Laird Harrison

March 08, 2017

ATLANTA — After consuming small amounts of wheat protein, some people with wheat allergy can become desensitized, according to new research.

If the findings are borne out in further studies, the therapy could reduce the risk associated with one of the most serious and common food allergies, said investigator Anna Nowak-Wegrzyn, MD, PhD, from the Mount Sinai Health System in New York City.

"Wheat is everywhere," she told Medscape Medical News. "Even though [the therapy] didn't cure the allergy, it provided significant protection. That's a big benefit."

She presented the study findings here at the American Academy of Allergy, Asthma and Immunology Meeting.

Wheat has a higher protein content than most other cereals or rice. In people allergic to wheat, trace amounts can sometimes lead to an anaphylactic reaction. But so far, only two small studies have tested oral immunotherapy to address this sensitivity.

So Dr Nowak-Wegrzyn and her colleagues decided to see if small amounts of wheat protein — in the form of vital wheat gluten flour that had undergone gamma radiation to improve sterility — could desensitize people with the allergy.

They chose vital wheat gluten flour because the protein content is so high; 1 oz contains 7.0 g of wheat protein, whereas 1 oz of wheat flour contains only 1.6 g of wheat protein. In addition, it is absorbed quickly, so delayed reactions are less likely.

At first, the vital wheat gluten flour was supplied in premeasured capsules and packets. Subsequently, it was supplied as a bulk powder that could be measured at home with a special scoop. The flavor is not strong, and the study participants typically sprinkled it on food.

All 48 participants tested positive on a wheat skin-prick test or had a serum wheat-specific immunoglobulin E level above 0.35 kUA/L, and all reacted to less than 1443 mg of wheat protein. Median age in the study cohort was 8.6 years (range, 4 - 22 years).

People deemed by the researchers to be at severe risk for anaphylaxis were excluded from the study.

Gradually Rising Dose of Wheat Gluten Flour

Over the course of 44 weeks, 24 patients were randomized to a gradually escalating dose of wheat gluten flour, to a maximum daily dose of 1445 mg. The 24 patients in the placebo group received corn starch in escalating doses.

At 1 year, 52.2% of the wheat group was able to consume 4443 mg of wheat protein without reacting, whereas 0.0% of the placebo group was — a significant difference (P < .0001).

For the next 52 weeks, people in the placebo group crossed over to a high-dose group, and they received vital wheat gluten flour in doses escalated to a daily maximum of 3870 mg. People in the original wheat group continued on the low dose.

At 2 years, 66.7% of the high-dose group was able to consume 4443 mg of wheat protein without reacting.

Although the difference between the high-dose and low-dose groups did not reach statistical significance, it suggests that a higher dose might be more effective, said Dr Nowak-Wegrzyn.

In the low-dose group, 39.1% of participants — who had been treated for 2 years — were able to consume 7443 mg of wheat protein, which is about as much wheat protein as is in a cup of pasta.

The low-dose group then stopped taking the wheat gluten flour. Two months later, three of the 23 (13%) participants were still able to consume 7443 mg of wheat protein without reacting, which the investigators defined as "sustained unresponsiveness."

This rate of sustained unresponsiveness is lower than has been achieved in some other oral immunotherapy trials, such as with egg, they point out.

Wheat allergies are scary.

After 1 year, levels of wheat-specific immunoglublin G4, considered a marker for food tolerance, were higher in the low-dose group than in the placebo group. These levels correlated with the ability of the participants to consume wheat.

Of the 21,044 doses of wheat gluten flour consumed in this trial, 11.2% were followed by adverse reactions, such as itchy throat, stomach ache, and nausea. Of these adverse reactions, 0.02% were severe and 0.05% were treated with epinephrine. There was no significant difference in adverse reactions between the high-dose and low-dose groups.

"I might say that this is not different from what has been reported in the literature for peanut or milk," said Dr Nowak-Wegrzyn.

Of the 7922 doses of placebo consumed, 6.0% were followed by adverse reactions, but none were severe and none of the patients were treated with epinephrine.

Two people dropped out while taking the placebo, three dropped out after crossing over to the high-dose group (one because of dosing symptoms), and five dropped out while taking the low dose of wheat gluten flour (three because of dosing symptoms).

People with wheat allergy should not attempt to desensitize themselves with wheat gluten flour because of the risk for serious adverse reactions, said study investigator Hugh Sampson, MD, from the Mount Sinai Medical Center in New York City. "You can run into big problems," he warned during a news conference.

Industry funding will be required for future research. "The problem is that these studies are very expensive," he explained.

After the presentation, a member of the audience asked how the oral immunotherapy for wheat in this study compared with oral immunotherapies for other foods.

"I would say that sustained unresponsiveness would be harder to achieve," said Dr Nowak-Wegrzyn. "The dose was not as high as with peanut, but it was comparable to egg, and compared with egg, our results are lower, for both desensitization and sustained unresponsiveness."

This study is important because wheat reactions can be very severe and little research has been done in this area, said Andrew Bird, MD, from the University of Texas Southwestern Medical Center in Dallas. "Wheat patients in general are challenging," he told Medscape Medical News. "Wheat allergies are scary."

But noting that only half the patients met the primary end point with the lower dose, Dr Bird said, "I just wonder how much the benefit was."

Also, he pointed out that the study was small and would need to be replicated before firm conclusions could be drawn.

The study was funded by Linda and Bill Friend and the Harris Family Foundation, Food Allergy Research & Education, and Thermo Fisher Scientific. Dr Nowak-Wegrzyn reports financial relationships with Merck, Nestle, Mead Johnson, Thermo Fisher Scientific, Nutricia, and the National Institutes of Health. Dr Bird reports relationships with Aimmune Therapeutics and DBV Technologies. Dr Sampson reports financial relationships with UCB, FARE, ITN, Thermo Fisher Scientific, and UpToDate.

American Academy of Allergy, Asthma and Immunology Meeting (AAAAI): Abstract L10. Presented March 5, 2017.


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