In the first head-to-head comparison between omalizumab monotherapy and omalizumab-facilitated multi-allergen oral immunotherapy, omalizumab alone demonstrated superior efficacy and safety for treating patients with multi-food allergy, according to research presented at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.
The findings build on previous research published in February 2024, which demonstrated omalizumab's effectiveness in increasing tolerance to multiple food allergens, with 67% of children who received omalizumab able to tolerate at least 600 mg of peanut protein compared to just 7% who were able to do so when treated with placebo.
At the meeting, investigators revealed that omalizumab monotherapy achieved the primary endpoint in the OUtMATCH Stage 2 trial—tolerance of ≥ 2,000 mg (cumulative = 4,044 mg) for all three trigger foods—with 36% of patients reaching that goal compared to 19% in the oral immunotherapy (OIT) group (odds ratio = 2.6, P = .031). Additionally, patients who received omalizumab experienced substantially fewer adverse events and treatment discontinuations than those who received OIT.
Study Design and Methodology
The randomized controlled trial included 117 participants (55% male, median age = 7 years) who were randomized to either omalizumab monotherapy with placebo-OIT or multi-allergen OIT with placebo omalizumab following 16 weeks of open-label omalizumab treatment for all participants.
The trial design featured a complex protocol where all participants initially received 16 weeks of open-label omalizumab. At week 9, OIT or placebo-OIT was introduced and escalated to a maintenance dose of 1,000 mg for each participant's study-specific food allergens. At week 16, participants transitioned to blinded injection therapy (either continuing omalizumab or switching to placebo) for 44 weeks before undergoing rechallenge with cumulative doses of 8,044 mg protein per food.
Disparity in Completion Rates, Safety
A difference emerged in study completion rates between the two treatment arms. In the omalizumab group, 51 of 58 participants (88%) completed stage 2, while only 30 of 59 participants in the OIT group (51%) finished the trial.
The intent-to-treat analysis demonstrated omalizumab's superiority for multiple secondary endpoints, including success for two or more foods (P = .004) in the intent-to-treat analysis. However, the per-protocol analysis, which excluded participants who dropped out, showed no significant differences between the treatments (P = .66 for primary endpoint).
The safety data also showed differences between the treatment approaches. Serious adverse events occurred in 0% of patients receiving omalizumab compared to 30.5% in the OIT group. Adverse events leading to treatment discontinuation occurred in 0% vs 22.0%, and adverse events requiring epinephrine were reported in 6.9% of omalizumab-treated patients compared to 37.3% in the OIT group.
"Omalizumab was superior to multi-allergen OIT in the treatment of multi-food allergy," the researchers reported in the The Journal of Allergy and Clinical Immunology. "These differences were largely driven by the high rate of adverse events leading to study discontinuation in the OIT-treated participants, despite receiving omalizumab treatment at the initiation of therapy."
