度普利尤单抗在有或无过敏性哮喘证据的中度至重度2型哮喘儿童中的评估
2023/04/21
摘要
背景：白细胞介素（IL）-4/5/13等细胞因子在包括过敏性哮喘在内的多种2型炎症性疾病中发挥着关键作用。度普利尤单抗一种人类单克隆抗体，阻断IL-4/IL-13的共享受体成分，抑制信号传导。在这项VOYAGE（NCT02948959）的事后分析中，对6-11岁的2型哮喘患者（有或没有过敏性哮喘证据）（基线血清总IgE≥30IU/mL和≥1个常年性空气过敏原特异性IgE≥0.35kU/L）进行了度普利尤单抗疗效评估。
方法：在治疗期间评估严重急性发作（AER）的年化率、支气管扩张前（pre-BD）每秒用力呼气量（FEV1）的变化、预测的支气管扩张前FEV1（ppFEV1）百分比和哮喘控制评分（ACQ）-7。
结果：纳入350名儿童（261名有过敏性哮喘，89名无过敏性哮喘）。度普利尤单抗与安慰剂相比，在有（0.24 vs 0.62，相对风险降低[RRRR]:62%[95%CI，39-76]，p<.0001）过敏性哮喘证据和没有（0.39 vs 0.80，RRR:51%[95%CI，0-76]，p<.05）过敏性支气管哮喘证据的患者中，显著降低了AER。在整个治疗期间，在有过敏性哮喘证据的患者中，度普利尤单抗与安慰剂相比，ppFEV1、支气管扩张前FEV1和ACQ-7评分显著改善。在没有过敏性哮喘证据的患者中，到第52周，观察到支气管扩张剂前FEV1和哮喘控制的数值改善。
结论：度普利尤单抗与安慰剂相比，无论过敏性哮喘的证据如何，都能减少2型哮喘儿童的哮喘发作；在肺功能的变化中也观察到类似的趋势。在有过敏性哮喘证据的患者中观察到哮喘控制的显著改善，但在没有过敏性哮喘的患者中没有。
Assessment of dupilumab in children with moderate-to-severe type 2 asthma with or without evidence of allergic asthma
Nikolaos G Papadopoulos, Stanley J Szefler, Leonard B Bacharier, Jorge F Maspero, Christian Domingo, Alessandro Fiocchi, Jason K Lee, Nadia Daizadeh, David J Lederer, Megan Hardin, Rebecca Gall, Michel Djandji, Shahid Siddiqui, Juby A Jacob-Nara, Yamo Deniz, Paul J Rowe
Abstract
Background: Cytokines, such as interleukins (IL)-4/5/13, play a key role in multiple type 2 inflammatory diseases, including allergic asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In this post hoc analysis of VOYAGE (NCT02948959), dupilumab efficacy was evaluated in patients aged 6-11 years with type 2 asthma with or without evidence of allergic asthma (baseline serum total IgE ≥30IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35kU/L).
Methods: Annualized rate of severe exacerbations (AER) and changes in pre-bronchodilator (Pre-BD) forced expiratory volume in one second (FEV1 ), percent-predicted pre-BD FEV1 (ppFEV1 ), and Asthma Control Score (ACQ)-7 were assessed during the treatment period.
Results: 350 children (261 with and 89 without evidence of allergic asthma) were included. Dupilumab vs placebo significantly reduced AER in patients with (0.24 vs 0.62, relative risk reduction[RRR]: 62% [95% CI, 39-76], p<.0001) and without (0.39 vs 0.80, RRR: 51% [95% CI, 0-76], p<.05) evidence of allergic asthma. Significant improvements in ppFEV1 , pre-bronchodilator FEV1 , and ACQ-7 scores were observed in dupilumab vs placebo throughout the treatment period in patients with evidence of allergic asthma. In patients without evidence of allergic asthma, numerical improvements in pre-bronchodilator FEV1 and asthma control were observed by Week 52.
Conclusion: Dupilumab vs placebo reduced asthma exacerbations in children with type 2 asthma irrespective of evidence of allergic asthma; similar trends were observed in changes in lung function. Significant improvement in asthma control was observed in patients with evidence of allergic asthma, but not in those without.
