美国阿肯色州儿童医院Stacie M Jones团队研究了口服免疫疗法对4岁以下花生过敏儿童的疗效和安全性。相关论文于2022年1月22日发表在《柳叶刀》杂志上。

对于花生过敏的幼童，目前的治疗标准是避免饮食。该研究旨在评估口服花生免疫治疗是否能在这一人群中诱导脱敏（治疗期间过敏反应阈值增加）或缓解（停止免疫治疗后无过敏的状态）。

研究组在五个美国学术医疗中心进行了一项随机、双盲、安慰剂对照研究。符合条件的参与者是12到48个月的儿童，他们在双盲、安慰剂对照的食物挑战（DBPCFC）中对500 mg或更少的花生蛋白过敏。

将参与者以2:1随机分配，分别接受花生口服免疫治疗（每天2000 mg花生蛋白）或安慰剂134周，然后停止26周，参与者、研究人员均双盲。主要结局是在治疗结束时（第134周）脱敏和停止治疗后缓解（160周），作为关键次要结局，DBPCFC在意向治疗人群中将其评估为5000 mg。在同一人群中评估安全性和免疫学参数。

2013年8月13日至2015年10月1日，研究组共招募了146名中位年龄为39.3个月的儿童，将其随机分配，其中96名接受花生口服免疫治疗，50名接受安慰剂治疗。在第134周，花生口服免疫治疗组中有68名（71%）患儿达到脱敏的主要结局，显著优于安慰剂组的1名（2%）。

第134周花生口服免疫治疗组的中位累积耐受剂量为5005 mg，显著高于安慰剂组的5 mg。停止治疗后，花生口服免疫治疗组中有20名（21%）患儿符合缓解标准，而安慰剂组有1名（2%），组间差异显著。

花生口服免疫治疗组在第160周的中位累积耐受剂量为755 mg，显著高于安慰剂组的0 mg。在134周通过5000 mg耐受剂量的花生口服免疫治疗的患儿中，有相当一部分在160周不再耐受5000 mg。接受安慰剂治疗的受试者在134周时脱敏，在160周时也获得缓解。

与安慰剂组相比，花生口服免疫治疗组在134周和160周时降低了花生特异性和Ara h2特异性IgE、皮肤点刺试验和嗜碱性粒细胞活化，并增加了花生特异性和Ara h2特异性IgG4。通过对花生口服免疫治疗组进行多变量回归分析，年龄较小和基线花生特异性IgE较低可预测病情缓解。

大多数参与者（98%接受花生口服免疫疗法，80%接受安慰剂）至少有一次口服免疫疗法给药反应，主要为轻度至中度反应，且在接受花生口服免疫疗法的参与者中发生频率更高。花生口服免疫治疗组中有21名参与者使用肾上腺素治疗35起中度症状的口服免疫治疗剂量事件。

研究结果表明，在花生过敏儿童中，4岁之前开始花生口服免疫治疗与脱敏和缓解的增加相关。病情缓解的发展与免疫学生物标志物相关。研究结果表明，在幼儿时期进行干预可缓解花生过敏症状。

附：英文原文

Title: Efficacy and safety of oral immunotherapy in children aged 1–3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study

Author: Stacie M Jones, Edwin H Kim, Kari C Nadeau, Anna Nowak-Wegrzyn, Robert A Wood, Hugh A Sampson, Amy M Scurlock, Sharon Chinthrajah, Julie Wang, Robert D Pesek, Sayantani B Sindher, Mike Kulis, Jacqueline Johnson, Katharine Spain, Denise C Babineau, Hyunsook Chin, Joy Laurienzo-Panza, Rachel Yan, David Larson, Tielin Qin, Don Whitehouse, Michelle L Sever, Srinath Sanda, Marshall Plaut, Lisa M Wheatley, A Wesley Burks

Issue&Volume: 2022/01/22

Abstract:

Background

For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.

Methods

We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.

Findings

Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8–44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61–80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05–11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59–79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755–5005) for peanut oral immunotherapy versus 5 mg (0–105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13–30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05–11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10–28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0–2755) for peanut oral immunotherapy and 0 mg (0–55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy.

Interpretation

In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy.

DOI: 10.1016/S0140-6736(21)02390-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02390-4/fulltext