A head-to-head matchup of Xolair versus oral immunotherapy (OIT) in desensitizing children with multiple food allergies came down in favor of Xolair.
Dr. Robert Wood, lead author on the influential OUtMATCH study, shared the latest results with fellow allergists at the 2025 AAAAI / World Allergy Congress.
After one year, 36 percent of patients taking omalizumab (Xolair) injections could consume at least 4 grams of each of three allergens. That’s a full or nearly full serving of foods such as milk, eggs, peanut, wheat and tree nuts.
Only 19 percent of participants treated first with Xolair injections then switched to OIT could tolerate 4 grams of each allergen.
Wood says the lower success rate in the Xolair-facilitated OIT group was largely because of a high dropout rate. Only 51 percent of the OIT group completed the study, compared to 88 percent in the Xolair group. He attributes the dropouts to a high rate of adverse reactions in the OIT group.
Those findings led OUtMATCH researchers to conclude that omalizumab, known by the brand Xolair, is the “superior” therapy in treating multiple food allergies.
However, some allergists are cautioning against drawing conclusions that Xolair is always better than OIT, based on these findings. They note to Allergic Living that the OIT protocol used in the OUtMATCH trial was “aggressive.”
All patients initially got regular Xolair injections, then a group in Stage 2 of this blinded study were moved onto multi-allergen OIT. Updosing in the group occurred rapidly.
Because they were taking Xolair, some patients escalated to their maintenance allergen dose on the very first day of treatment. Daily maintenance doses were also high for each allergenic food.
Each of these factors could have made OIT difficult for patients.
Xolair Vs. OIT: Aggressive Updosing
“The outcomes could have been different if it had ended at a lower dose for maintenance, or updosing had occurred more slowly,” says Dr. Julia Upton, an allergist-immunologist at The Hospital for Sick Children in Toronto.
Dr. Brian Vickery, a study co-author and chief of allergy and immunology at Emory University, says the findings “suggest that omalizumab-facilitation did not completely protect” participants from OIT reactions.
However, Vickery notes the dropouts in the OIT group are understandable. “It was a demanding study for patients, with multiple food challenges and lab draws, and three daily doses of up to 1,000 milligrams of each food,” he says.
Desensitization to three foods at the same time on an accelerated updosing schedule is a lot for the immune system to adjust to quickly, he says. “It’s possible that in addition to a large daily volume, the more rapid updosing could have played a role.”
Wood too acknowledges that OUtMATCH’s OIT protocol was aggressive. The results, he said, do not mean that Xolair is best for all patients. Treatment choices, including Xolair shots, OIT or food avoidance, “must be determined patient by patient, with an individualized approach,” says Wood, the director of pediatric allergy and immunology at Johns Hopkins Children’s Center.
The patients who participated in the OUtMATCH trial had allergies to peanut and at least two of milk, egg, walnut, hazelnut, wheat and cashew.
Stage 1 of the Phase 3 controlled study involved 177 children and teens with food allergies and analyzed omalizumab as a solo therapy. After four months of Xolair injections, 67 percent could tolerate at least 600 milligrams (mg) of peanut protein, or 2½ peanuts. About 66 percent could tolerate about 1,000 mg of milk (2 tablespoons), while other foods ranged from 67 percent for egg to 41 percent for cashew.
Full Servings of Milk, Peanut, Eggs and More
The strong Stage 1 findings led to the FDA’s approval of omalizumab in 2024 as the first medication for preventing allergic reactions from accidental allergen exposures.
But investigators hoped Xolair might protect against more than just accidents. They wanted to know if the medication could allow children to eat their allergenic foods.
Stage 2 of OUtMATCH involved 117 patients to compare Xolair against multi-allergen OIT, facilitated by Xolair shots. Patients were divided into two groups. Both received Xolair shots for 16 weeks. But at Week 8, one group started OIT for their three allergens while getting placebo Xolair shots. The other group received placebo OIT but continued getting real Xolair shots.
That meant for the next 44 weeks, one group received Xolair and the other, OIT.
After one year, the children and teens in the study were challenged. This is when 36 percent of patients taking Xolair alone could consume at least 4 grams of each of three allergens. Again, only 19 percent of participants treated with OIT could tolerate that amount.
Yet, when only the children who completed the study were considered, the percentage who could consume 4 grams of their three allergens was much closer. Wood told the meeting that 37 percent for OIT and 41 percent for Xolair achieved this.
But the OIT group struggled with reactions, some serious, that led to dropouts – with only 51 percent staying until the study’s end.
On Day One of treatment, “because they were taking Xolair, some patients consumed an amount equal to their maintenance dose,” Vickery says.
If unable to consume the full amount, dosing could be adjusted. Still, “this was a much more compressed schedule compared to the low-dose initial day, followed by 6 months of gradual updosing,” that is more typical of OIT, he says.
Xolair vs. OIT: Pros, Cons
Wood noted that children in the OIT group had to remain above 250 mg as a daily dose for each allergen to remain in the study. This gave researchers “less flexibility” than allergists would have with OIT in practice.
Of the OIT dropouts, nine quit during the buildup and 14 during maintenance. There were 16 incidents of anaphylaxis in the OIT group compared to one in the Xolair group. Three patients on OIT developed eosinophils esophagitis (EoE). No one taking Xolair did.
Upton said that future studies involving the two therapies could try a slower updosing schedule, a lower top dose, or weaning patients off omalizumab instead of stopping abruptly. “This drug has a lot of potential,” she says.
Wood shared that 24 percent of kids taking Xolair on its own could even eat 8 grams of all three their foods. “That’s a whole glass of milk, 1½ or 2 eggs, 2 slices of bread, or having 32 peanuts,” he says.
Dr. David Fleischer, director of the Allergy and Immunology Center at Children’s Hospital Colorado, says the OIT dropout rate wasn’t surprising given the length and demands of the trial, which included numerous food challenges.
He has 75 food allergy patients taking Xolair. He has also treated hundreds with OIT. Both have pluses and minuses.
“The hard part with OIT is it’s a daily treatment versus an injection every two weeks or every month,” he says. OIT also has a higher risk of anaphylaxis because the patient is eating the food. Yet, “for the right patient at the right time,” OIT can build tolerance to allergens without requiring shots.
OIT also may be “disease-modifying.” With Xolair, published research suggests the protection goes away when the shots stop. But with OIT, at least in very young children, there is evidence it can bring about lasting remission of food allergy.
Is Goal to Eat the Food or Not?
A child’s age, their mix of allergies, and whether they intend to eventually eat the foods can also impact whether families and patients choose Xolair or OIT.
“Some just want the protection and they don’t want to eat the foods. We see this with peanut, tree nuts and seafood,” Fleischer says. “But patients who have milk, egg, and wheat allergies often want to eat them.”
Both OIT and Xolair are important in helping patients reach their goals. “There are creative ways to use a product like Xolair that can change the lives of patients,” he says.
OUtMATCH was funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Consortium for Food Allergy Research (CoFAR).
Related Reading:
Xolair Desensitizes Food-Allergic Kids with Fewer Reactions Than OIT
In Toddlers, OIT Can Lead to Peanut Allergy Remission: Study
Multiple Food Allergies ‘Remarkably Common,’ Study Finds
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