Project Summary
Food allergy (FA) impacts approximately 33 million people in the US, contributing to substantial economic and emotional
burdens. Oral immunotherapy (OIT) is an effective treatment strategy to induce desensitization to specific food allergens,
in which participants consume increasing amounts of allergenic foods daily. However, there are several remaining
concerns that hinder its widespread implementation including the burdens of daily OIT maintenance dosing and
gastrointestinal complications such as the development of eosinophilic esophagitis (EoE).
OIT participants often find that continued daily OIT maintenance dosing is challenging, causing some participants to
discontinue dosing and potentially revert to their pre-OIT allergic state with rapid loss of desensitization and increased
risk of anaphylaxis. Therefore, there is an urgent need to identify whether less frequent OIT maintenance dosing
regimens can allow participants to maintain desensitization. Long-term follow up studies for participants who have
completed OIT clinical trials at our center show that 53% of participants had difficulty with continued OIT dosing, largely
due to lifestyle restrictions of when they can safely consume their daily OIT maintenance dose. This led to 30% of
participants discontinuing dosing for all their allergenic foods, highlighting the need for less burdensome maintenance
dosing options. Non-daily dosing regimen with 300 mg peanut allergen has not been sufficient, however higher
concentrations of non-daily dosing have not been investigated. In our CoFAR network-wide clinical trial we propose to
evaluate the safety and efficacy of non-daily OIT maintenance doses in maintaining peanut desensitization.
Gastrointestinal symptoms are common during oral immunotherapy (OIT) for food allergy (FA), with the majority of
patients experiencing mild to moderate symptoms of abdominal pain, nausea, or vomiting at some point during the
desensitization process. This raises concern for eosinophilic esophagitis which is a potential and serious side effect of OIT,
estimated to occur in 2-5% of patients on OIT. The diagnosis of EoE during OIT requires an endoscopy with biopsy to
confirm diagnosis, however, many patients forgo this procedure leading to inaccurate estimates of the true incidence.
Additionally, in a pilot study conducted by our site (POISED study), baseline eosinophilia exists in FA patients avoiding the
culprit antigen. Furthermore, OIT-induced gastrointestinal eosinophilia was mostly transient and asymptomatic. In
contrast, although most cases of OIT-associated EoE resolve with dose modification or cessation of OIT, a small subset of
FA participants have EoE symptoms that persist after stopping OIT. However, the mechanisms that drive these differences
in the clinical heterogeneity of EoE during FA treatment are not understood. FA and EoE are associated with changes in
the abundance and expression of key immune cells: eosinophils, mast cells, and gene expression profile of type 2 CD4+ T
cells in prospectively collected biopsies. Exploring these characteristics can provide valuable insights into the underlying
mechanisms and potentially help tailor treatment approaches and drive novel diagnostic techniques.