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Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma.

ABSTRACT: 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 ?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·?L-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·?L-1Baseline clinical factors and blood eosinophil counts can help identify patients potentially responsive to benralizumab.

SUBMITTER: Bleecker ER

PROVIDER: S-EPMC6203407 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma.

Bleecker Eugene R ER Wechsler Michael E ME FitzGerald J Mark JM Menzies-Gow Andrew A Wu Yanping Y Hirsch Ian I Goldman Mitchell M Newbold Paul P Zangrilli James G JG

The European respiratory journal 20181018 4

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, uncon ...[more]

PMID: 30139780

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Project description:PurposeIn the Phase III SIROCCO trial (NCT01928771), benralizumab significantly reduced asthma exacerbations and improved lung function and symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate efficacy and safety of benralizumab for Korean patients in SIROCCO.MethodsSIROCCO was a randomized, double-blind, parallel-group, placebo-controlled trial of 1,204 patients aged 12-75 years with severe asthma uncontrolled by high-dosage inhaled corticosteroids/long-acting β₂-agonists (ICS/LABA). Patients received benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W) or placebo Q4W for 48 weeks. The primary analysis population comprised patients with blood eosinophil counts ≥ 300 cells/μL. This subgroup analysis evaluated Korean patients from this group.ResultsOf 122 Korean patients randomized, 86 had blood eosinophil counts ≥ 300 cells/μL. Benralizumab reduced the annual asthma exacerbation rate by 70% (Q4W: rate estimate 0.79, rate ratio 0.30 [95% confidence interval {CI}, 0.13-0.65], nominal P = 0.003; n = 28) and 85% (Q8W: rate estimate 0.40, rate ratio 0.15 [95% CI, 0.06-0.36], nominal P < 0.001; n = 30) vs. placebo (rate estimate 2.67, n = 28). Prebronchodilator forced expiratory volume in 1 second was increased with benralizumab treatment by 0.270 L (Q4W: 95% CI, 0.039-0.500, nominal P = 0.023; n = 28) and 0.362 L (Q8W: 95% CI, 0.143-0.582, nominal P = 0.002; n = 30) vs. placebo (n = 27). Total asthma symptom score was similar for patients receiving either benralizumab Q4W (-0.27 [95% CI, -0.83 to 0.30], nominal P = 0.356; n = 27) or benralizumab Q8W (0.10 [95% CI, -0.44 to 0.65], nominal P = 0.708; n = 30) vs. placebo (n = 28). Drug-related adverse events were experienced by 2%, 8%, and 5% of patients in the placebo, benralizumab Q4W, and benralizumab Q8W arms.ConclusionsBenralizumab reduced annual asthma exacerbation rates, increased lung function, and was well-tolerated by Korean patients with severe, uncontrolled eosinophilic asthma.

Project description: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.

Project description:IntroductionFor 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.MethodsAnalyses 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.ResultsExacerbation 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.ConclusionBaseline 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 registrationClinicalTrials.gov: SIROCCO, NCT01928771; CALIMA, NCT01914757.

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Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma.

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Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma.

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