Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial.
Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial.
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DOI：
10.1016/s0140-6736(13)62301-6
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发表时间：
2014-04-12
期刊：
影响因子：
168.9
通讯作者：
Clark, Andrew
中科院分区：
文献类型：
--
作者：
Anagnostou, Katherine;Islam, Sabita;King, Yvonne;Foley, Loraine;Pasea, Laura;Bond, Simon;Palmer, Chris;Deighton, John;Ewan, Pamela;Clark, Andrew
小型研究表明，花生口服免疫疗法（OIT）可能是有效的治疗花生过敏。我们的目的是确定OIT对花生过敏儿童脱敏的疗效。我们在NIHR/Wellcome Trust剑桥临床研究机构（剑桥，英国）进行了一项随机对照交叉试验，以比较主动OIT（使用特征花生粉;蛋白质剂量为2-800 mg/天）与对照（避免花生，目前的护理标准）的疗效。随机化（1：1）通过使用稽查的在线系统进行;组分配未设盲。符合条件的参与者年龄在7-16岁之间，摄入花生后出现速发型超敏反应，花生皮肤点刺试验阳性，双盲安慰剂对照食物激发试验（DBPCFC）阳性。如果参与者患有严重的慢性疾病，如果护理提供者或目前的家庭成员怀疑或诊断对花生过敏，或者如果不愿意或无法遵守研究程序，我们将其排除在外。我们的主要结果是脱敏，定义为6个月时花生激发（DBPCFC中1400 mg蛋白质）阴性（第一阶段）。对照组参与者在第二阶段接受OIT，随后接受DBPCFC。免疫学参数和疾病特异性生活质量评分进行了测量。分析是通过意向性治疗。Fisher精确检验用于比较第一阶段结束时活性组和对照组之间6个月后对花生脱敏的比例。本试验在Current Controlled Trials注册，编号ISRCTN 62416244。在第一阶段后，活性组中62%（39名参与者中的24名; 95%CI 45-78）记录了主要结局，脱敏，而对照组中没有（0/46; 95%CI 0-9; p<0.001）。84%（95% CI 70-93）的活性组耐受每日摄入800 mg蛋白质（相当于大约5个花生）。OIT后花生阈值增加的中位数为1345 mg（范围45-1400; p<0.001）或25.5倍（范围1.82 -280; p<0.001）。在第二阶段后，54%（95% CI 35-72）耐受1400 mg挑战（相当于大约10个花生），91%（79-98）耐受每日摄入800 mg蛋白质。OIT后生活质量评分改善（降低）（中位数变化-1.61; p<0.001）。大多数参与者的副作用轻微。总体而言，胃肠道症状最常见（31例受试者出现恶心，31例出现呕吐，1例出现腹泻），然后是6.3%剂量后的口腔瘙痒（76例受试者）和0.41%剂量后的喘息（21例受试者）。在0.01%剂量（1名受试者）后使用肌内肾上腺素。OIT成功地诱导了研究人群中大多数患有任何严重程度花生过敏的儿童的脱敏，花生阈值有临床意义的增加。干预后生活质量得到改善，并且具有良好的安全性。免疫学变化与临床脱敏一致。建议在更广泛的人群中进行进一步的研究;花生OIT不应在非专业环境中进行，但在研究的年龄组中有效且耐受性良好。MRC-NIHR伙伴关系。
Small studies suggest peanut oral immunotherapy (OIT) might be effective in the treatment of peanut allergy. We aimed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts. We did a randomised controlled crossover trial to compare the efficacy of active OIT (using characterised peanut flour; protein doses of 2–800 mg/day) with control (peanut avoidance, the present standard of care) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility (Cambridge, UK). Randomisation (1:1) was by use of an audited online system; group allocation was not masked. Eligible participants were aged 7–16 years with an immediate hypersensitivity reaction after peanut ingestion, positive skin prick test to peanuts, and positive by double-blind placebo-controlled food challenge (DBPCFC). We excluded participants if they had a major chronic illness, if the care provider or a present household member had suspected or diagnosed allergy to peanuts, or if there was an unwillingness or inability to comply with study procedures. Our primary outcome was desensitisation, defined as negative peanut challenge (1400 mg protein in DBPCFC) at 6 months (first phase). Control participants underwent OIT during the second phase, with subsequent DBPCFC. Immunological parameters and disease-specific quality-of-life scores were measured. Analysis was by intention to treat. Fisher's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase. This trial is registered with Current Controlled Trials, number ISRCTN62416244. The primary outcome, desensitisation, was recorded for 62% (24 of 39 participants; 95% CI 45–78) in the active group and none of the control group after the first phase (0 of 46; 95% CI 0–9; p<0·001). 84% (95% CI 70–93) of the active group tolerated daily ingestion of 800 mg protein (equivalent to roughly five peanuts). Median increase in peanut threshold after OIT was 1345 mg (range 45–1400; p<0·001) or 25·5 times (range 1·82–280; p<0·001). After the second phase, 54% (95% CI 35–72) tolerated 1400 mg challenge (equivalent to roughly ten peanuts) and 91% (79–98) tolerated daily ingestion of 800 mg protein. Quality-of-life scores improved (decreased) after OIT (median change −1·61; p<0·001). Side-effects were mild in most participants. Gastrointestinal symptoms were, collectively, most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), then oral pruritus after 6·3% of doses (76 participants) and wheeze after 0·41% of doses (21 participants). Intramuscular adrenaline was used after 0·01% of doses (one participant). OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes corresponded with clinical desensitisation. Further studies in wider populations are recommended; peanut OIT should not be done in non-specialist settings, but it is effective and well tolerated in the studied age group. MRC-NIHR partnership.