A head-to-head trial found that continued omalizumab achieved higher overall treatment success than omalizumab-facilitated multiallergen oral immunotherapy, largely by helping patients avoid the adverse events and treatment discontinuations that limited MOIT.
Study: Treatment of Multifood Allergy With Omalizumab or Multiallergen Oral Immunotherapy. Image credit: New Africa/Shutterstock.com
A recent JAMA Pediatrics study compared continued omalizumab with omalizumab-facilitated multiallergen oral immunotherapy (MOIT) for the treatment of patients with multifood allergy.
Epidemiology and burden of food allergy
Food allergies are prevalent in the United States, affecting approximately 8% of children and 10% of adults, with a significant proportion allergic to multiple foods. These allergies frequently cause substantial morbidity and are a leading cause of anaphylaxis. For individuals with multiple allergies, avoiding trigger foods is especially challenging. The impact on quality of life is considerable, placing a significant burden on patients, families, and the health care system.
In 2024, omalizumab was approved for treating food allergy, specifically to reduce allergic reactions, including anaphylaxis, following accidental exposure to one or more foods. Presently, the only other US Food and Drug Administration (FDA)-approved treatment is a peanut oral immunotherapy (OIT) product.
Despite this, commercial, non–FDA-approved OIT products are frequently used in clinical practice, underscoring the need for well-controlled studies to compare available therapies. While some studies have assessed OIT combined with omalizumab, direct comparisons between omalizumab and OIT are lacking.
Researchers compared continued omalizumab with omalizumab-facilitated multiallergen OIT in food allergy
The Omalizumab as Monotherapy and as Adjunct Therapy to Multiallergen OIT in Children and Adults With Food Allergy (OUTMATCH) trial demonstrated the effectiveness of omalizumab as monotherapy for multifood allergy. The current study describes the second phase of the trial.
Stage 2 of the OUTMATCH trial was a multicenter, double-blind, placebo-controlled study involving participants aged 1 to 55 years who were allergic to peanuts and at least two additional specified foods, such as milk, eggs, wheat, cashews, hazelnuts, or walnuts. Key eligibility criteria included appropriate weight and IgE levels for omalizumab dosing, as well as specific oral food challenge (OFC) thresholds.
Participants with certain conditions, such as poorly controlled asthma, severe anaphylaxis history, eosinophilic GI disease, or recent immunomodulatory therapy, were excluded. Stage 1 involved 16–20 weeks of omalizumab or placebo, followed by food challenges. The first 60 to complete stage 1 joined a 24-week open-label omalizumab extension; the rest proceeded to stage 2.
After efficacy was established, additional participants enrolled in stage 2. They were randomized to receive either omalizumab-facilitated MOIT or placebo MOIT, with all participants initially receiving 16 weeks of open-label omalizumab and adding MOIT or placebo-MOIT at week 8.
At week 16, participants switched to blinded injections for 44 weeks, escalating to a maintenance dose of 250–1000 mg/food over 24 weeks. After 52 weeks, food challenges measured cumulative tolerated dose (CTD).
The primary endpoint was achieving a CTD of 4044 mg or greater for all three participant-specific foods; failure or withdrawal before the final challenge was counted as failure. Secondary endpoints included alternative CTD thresholds. Safety was evaluated by tracking adverse events (AEs), serious AEs (SAEs), and epinephrine use.
Omalizumab and MOIT increase food allergen tolerance
This study enrolled 117 participants aged 1 to 29 years and randomized them to receive either omalizumab-facilitated MOIT or continued omalizumab. The omalizumab group had a higher completion rate (88% vs 51%), mainly because adverse events led to more dropouts in the MOIT group.
Omalizumab was significantly more effective than MOIT in the intention-to-treat analysis, with 36% of omalizumab recipients achieving success compared to 19% in the MOIT group. This benefit extended to several secondary outcomes, especially greater tolerance to higher doses of multiple allergens such as peanuts, milk, and eggs in the intention-to-treat analysis. However, no efficacy difference was seen in the per-protocol analysis, likely due to the high dropout rate in the MOIT arm.
Exploratory analyses suggested that longer omalizumab treatment might improve results. A trend toward better outcomes was also seen in those receiving the highest MOIT maintenance dose, though sample size was limited. Younger children may benefit more from treatment, but this was not statistically confirmed. Receiving omalizumab in both study stages showed a possible advantage in exploratory analyses. High baseline peanut IgE predicted discontinuation in the MOIT group; no other baseline factors were linked to dropout.
Safety data showed the MOIT group had more serious adverse events, including anaphylaxis, epinephrine-treated reactions, and adverse events leading to treatment discontinuation, as well as three cases of eosinophilic esophagitis. A temporary study pause due to mold growth showed no evidence of affecting study outcomes.
Individual risks and benefits should guide treatment choice
In conclusion, omalizumab led to higher treatment success mainly due to fewer adverse events and dropouts compared to MOIT, not because of greater efficacy among those who completed therapy. Both omalizumab and omalizumab-facilitated MOIT represent viable treatment options for patients with multifood allergy, but each has unique risks and benefits that should be weighed for individual patients.
Because the study enrolled a highly food-reactive population and used an intensive, protocol-driven MOIT regimen, the findings may not fully generalize to all patients receiving OIT in routine clinical practice. Further studies, including cost-benefit analyses, are needed to guide optimal personalized treatment choices.
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