Tolerance induction through non-avoidance to prevent persistent food allergy

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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.