-Study shows oral immunotherapy can retrain the immune system
Giving children with egg allergies increasingly higher doses of the very food they are allergic to can eliminate or ease reactions in most of them, according to results from a federally funded study conducted at Johns Hopkins Children’s Center and four other U.S. institutions.
The research findings, published July 19 in The New England Journal of Medicine, add to a growing body of evidence showing that feeding escalating doses of a food — an approach known as oral immunotherapy — can, over time, condition the immune system to tolerate the food with minimal or no reactions. Recent, smaller studies conducted at Johns Hopkins and elsewhere have shown the approach can also be useful in treating children allergic to milk and peanuts.
The researchers say the results are promising but caution that, at present, oral immunotherapy is still considered experimental and should not be used outside of a strictly controlled research protocol.
In the current study, conducted as part of the NIH-funded Consortium of Food Allergy Research, 35 of 40 children treated with egg immunotherapy experienced improvement. Five of the 40 patients dropped out of the study, four of them due to allergic reactions related to treatment. Eleven of the 35 patients experienced complete long-term elimination of egg-related allergic reactions, the most sought-after therapeutic outcome. The rest of the children were able to tolerate higher doses of egg with only mild or no symptoms, but lost some of their tolerance after discontinuing treatment. However, a higher threshold of tolerance, the researchers say, is an important therapeutic endpoint because it can protect against serious allergic reactions from accidental or incidental exposures and give patients and parents a peace of mind at restaurants, parties and other venues where food control is difficult or impossible.
“More than a quarter of the children in our study lost their egg allergies altogether, but we also saw dramatic improvements in those who didn’t, which in and of itself is an important therapeutic achievement,” says Robert Wood, M.D., director of allergy and immunology at Johns Hopkins Children’s Center. “These children went from having serious allergic reactions after a single bite of an egg-containing cookie to consuming eggs with minimal or no symptoms.”
In the study, 55 children, ages 5 through 18, received escalating doses of egg-white powder or a cornstarch placebo for 10 months. Thirteen of the 15 patients treated with placebo failed an oral food challenge, which requires a child to eat under medical observation 5 grams of egg protein, or the equivalent of half a large egg. Two placebo patients had dropped out before the challenge.
After the initial 10-month buildup, 22 of 35 children treated with egg whites were able to consume 5 grams of egg protein, 14 of them without symptoms. All 35 children continued to consume small doses of egg whites daily for 22 more months — the so-called maintenance phase, during which daily exposure to small doses of the allergen is believed to build tolerance. At the end of the 22-month maintenance phase, children underwent a food challenge with 10 grams of egg whites. Thirty out of the 35 children passed the 22-month food challenge. Those who passed the 10-gram food challenge then ceased all egg consumption for four to six weeks and underwent a final food challenge after the “abstinence” period. Eleven children were still able to tolerate 10 grams of egg protein — the equivalent of a large egg — without any symptoms and were considered completely cured of their allergy. Being able to consume eggs without a reaction after a period of abstinence is considered the true marker of sustained tolerance, the scientists say. During a phone follow-up one year later, all 11 reported eating eggs and egg-containing products without symptoms as frequently or as infrequently as they chose.
The fact that most children lost some of their tolerance after only a month of abstinence underscores the importance of daily exposure to an allergen to maintain tolerance, the researchers say.
An estimated 4 percent of U.S. children have food allergies and, by age 3, nearly 3 percent of children have evidence of egg allergies, the researchers say. Some children outgrow their food allergies, but for many they are life long and require complete avoidance to prevent serious or life-threatening reactions.
Other institutions participating in the study included Duke University, University of Arkansas, National Jewish Health, and Mt. Sinai School of Medicine in New York.
A. Wesley Burkes, M.D., of the University of North Carolina, and Stacie Jones, M.D., of the University of Arkansas, were lead authors on the NEJM report.
The research was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, under grants U19AI066738 and U01AI066560.