Lower, high doses of wheat oral immunotherapy desensitized majority of children

ATLANTA — Lower and high doses of wheat oral immunotherapy induced significant desensitization in most wheat-allergic children following 1 year of treatment, according to data presented at the annual meeting of the American Academy of Allergy, Asthma & Immunology.

“While the majority of children outgrow wheat allergy, the subgroup that does retain it tend to have severe reactions when they experience accidental ingestion, and trying to avoid wheat in the American diet is difficult,” Hugh A. Sampson, MD, from the department of pediatrics at the Icahn School of Medicine at Mount Sinai, said during a press conference. “Wheat is also different than other proteins, such as milk, egg, peanut, in which the allergenic protein is well-characterized – this is not the case with wheat.”

Hugh A. Sampson

To determine safety and efficacy of wheat oral immunotherapy, Sampson and colleagues enrolled children with wheat allergies (n=46) were randomized 1:1 to receive wheat oral immunotherapy with high-gluten wheat flour or placebo.

At the baseline double-blind placebo-controlled food challenge, both groups successfully consumed a median of 43 mg of wheat protein. The wheat skin prick test results were also comparable between placebo (4.6 mm) and oral immunotherapy (3.4 mm) groups at baseline.

For the study, researchers escalated doses biweekly for 44 weeks up to a maximum dosage of 1,445 mg wheat protein for at least eight weeks of maintenance.

After the first year, patients in the placebo group were crossed over to receive wheat oral immunotherapy for 52 weeks at a maximum dose of 3,870 mg, while patients in the treatment group continued with maintenance at a maximum dose of 2,035 mg. Immunotherapy patients continued for an additional year, underwent another double-blind placebo-controlled food challenge at year 2, and if they passed, were taken off treatment.

According to study results, following two years of lower dose wheat oral immunotherapy, 30.4% of patients achieved desensitization while 13% had sustained unresponsiveness 8-10 weeks after wheat immunotherapy had been stopped.

Following the first year of the trial, 66.7% of crossover patients receiving the high dose passed the 4,443 mg oral challenge while 57.1% were desensitized with a median successfully consumed dose of 7,443 mg.

Sampson and colleagues found that among patients who had received oral immunotherapy, median serum IgG4 levels after 1 year were greater than placebo patients: wheat (22.0 vs. 3.05 mgA/L, P=.0005), omega-5-gliadin (7.34 vs 0.62 mgA/L, P=.0001). Additionally, the researchers noted that the successfully consumed dose after year one was associated with year one wheat (rho statistic 0.56, P=.0002) and omega-5-gliadin-sIgG4 (0.49, P= .002).

Among 21,044 wheat immunotherapy/crossover-doses, only 11.2% experienced adverse reactions, with 0.05% receiving epinephrine, compared to 6% adverse reactions among 7,922 placebo-doses.

“Oral immunotherapy with vital wheat gluten did lead to significant increase in a threshold of reactivity for the majority of patients who received it,” Sampson said. “The higher dose did seem to generate higher tolerance for a higher threshold than did the lower dose, and the adverse reaction rate was not significantly different — perhaps the higher dose will be an even more effective route.” – by Bob Stott

Reference:

Sampson H, et al. Abstract L10. Presented at: American Academy of Allergy, Asthma & Immunology Annual Meeting; March 3-6, 2017; Atlanta.

Disclosure: The researchers report no relevant financial disclosures.