Sindher Sayantani B, Nadeau Kari C, Chinthrajah R Sharon, Leflein Jeffrey G, Bégin Philippe, Ohayon Jason A, Ponda Punita, Wambre Erik, Liu Jinzhong, Khokhar Faisal A, Akinlade Bolanle, Maloney Jennifer, Orengo Jamie M, Hamilton Jennifer D, Kamal Mohamed A, Hooper Andrea T, Patel Naimish, Patel Kiran, Laws Elizabeth, Mannent Leda P, Radin Allen R
Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, California, USA.
Harvard School of Public Health, Boston, Massachusetts, USA.
Allergy. 2025 Jan;80(1):227-237. doi: 10.1111/all.16404. Epub 2024 Dec 14.
Peanut allergy is a potentially life-threatening food allergy in children. This study explored whether dupilumab, a human monoclonal immunoglobulin (Ig)G4 antibody that blocks the activity of interleukin (IL)-4/IL-13, improved safety and desensitization to peanut exposure in children with peanut allergy.
A Phase II, 24-week, multicenter, single-arm, open-label, proof-of-concept study was conducted in the USA and Canada (NCT03793608). Children/adolescents with peanut allergy received subcutaneous dupilumab 300 mg (≥ 60 kg) or 200 mg (≥ 20 to < 60 kg) every 2 weeks. The primary endpoint was the proportion of participants who passed a double-blind placebo-controlled food challenge (DBPCFC) with ≥ 444 mg (cumulative) of peanut protein at week 24. Secondary endpoints included safety measures (Consortium of Food Allergy Research grading system) and change from baseline in peanut-specific (ps)-IgG4, total IgE, and ps-IgE.
Twenty-four participants enrolled and received dupilumab: 75.0% were male, 79.2% were white, mean (standard deviation) age was 11.7 (3.3) years. Most (95.8%) participants had not received allergen immunotherapy. Two participants (8.3%) achieved the primary endpoint and passed the DBPCFC at week 24. Fifteen participants (62.5%) reported 66 treatment-emergent adverse events, all being mild or in moderate intensity. At the week 24 DBPCFC, 8 participants (33.3%) had a grade 2 allergic reaction (no grade 3 or above); 10 (41.7%) used adrenaline as a rescue medication. Dupilumab treatment resulted in a median reduction of total and ps-IgE of -54% and -49%, respectively, and a 0% change in ps-IgG4.
Dupilumab monotherapy treatment for 24 weeks did not improve desensitization to peanut exposure after food challenge.
花生过敏是儿童中一种可能危及生命的食物过敏。本研究探讨了度普利尤单抗（一种阻断白细胞介素（IL）-4/IL-13活性的人源单克隆免疫球蛋白（Ig）G4抗体）是否能改善花生过敏儿童对花生暴露的安全性和脱敏效果。
在美国和加拿大进行了一项II期、为期24周、多中心、单臂、开放标签的概念验证研究（NCT03793608）。花生过敏的儿童/青少年每2周接受皮下注射度普利尤单抗300mg（≥60kg）或200mg（≥20至<60kg）。主要终点是在第24周通过双盲安慰剂对照食物激发试验（DBPCFC）且花生蛋白累积量≥444mg的参与者比例。次要终点包括安全指标（食物过敏研究联盟分级系统）以及花生特异性（ps）-IgG4、总IgE和ps-IgE相对于基线的变化。
24名参与者入组并接受了度普利尤单抗治疗：75.0%为男性，79.2%为白人，平均（标准差）年龄为11.7（3.3）岁。大多数（95.8%）参与者未接受过过敏原免疫治疗。两名参与者（8.3%）达到主要终点并在第24周通过了DBPCFC。15名参与者（62.5%）报告了66起治疗中出现的不良事件，均为轻度或中度。在第24周的DBPCFC中，8名参与者（33.3%）出现2级过敏反应（无3级及以上反应）；10名（41.7%）使用肾上腺素作为急救药物。度普利尤单抗治疗使总IgE和ps-IgE的中位数分别降低了-54%和-49%，而ps-IgG4无变化。
度普利尤单抗单药治疗24周并未改善食物激发试验后对花生暴露的脱敏效果。
