Oral Immunotherapy Promising for Wheat Allergy

Diana Swift

November 06, 2018

Safe and effective oral immunotherapy (OIT) for wheat allergy has taken a step forward with promising results from a new trial. OIT with escalating doses of vital wheat gluten (VWG) successfully induced desensitization in more than half of children with wheat allergy who underwent treatment. The multicenter, randomized, placebo-controlled trial was published published online October 30 in the Journal of Allergy and Clinical Immunology.

But OIT for wheat allergy may require larger doses and longer treatment than that for other food allergies, the researchers say.

The study, led by Anna Nowak-Węgrzyn, MD, PhD, a researcher at the Elliot and Roslyn Jaffe Food Allergy Institute at the Icahn School of Medicine at Mount Sinai, New York City, randomly assigned 46 young people (mean age, 8.7 years; range, 4.2 – 22.3 years) with severe wheat allergy, as proven by skin prick challenge, to receive either placebo or low-dose VWG (70% wheat protein). Over 52 weeks, the VWG dose was increased every 2 weeks to 1445 mg of wheat protein.

After 52 weeks of treatment, 12 of 23 patients (52.2%) who received OIT were able to eat 4443 mg of wheat protein with no adverse reaction (the primary study endpoint), compared with 0% of 23 placebo recipients (P < .0001). That amount of wheat protein is approximately equivalent to one serving (one or two slices of bread, a hamburger bun, or a half cup of cooked pasta). At year 2, 7 of 23 (30.4%) low-dose VWG-treated participants were desensitized to a dose of 7443 mg of wheat protein, but only three (13%) were able to sustain unresponsiveness 8 to 10 weeks after discontinuation of therapy. At baseline, the median successfully consumed dose of wheat protein was 43 mg in both study groups.

The initial group that received active treatment continued to receive low-dose VWG for an additional year. These patients were retested for sustained unresponsiveness to wheat protein challenge.

After completing the double-blind phase, the placebo group crossed over to open-label treatment with a higher dose of VWG to a maximum of 2748 mg of wheat protein. Among these, 12 of 21 (57.1%) were desensitized after a year; these patients tolerated a median dose of 7443 mg of wheat protein.

Compared with OIT for egg allergy, however, VWG OIT led to desensitization and sustained unresponsiveness in fewer wheat-allergic patients treated for 2 years, suggesting the need for a higher dose, longer treatment duration, or both. Clinical trials in hen's egg, peanut, and cow's milk allergies have shown OIT desensitization rates of 70% to 80% with acceptable safety.

In comparison, in a multicenter trial of egg OIT, 55% of patients were desensitized to 3.75 g at month 10, 75% were desensitized to 6 g at month 22, and 28% achieved sustained unresponsiveness at month 24 (8 weeks off therapy). These results suggest that longer OIT translates to greater efficacy, the authors note.

Overall, 11 participants (24%) discontinued treatment. Of 7822 low-dose VWG doses in the first year, 15.4% were associated with adverse reactions; of these, 0.04% were severe, with 0.08% of participants requiring epinephrine rescue. Among 7921 placebo doses, 5.8% were associated with adverse reactions, none of which were severe. Reaction rates were similar to those in OIT trials for other food allergies.

Katherine Anagnostou, MD, PhD, an associate professor of pediatrics in the Section of Immunology, Allergy, and Rheumatology at Baylor College of Medicine, Houston, Texas, told Medscape Medical News, "This a very well-designed multicenter study and a welcome addition to the literature on wheat allergy. Even though the response was lower than the 60% to 80% we see with peanut allergy oral immunotherapy, the results are still very promising."

Anagnostou cautioned, however, that the study sample was small, that it consisted of severely allergic children, and that the rate of patients who dropped out of the study because of adverse reactions was high. "We might see more efficacy in a wider population with mild to moderate wheat allergy," she said. The next step should be to conduct larger trials using different doses in more diverse populations that represent the whole spectrum of wheat allergy severity.

Five pilot studies of OIT for pediatric wheat allergy have reported variable success with desensitization.

Explaining the lower response rate in a news release, Nowak-Węgrzyn, who is also a professor of pediatrics at the Icahn School of Medicine at Mount Sinai, said, "Wheat contains relatively low amounts of protein compared to peanut or milk, making it a little more challenging to study. Our results suggest that wheat allergy might be less responsive to OIT, thus requiring higher maintenance doses and likely a longer course of OIT." The authors call for larger studies to determine the optimal maintenance dose and duration of OIT for wheat allergy.

The study was supported by Linda and Bill Friend and the Harris Family Foundation, Food Allergy Research & Education, Inc, and Thermo Fisher Scientific. Dr Nowak-Wegrzyn and several study authors have disclosed financial relationships with one or more of the following companies or organizations: DBV Technologies, Astellas Pharma, Nutricia, Nestlé, UpToDate, the Gerber Institute, Merck, ALK-Abelló, Sanofi Aventis, Aimmune, HAL Allergy, Food Allergy Research & Education, Emmes Corporation, Danone, DST Diagnostic, Hipp, Hycor Biomedical, Thermo Fisher, ALK-Abelló, Allergo Pharma, Bausch & Lomb, Meda Pharma, MedUpdate, Nestlé, Novartis, Unilever, N-Fold, UCB SA, and Elsevier. Dr Anagnostou is principal investigator in several peanut allergy trials. She has disclosed no relevant financial relationships.

J Allergy Clin Immunol. Published online October 30, 2018. Abstract

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