Tolerance induction through non-avoidance to prevent persistent food allergy

患有花生（PN）和树坚果（TN）过敏的患者很少能摆脱他们的疾病。原因可能是患者保持严格的排除性饮食，与诱导剂量（ED）无关。因此，我们在第一个资助期开始了一项随机安慰剂对照试验（RCT），研究对象是PN或tn过敏且ED≥300 mg蛋白的患者。我们假设，与完全不摄入ED的患者相比，定期摄入低于ED的ED是安全的，并且在一年内会导致临床耐受性或ED增加。同时，我们对敏感但耐受的患者进行了一项观察性研究（OS），假设定期食用过敏原可以防止食物过敏（FA）的再次发生。尽管受到COVID - 19大流行的重大限制，139名患者（84名儿童和55名成人）完成了筛查双盲、安慰剂对照的食物挑战。72例患者在≥300 mg蛋白质时发生反应，并被纳入RCT，其中34例患者随机分为避免饮食组，38例患者随机分为自由饮食组。28例患者耐受并进入OS。我们观察到儿童和成人患者在症状方面的主要差异，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人中，但很少发生在儿童中。此外，与儿童相比，成人的fa特异性生活质量受损程度更高。到目前为止，有28名患者完成了这项随机对照试验。自由饮食组的ED显著增加，这在避免过敏原组中没有观察到。没有因食用过敏原引起的严重不良事件的报道。在OC中，10例患者完成了为期1年的评估。所有患者都频繁食用过敏原。我们会申请以成本中立方式延长一年，以完成招募及跟进RCT及法团的工作。与此同时，我们将在第二个资助期对招募的患者进行为期一年的随访。使用自由饮食的过敏患者将继续这种饮食一年，并进一步增加过敏原的量，以评估长期疗效和安全性。严格避免过敏原组的病人会转到消费组这样就可以直接比较严格避免过敏原和自由饮食的病人。所有临床耐受的患者将进入生存期。我们的数据将显示游离饮食是否安全，并促进已确诊FA患者的口服耐受性发展。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.