临床试验找到治疗花生过敏新方法

                                                    临床试验找到治疗花生过敏新方法
" }( p& `6 K7 l: y* q3 d- D对于一些孩子来说，即使是非常少量的花生都可能致命。但迄今为止，除了完全避免接触花生，这些对花生过敏的儿童还没有其他疗法可供选择。一个新的临床试验结果可能会改变这一现状。科学家发现，让过敏儿童每天摄入少量的花生蛋白质（被称作口服免疫治疗）有助于治疗过敏症。
7 l: v. _7 f4 X/ A9 R+ y8 r并未参与该研究的英国伦敦大学国王学院儿童过敏症专科医师Gideon Lack说：“这是非常重要的第一步。但我认为，我们还没有作好进入临床实践阶段的准备。”
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在一些发达国家（例如美国、英国），约1%的儿童对花生过敏。患儿的免疫系统会对坚果中的蛋白质产生反应，在某些严重病例中，这种反应会导致呼吸停止、血压急剧下降、器官缺氧。参与该研究的剑桥大学医院NHS信托基金会儿童过敏症专科医师Andrew Clark说，这种情况给患儿家庭造成很大压力，因为即使一些中度过敏的孩子也可能发生命悬一线的意外。

* i6 j" _, l* q' F* C# v1 p2 f一些研究显示，让孩子逐渐增加对花生的接触剂量可使他们脱敏，但一直没有大型临床试验证明这一点。20世纪90年代，一些研究尝试皮内注射抗原，但副作用很严重。在一项研究中，一名患者因剂量错误而死亡。Clark说：“正因为如此，近十到二十年没有人再尝试该领域的研究。”

( G7 r7 ^- p# q& {4 s) MClark和同事选择了39名7~16岁儿童过敏患者作为研究对象。这些患儿食谱中包括少量的花生粉——摄取剂量从2毫克逐渐增加至800毫克（约相当于5个花生）。实验对照组是46个花生过敏患儿，他们被要求严格避免任何坚果。6个月后，39名治疗组儿童中有24名完成实验，并可以耐受1400毫克的花生且不会出现过敏反应。而对照组则没有一人获得这样的缓解。该研究发表于近日的《柳叶刀》杂志上。


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Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial文献检索：doi:10.1016/S0140-6736(13)62301-6
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Background
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1 l$ v/ S$ c2 {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.
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Methods

; v7 m, ?9 V, H1 x' g& m- e& x8 wWe 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.

Findings

: ]5 D: h7 N+ @. M6 U" }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). Interpretation

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.