A head-to-head study found that continuing omalizumab had higher overall treatment success rates than omalizumab-promoted multiallergen oral immunotherapy, primarily because patients avoided MOIT-limiting adverse events and treatment discontinuation.
Study: Treatment of multiple food allergies with omalizumab or multiple allergen oral immunotherapy. Image credit: New Africa/Shutterstock.com
recent JAMA Pediatrics This study compared omalizumab continuation with omalizumab-promoted multiallergen oral immunotherapy (MOIT) in the treatment of patients with multiple food allergies.
Epidemiology and burden of food allergies
Food allergies are prevalent in the United States, affecting approximately 8% of children and 10% of adults, and a significant proportion are allergic to more than one food. These allergies often cause significant morbidity and are the leading cause of anaphylaxis. Avoiding trigger foods is especially difficult for people with multiple allergies. The impact on quality of life is significant, placing a heavy burden on patients, families, and healthcare systems.
In 2024, omalizumab was approved to treat food allergies, specifically to reduce allergic reactions, including anaphylaxis, after accidental exposure to one or more foods. Currently, the only other U.S. Food and Drug Administration (FDA)-approved treatment is peanut oral immunotherapy (OIT) products.
Nevertheless, commercially available OIT products that are not FDA approved are frequently used in clinical practice, highlighting the need for well-controlled studies to compare available treatments. Although several studies have evaluated the combination of OIT and omalizumab, direct comparisons between omalizumab and OIT are lacking.
Researchers compared omalizumab continuation to omalizumab-promoted multiallergen OIT in food allergy.
The Omalizumab Monotherapy and Adjunct Therapy to Multiallergen OIT in Children and Adults with Food Allergies (OUTMATCH) trial demonstrated the efficacy of omalizumab as monotherapy for multiple food allergies. The current study describes the second phase of the trial.
The second phase of the OUTMATCH study was a multicenter, double-blind, placebo-controlled study in participants aged 1 to 55 years who were allergic to peanuts and at least two additional specified foods, including milk, eggs, wheat, cashews, hazelnuts, and walnuts. Key eligibility criteria include appropriate body weight and IgE levels for omalizumab administration, as well as specific oral food challenge (OFC) thresholds.
Participants with certain conditions such as poorly controlled asthma, history of severe anaphylaxis, eosinophilic gastrointestinal disease, or recent immunomodulatory therapy were excluded. Stage 1 involved 16 to 20 weeks of omalizumab or placebo, followed by a dietary challenge. The first 60 patients who completed Stage 1 entered a 24-week open-label omalizumab extension study. The rest progressed to stage 2.
Additional participants were enrolled in Stage 2 after efficacy was established. Participants were randomized to receive either omalizumab-promoted 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 blind injections for 44 weeks, with maintenance doses increasing from 250 to 1000 mg/meal over 24 weeks. After 52 weeks, cumulative tolerated dose (CTD) was determined by food challenge.
The primary endpoint was achieving a CTD of 4044 mg or higher for all three participant-specific foods. Failure or withdrawal before the final challenge will count as a failure. Secondary endpoints included surrogate CTD thresholds. Safety was assessed by tracking adverse events (AEs), serious AEs (SAEs), and epinephrine use.
Omalizumab and MOIT increase food allergen tolerance
The study enrolled 117 participants, ages 1 to 29 years, who were randomly assigned to receive omalizumab-promoted MOIT or continued omalizumab. Completion rate was higher in the omalizumab group (88% vs. 51%). This was mainly due to more dropouts in the MOIT group due to adverse events.
Omalizumab was significantly more effective than MOIT in an intention-to-treat analysis, with 36% of those receiving omalizumab achieving success versus 19% of those receiving MOIT. This benefit extended to several side effects, particularly improved tolerance to high doses of multiple allergens such as peanuts, milk, and eggs. In intention-to-treat analyses. However, a per-protocol analysis showed no difference in efficacy, possibly due to a higher dropout rate in the MOIT group.
Exploratory analyzes suggested that longer omalizumab treatment may improve outcomes. Although the sample size was limited, there was a trend toward better outcomes even in patients receiving the highest MOIT maintenance doses. It is possible that younger children benefit from treatment, but this has not been statistically confirmed. Receiving omalizumab during both study phases showed potential benefit in an exploratory analysis. Higher baseline peanut IgE predicted discontinuation in the MOIT group. No other baseline factors were associated with dropout.
Safety data showed three cases of eosinophilic esophagitis occurred in the MOIT group, as well as more serious adverse events including anaphylaxis, epinephrine treatment response, and adverse events leading to treatment discontinuation. There was no evidence that the suspension of the study due to the mold outbreak affected the study results.
Individual risks and benefits should guide treatment selection
In conclusion, omalizumab resulted in higher treatment success primarily because it had fewer adverse events and dropouts compared to MOIT, rather than because of higher efficacy in patients who completed treatment. Both omalizumab and omalizumab-promoted MOIT are viable treatment options for patients with multiple food allergies, but each has unique risks and benefits that must be weighed for each individual patient.
Because this study enrolled a highly food-responsive population and used an intensive protocol-based MOIT regimen, the results may not be completely generalizable to all patients receiving OIT in daily clinical practice. Further research, including cost-effectiveness analysis, is needed to guide the selection of optimal individualized treatments.
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