil counts lower than 300 cells/μL, we evaluated the effect of applying an eosinophil cutoff of ≥150 cells/μL., Methods: Adult patients with uncontrolled asthma despite high-dosage ICS/LABA ± additional asthma controller(s) received subcutaneous benralizumab 30 mg every 8 weeks (Q8W; first three doses every 4 weeks) or placebo for 48 (SIROCCO) or 56 (CALIMA) weeks. Efficacy measures including annual exacerbation rate, prebronchodilator FEV 1 , and total asthma symptom score were analyzed by baseline blood eosinophil counts ≥150 vs. <150 cells/μL., Results: Benralizumab reduced asthma exacerbation rates by 42% in SIROCCO (rate ratio = 0.58; 95% CI = 0.46-0.74; p < 0.001; n = 325) and 36% in CALIMA (rate ratio = 0.64; 95% CI = 0.50-0.81; p < 0.001; n = 300) vs. placebo (n = 306 for SIROCCO, n = 315 for CALIMA) for patients with blood eosinophil counts ≥150 cells/μL. Benralizumab increased prebronchodilator FEV 1 (both studies, p ≤ 0.002) and improved total asthma symptom score in SIROCCO (p = 0.009) at end of treatment vs. placebo for patients with blood eosinophil counts ≥150 cells/μL. The overall adverse events frequency was similar between treatment groups and eosinophil count cohorts., Conclusion: These results support the efficacy and safety of benralizumab for patients with severe asthma and blood eosinophil counts ≥150 cells/μL.

Background: Patients with severe, uncontrolled asthma experience debilitating symptoms that result in meaningful reductions to health-related quality of life. Benralizumab is an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody that reduces exacerbations and improves asthma symptoms for patients with severe, uncontrolled eosinophilic asthma. Objective: The objective of this study was to evaluate improvements in daily asthma-related health status outcomes following treatment with benralizumab. Methods: Pooled results from the SIROCCO (NCT01928771) and CALIMA (NCT01914757) Phase III studies were analyzed. Patients aged 12–75 years with severe, uncontrolled asthma, and blood eosinophil counts (BEC) ≥300 and ≥150 cells/µL were evaluated. Patients received subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W, first three doses Q4W) or placebo and completed a daily diary reporting rescue medication use, night-time awakening requiring rescue medication use, perceived tiredness, and asthma-related activity impairment. Outcome measures were compared across treatment arms from baseline to end of treatment (EOT) using a mixed-effect model for repeated measures analyses. Results: Patients with BEC ≥300 cells/µL receiving benralizumab Q8W had greater improvements in all patient-reported outcomes at EOT relative to baseline than patients receiving placebo (all nominal P≤0.013). Effects were reported as early as 3 days following the initial dose and sustained throughout treatment for daily and night-time rescue medication use and night-time awakenings requiring rescue medication. For patients with BEC ≥300 and ≥150 cells/µL, sustained improvements in activity impairment items (all nominal P<0.05) were achieved with benralizumab Q8W at week 2. Conclusion: Benralizumab produces sustained reductions by as early as 3 days in rescue medication use and activity impairment for patients with severe, uncontrolled eosinophilic asthma. [ABSTRACT FROM AUTHOR]

B PURPOSE: b We previously reported shifts in blood eosinophil count (BEC) group with repeated BEC measurements for individual patients with asthma (Ann Allergy Asthma Immunol 2018;121[Suppl 5]:S39-40). Patients with OCS use also have a greater tendency to shift to a different BEC group regardless of BEC baseline values. [Extracted from the article]