Published online: October 30, 2018
Wheat is one of the most common childhood food allergens capable of inducing anaphylaxis. Management of wheat allergy is challenging due to the ubiquitous presence of wheat in the diet. Patients with high wheat IgE levels are likely to have persistent wheat allergy. Oral immunotherapy (OIT) for foods such as cow’s milk, egg, and peanut showed promising results, including a high rate (70-80%) of subjects reaching desensitization with an acceptable safety profile.
The results of the first multicenter, randomized, double-blind placebo-controlled clnical trial of wheat OIT were recently published in The Journal of Allergy and Clinical Immunology (JACI) by Nowak-Wegrzyn et al. The investigators at five US centers led by Hugh A. Sampson, MD, conducted OIT with high protein vital wheat gluten flour. Forty-six wheat-allergic subjects, median age 8.7 years (range: 4.2-22.3) were randomized 1:1 to low-dose-OIT or placebo, with escalation every 2 weeks to 1445 mg wheat protein. After 1 year, active subjects underwent a wheat challenge to evaluate for desensitization (ability to ingest an increased dose of wheat compared to pre-treatment dose) while on OIT, and then were continued low-dose wheat OIT for another year. After 2 years, they underwent a repeat wheat challenge, and if passed, a subsequent off-therapy wheat challenge to evaluate sustained unresponsiveness (a surrogate term for continued desensitization off therapy). Placebo subjects crossed-over to a high-dose-OIT, maximum 2748 mg wheat protein daily dose and underwent a desensitization oral wheat challenge after 1 year.
OIT with low and high doses of vital wheat gluten flour induced desensitization in the majority of treated subjects after 1 year of therapy; 52.2% in the low dose OIT and 57.1% in the high dose wheat OIT. Following 2 years of lower dose wheat OIT, 13% of the treated subjects achieved sustained unresponsiveness, defined as ability to ingest a full serving of wheat without any allergic symptoms afer having stopped wheat OIT for 8 –10 weeks. The profile of dose-related adverse reactions in wheat OIT was comparable with oral immunotherapy to other foods. Low- and high-dose wheat OIT were not significantly different regarding dosing symptoms. Overall 24% of the subjects discontinued the trial, predominantly due to the gastrointestinal symptoms of abdominal pain / discomfort, and vomiting.
In this first multicenter rigorous clinical trial of low-and high-dose wheat OIT, desensitization was induced in the majority of the treated subjects after one year of treatment. Compared to egg, milk or peanut OIT, wheat OIT induced desensitization and sustained unresponsiveness in a lower percentage of subjects treated for 2 years, suggesting that a higher dose and or longer duration may be necessary for wheat-allergic subjects. The profile of dose-related adverse events in wheat OIT was comparable with OIT to other foods. This trial provides the first safety and efficacy results for wheat OIT in a large group of patients with wheat allergy, and supports further study to establish the optimal maintenance dose and duration of wheat OIT.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
Multicenter, randomized, double-blinded, placebo-controlled clinical trial of vital wheat gluten oral immunotherapy