Patients who take omalizumab prior to starting oral immunotherapy (OIT) may skip much of the latter treatment’s onerous dose escalation process, according to a new study presented at the American College of Allergy, Asthma & Immunology (ACAAI) 2025 Annual Meeting in Orlando, Florida. The authors have not yet submitted the study for publication.

Most OIT protocols require initial multistep dose escalations, entailing up to 15 visits. Omalizumab allows for patients to start at maintenance doses, decreasing the number of up-dosing visits.

Up-dosing can be “a barrier to some patients receiving care, because it can be very challenging for patients to miss school time or for parents to have to take time off of work to come in” repeatedly, said Colleen Shannon, MD, MPH, a fellow physician in the allergy program at Children’s Hospital of Philadelphia (CHOP), who led the study. “My hope is that omalizumab could allow patients who otherwise might not be able to complete the therapy, to be able to do it.” 

Food allergy occurs in up to 8% of children and 10% of adults in the United States. The current standard of care is avoidance of the allergen and treatment of anaphylaxis with epinephrine. But OIT is used to increase the threshold that triggers a reaction and provide protection against accidental ingestion of the allergen. The FDA has approved only one OIT product, Palforzia, for the mitigation of allergic reactions from accidental exposure to peanut. 

In 2024, the agency approved omalizumab (Xolair) for reduction of allergic reactions that may occur with accidental exposure to one or more foods. It is to be used in conjunction with food allergen avoidance. 

The approval was based on the OUtMATCH study, which found that omalizumab was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. The second stage of the study compared omalizumab to omalizumab-facilitated OIT in the treatment of multiple food allergy. An abstract of the study, published in February, concluded omalizumab is superior to OIT due to high rates of adverse events leading to study discontinuation in the OIT-treated participants. 

In the new prospective cohort study, 54 patients aged 1-24 years who were treated in the OIT program at CHOP received an omalizumab injection at least 8 weeks before starting a two-dose challenge of a food allergen, and for 8 weeks after reaching the maintenance dose. Those who tolerated the allergen challenge received daily allergen dosing of 100 mg for cashew and 200-400 mg for peanut, other tree nuts, egg, milk, soy, wheat, and sesame. 

The usual starting dose for OIT is around 1-2 mg of food protein. However, after 8 weeks of omalizumab, patients can start therapy at approximately 300 mg for most foods and do not need to return for up-dosing visits. 

Shannon said patients seemed to tolerate the treatment well. In the first 12 months, 54 patients underwent 93 initiation challenges to 12 different foods, and patients tolerated the maximum dose in 89% of challenges.

Jennifer Dantzer, MD, assistant professor of pediatrics in the Division of Allergy, Immunology and Rheumatology at Johns Hopkins University School of Medicine in Baltimore, said that since the approval of omalizumab, allergists “have been trying to figure out the best way to use omalizumab in the clinical setting.” 

The findings from the new study “reinforce what other studies have shown,” said Dantzer, an investigator on the OUtMATCH study.

A consensus-based guidance by a subcommittee of the American Academy of Allergy, Ashtma & Immunology published in January said clinicians who offer off-label uses of omalizumab, including for facilitation of OIT, should consider obtaining informed consent and documenting whatever protocol or practice style is recommended for the patient.

Different Protocols

The major difference between OUtMATCH and CHOP’s study was that the latter protocol gave patients a lower target maintenance dose of food protein. A lower dose of the immunotherapy has been shown to be associated with less side effects, said Antonella Cianferoni, MD, PhD, medical director of the OIT program at CHOP and senior author of the study.

While the OUtMATCH trial only included patients who had low tolerance to food allergens, the new study included those with higher tolerance levels that are typical in clinical OIT programs. 

The OUtMATCH stage 2 trial showed adverse event rates leading to treatment discontinuation of 0% in the omalizumab-only group vs 22% in the omalizumab-facilitated OIT group. 

Meanwhile, roughly one third of patients in the CHOP study had mostly mild adverse events and most were able to continue therapy. Two patients (8%) discontinued therapy after reaching maintenance because of adverse effects.

Cianferoni said that OIT has become increasingly popular, but without uniformity in application. 

“Many more centers are now offering it with different protocols because there is no FDA-approved protocol,” she said. “We have more than 2000 patients waiting to join the OIT program in our center.”

Shannon and Cianferoni reported no financial disclosures. Dantzer has received research funding from the National Institutes of Health and Food Allergy Research & Education. 

Brenda Sandburg is a freelance journalist based in New York City. She has written about the biopharmaceutical industry and legal issues for The Pink Sheet and The American Lawyer.