度普利尤单抗在未控制的中度至重度2型哮喘患者中的疗效，无论其是否对常年性气传变应原致敏。
Dupilumab Efficacy in Patients with Uncontrolled Moderate-to-Severe Type 2 Asthma Regardless of Perennial Aeroallergen Sensitization.
作者信息
Corren Jonathan, Jackson David J, Casale Thomas B, Borish Larry, Rabe Klaus F, Busse William W, Maspero Jorge F, Jackson Daniel J, Daizadeh Nadia, Altincatal Arman, Radwan Amr, Khodzhayev Angela, Djandji Michel, Jacob-Nara Juby A, Rowe Paul J, Deniz Yamo
机构信息
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
King's College London, London, UK.
出版信息
J Asthma Allergy. 2023 Mar 7;16:249-260. doi: 10.2147/JAA.S385645. eCollection 2023.
PURPOSE
Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 (T2) inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), dupilumab vs placebo significantly reduced asthma exacerbation rates (AER) and improved pre-bronchodilator forced expiratory volume in 1 second (FEV) in patients with uncontrolled, moderate-to-severe asthma, with greater effects in patients with elevated T2 biomarkers (≥150 eosinophils/µL or fractional exhaled nitric oxide [FeNO] ≥25 parts per billion). Overall safety was consistent with the known dupilumab safety profile. This post hoc analysis assessed dupilumab efficacy in QUEST patients with T2 asthma with evidence of an allergic phenotype (baseline serum IgE ≥30 IU/mL and aeroallergen-specific IgE ≥0.35 IU/mL) by number of aeroallergen sensitizations: 1, 2, 3, or ≥4. Non-sensitized patients (serum total IgE <30 IU/mL without evidence of allergic phenotype) were also assessed.
PATIENTS AND METHODS
Endpoints were annualized AER, change from baseline in pre-bronchodilator FEV and asthma control (5-item Asthma Control Questionnaire [ACQ-5]), and FeNO and serum total IgE levels over the 52-week treatment period.
RESULTS
In all subgroups by number of allergens sensitized, dupilumab vs placebo reduced AER by 35-67% and improved both pre-bronchodilator FEV at Week 12 (least squares mean differences: 0.10-0.26 L across subgroups) and ACQ-5 score at Week 52 (-0.26 to -0.43). Dupilumab significantly reduced FeNO and total IgE levels at Week 52 compared with placebo. Similar results were observed in non-sensitized patients.
CONCLUSION
Dupilumab improved clinical outcomes and reduced biomarker levels in patients with uncontrolled, moderate-to-severe T2 asthma irrespective of allergen sensitization status or number.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02414854.
目的
度普利尤单抗是一种全人源单克隆抗体，可阻断白细胞介素-4/ -13的共享受体成分，白细胞介素-4/ -13是多种疾病中2型（T2）炎症的关键驱动因素。在3期QUEST研究（NCT02414854）中，对于未得到控制的中重度哮喘患者，度普利尤单抗对比安慰剂可显著降低哮喘急性加重率（AER），并改善支气管扩张剂使用前1秒用力呼气容积（FEV），对T2生物标志物升高（≥150个嗜酸性粒细胞/微升或呼出气一氧化氮分数[FeNO]≥25 ppb）的患者效果更佳。总体安全性与已知的度普利尤单抗安全性特征一致。这项事后分析按吸入性过敏原致敏数量（1、2、3或≥4种）评估了QUEST研究中具有过敏表型证据（基线血清IgE≥30 IU/mL且吸入性过敏原特异性IgE≥0.35 IU/mL）的T2哮喘患者使用度普利尤单抗的疗效。还评估了未致敏患者（血清总IgE<30 IU/mL且无过敏表型证据）。
患者和方法
观察指标为年化AER、支气管扩张剂使用前FEV自基线的变化以及哮喘控制情况（5项哮喘控制问卷[ACQ-5]），以及52周治疗期内的FeNO和血清总IgE水平。
结果
在所有按致敏过敏原数量划分的亚组中，度普利尤单抗对比安慰剂可使AER降低35%-67%，并改善第12周时支气管扩张剂使用前FEV（各亚组的最小二乘均值差异为0.10-0.26升）以及第52周时的ACQ-5评分（-0.26至-0.43）。与安慰剂相比，度普利尤单抗在第52周时显著降低了FeNO和总IgE水平。在未致敏患者中也观察到了类似结果。
结论
无论过敏原致敏状态或数量如何，度普利尤单抗均可改善未得到控制的中重度T2哮喘患者的临床结局并降低生物标志物水平。
临床试验注册
ClinicalTrials.gov标识符：NCT02414854。
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