Omalizumab vs Oral Immunotherapy: No Clear Winner

SAN DIEGO — Treatment options for food allergies are expanding, but interpreting research findings for individualized clinical care is tricky. That theme emerged at the American Academy of Allergy, Asthma, & Immunology (AAAAI) 2025 Annual Meeting/World Allergy Organization (WAO) Joint Congress, where a recent symposium highlighted new data from studies that compared omalizumab (Xolair) with oral immunotherapy (OIT) and assessed its durability in people with multiple food allergies.

“Is there a best approach? The answer is no,” Robert Wood, MD, said after he and Jennifer Dantzer, MD, both of Johns Hopkins University School of Medicine in Baltimore, reported on the three-stage OUtMATCH trial.

Last year, the US Food and Drug Administration (FDA) approved omalizumab— an injectable medication already used for allergic asthma, chronic hives, and nasal polyps — for food allergies in adults and children as young as 1 year. Unlike immunotherapy, omalizumab does not directly educate the immune system. Instead, the shots work by blocking immunoglobulin E antibodies.

The FDA’s decision came just before the data were published in The New England Journal of Medicine. That initial OUtMATCH stage compared omalizumab with placebo shots in 177 highly atopic patients (mostly teens and children) with reactivity to peanuts plus at least two other foods, such as cashew, egg, milk, walnut, wheat, or hazelnuts.

The first 60 participants to finish OUtMATCH 1 moved into open-label omalizumab, whereas the rest (n = 117) rolled into the second stage of the study, which compared omalizumab with “omalizumab-facilitated OIT” — use of OIT preceded by 8 weeks of omalizumab.

OUtMATCH Stage 2

The primary endpoint of OUtMATCH 2 required participants to tolerate at least 2 g (cumulative 4044 mg) for each food — nearly four times the amount in the phase 3 Palforzia trial of peanut OIT.

In the omalizumab group, 51/58 (88%) patients finished the study compared with 30/59 (51%) of those who received the combination approach. Eosinophilic esophagitis, reactions requiring epinephrine, and aversion were among the reasons for stopping. In the omalizumab group, no patient dropped out due to adverse events; study burden was the main reason, according to the researchers.

OIT dropouts strongly influenced results. In an intention-to-treat analysis, which includes all participants, almost twice as many participants in the omalizumab group (21/58 or 36%) successfully consumed all their challenge doses compared with 11/59 (19%) of those in the other arm. However, in the per-protocol analysis of those who completed the trial, success evened out: 41% for omalizumab and 37% for combination therapy.

Some saw a glass-half-full takeaway for patients. “If you’re OK with shots, you can likely get a great benefit. If you are OK with oral immunotherapy and can tolerate it, you can likely get a great benefit,” said Edwin Kim, MD, director of the University of North Carolina (UNC) Food Allergy Initiative at the UNC School of Medicine at Chapel Hill, North Carolina, and a co-investigator on the stage 2 trial. “There is no one-size-fits-all.”

Others found the data hard to interpret. In the clinic, most patients start on low doses of OIT that increase gradually as tolerance builds, taking 6 months or longer to reach maintenance, said Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in North Aurora, Illinois. However, OUtMATCH had “an incredibly compressed and aggressive timeline.”

OUtMATCH Stage 3

Dantzer reported on the initial 60 participants from the first stage of the trial who received 24 weeks of open-label omalizumab before entering OUtMATCH 3. The third stage asked a practical question: If treatment stops, can allergens be introduced into the diet?

Participants who tolerated a 600 mg dose (1000 mg cumulative) of a study food at the end of the open-label period were eligible to consume retail versions of the allergen. Food choices and amounts could vary based on symptoms and preferences. The aim was to gauge protection against allergic reactions at 3, 6, 9, and 12 months after stopping OIT.

If tolerance dipped below 300 mg, participants shifted to avoidance or started rescue oral immunotherapy. They could resume dietary consumption if rescue immunotherapy could get them to the 300-mg threshold.

At the start of the third stage, 95% of participants (57/60) were incorporating at least one food into their diet and 68% (41/60) were consuming all three study foods. By the end of the 12-month follow-up, 80% of total participants (48/60) were eating at least one food at home, 58% (35/60) were still eating all three, 18% (10/60) were avoiding all three foods, and 3% (2/60) were on rescue immunotherapy for all foods, Dantzer reported.

The drug’s benefit waned over the 12 months, and success was lower for those who introduced nuts into their diet.

Regarding safety, the 26 participants on dietary consumption throughout the third stage reported 104 adverse events, although only five met the criteria for anaphylaxis and six required epinephrine — “relatively small” considering they consumed three allergens daily for up to a year, Dantzer said.

Wood alluded to the possibility that pretreatment with omalizumab could improve the tolerability of OIT and said OUtMATCH might have had fewer adverse events “if we were doing this in practice” due to “more flexibility in how you dose.” The data from OUtMATCH 3 should be published “very soon,” he added.

Marcus Shaker, MD, MS, professor of pediatrics and medicine at Geisel School of Medicine at Dartmouth, in Hanover, New Hampshire, said the results are not clear-cut.

“Omalizumab has an effect for some patients, not for everyone,” Shaker told Medscape Medical News. “It’s hard to know who it helps and who it doesn’t help. You’re going to have a conversation about what patient goals and preferences are.”

OUtMATCH is funded by the National Institute of Allergy and Infectious Diseases (NIAID) through the Consortium for Food Allergy Research. Genentech/Novartis provided the investigational product and monetary support to Johns Hopkins University and collaborated on the study design.

Dantzer received grant funding from the National Institutes of Health/NIAID.

Wood received research support from NIAID, Food Allergy Research & Education, Aimmune, ALK-Abelló, DBV Technologies, Genentech, Novartis, Regeneron Pharmaceuticals, Sanofi, and Siolta Therapeutics, and consultant fees from Genentech.

Kim has served as a consultant for ALK-Abelló, Cellergy Pharma, Inc., DBV Technologies, Genentech, Hanimune Therapeutics, Inc., Novartis, Phylaxis BioScience, LLC, Revolo Biotherapeutics, and Ukko.

Bajowala participated on the Novartis Food Allergy Advisory Board in 2023 and owns WisePrince, LLC (a health technology company that creates software for food allergen desensitization).

Shaker is a member of the Joint Task Force on Practice Parameters, serves on the editorial board of The Journal of Allergy and Clinical Immunology: In Practice, is an associate editor of Annals of Allergy, Asthma & Immunology, and serves on the Board of Directors of the American Academy of Allergy, Asthma & Immunology.

Esther Landhuis is a freelance science and health journalist in the San Francisco Bay Area. She can be found on X @elandhuis.