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Head-to-Head Comparison of Treatments for Multiple Food Allergies: Omalizumab Comes Out Ahead, but the Key Is Not Just the Amount Tolerated
A U.S. randomized trial found that participants who continued the anti-IgE antibody were more likely to pass high-dose challenges with three foods; however, the difference was driven mainly by more adverse reactions and withdrawals with oral immunotherapy, rather than a large disparity in efficacy among those who completed treatment.
For families living with the fear of peanuts, eggs, milk, or tree nuts at the same time, the goal of treatment is not only to prevent an accidental exposure from becoming a medical emergency, but also to hope that one day these foods can return to the table. A U.S. multicenter randomized trial has now directly compared two approaches: continuing injections of the anti-IgE antibody omalizumab, or, after using the drug to help initiate treatment, switching to multiple-food oral immunotherapy that gradually increases allergen intake.
The trial, named OUtMATCH and registered as NCT03881696, was sponsored by the U.S. National Institute of Allergy and Infectious Diseases and conducted at 10 academic medical centers. Stage 2 enrolled 117 participants allergic to peanuts and at least two specified foods, ranging in age from 1 to 29 years, with a median age of 7; researchers tracked peanut and two other allergenic foods for each participant. Everyone first received 16 weeks of open-label omalizumab, then was randomly assigned either to continue the drug or to receive multi-allergen oral immunotherapy initiated with its assistance.
After treatment ended, the research team assessed tolerance through medically supervised, double-blind food challenges. The primary endpoint required participants to consume a cumulative total of at least 4,044 milligrams of protein from each of the three foods without dose-limiting symptoms. In the intention-to-treat analysis, 21 participants who continued omalizumab, or 36%, met the endpoint, compared with 11 participants, or 19%, in the oral immunotherapy group. Omalizumab therefore showed greater efficacy in the overall analysis.
However, the figures cannot be reduced to “injections are necessarily more effective than oral treatment.” Only 51% of the oral immunotherapy group completed the trial, compared with 88% of the omalizumab group; when the analysis was limited to participants who completed treatment according to the protocol, there was no significant difference in efficacy between the groups. In other words, the overall results reflected to a considerable extent whether treatment could be completed safely and consistently, not only how much the treatment itself could raise the tolerance threshold.
The safety difference was more pronounced. In the oral immunotherapy group, approximately 31% experienced serious adverse events, 22% discontinued treatment because of adverse events, and 37% received epinephrine for an event; the corresponding figures in the omalizumab group were 0%, 0%, and 7%. Oral immunotherapy requires repeated ingestion of allergenic foods, which can itself trigger reactions; this burden is particularly evident for patients managing multiple allergens at once.
Omalizumab was approved in the United States in 2024 to reduce the risk of reactions from accidental exposure in patients with food allergies aged one year and older, but it does not eliminate the allergy and cannot replace food avoidance and emergency preparedness. The new trial advances the question to whether patients can tolerate a full serving, but it remains limited by a sample size below the originally planned enrollment, uneven withdrawal rates, and a study population with more severe allergies. The results support a role for both strategies and also show that, when choosing treatment in the future, cost, the burden of injections, patient preferences, and the ability to tolerate adverse reactions may be as important as food-challenge endpoints.