New research, led by Johns Hopkins Children's Center investigators and sponsored by the National Institutes of Health's (NIH) National Institute of Allergy and Infectious Diseases (NIAID), finds that omalizumab, a U.S. Food and Drug Administration-approved (FDA) injectable drug for food allergies, performed better than oral immunotherapy. A subsequent phase of the study also found that patients may be able to introduce allergenic foods into their diets after stopping the medicine.
The findings were published in a special supplement of the Journal of Allergy and Clinical Immunology and presented on Sunday, March 2, at 2 p.m. PST during a late-breaking symposium at the American Academy of Allergy, Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress in San Diego.
According to researchers, up to 8% of children and 10% of adults have at least one food allergy, and up to 86% of these children are allergic to more than one food. Last year,Robert Wood, M.D., director of the Eudowood Division of Allergy, Immunology and Rheumatology at Johns Hopkins Children's Center, reported on the first stage of the three-stage Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants (OUtMATCH) study, which is sponsored and funded by the NIAID/NIH in collaboration with additional support from the pharmaceutical industry. The study found that omalizumab, a medicine previously approved to treat asthma and other allergic conditions, was highly effective in preventing reactions in patients with a severe food allergy. In February 2024, findings from this landmark study were published in the New England Journal of Medicine, and led to FDA approval of omalizumab for the treatment of food allergy, including patients as young as 1 year old. Prior to the study, management of food allergies had mostly relied on avoidance and emergency treatment with epinephrine when an accidental exposure occurs. Another approach to treating food allergies in the U.S. has been oral immunotherapy, which involves eating gradually increasing doses of a food allergen to reduce the allergic response to it.
In the second stage of the OUtMATCH study, which will be presented this March, the research team sought to compare omalizumab with oral immunotherapy. In this phase, all 117 participants - who were 55% male, a median age of 7 and allergic to peanuts and at least two other common food allergens (milk, egg, cashew, wheat, walnut or hazelnut) - received 16 weeks of omalizumab injections. At Week 9, about half of the group began receiving oral immunotherapy, and the other half received placebo oral immunotherapy. Intake of each participant's specific food allergen was escalated to the maintenance goal of 1,000 mg. At Week 16, participants began double-blind injection therapy, receiving either omalizumab or a placebo injection, for 44 weeks before being rechallenged to a cumulative amount of 8,044 mg of protein for their respective food allergens. Participants had to tolerate at least 4,044 mg of all three of their food allergens for treatment to be considered a success.
The study found that the success rate for tolerating these amounts - equivalent to about 20 peanuts or ½ cup of milk - of all three foods after treatment was 36% for those on omalizumab compared with 19% for those on real OIT and placebo injections. Researchers say these differences were largely driven by a higher percentage of those on OIT dropping out of the study due to adverse effects of the treatment, with 88% (omalizumab group) versus 51% (real OIT and placebo injection group) completing Stage 2. No participants in the active omalizumab group experienced serious adverse reactions, compared with more than 30% in those who received OIT.
"This is the first time we've been able to directly compare these two treatments for multiple food allergies, and our study shows omalizumab was superior to oral immunotherapy," says Wood, who was principal investigator throughout the entire study. "This is an important distinction for clinicians who are weighing which treatment to recommend to their patients."
In addition to the Stage 2 data, preliminary results for Stage 3 of the study will be presented this March. The first 60 participants who completed Stage 1 (58% were male, with a median age of 8.5 years old) received an additional 24 weeks of omalizumab, and then entered Stage 3 after stopping omalizumab. Stage 3 could include dietary consumption (eating retail food products), oral immunotherapy or food avoidance, depending on the participant's outcome from the final food challenge and their preferences. More than 80% of initial participant treatment plans began with dietary consumption. In most cases, the amount of allergens consumed declined throughout the study phase, except for wheat. For those who started eating their food allergens, success was defined as consuming a median of more than 300 mg of food protein each day over a 12-month period, assessed in quarterly intervals. Overall, consumption of milk, egg and wheat had a greater success rate (61% to 70%) than peanuts and tree nuts (38% to 56%). Researchers say reduced consumption appeared to be related to both side effects and other factors, such as taste and aversion. Some adverse events occurred among participants in Stage 3, including anaphylaxis and reactions requiring epinephrine, and many participants returned to avoiding one or more specific food allergens by the end of the study phase.
"While the results of Stage 3 are still preliminary, the majority of the first 60 participants were able to successfully introduce allergenic foods into their diet after stopping omalizumab," says Jennifer Dantzer, M.D., pediatric allergist at Johns Hopkins Children's Center who is also an assistant professor of pediatrics at the Johns Hopkins University School of Medicine and first author of the Stage 3 research. "Omalizumab is currently approved in the U.S. for the reduction of allergic reactions that may occur with accidental exposures. These results indicate that omalizumab may have additional uses that may be valuable for patients, but the potential risks should be recognized."
Stage 3 is ongoing, with expected completion in summer 2025. In the coming year, researchers plan to analyze the full results of Stage 3, which will include additional participants.
The research described in this press release was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM2AI130836, UM1AI130838, UM1AI130570, UM1AI130839, UM1AI130936, UM1AI130781, UM1AI130780, UM1AI130934, UM1AI182034, U01AI178772, and UM2AI117870.
Funding and a product for the study described in this press release was provided by Genentech. Robert Wood is a paid consultant to Genentech. This arrangement has been reviewed and approved by The Johns Hopkins University in accordance with its conflict-of-interest policies.
