Omalizumab received FDA approval in 2024 as the first agent indicated to reduce the risk of allergic reactions, including anaphylaxis, following accidental exposure to 1 or more foods. Oral immunotherapy using non-FDA-approved commercial products remains common in clinical practice, but no trial had directly compared the 2 approaches before OUTMATCH. This trial enrolled 117 participants with allergy to peanuts and ≥ 2 additional foods across 10 US academic centers.¹
"Both treatments can be effective, and both will provide protection from small exposures and even the ability to start eating the food directly," Robert A. Wood, MD, professor of pediatrics, Johns Hopkins University School of Medicine, told HCPLive. "The biggest difference we found was the side effects from oral immunotherapy were such a far larger group of patients really couldn't tolerate the therapy."
Omalizumab Efficacy in OUTMATCH Stage 2
Participants (median age, 7 years) were randomized to active MOIT (n = 58) or active omalizumab (n = 59) following a 16-week open-label omalizumab run-in. MOIT was escalated toward a goal maintenance dose of 1000 mg per food (3000 mg total protein), while the omalizumab arm transitioned to 44 weeks of blinded injections. The primary endpoint was cumulative tolerated dose of ≥ 4044 mg for all 3 foods on double-blind, placebo-controlled food challenge.¹
In the intention-to-treat (ITT) population, omalizumab was superior to MOIT for the primary endpoint (36% vs 19%; odds ratio [OR], 2.6; 95% CI, 1.1-6.3; P =.03). This difference disappeared in the per-protocol population (OR, 1.2; 95% CI, 0.5-3.3; P =.66), reflecting a substantially higher discontinuation rate in the MOIT arm (49%) compared with omalizumab (12%) most driven by adverse events.¹
Omalizumab Safety versus Multiallergen Oral Immunotherapy
Omalizumab also showed superiority across secondary endpoints in the ITT population, including cumulative tolerated dose of ≥ 4044 mg for ≥ 2 foods (OR, 3.3; 95% CI, 1.5-7.3; P =.002) and for individual foods including peanuts (OR, 4.3; 95% CI, 1.9-9.7; P <.001), milk (OR, 6.2; 95% CI, 1.4-27.6; P =.02), and eggs (OR, 11.7; 95% CI, 1.9-70.2; P =.004). For protection against small unintentional exposures, 72% of the omalizumab arm tolerated ≥ 444 mg of all 3 allergens compared with 39% of the MOIT arm.¹
Frequently Asked Questions
What did the OUTMATCH stage 2 trial show?
Omalizumab produced higher treatment success than omalizumab-facilitated multiallergen oral immunotherapy in the intention-to-treat population, but the difference largely disappeared once high MOIT discontinuation rates were accounted for in the per-protocol analysis.
How does omalizumab compare with oral immunotherapy for multifood allergy?
Both approaches showed similar efficacy among participants who completed treatment, but MOIT carried significantly higher rates of serious adverse events, epinephrine-treated reactions, and anaphylaxis, driving nearly half of MOIT participants to discontinue.
Is omalizumab safe for patients with multiple food allergies?
Across the full OUTMATCH program, no anaphylactic events were attributed to omalizumab injections, and reactions were largely limited to non-dose-limiting local injection-site reactions.
The MOIT arm carried a substantially heavier safety burden, with more serious adverse events (31% vs 0%), events treated with epinephrine (37% vs 7%) and events meeting anaphylaxis criteria (27% vs 2% [than the omalizumab arm. Investigators also identified 3 cases of biopsy-confirmed eosinophilic esophagitis in the MOIT group.¹
"The adverse event profile of omalizumab is very reassuring, and this phase of the study confirmed the adverse events are very small," Wood said. "We've now, in the entirety of OUTMATCH, not seen any anaphylactic events [with omalizumab].”
However, Wood noted that omalizumab has a black box warning for anaphylaxis with an estimated risk of 1 in 500 to 1 in 1000 patients.
“What that translates to is that the first doses are given under observation,” he said.
Wood noted reactions to omalizumab in the trial were largely limited to local injection-site reactions, consistent with prior stage 1 findings, and were not dose-limiting in any participant.
The investigators pointed to protocol-imposed rigidity in MOIT dosing, including the inability to adjust individual food doses, as a possible contributor to the arm's high discontinuation rate, suggesting real-world flexibility could improve tolerability. Additional trials comparing OIT with anti-IgE strategies, including cost-benefit analyses, are needed to guide personalized treatment selection.¹
Editor’s note: Reported disclosures for Wood include Genentech and Novartis Pharmaceuticals Corporation.
References
Wood RA, Togias A, Burk CM, et al. Treatment of multifood allergy with omalizumab or multiallergen oral immunotherapy: a randomized clinical trial. JAMA Pediatr. Published online July 27, 2026. doi:10.1001/jamapediatrics.2026.2910
