Tolerance induction through non-avoidance to prevent persistent food allergy

对花生(PN)和坚果(TN)过敏的患者很少长大后就会康复。原因可能是患者保持严格的排泄饮食，独立于他们的引诱剂量(ED)。因此，我们在第一个资助期开始了一项针对PN或TN过敏和ED≥300mg蛋白质患者的随机安慰剂对照试验。我们假设，定期摄入低于ED是安全的，与完全避免的患者相比，将导致临床耐受性或一年内ED增加。同时，我们对致敏但耐受的患者进行了一项观察性研究(OS)，假设有规律的过敏原摄入可以防止食物过敏(FA)的再次发展。尽管由于COVID 19大流行而受到重大限制，139名患者(84名儿童和55名成人)完成了筛查双盲、安慰剂控制的食物挑战。72例患者在≥300 mg蛋白水平下发生反应，纳入随机对照试验，其中34例患者被随机分为避免饮食组和38例自由饮食组。28例患者耐受，进入OS。我们观察了儿童和成人患者的症状特征的主要差异，并在现有数据中进一步分析了这一点。我们的数据显示，心血管症状经常发生在成年人身上，但很少发生在儿童身上。此外，成年人比儿童对FA特有的生活质量的损害更大。到目前为止，有28名患者完成了随机对照试验。自由饮食组的ED显著增加，而避免过敏原组没有观察到这一点。没有因食用过敏原而引起的严重不良事件的报告。在OC组，10名患者完成了1年的评估。所有患者都经常食用过敏原。我们将申请费用中性的延长1年，以最终确定RCT和OC的招募和随访。同时，我们将在第二个资助期内对招募的患者再进行一年的随访。有自由饮食的过敏症患者将继续这种饮食一年，并进一步增加过敏原量，以评估长期疗效和安全性。来自严格避免过敏原组的患者将交叉进入消耗组，允许在同一患者体内直接比较严格避免过敏原与自由饮食。所有临床耐受的患者都将进入OSs。我们的数据将显示自由饮食是否安全，并促进已建立FA的患者的口服耐受发展。获得的生物样本(血清、PBMCs、唾液、粪便和皮肤交换)将支持该临床研究单位内的机械项目，以更好地表征和预测FA和耐受性。

Patients with peanut (PN) and tree nut (TN) allergy rarely outgrow their disease. The reason might be that patients maintain a strict elimination diet independent of their eliciting dose (ED). Therefore, we started in the 1st funding period a randomized placebo controlled trial (RCT) in patients with PN- or TN-allergy and ED ≥ 300 mg protein. We hypothesized that regularly consumption below the ED is safe and will result in clinical tolerance or an ED increase within one year compared to patients on complete avoidance. In parallel, we performed an observational study (OS) on sensitized but tolerant patients with the hypothesis that regular allergen consumption prevents the re-development of food allergy (FA).Despite major restrictions due to the COVID 19 pandemic, 139 patients (84 children and 55 adults) completed the screening double blind, placebo-controlled food challenge. 72 patients reacted at ≥ 300 mg protein and were included in the RCT with 34 patients randomized to the avoidance and 38 patients to the liberal diet group. 28 patients were tolerant and entered the OS. We observed major differences in the symptom profile of pediatric and adult patients and analyzed this further in existing data. Our data showed that cardiovascular symptoms are often occurring in adults but rarely in children. Furthermore, adults suffer from a higher impairment of the FA-specific quality of life than children. So far 28 patients completed the RCT. The group with the liberated diet showed a significant increase in the ED, which was not observed in the allergen avoidance group. No serious adverse events due to allergen consumption have been reported. In the OC, 10 patients completed the 1-year assessment. All patients consumed the allergen frequently.We will apply for a cost-neutral prolongation of 1 year in order to finalize the recruitment and follow-up of the RCT and the OC. In parallel we will follow-up the recruited patients for another year in the 2nd funding period. Allergic patients with a liberated diet will continue this diet for another year with a further increase of the allergen amounts in order to assess long-term efficacy and safety. Patients from the strict allergen avoidance group will cross-over to the consumption group allowing the direct comparison of strict allergen avoidance versus a liberated diet within the same patient. All patients who became clinically tolerant will enter the OS.Our data will show whether a liberated diet is safe and promotes oral tolerance development in patients with established FA. The obtained bio samples (serum, PBMCs, saliva, stool and skin swaps) will support the mechanistic projects within this clinical research unit to better characterize and predict FA and tolerance.