Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA.
Departments of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, USA.
Lancet. 2022 Jan 22;399(10322):359-371. doi: 10.1016/S0140-6736(21)02390-4.
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.
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.
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.
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.
National Institute of Allergy and Infectious Disease, Immune Tolerance Network.
对于患有花生过敏的幼儿，饮食回避是目前的标准治疗方法。我们旨在评估花生口服免疫疗法是否可以在该人群中诱导脱敏（治疗过程中过敏反应阈值增加）或缓解（免疫治疗停止后无反应状态）。
我们在美国五家学术医疗中心进行了一项随机、双盲、安慰剂对照研究。符合条件的参与者为年龄在 12 至 48 个月之间、在双盲安慰剂对照食物挑战（DBPCFC）中对 500 毫克或以下花生蛋白呈阳性反应的儿童。参与者通过计算机以 2:1 的分配比例随机分配，接受花生口服免疫疗法或安慰剂治疗 134 周（每天 2000 毫克花生蛋白），然后进行 26 周的回避，参与者、研究人员和研究人员对组治疗分配均设盲。主要结局是治疗结束时（第 134 周）的脱敏，以及回避后的缓解（第 160 周），作为关键次要结局，在意向治疗人群中通过 DBPCFC 评估至 5000 毫克。安全性和免疫参数也在同一人群中进行了评估。这项试验在 ClinicalTrials.gov 上注册，NCT03345160。
在 2013 年 8 月 13 日至 2015 年 10 月 1 日期间，共有 146 名儿童入组，中位年龄为 39.3 个月（IQR 30.8-44.7），随机分配接受花生口服免疫疗法（96 名参与者）或安慰剂（50 名参与者）。在第 134 周时，96 名接受花生口服免疫疗法的参与者中有 68 名（71%，95%CI 61-80）与 50 名接受安慰剂的参与者中的 1 名（2%，0.05-11）达到了脱敏的主要结局（风险差异[RD] 69%，95%CI 59-79；p<0.0001）。在第 134 周的 DBPCFC 中，接受花生口服免疫疗法的参与者的累积耐受剂量中位数为 5005 毫克（IQR 3755-5005），而接受安慰剂的参与者为 5 毫克（0-105）（p<0.0001）。回避后，96 名接受花生口服免疫疗法的参与者中有 20 名（21%，95%CI 13-30）与 50 名接受安慰剂的参与者中的 1 名（2%，0.05-11）达到了缓解标准（RD 19%，95%CI 10-28；p=0.0021）。在第 160 周的 DBPCFC 中，接受花生口服免疫疗法的参与者的累积耐受剂量中位数为 755 毫克（IQR 0-2755），而接受安慰剂的参与者为 0 毫克（0-55）（p<0.0001）。在第 134 周通过 5000 毫克 DBPCFC 的接受花生口服免疫疗法的参与者中，有相当一部分人在第 160 周时不能再耐受 5000 毫克（p<0.001）。在第 134 周时被脱敏的接受安慰剂的参与者也在第 160 周时达到了缓解。与安慰剂相比，花生口服免疫疗法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激活，并在第 134 周和第 160 周增加了花生特异性和 Ara h2 特异性 IgG4。通过对接受花生口服免疫疗法的参与者进行多变量回归分析，年龄较小和基线花生特异性 IgE 较低与缓解相关。大多数参与者（98%接受花生口服免疫疗法与 80%接受安慰剂）有至少一次口服免疫疗法剂量反应，主要为轻至中度，且在接受花生口服免疫疗法的参与者中更常见。在 21 名接受花生口服免疫疗法的参与者中，有 35 次口服免疫疗法剂量事件出现中度症状，用肾上腺素治疗。
在患有花生过敏的儿童中，在 4 岁之前开始花生口服免疫疗法与脱敏和缓解的增加有关。缓解的发展与免疫生物学标志物相关。这些结果表明，在儿童时期存在一个干预的机会窗口，可以诱导花生过敏的缓解。
国家过敏和传染病研究所，免疫耐受网络。
