Dupilumab Efficacy in Children With Type 2 Asthma Receiving High/Medium-Dose ICS (VOYAGE).

IF 8.2 1区医学 Q1 ALLERGY Journal of Allergy and Clinical Immunology-In Practice Pub Date : 2024-08-27 DOI:10.1016/j.jaip.2024.08.038

Jorge F Maspero, Martti A Antila, Antoine Deschildre, Leonard B Bacharier, Arman Altincatal, Elizabeth Laws, Eric Mortensen, Amr Radwan, Juby A Jacob-Nara, Yamo Deniz, Paul J Rowe, David J Lederer, Megan Hardin

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Abstract

Background: In phase 3 VOYAGE (NCT02948959), dupilumab showed clinical efficacy with an acceptable safety profile in children (6-11 years) with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb).

Objective: We analyzed dupilumab's efficacy in children with type 2 asthma by high- or medium-dose inhaled corticosteroids (ICS) at baseline.

Methods: Children were randomized to receive add-on dupilumab 100/200 mg (by body-weight ≤30 kg/>30 kg) every 2 weeks or placebo for 52 weeks and stratified by high- or medium-dose ICS at baseline. Endpoints were annualized severe exacerbation rate, changes from baseline in percent-predicted forced expiratory volume in 1 second (ppFEV₁) and 7-item Asthma Control Questionnaire - Interviewer Administered (ACQ-7-IA) score, proportions of ACQ-7-IA responders (improvement ≥0.5), and biomarker changes.

Results: In children receiving high- (n = 152) or medium- (n = 195) dose ICS at baseline, dupilumab versus placebo reduced severe exacerbation rates by 63% (P < .001) and 59% (P = .003), respectively. At week 52, dupilumab improved ppFEV₁ by least squares mean difference versus placebo of 5.7 percentage points (P = .02) and 9.35 points (P < .001), and reduced ACQ-7-IA scores by 0.53 points (P < .001) and 0.40 points (P < .001), respectively. No significant treatment interactions between ICS subgroups were detected at week 52. Significant improvements were observed in ACQ-7-IA responder rates and most type 2 biomarker levels.

Conclusion: Dupilumab reduced severe exacerbation rates and improved lung function and asthma control in children with uncontrolled, moderate-to-severe type 2 asthma, regardless of ICS dose at baseline.

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杜匹单抗对接受大/中剂量 ICS 的 2 型哮喘患儿的疗效（VOYAGE）。

研究背景在VOYAGE（NCT02948959）3期研究中，dupilumab对未得到控制的中重度2型哮喘儿童（6-11岁）（血嗜酸性粒细胞≥150 cells/μL或呼气一氧化氮分数≥20 ppb）显示出临床疗效，且安全性可接受：我们分析了dupilumab对基线使用大剂量或中剂量吸入皮质类固醇（ICS）的2型哮喘患儿的疗效：儿童被随机分配接受每两周一次的加用杜比鲁单抗 100/200 毫克（按体重≤30 千克/>30 千克计算）或安慰剂治疗 52 周，并按基线时的高剂量或中等剂量 ICS 进行分层。终点是年化严重恶化率、1秒内预测用力呼气容积百分比（ppFEV1）和7项哮喘控制问卷-访谈者管理（ACQ-7-IA）评分与基线相比的变化、ACQ-7-IA应答者比例（改善≥0.5）以及生物标志物变化：在基线接受高剂量（n = 152）或中剂量（n = 195）ICS治疗的儿童中，dupilumab与安慰剂相比，严重恶化率分别降低了63%（P < .001）和59%（P = .003）。第 52 周时，dupilumab 与安慰剂相比，ppFEV1 分别提高了 5.7 个百分点（P = .02）和 9.35 个百分点（P < .001），ACQ-7-IA 评分分别降低了 0.53 分（P < .001）和 0.40 分（P < .001）。第 52 周时，未发现 ICS 亚组之间存在明显的治疗交互作用。ACQ-7-IA应答率和大多数2型生物标志物水平均有显著改善：结论：无论基线时的 ICS 剂量如何，杜匹单抗都能降低中重度 2 型哮喘患儿的严重恶化率，改善肺功能和哮喘控制。

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来源期刊

Journal of Allergy and Clinical Immunology-In Practice ALLERGYIMMUNOLOGY-IMMUNOLOGY

CiteScore

11.10

自引率

9.60%

发文量

683

审稿时长

50 days

期刊介绍： JACI: In Practice is an official publication of the American Academy of Allergy, Asthma & Immunology (AAAAI). It is a companion title to The Journal of Allergy and Clinical Immunology, and it aims to provide timely clinical papers, case reports, and management recommendations to clinical allergists and other physicians dealing with allergic and immunologic diseases in their practice. The mission of JACI: In Practice is to offer valid and impactful information that supports evidence-based clinical decisions in the diagnosis and management of asthma, allergies, immunologic conditions, and related diseases. This journal publishes articles on various conditions treated by allergist-immunologists, including food allergy, respiratory disorders (such as asthma, rhinitis, nasal polyps, sinusitis, cough, ABPA, and hypersensitivity pneumonitis), drug allergy, insect sting allergy, anaphylaxis, dermatologic disorders (such as atopic dermatitis, contact dermatitis, urticaria, angioedema, and HAE), immunodeficiency, autoinflammatory syndromes, eosinophilic disorders, and mast cell disorders. The focus of the journal is on providing cutting-edge clinical information that practitioners can use in their everyday practice or to acquire new knowledge and skills for the benefit of their patients. However, mechanistic or translational studies without immediate or near future clinical relevance, as well as animal studies, are not within the scope of the journal.