无论过敏性哮喘表型如何，度普利尤单抗对中度至重度GINA定义的2型哮喘患者有效
2022/09/20
摘要
背景：全球哮喘倡议报告建议血液嗜酸性粒细胞≥150个细胞/μL，呼出气一氧化氮分数（FeNO）≥20ppb（十亿分之一）的不能通过大剂量吸入性皮质类固醇控制的2型炎症哮喘患者加用生物制剂治疗。在QUEST（NCT02414854）中，与安慰剂相比，添加度普利尤单抗对不受控制的中重度哮喘患者有效，包括嗜酸性粒细胞≥150细胞/μL和/或FeNO≥25ppb的患者。
目的：在存在或不存在过敏性哮喘表型的情况下，评估度普利尤单抗对2型表型患者的疗效。
方法：12岁或12岁以上的患者每2周接受一次200/300 mg度普利尤单抗或安慰剂对照的治疗，共52周。过敏性哮喘表型定义为基线血清总IgE≥30 IU/mL，以及1个或多个常年性空气过敏原特异性IgE水平≥0.35 kU/L。评估基线血液嗜酸性粒细胞≥150个细胞/μL和/或FeNO≥20ppb，且有基线支气管扩张剂前/后FEV1的具有过敏性和非过敏性表型的患者急性发作的年化率及其变化。
结果：在1902名QUEST患者中，83.3%的患者的嗜酸性粒细胞和/或FeNO高于全球哮喘阈值倡议；56.9%有过敏性哮喘的证据。在有（48.8%）和无（64.0%）过敏性哮喘证据的患者中，度普利尤单抗显著降低了重症哮喘急性发作的发生率，并且在2型生物标志物升高的患者中改善了支气管扩张剂前和支气管扩张剂后FEV1，无论其是否显示过敏性哮喘表型。
结论：在超过全球哮喘倡议的2型生物标志物阈值的患者中，度普利尤单抗显著减少了病情恶化并改善了肺功能，疗效不受过敏状态的影响。
Dupilumab Is Effective in Patients With Moderate-to-Severe Uncontrolled GINA-Defined Type 2 Asthma Irrespective of an Allergic Asthma Phenotype
Klaus F Rabe, J Mark FitzGerald, Eric D Bateman, Mario Castro, Ian D Pavord, Jorge F Maspero, William W Busse, Kenji Izuhara, Nadia Daizadeh, Benjamin Ortiz, Nami Pandit-Abid, Paul J Rowe, Yamo Deniz
Abstract
Background：The Global Initiative for Asthma report recommends consideration of add-on biologics for patients with type 2 inflammation (blood eosinophils ≥150 cells/μL, fractional exhaled nitric oxide [Feno] ≥20 parts per billion or allergic asthma) whose asthma cannot be controlled by high-dose inhaled corticosteroids. In QUEST (NCT02414854), add-on dupilumab versus placebo was efficacious in patients with uncontrolled, moderate to severe asthma, including those with eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 25 parts per billion.
Objective：To assess dupilumab efficacy in patients with a type 2 phenotype in the presence or absence of allergic asthma phenotype.
Methods：Patients aged 12 years or older received add-on dupilumab 200/300 mg versus matched placebo every 2 weeks for 52 weeks. Allergic asthma phenotype was defined as baseline serum total IgE greater than or equal to 30 IU/mL and 1 or more perennial aeroallergen-specific IgE level greater than or equal to 0.35 kU/L. Annualized rate of severe asthma exacerbations and changes from study baseline in prebronchodilator and postbronchodilator FEV1 were evaluated in patients with allergic and nonallergic phenotype with baseline blood eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 20 parts per billion.
Results：Of 1902 patients in QUEST, 83.3% had eosinophils and/or Feno above Global Initiative for Asthma thresholds; 56.9% had evidence for allergic asthma. Dupilumab significantly reduced the rate of severe asthma exacerbations in patients with (48.8%) and without (64.0%) evidence of allergic asthma and improved prebronchodilator and postbronchodilator FEV1 in patients with elevated type 2 biomarkers, irrespective of whether they showed evidence of an allergic asthma phenotype.
Conclusions：In patients with type 2 biomarkers over Global Initiative for Asthma thresholds, dupilumab significantly reduced exacerbations and improved lung function. Efficacy was not impacted by allergic status.
