血清IgE浓度预测重度嗜酸性粒细胞哮喘患者恶化风险的能力和Benralizumab疗效
2022/02/28
摘要
引言：对于具有过敏特征的嗜酸性粒细胞性哮喘患者，了解发作的关键驱动因素对于确定最佳治疗策略非常重要。Benralizumab是一种IL5受体α导向的细胞溶解性单克隆抗体，可显著降低严重、不受控制的嗜酸性粒细胞性哮喘患者的恶化频率。我们评估了基线血嗜酸性粒细胞计数与血清免疫球蛋白E（IgE）浓度对加重风险的预测价值，以及这些变量与benralizumab治疗效果的相关性。
方法：使用Ⅲ期SIROCCO和CALIMA benralizumab 试验的数据进行分析，根据基线血液嗜酸性粒细胞计数和血清IgE浓度，使用预先设定的血液嗜酸性粒细胞计数类别（＜150，≥150至＜300，≥300至＜450，≥450个细胞/ul），确定安慰剂的哮喘急性发作率（AERs）。和IgE浓度四分位数（＜62，≥62至＜176.2，大于等于176.2至＜453.4，≥453.4ku/L）。我们通过回归方法和连续使用局部加权回归平滑分析，比较了接受Benralizumab 30mg每8周（前3次每4周给药）的患者与安慰剂的AERs与基线血嗜酸性粒细胞计数类别和血清IgE浓度四分位数的重叠情况。
结果：接受安慰剂的重度哮喘患者的恶化风险随着基线血嗜酸性粒细胞计数的增加而增加，但随着血清IgE浓度的增加而不增加。基线特应性状态的增加不影响接受安慰剂的患者IgE浓度和恶化风险之间的关系。在所有血清IgE浓度四分位数中，血液嗜酸性粒细胞计数≥300个/ul的患者与安慰剂相比，benralizamab的家中风险持续降低。
结论：基线血嗜酸性粒细胞计数，而不是血清IgE浓度，是恶化风险的重要预测因子。无论IgE浓度如何，接受benralizumab治疗的重度嗜酸性粒细胞性哮喘患者的恶化风险均持续降低。
Ability of Serum IgE Concentration to Predict Exacerbation Risk and Benralizumab Efficacy for Patients with Severe Eosinophilic Asthma
David J Jackson, Marc Humbert , Ian Hirsch , Paul Newbold , Esther Garcia Gil
Abstract
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.
引言：对于具有过敏特征的嗜酸性粒细胞性哮喘患者，了解发作的关键驱动因素对于确定最佳治疗策略非常重要。Benralizumab是一种IL5受体α导向的细胞溶解性单克隆抗体，可显著降低严重、不受控制的嗜酸性粒细胞性哮喘患者的恶化频率。我们评估了基线血嗜酸性粒细胞计数与血清免疫球蛋白E（IgE）浓度对加重风险的预测价值，以及这些变量与benralizumab治疗效果的相关性。
方法：使用Ⅲ期SIROCCO和CALIMA benralizumab 试验的数据进行分析，根据基线血液嗜酸性粒细胞计数和血清IgE浓度，使用预先设定的血液嗜酸性粒细胞计数类别（＜150，≥150至＜300，≥300至＜450，≥450个细胞/ul），确定安慰剂的哮喘急性发作率（AERs）。和IgE浓度四分位数（＜62，≥62至＜176.2，大于等于176.2至＜453.4，≥453.4ku/L）。我们通过回归方法和连续使用局部加权回归平滑分析，比较了接受Benralizumab 30mg每8周（前3次每4周给药）的患者与安慰剂的AERs与基线血嗜酸性粒细胞计数类别和血清IgE浓度四分位数的重叠情况。
结果：接受安慰剂的重度哮喘患者的恶化风险随着基线血嗜酸性粒细胞计数的增加而增加，但随着血清IgE浓度的增加而不增加。基线特应性状态的增加不影响接受安慰剂的患者IgE浓度和恶化风险之间的关系。在所有血清IgE浓度四分位数中，血液嗜酸性粒细胞计数≥300个/ul的患者与安慰剂相比，benralizamab的家中风险持续降低。
结论：基线血嗜酸性粒细胞计数，而不是血清IgE浓度，是恶化风险的重要预测因子。无论IgE浓度如何，接受benralizumab治疗的重度嗜酸性粒细胞性哮喘患者的恶化风险均持续降低。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Adv Ther.2020 Feb;37(2):718-729.doi: 10.1007/s12325-019-01191-2.)
(Adv Ther.2020 Feb;37(2):718-729.doi: 10.1007/s12325-019-01191-2.)
Ability of Serum IgE Concentration to Predict Exacerbation Risk and Benralizumab Efficacy for Patients with Severe Eosinophilic Asthma
David J Jackson, Marc Humbert , Ian Hirsch , Paul Newbold , Esther Garcia Gil
Abstract
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.
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