Department of Respiratory Disease, University of Montpellier, Montpellier University Hospital, Hôpital Arnaud de Villeneuve, 371 avenue du Doyen Gaston Giraud, 34295, Montpellier, Cedex 5, France.
Universitätsmedizin Rostock, Abteilungen für Pneumologie und Internistische Intensivmedizin, Ernst-Heydemannstrasse 6, 18055, Rostock, Germany.
Respir Med. 2022 Oct;202:106938. doi: 10.1016/j.rmed.2022.106938. Epub 2022 Aug 11.
Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks reduced severe exacerbations, improved pre-bronchodilator forced expiratory volume in 1 s (FEV), and was generally well tolerated in patients with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed dupilumab efficacy in subpopulations of patients with type 2 asthma and high-dose inhaled corticosteroids (ICS).
Adjusted annualized severe exacerbation rates over the treatment period, least squares (LS) mean change from baseline at Week 12 in pre-bronchodilator FEV, and LS mean change from baseline at Week 24 in 5-item Asthma Control Questionnaire (ACQ-5) scores were analyzed in subgroups of patients receiving high-dose (>500 μg) ICS with baseline blood eosinophils ≥150 cells/μL and/or fractional exhaled nitric oxide ≥25 ppb. Subgroups included allergic phenotype (with/without), comorbid chronic rhinosinusitis and/or nasal polyposis (with/without), pre-bronchodilator FEV/forced vital capacity (<70%/≥70%), blood eosinophil level, exacerbation history, median baseline pre-bronchodilator FEV, age at asthma onset (≤40/>40 years), median FEV reversibility, body mass index (<30/≥30 kg/m), and sex.
Dupilumab vs placebo reduced exacerbations and improved pre-bronchodilator FEV at Week 12 and ACQ-5 at Week 24 across subgroups of patients with type 2 asthma and high-dose ICS at baseline. Dupilumab was also effective in patients receiving medium-dose ICS.
Dupilumab reduced severe exacerbations and improved lung function and asthma control in subgroups of patients with type 2 asthma and high-dose ICS at baseline.
NCT02414854.
度普利尤单抗阻断白细胞介素（IL）-4/IL-13 的共用受体成分，后者是多种疾病中 2 型炎症的关键和中心驱动因素。在 3 期 QUEST 试验（NCT02414854）中，每 2 周添加度普利尤单抗 200mg 和 300mg 可减少重度恶化，改善支气管扩张剂前用力呼气 1 秒量（FEV1），并且在未得到控制的中重度哮喘患者中通常具有良好的耐受性。本事后分析评估了度普利尤单抗在 2 型哮喘和高剂量吸入性皮质类固醇（ICS）患者亚组中的疗效。
在治疗期间，根据调整后的年度重度恶化发生率、第 12 周支气管扩张剂前 FEV1 的最小二乘均数（LS）变化以及第 24 周 5 项哮喘控制问卷（ACQ-5）评分的 LS 均值变化，对基线时血嗜酸性粒细胞≥150 个/μL 和/或呼出气一氧化氮分数≥25 ppb、接受高剂量（＞500μg）ICS 的患者亚组进行分析。亚组包括过敏表型（有/无）、合并慢性鼻-鼻窦炎和/或鼻息肉（有/无）、支气管扩张剂前 FEV1/用力肺活量（＜70%/≥70%）、血嗜酸性粒细胞水平、恶化史、支气管扩张剂前 FEV1 的中位数、哮喘发病年龄（≤40 岁/＞40 岁）、FEV1 可逆性的中位数、体质指数（＜30/≥30kg/m2）和性别。
与安慰剂相比，度普利尤单抗在基线时接受 2 型哮喘和高剂量 ICS 的患者亚组中，在第 12 周时降低了恶化发生率并改善了支气管扩张剂前 FEV1，在第 24 周时改善了 ACQ-5。度普利尤单抗在接受中剂量 ICS 的患者中也有效。
度普利尤单抗降低了基线时接受高剂量 ICS 的 2 型哮喘患者亚组的重度恶化发生率，并改善了肺功能和哮喘控制。
NCT02414854。
