Oral Immunotherapy for Food Allergy

The goal of this clinical trial is to learn whether oral immunotherapy (OIT) is safe and effective for treating food allergy in children aged 0-2 years with peanut, tree nut, or sesame allergy. The study also aims to identify biological mechanisms and biomarkers associated with natural tolerance development and successful OIT using a systems biology approach. The main questions it aims to answer are: 1. Does oral immunotherapy increase the likelihood of successful desensitization and sustained unresponsiveness compared with allergen avoidance? 2. Can immune, microbiome, metabolomic, genetic, and epigenetic profiles predict treatment response, natural tolerance development, and long-term outcomes? Researchers will compare children receiving oral immunotherapy with children receiving standard care (allergen avoidance) to determine differences in treatment success, sustained unresponsiveness, safety, quality of life, and biological markers. Participants will: * Be randomized to either oral immunotherapy or allergen avoidance for 18-24 months. * Undergo oral food challenges at study visits to assess allergic reactivity and treatment outcomes. * Provide blood, urine, hair, skin swabs, skin tape strips, throat swabs, nasal lining fluid, and stool samples at baseline and at the end of the study for immune, microbiome, metabolomic, gene expression, and epigenetic analyses. * Complete allergy assessments, including skin prick testing and clinical evaluations. * Have allergic symptoms, adverse reactions, and development of other allergic diseases monitored throughout the study. * Have parents complete questionnaires assessing food allergy-related quality of life, anxiety, and coping.

This study aims to evaluate the efficacy and safety of multi-food oral immunotherapy (multi-OIT) using peanut and tree nuts proteins in children with confirmed food allergy to at least two allergens. Participants will be randomized in a 2:1 ratio to receive either multi-OIT or standard management consisting of an elimination diet. The primary objective is to evaluate immunotherapy efficacy defined as achieving tolerance to a cumulative dose of 4444 mg of protein during an oral food challenge (OFC-2) for at least one allergen that elicited a reaction during baseline challenge (OFC-1), compared with the control group. Secondary outcomes include the proportion of participants tolerating multiple allergens at the target cumulative dose; the incidence, type, and severity of adverse events classified according to the World Allergy Organization (WAO) grading system; changes in immunological parameters, including allergen-specific IgE and IgG4 levels; changes in skin prick test responses; changes in the quality of life of patients and their families.

Most food allergies that begin in early childhood are mild and resolve by school age, but nut allergies persist in about 80-90% of individuals into adulthood. The consumption of nuts, particularly cashew nuts, has increased dramatically in Finland in the 21st century, leading to a rise in severe allergic reactions to cashew nuts among young children. Of the food anaphylaxis cases reported in the Finnish Anaphylaxis Registry between 2015-2020, 49% were caused by nuts, with cashew nuts being the most common trigger. The standard treatment for nut allergies is strict avoidance of nuts and symptom management with emergency medications. Oral immunotherapy (OIT) is a food allergy treatment that increases tolerance, and it has primarily been studied in school-aged children, with desensitization achieved in about 80% of cases. Permanent tolerance, depending on the allergen, develops in 30-50% of cases within five years. International guidelines recommend peanut OIT for children over the age of 4 who have severe peanut allergies. The likelihood of achieving tolerance, especially permanent tolerance, appears to improve the earlier the treatment is started. To date, only one study (NUIT CRACKER) has been published on cashew nut desensitization in children over 4 years old, involving 50 children, where 88% achieved desensitization to both cashew nuts and pistachios. The aim of this study is to develop a cashew nut desensitization protocol and investigate its effectiveness in achieving tolerance and permanent desensitization in children aged 1-17 years, compared to cashew nut avoidance. The study will assess the safety of cashew nut desensitization and its impact on the quality of life of patients and their families.