Maspero Jorge F, Antila Martti A, Deschildre Antoine, Bacharier Leonard B, Altincatal Arman, Laws Elizabeth, Mortensen Eric, Radwan Amr, Jacob-Nara Juby A, Deniz Yamo, Rowe Paul J, Lederer David J, Hardin Megan
Fundación CIDEA, Buenos Aires, Argentina.
Clínica de Alergía, Sorocaba, Sao Paulo, Brazil.
J Allergy Clin Immunol Pract. 2024 Dec;12(12):3303-3312. doi: 10.1016/j.jaip.2024.08.038. Epub 2024 Aug 28.
In phase 3 VOYAGE (NCT02948959; Evaluation of Dupilumab in Children With Uncontrolled Asthma), dupilumab showed clinical efficacy with an acceptable safety profile in children aged 6 to 11 years with uncontrolled moderate to severe type 2 asthma (blood eosinophils ≥150 cells/μL or FeNO ≥20 ppb).
We analyzed dupilumab's efficacy in children with type 2 asthma by high- or medium-dose inhaled corticosteroids (ICS) at baseline.
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. End points were annualized severe exacerbation rate, changes from baseline in percent predicted FEV, and seven-item Asthma Control Questionnaire-Interviewer Administered (ACQ-7-IA) score, proportions of ACQ-7-IA responders (improvement ≥0.5), and biomarker changes.
In children receiving high-dose (n = 152) or medium-dose (n = 195) ICS at baseline, dupilumab versus placebo reduced severe exacerbation rates by 63% (P < .001) and 59% (P = .003), respectively. At week 52, dupilumab improved percent predicted FEV 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.
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.
在3期VOYAGE研究（NCT02948959；度普利尤单抗治疗未控制哮喘儿童的疗效评估）中，度普利尤单抗在6至11岁未控制的中度至重度2型哮喘（血液嗜酸性粒细胞≥150个/μL或呼出一氧化氮≥20 ppb）儿童中显示出临床疗效，且安全性可接受。
我们根据基线时高剂量或中剂量吸入性糖皮质激素（ICS）分析了度普利尤单抗在2型哮喘儿童中的疗效。
将儿童随机分组，每2周接受一次度普利尤单抗100/200 mg（根据体重≤30 kg/>30 kg）或安慰剂治疗52周，并根据基线时高剂量或中剂量ICS进行分层。终点指标为年化严重加重率、预计第一秒用力呼气容积（FEV）自基线的变化、七项哮喘控制问卷-访谈者管理版（ACQ-7-IA）评分、ACQ-7-IA应答者（改善≥0.5）比例以及生物标志物变化。
在基线时接受高剂量（n = 152）或中剂量（n = 195）ICS的儿童中，度普利尤单抗与安慰剂相比，严重加重率分别降低了63%（P <.001）和59%（P =.003）。在第52周时，度普利尤单抗与安慰剂相比，预计FEV百分比改善的最小二乘均数差异分别为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）。在第52周时，未检测到ICS亚组之间有显著的治疗交互作用。在ACQ-7-IA应答率和大多数2型生物标志物水平方面观察到显著改善。
无论基线时ICS剂量如何，度普利尤单抗均可降低未控制的中度至重度2型哮喘儿童的严重加重率，并改善肺功能和哮喘控制情况。
