中重度哮喘患儿病情加重史对杜匹单抗疗效的影响：LIBERTY ASTHMA VOYAGE 研究

IF 3.7 3区医学 Q2 ALLERGY

Journal of Asthma and Allergy Pub Date : 2024-03-05 DOI:10.2147/jaa.s416292

Theresa W Guilbert, Alberto Tolcachier, Alessandro G Fiocchi, Constance H Katelaris, Wanda Phipatanakul, Philippe Begin, Inés de Mir, Arman Altincatal, Rebecca Gall, Olivier Ledanois, Amr Radwan, Juby A Jacob-Nara, Yamo Deniz, Paul J Rowe

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引用次数: 0

摘要

目的：杜匹单抗是一种全人源单克隆抗体，可阻断白细胞介素-4/-13的共同受体成分，而白细胞介素-4/-13是多种疾病中2型炎症的关键和核心驱动因素。这项LIBERTY ASTHMA VOYAGE 3期研究（NCT02948959）的事后分析评估了杜匹鲁单抗对6至11岁中重度哮喘患儿的疗效，这些患儿具有2型炎症表型（血嗜酸性粒细胞计数≥150 cells/μL或部分呼出一氧化氮[FeNO]≥20 ppb），既往有1次、2次或≥3次加重病史。研究还探讨了基线2型生物标志物水平对杜匹单抗在该人群中疗效的影响：根据患者上一年的病情加重次数（1、2 或≥ 3 次）和基线时 FeNO 或血液嗜酸性粒细胞计数水平对患者进行分层。终点包括严重恶化率、非恶化者百分比以及肺功能参数（支气管扩张剂[BD]前后1 s内预测用力呼气容积百分比（ppFEV1）和ppFEV1/用力呼气容积[FVC]比值）和哮喘控制问卷7受访者管理（ACQ-7-IA）评分与基线相比的变化：本次分析共纳入 350 名患者。在既往有1次、2次或≥3次哮喘加重和不同水平的2型生物标志物的患者中，与安慰剂相比，杜匹鲁单抗可将严重哮喘加重的风险降低53.0%-96.0%，并在第52周改善哮喘发作前的ppFEV1和哮喘发作前的FEV1/FVC比值。到第52周时，杜匹鲁单抗可显著降低各组患者的ACQ-7-IA评分：结论：对于未受控制的中重度 2 型哮喘患儿，无论是否有哮喘加重史，杜匹鲁单抗都能持续降低哮喘加重风险、改善肺功能并降低 ACQ-7-IA 评分。关键词：小儿哮喘、2型哮喘、肺功能、哮喘控制、生物制剂、抗白细胞介素-4和-13

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Impact of Exacerbation History on Dupilumab Efficacy in Children with Uncontrolled Moderate-to-Severe Asthma: LIBERTY ASTHMA VOYAGE Study

Purpose: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 inflammation in multiple diseases. This post hoc analysis of the Phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959) evaluated the efficacy of dupilumab in children aged 6 to 11 years with moderate-to-severe asthma with a type 2 inflammatory phenotype (blood eosinophil count ≥ 150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥ 20 ppb) and a history of 1, 2, or ≥ 3 prior exacerbations. The impact of baseline type 2 biomarker levels on the efficacy of dupilumab in this population was also investigated.
Patients and Methods: Patients were stratified by the number of exacerbations in the prior year (1, 2, or ≥ 3) and level of FeNO or blood eosinophil count at baseline. Endpoints included rate of severe exacerbations, percentage of non-exacerbators, and change from baseline in both lung function parameters (pre- and post-bronchodilator [BD] percent predicted forced expiratory volume in 1 s (ppFEV₁) and ppFEV₁/forced vital capacity [FVC] ratio) and Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) score.
Results: A total of 350 patients were included in this analysis. Across patients with 1, 2, or ≥ 3 prior exacerbations and different levels of type 2 biomarkers, dupilumab reduced the risk of severe asthma exacerbations vs placebo by 53.0– 96.0% and improved both pre-BD ppFEV₁ and pre-BD FEV₁/FVC ratio at Week 52. Dupilumab led to significant reductions in ACQ-7-IA scores in all groups of patients by Week 52.
Conclusion: In children with uncontrolled, moderate-to-severe asthma with a type 2 phenotype, dupilumab consistently reduced the risk of asthma exacerbations, improved lung function, and reduced ACQ-7-IA scores, regardless of exacerbation history.

Keywords: pediatric asthma, type 2 asthma, lung function, asthma control, biologics, anti-interleukin-4 and -13

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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.