The high rate of side effects from oral immunotherapy in the NIH trial explains the superiority of omalizumab.

A clinical trial found that omalizumab (Xolair) was more effective than oral immunotherapy (OIT) in treating multi-food allergies, particularly in individuals who react to very small amounts of common food allergens. OIT, the standard food allergy treatment in the U.S., involves gradually increasing exposure to an allergen to build tolerance.

By the end of the study, 36% of participants who received an extended course of omalizumab could tolerate at least 2 grams of peanut protein—equivalent to about eight peanuts—along with two other allergens. In contrast, only 19% of those who underwent multi-food OIT achieved the same level of tolerance. Researchers largely attributed this difference to the high incidence of allergic reactions and intolerable side effects among OIT participants, which led 25% to discontinue treatment. However, when only those who completed therapy were analyzed, both groups had an equal proportion of participants who could tolerate at least 2 grams of all three allergens.

The findings were published in an online supplement to The Journal of Allergy and Clinical Immunology and presented at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress in San Diego on Sunday, March 2, 2025.

“People with highly sensitive multi-food allergy previously had only one treatment option—oral immunotherapy—for reducing their allergic response to moderate amounts of those foods,” said Jeanne Marrazzo, M.D., M.P.H., director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID), the study’s funder and regulatory sponsor. “This study shows that omalizumab is a good alternative because most people tolerate it very well. Oral immunotherapy remains an effective option if treatment-related adverse effects are not an issue.”

How Omalizumab Works

Omalizumab works by binding to the allergy-causing antibody called immunoglobulin E in the blood and preventing it from arming key immune cells responsible for allergic reactions. This renders these cells much less sensitive to stimulation by any allergen.

The current study is the second stage of a landmark clinical trial that found a 16-week course of omalizumab increased the amount of peanut, tree nuts, egg, milk, and wheat that multi-food allergic children as young as 1 year could consume without an allergic reaction. This next stage of the trial was designed to directly compare omalizumab with OIT for the first time.

Study Design and Participant Breakdown

At 10 locations across the United States, the study team enrolled 177 children and adolescents ages 1 to 17 years and three adults ages 18 to 55 years, all with confirmed allergies to less than half a peanut and similarly small amounts of at least two other common foods among milk, egg, cashew, wheat, hazelnut or walnut. After completing the first stage of the trial, 117 individuals entered the second stage of the trial.

Upon beginning Stage 2, all participants received injections of omalizumab for eight weeks. Then the participants were randomly divided in half and placed into one of two groups. Group A received omalizumab injections and multi-allergen OIT for eight weeks, while group B received omalizumab injections and placebo OIT for eight weeks. Subsequently, group A received placebo injections and multi-allergen OIT for 44 weeks, while group B continued to receive omalizumab injections and placebo OIT for 44 weeks. Neither the participants nor the investigators knew who was in which treatment group.

Group A received omalizumab before and during their early months of OIT because data from prior studies suggested that pretreatment with the medication would significantly augment the safety of OIT, and continuing omalizumab during the early months of OIT would provide additional benefit.

High Dropout Rates in the OIT Group

During the study treatment period, 29 of 59 participants in group A discontinued therapy: 15 due to allergic reactions—some severe—or other intolerable symptoms of OIT, and 14 for other reasons, including aversion to the study foods or the burden of participating in the trial. No participants in group B had allergic reactions or other side effects from omalizumab that led them to discontinue therapy, but seven participants in group B left the study mainly due to the burden of participating in it. In all, 30 of the original 59 members of group A (51%) and 51 of the original 58 members of group B (88%) completed treatment.

After the study treatment period, the clinical trial team tested whether the participants who completed therapy could eat at least 2 grams of peanut protein and their two other study foods without an allergic reaction. Twenty-one of the original 58 participants in group B, or 36%, could tolerate at least 2 grams of all three foods, while only 11 of the original 59 participants in group A (the OIT-treated group), or 19%, could do so. When evaluating only the participants who completed therapy, however, the same proportion of each group could tolerate at least 2 grams of all three foods.

These results showed that omalizumab was more effective than OIT at treating multi-food allergies in people who originally had a very low tolerance to common food allergens. Investigators attributed this outcome mainly to the high rate of allergic reactions and other side effects leading to treatment discontinuation among the OIT-treated participants, despite receiving omalizumab before and during the early months of therapy.

Reference: “Treatment of Multi-Food Allergy with Omalizumab Compared to Omalizumab-Facilitated Multi-Allergen OIT” by Robert Wood, Stacie Jones, Jennifer Dantzer, Scott Sicherer, Julie Wang, Wayne Shreffler, David Pyle, Edwin Kim, Corinne Keet, Michael Kulis, Sayantani Sindher, Andrew Long, Amy Scurlock, Donald Leung, Bruce Lanser, J. Andrew Bird, Christopher Parrish, Brian Vickery, Idil Ezhuthachan, Jonathan Spergel and R. Sharon Chinthrajah, 10 February 2025, Journal of Allergy and Clinical Immunology.
DOI: 10.1016/j.jaci.2024.12.1022

The trial is called Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Children and Adults, or OUtMATCH. The NIAID-funded Consortium for Food Allergy Research (CoFAR) is conducting the trial under the leadership of Robert Wood, M.D., and R. Sharon Chinthrajah, M.D. Dr. Wood is the Julie and Neil Reinhard Professor of Pediatric Allergy and Immunology and director of the Pediatric Clinical Research Unit at the Johns Hopkins University School of Medicine, Baltimore. Dr. Chinthrajah is an associate professor of medicine and of pediatric allergy and clinical immunology and the co-director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University School of Medicine, Stanford, California.

NIAID funds the ongoing trial with additional financial support from and collaboration with Genentech, a member of the Roche Group, and Novartis Pharmaceuticals Corporation. The two companies collaborate to develop and promote omalizumab and are supplying it for the trial.

Further information about the OUtMATCH trial is available at ClinicalTrials.gov under study identifier NCT03881696.