Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study.

IF 3.7 3区医学 Q2 ALLERGY

Journal of Asthma and Allergy Pub Date : 2024-02-08 eCollection Date: 2024-01-01 DOI:10.2147/JAA.S425101

Theresa W Guilbert, Kevin R Murphy, Eckard Hamelmann, Kristie R Ross, Atul Gupta, Alessandro Fiocchi, Changming Xia, Rebecca Gall, Olivier Ledanois, Amr Radwan, Juby A Jacob-Nara, Paul J Rowe, Yamo Deniz

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引用次数: 0

Abstract

Background: Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab.

Methods: This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥5% or ≥10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV₁) by Week 12, annualized severe asthma exacerbation rates from Week 12-52, and mean change from baseline in ppFEV₁ to Week 12.

Results: At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥5% in ppFEV₁; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV₁ ≥10%. During the Week 12-52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52-60% (all P<0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV₁ (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥5%.

Conclusion: Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV₁, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV₁ response at Week 12.

Trial registration: NCT02948959.

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肺功能对使用杜匹单抗治疗的儿童哮喘恶化率的影响：VOYAGE研究

背景：儿童严重、失控的哮喘和哮喘恶化与肺功能和气道发育异常以及成年后罹患慢性阻塞性肺病的风险增加有关。这项事后分析的目的是探讨接受杜比单抗治疗的儿童哮喘加重率的变化与肺功能之间的关系：这项事后分析纳入了在LIBERTY ASTHMA VOYAGE 3期研究（NCT02948959）中接受杜比单抗或安慰剂治疗的6至11岁未受控制的中重度2型哮喘儿童（血液嗜酸性粒细胞≥150 cells/μL或呼气一氧化氮分数≥20 ppb）。研究终点为：第12周时，支气管扩张剂前1秒内预测用力呼气容积（ppFEV1）达到有临床意义的改善（≥5%或≥10%）的患者比例、第12-52周的年化严重哮喘加重率以及ppFEV1从基线到第12周的平均变化：在VOYAGE第12周，141/236（60%）名接受dupilumab治疗的儿童和57/114（50%）名接受安慰剂治疗的儿童的ppFEV1改善幅度≥5%；106/236（45%）名接受dupilumab治疗的儿童和36/114（32%）名接受安慰剂治疗的儿童的ppFEV1改善幅度≥10%。在第12-52周治疗期间，在所有亚组中，dupilumab与安慰剂相比显著降低了52%-60%的严重恶化率（所有P1（第12周最小平方均值差[95% CI]与安慰剂相比：3.54 [0.30, 6.78]个百分点；P=0.03），这些儿童的病情改善率≥5%：结论：杜匹单抗与安慰剂相比能显著改善支气管舒张剂前的ppFEV1，在第12周获得有临床意义应答的患者比例更高。杜比鲁单抗还能显著降低严重恶化率，与第12周时支气管舒张前ppFEV1反应无关：试验注册：NCT02948959。

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来源期刊

Journal of Asthma and Allergy Medicine-Immunology and Allergy

CiteScore

5.30

自引率

6.20%

发文量

185

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed journal publishing original research, reports, editorials and commentaries on the following topics: Asthma; Pulmonary physiology; Asthma related clinical health; Clinical immunology and the immunological basis of disease; Pharmacological interventions and new therapies. Although the main focus of the journal will be to publish research and clinical results in humans, preclinical, animal and in vitro studies will be published where they shed light on disease processes and potential new therapies.