背景：全球哮喘倡议报告建议血液嗜酸性粒细胞≥150个细胞/μL，呼出气一氧化氮分数（FeNO）≥20ppb（十亿分之一）的不能通过大剂量吸入性皮质类固醇控制的2型炎症哮喘患者加用生物制剂治疗。在QUEST（NCT02414854）中，与安慰剂相比，添加度普利尤单抗对不受控制的中重度哮喘患者有效，包括嗜酸性粒细胞≥150细胞/μL和/或FeNO≥25ppb的患者。
目的：在存在或不存在过敏性哮喘表型的情况下，评估度普利尤单抗对2型表型患者的疗效。
方法：12岁或12岁以上的患者每2周接受一次200/300 mg度普利尤单抗或安慰剂对照的治疗，共52周。过敏性哮喘表型定义为基线血清总IgE≥30 IU/mL，以及1个或多个常年性空气过敏原特异性IgE水平≥0.35 kU/L。评估基线血液嗜酸性粒细胞≥150个细胞/μL和/或FeNO≥20ppb，且有基线支气管扩张剂前/后FEV1的具有过敏性和非过敏性表型的患者急性发作的年化率及其变化。
结果：在1902名QUEST患者中，83.3%的患者的嗜酸性粒细胞和/或FeNO高于全球哮喘阈值倡议；56.9%有过敏性哮喘的证据。在有（48.8%）和无（64.0%）过敏性哮喘证据的患者中，度普利尤单抗显著降低了重症哮喘急性发作的发生率，并且在2型生物标志物升高的患者中改善了支气管扩张剂前和支气管扩张剂后FEV1，无论其是否显示过敏性哮喘表型。
结论：在超过全球哮喘倡议的2型生物标志物阈值的患者中，度普利尤单抗显著减少了病情恶化并改善了肺功能，疗效不受过敏状态的影响。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(J Allergy Clin Immunol Pract. 2022 Aug 23;S2213-2198(22)00651-1. doi: 10.1016/j.jaip.2022.06.036.)
(J Allergy Clin Immunol Pract. 2022 Aug 23;S2213-2198(22)00651-1. doi: 10.1016/j.jaip.2022.06.036.)
Dupilumab Is Effective in Patients With Moderate-to-Severe Uncontrolled GINA-Defined Type 2 Asthma Irrespective of an Allergic Asthma Phenotype
Klaus F Rabe, J Mark FitzGerald, Eric D Bateman, Mario Castro, Ian D Pavord, Jorge F Maspero, William W Busse, Kenji Izuhara, Nadia Daizadeh, Benjamin Ortiz, Nami Pandit-Abid, Paul J Rowe, Yamo Deniz
Abstract
Background：The Global Initiative for Asthma report recommends consideration of add-on biologics for patients with type 2 inflammation (blood eosinophils ≥150 cells/μL, fractional exhaled nitric oxide [Feno] ≥20 parts per billion or allergic asthma) whose asthma cannot be controlled by high-dose inhaled corticosteroids. In QUEST (NCT02414854), add-on dupilumab versus placebo was efficacious in patients with uncontrolled, moderate to severe asthma, including those with eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 25 parts per billion.
Objective：To assess dupilumab efficacy in patients with a type 2 phenotype in the presence or absence of allergic asthma phenotype.
Methods：Patients aged 12 years or older received add-on dupilumab 200/300 mg versus matched placebo every 2 weeks for 52 weeks. Allergic asthma phenotype was defined as baseline serum total IgE greater than or equal to 30 IU/mL and 1 or more perennial aeroallergen-specific IgE level greater than or equal to 0.35 kU/L. Annualized rate of severe asthma exacerbations and changes from study baseline in prebronchodilator and postbronchodilator FEV1 were evaluated in patients with allergic and nonallergic phenotype with baseline blood eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 20 parts per billion.
Results：Of 1902 patients in QUEST, 83.3% had eosinophils and/or Feno above Global Initiative for Asthma thresholds; 56.9% had evidence for allergic asthma. Dupilumab significantly reduced the rate of severe asthma exacerbations in patients with (48.8%) and without (64.0%) evidence of allergic asthma and improved prebronchodilator and postbronchodilator FEV1 in patients with elevated type 2 biomarkers, irrespective of whether they showed evidence of an allergic asthma phenotype.
Conclusions：In patients with type 2 biomarkers over Global Initiative for Asthma thresholds, dupilumab significantly reduced exacerbations and improved lung function. Efficacy was not impacted by allergic status.
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