背景：白细胞介素（IL）-4/5/13等细胞因子在包括过敏性哮喘在内的多种2型炎症性疾病中发挥着关键作用。度普利尤单抗一种人类单克隆抗体，阻断IL-4/IL-13的共享受体成分，抑制信号传导。在这项VOYAGE（NCT02948959）的事后分析中，对6-11岁的2型哮喘患者（有或没有过敏性哮喘证据）（基线血清总IgE≥30IU/mL和≥1个常年性空气过敏原特异性IgE≥0.35kU/L）进行了度普利尤单抗疗效评估。
方法：在治疗期间评估严重急性发作（AER）的年化率、支气管扩张前（pre-BD）每秒用力呼气量（FEV1）的变化、预测的支气管扩张前FEV1（ppFEV1）百分比和哮喘控制评分（ACQ）-7。
结果：纳入350名儿童（261名有过敏性哮喘，89名无过敏性哮喘）。度普利尤单抗与安慰剂相比，在有（0.24 vs 0.62，相对风险降低[RRRR]:62%[95%CI，39-76]，p<.0001）过敏性哮喘证据和没有（0.39 vs 0.80，RRR:51%[95%CI，0-76]，p<.05）过敏性支气管哮喘证据的患者中，显著降低了AER。在整个治疗期间，在有过敏性哮喘证据的患者中，度普利尤单抗与安慰剂相比，ppFEV1、支气管扩张前FEV1和ACQ-7评分显著改善。在没有过敏性哮喘证据的患者中，到第52周，观察到支气管扩张剂前FEV1和哮喘控制的数值改善。
结论：度普利尤单抗与安慰剂相比，无论过敏性哮喘的证据如何，都能减少2型哮喘儿童的哮喘发作；在肺功能的变化中也观察到类似的趋势。在有过敏性哮喘证据的患者中观察到哮喘控制的显著改善，但在没有过敏性哮喘的患者中没有。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Allergy. 2023 Apr 14. doi: 10.1111/all.15743.)
(Allergy. 2023 Apr 14. doi: 10.1111/all.15743.)
Assessment of dupilumab in children with moderate-to-severe type 2 asthma with or without evidence of allergic asthma
Nikolaos G Papadopoulos, Stanley J Szefler, Leonard B Bacharier, Jorge F Maspero, Christian Domingo, Alessandro Fiocchi, Jason K Lee, Nadia Daizadeh, David J Lederer, Megan Hardin, Rebecca Gall, Michel Djandji, Shahid Siddiqui, Juby A Jacob-Nara, Yamo Deniz, Paul J Rowe
Abstract
Background: Cytokines, such as interleukins (IL)-4/5/13, play a key role in multiple type 2 inflammatory diseases, including allergic asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In this post hoc analysis of VOYAGE (NCT02948959), dupilumab efficacy was evaluated in patients aged 6-11 years with type 2 asthma with or without evidence of allergic asthma (baseline serum total IgE ≥30IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35kU/L).
Methods: Annualized rate of severe exacerbations (AER) and changes in pre-bronchodilator (Pre-BD) forced expiratory volume in one second (FEV1 ), percent-predicted pre-BD FEV1 (ppFEV1 ), and Asthma Control Score (ACQ)-7 were assessed during the treatment period.
Results: 350 children (261 with and 89 without evidence of allergic asthma) were included. Dupilumab vs placebo significantly reduced AER in patients with (0.24 vs 0.62, relative risk reduction[RRR]: 62% [95% CI, 39-76], p<.0001) and without (0.39 vs 0.80, RRR: 51% [95% CI, 0-76], p<.05) evidence of allergic asthma. Significant improvements in ppFEV1 , pre-bronchodilator FEV1 , and ACQ-7 scores were observed in dupilumab vs placebo throughout the treatment period in patients with evidence of allergic asthma. In patients without evidence of allergic asthma, numerical improvements in pre-bronchodilator FEV1 and asthma control were observed by Week 52.
Conclusion: Dupilumab vs placebo reduced asthma exacerbations in children with type 2 asthma irrespective of evidence of allergic asthma; similar trends were observed in changes in lung function. Significant improvement in asthma control was observed in patients with evidence of allergic asthma, but not in those without.
上一篇：
应用ICS-福莫特罗或ICS-沙美特罗维持治疗的哮喘患者中按需福莫特罗的安全性和有效性
下一篇：
升麻素与SPR结合以非酶方式调节其蛋白表达进而抑制2型气道炎症
