对伴有或不伴有过敏性哮喘证据的 2 型哮喘患儿进行长期杜度单抗评估

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology Pub Date : 2024-10-25 DOI:10.1016/j.anai.2024.08.051

N. Papadopoulos , L. Bacharier , W. Phipatanakul , E. Hamelmann , A. Fiocchi , A. Altincatal , R. Gall , O. Ledanois

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引用次数: 0

摘要

导言：在VOYAGE（NCT02948959）和单臂、开放标签EXCURSION（NCT035604666）扩展研究中，阻断白细胞介素4/13信号传导的人类单克隆抗体Dupilumab对中重度2型哮喘儿童（6-11岁）（血嗜酸性粒细胞≥150cells/μL或呼气一氧化氮分数≥20ppb）具有疗效。我们在 EXCURSION 中评估了有/无过敏性哮喘证据（基线时血清总 IgE ≥30IU/mL，且≥1 种常年性空气过敏原特异性 IgE ≥0.35kU/L）的儿童使用杜比鲁单抗的疗效。方法在 VOYAGE 中，儿童接受额外的杜比鲁单抗 100/200mg q2w（按体重计算）或安慰剂治疗 52 周；在 EXCURSION 中，所有儿童接受杜比鲁单抗治疗 52 周。终点：年化严重恶化率；与 VOYAGE 基线相比，存在/不存在过敏性哮喘的支气管扩张剂前预测 1 秒用力呼气容积百分比 (ppFEV1) 的变化。结果在 VOYAGE 中，dupilumab 可使有过敏性哮喘证据的患者的病情加重率降低 57.0%，使无过敏性哮喘证据的患者的病情加重率降低 49.1%。在 EXCURSION 中，减少的情况得以持续。在第52周（VOYAGE）：dupilumab能显著改善过敏性哮喘患儿支气管扩张剂前的ppFEV1（与安慰剂相比的最小二乘法[LS]平均差[95% CI]：9.45 [5.14 至 13.77]；P<0.0001），对非过敏性哮喘患儿的数值改善（4.60 [-1.99 至 11.20]；P=0.1685）。在EXCURSION（第52周）中，无论过敏状态如何，支气管扩张剂前ppFEV1的改善都是持续的：有过敏性哮喘的dupilumab-dupilumab/安慰剂-dupilumab组的平均（标度）变化为13.1% (19.5)/9.9% (15.9)，而无过敏性哮喘的dupilumab-dupilumab/安慰剂-dupilumab组的平均（标度）变化为11.结论杜匹鲁单抗可减少中重度2型哮喘患儿的严重病情恶化，并改善肺功能长达2年，与过敏状态无关。

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LONG-TERM DUPILUMAB ASSESSMENT IN CHILDREN WITH TYPE 2 ASTHMA WITH OR WITHOUT EVIDENCE ALLERGIC ASTHMA

Introduction

Dupilumab, a human monoclonal antibody blocking interleukins 4/13 signaling, demonstrated efficacy in children (6–11 years) with moderate-to-severe type 2 asthma (blood eosinophils ≥150cells/µL or fractional exhaled nitric oxide ≥20ppb) in VOYAGE (NCT02948959) and in the single-arm, open-label EXCURSION (NCT035604666) extension study. We assessed dupilumab efficacy in children in EXCURSION, with/without evidence of allergic asthma (total serum IgE ≥30IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35kU/L at baseline).

Methods

In VOYAGE, children received add-on dupilumab 100/200mg q2w (by bodyweight) or placebo for 52 weeks; in EXCURSION, all received dupilumab for 52 weeks. Endpoints: annualized severe exacerbation rates; change from VOYAGE baseline in pre-bronchodilator percent predicted forced expiratory volume in 1 second (ppFEV₁) by presence/absence of allergic asthma. Only descriptive analyses are available for EXCURSION outcomes.

Results

In VOYAGE, dupilumab reduced exacerbations by 57.0% in patients with evidence of allergic asthma and by 49.1% in those without. Reductions were sustained in EXCURSION. At Week 52 (VOYAGE): dupilumab significantly improved pre-bronchodilator ppFEV₁ in children with allergic asthma (least squares [LS] mean difference vs placebo [95% CI]: 9.45 [5.14 to 13.77]; P<0.0001), with a numerical improvement in those without (4.60 [−1.99 to 11.20]; P=0.1685). In EXCURSION (Week 52), pre-bronchodilator ppFEV₁ improvements were sustained regardless of allergic status: mean (SD) change 13.1% (19.5)/9.9% (15.9) for dupilumab-dupilumab/placebo-dupilumab groups with allergic asthma, and 11.2% (13.5)/8.4% (17.3) in children without allergic asthma.

Conclusions

Dupilumab reduced severe exacerbations and improved lung function up to 2 years in children with moderate-to-severe type 2 asthma, irrespective of allergic status.

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来源期刊

Annals of Allergy Asthma & Immunology 医学-过敏

CiteScore

6.50

自引率

6.80%

发文量

437

审稿时长

33 days

期刊介绍： Annals of Allergy, Asthma & Immunology is a scholarly medical journal published monthly by the American College of Allergy, Asthma & Immunology. The purpose of Annals is to serve as an objective evidence-based forum for the allergy/immunology specialist to keep up to date on current clinical science (both research and practice-based) in the fields of allergy, asthma, and immunology. The emphasis of the journal will be to provide clinical and research information that is readily applicable to both the clinician and the researcher. Each issue of the Annals shall also provide opportunities to participate in accredited continuing medical education activities to enhance overall clinical proficiency.