美国斯坦福大学Kari C Nadeau研究团队在研究中取得进展。他们探讨了花生过敏口服免疫疗法（OIT）的效果。 2019年9月12日，知名学术期刊《柳叶刀》在线发表了这一成果。
2014年4月15日至2016年3月2日，课题组在斯坦福大学肖恩帕克过敏和哮喘研究中心进行了一项随机、双盲、安慰剂对照的临床2期试验，招募了120名7-55岁的花生过敏患者，皮肤点刺试验（SPT）结果阳性，花生特异性免疫球蛋白（lg）E浓度大于4 kU/L。参与者按2.4：1.4：1随机分配，所有人均每日进食4000 mg花生蛋白并持续104周，之后停止摄入（花生0组，60例），或每天摄入300 mg花生蛋白（花生300组，35例），或摄入燕麦粉（安慰剂组，25例），持续52周。花生粉和燕麦粉外观和味道相似，必要时参与者可戴上鼻夹，以掩盖味道。
花生0组中有21例（35%）参与者在104周和117周进食4000 mg花生蛋白未发生过敏，安慰剂组中有1名（4%），优势比为12.7。在整个研究中，最常见的不良反应是轻度胃肠道症状，共有90例发生，其中花生0组50例，花生300组29例，安慰剂组11例；其次为皮肤病，共有50例发生，其中花生0组26例，花生300组15例，安慰剂组9例。随着时间的推移，各组不良反应逐渐减少。3年的研究中，共有2名参与者发生严重不良反应。第156周，花生0组中有8名（13%）参与者进食4000 mg花生蛋白未发生过敏，更高的基线花生特异性lgG4 / lgE比值，更低的Ara h 2 IgE与持续的低过敏反应显著相关。未发生与治疗相关的死亡事件。
研究表明，花生OIT可使4000 mg花生蛋白过敏的人脱敏，但停药或减量至每日300 mg，仍会增加临床上花生再过敏的可能性。
附：英文原文
Title: Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study
Author: R Sharon Chinthrajah, Natasha Purington, Sandra Andorf, Andrew Long, Katherine L OLaughlin, Shu Chen Lyu, Monali Manohar, Scott D Boyd, Robert Tibshirani, Holden Maecker, Marshall Plaut, Kaori Mukai, Mindy Tsai, Manisha Desai, Stephen J Galli, Kari C Nadeau
Issue&Volume: 12 September 2019
Summary:
Background
Dietary avoidance is recommended for peanut allergies. We evaluated the sustained effects of peanut allergy oral immunotherapy (OIT) in a randomised long-term study in adults and children.
Methods
In this randomised, double-blind, placebo-controlled, phase 2 study, we enrolled participants at the Sean N Parker Center for Allergy and Asthma Research at Stanford University (Stanford, CA, USA) with peanut allergy aged 7–55 years with a positive result from a double-blind, placebo-controlled, food challenge (DBPCFC; ≤500 mg of peanut protein), a positive skin-prick test (SPT) result (≥5 mm wheal diameter above the negative control), and peanut-specific immunoglobulin (Ig)E concentration of more than 4 kU/L. Participants were randomly assigned (2·4:1·4:1) in a two-by-two block design via a computerised system to be built up and maintained on 4000 mg peanut protein through to week 104 then discontinued on peanut (peanut-0 group), to be built up and maintained on 4000 mg peanut protein through to week 104 then to ingest 300 mg peanut protein daily (peanut-300 group) for 52 weeks, or to receive oat flour (placebo group). DBPCFCs to 4000 mg peanut protein were done at baseline and weeks 104, 117, 130, 143, and 156. The pharmacist assigned treatment on the basis of a randomised computer list. Peanut or placebo (oat) flour was administered orally and participants and the study team were masked throughout by use of oat flour that was similar in look and feel to the peanut flour and nose clips, as tolerated, to mask taste. The statistician was also masked. The primary endpoint was the proportion of participants who passed DBPCFCs to a cumulative dose of 4000 mg at both 104 and 117 weeks. The primary efficacy analysis was done in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02103270.
Findings
Between April 15, 2014, and March 2, 2016, of 152 individuals assessed, we enrolled 120 participants, who were randomly assigned to the peanut-0 (n=60), peanut-300 (n=35), and placebo groups (n=25). 21 (35%) of peanut-0 group participants and one (4%) placebo group participant passed the 4000 mg challenge at both 104 and 117 weeks (odds ratio [OR] 12·7, 95% CI 1·8–554·8; p=0·0024). Over the entire study, the most common adverse events were mild gastrointestinal symptoms, which were seen in 90 of 120 patients (50/60 in the peanut-0 group, 29/35 in the peanut-300 group, and 11/25 in the placebo group) and skin disorders, which were seen in 50/120 patients (26/60 in the peanut-0 group, 15/35 in the peanut-300 group, and 9/25 in the placebo group). Adverse events decreased over time in all groups. Two participants in the peanut groups had serious adverse events during the 3-year study. In the peanut-0 group, in which eight (13%) of 60 participants passed DBPCFCs at week 156, higher baseline peanut-specific IgG4 to IgE ratio and lower Ara h 2 IgE and basophil activation responses were associated with sustained unresponsiveness. No treatment-related deaths occurred.
Interpretation
Our study suggests that peanut OIT could desensitise individuals with peanut allergy to 4000 mg peanut protein but discontinuation, or even reduction to 300 mg daily, could increase the likelihood of regaining clinical reactivity to peanut. Since baseline blood tests correlated with week 117 treatment outcomes, this study might aid in optimal patient selection for this therapy.
DOI: 10.1016/S0140-6736(19)31793-3
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31793-3/fulltext
LANCET：《柳叶刀》，创刊于1823年。隶属于爱思唯尔出版社，最新IF：202.731
官方网址：http://www.thelancet.com/
投稿链接：http://ees.elsevier.com/thelancet
本期文章：《柳叶刀》：Online/在线发表
