The immunoglobulin E-blocking drug omalizumab limited the risk of adverse effects associated with oral immunotherapy (OIT) and increased OIT’s overall efficacy in participants with multiple food allergies, a phase 2 clinical trial at Stanford University found.
Food allergies affect 4 to 6 percent of children in the United States; 30 percent of those children have allergies to multiple foods. Despite the serious nature of some allergic reactions and the rising prevalence of food allergies, no approved treatment exists beyond avoiding triggers and carrying epinephrine in case of emergency.
The risk of adverse events has kept OIT from being approved to treat food allergies as well, but lack of treatment options has spurred a number of studies on this approach, which involves exposing patients to food allergens in small but steadily increasing amounts to raise their tolerance to triggers.
While some patients in clinical trials become desensitized to small amounts of foods, few achieve full desensitization, says Mark Glaum, MD, PhD, Associate Professor of Medicine and Pediatrics, Allergy and Immunology at the University of South Florida’s Morsani College of Medicine.
Moreover, comparatively few studies have examined OIT’s effectiveness in addressing multiple food allergies simultaneously, and due to the length of time OIT requires — months in some cases — building desensitization to multiple allergies could take years if they were addressed one at a time. That means increased cost and inconvenience for patients should OIT become an accepted treatment method.
The search for improved safety and efficacy during OIT has led to research, published in Allergy, Asthma & Clinical Immunology and elsewhere, on combining OIT with the administration of omalizumab.
“Omalizumab is a medication specifically designed to block the allergy antibody, immunoglobulin E (IgE), which is a small molecule that begins the process of an allergic reaction,” says Carla McGuire Davis, MD, Chief of the Section of Immunology, Allergy and Rheumatology in the Department of Pediatrics at Baylor College of Medicine. “The drug stops the allergic reaction from happening for patients who have a high level of IgE in their blood.”
After numerous studies detailed the protective effects of omalizumab during OIT, the National Institutes of Health funded a phase 2 clinical trial to further explore the drug. The results of the double-blind, randomized, controlled trial were published recently in The Lancet Gastroenterology & Hepatology.
Approximately 50 children with multiple food allergies received omalizumab or a placebo for 16 weeks.
“At the eight-week mark, we introduced two to five culprit food allergens in an OIT program,” says study author Sharon Chinthrajah, MD, Director of the Clinical Translational Research Unit at the Sean N. Parker Center for Allergy and Asthma Research at Stanford. “At 36 weeks, we looked for the ability of participants to pass a food challenge.”
Participants received two grams of protein from each of their two or more food allergens.
“To put two grams in perspective, that’s about half a tablespoon of peanut butter or a quarter cup of milk,” Dr. Chinthrajah says. “For those who are particularly sensitive to even a minute amount of food, this is quite a significant change.”
At the end of the study, 83 percent of the 36 participants who received omalizumab passed the challenge for two foods. Results were similar for participants who passed the challenge for three foods (81 percent of 26 participants) or more (76 percent of 17 participants).
By comparison, only 33 percent of the 12 participants in the placebo group passed the food challenge for two foods, and there were even fewer for three foods: 29 percent of seven participants. None of the five participants in the placebo group with four or more food allergies passed the food challenge for all trigger foods.
The study also found that cross-desensitization could be achieved with OIT. All patients who were allergic to walnuts and pecans passed food challenges for both after receiving an OIT regimen that included walnut. Over 80 percent of participants with both cashew and pistachio allergies achieved the same result when given only cashews as part of their regimen.
Only expected minor adverse reactions occurred during the study. About one in five participants in the omalizumab group had gastrointestinal reactions, compared with 54 percent in the placebo group. No participants experienced major reactions such as anaphylaxis.
“The best time period to examine adverse events was week eight to week 16,” says another author of the study, Amanda Rudman Spergel, MD, Medical Officer at the National Institute of Allergy and Infectious Diseases. “If participants were considered treatment failures at week 17, they were given open-label omalizumab.”
The researchers are pursuing further phase 2 trials to determine if sustained unresponsiveness to food allergens can be achieved through OIT.
“The results of the study were dramatic and tell us that a larger study needs to be done to see whether the results can be replicated,” Dr. Rudman Spergel says. “The larger study could take the end point a little farther so that we can see how to really apply this for patients with food allergies [long-term].”