In a recent study published in The New England Journal of Medicine, a group of researchers evaluated the efficacy and safety of omalizumab as a standalone treatment in increasing the allergen tolerance of individuals with multiple food allergies.
Study: Omalizumab for the Treatment of Multiple Food Allergies. Image Credit: Dejan Stanisavljevic / Shutterstock
Background
Food allergies affect a significant portion of the United States (U.S.) population, leading to a high demand for vigilance and negatively impacting individuals' well-being and healthcare costs. The only Food and Drug Administration (FDA)-approved treatment, oral immunotherapy for peanut allergies, is complex and can cause adverse effects. Omalizumab, an Immunoglobulin-E (IgE)-targeting monoclonal antibody approved for other allergic conditions, shows potential in managing multiple food allergies by improving allergen tolerance, reducing reactions, and enhancing life quality. However, further research is needed to confirm omalizumab's long-term safety, effectiveness, and the best dosing for treating various food allergies in different demographics.
About the study
The Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy (OIT) in Food Allergic Children and Adults (OUtMATCH)
The OUtMATCH trial, a multi-stage, double-blind, placebo-controlled study at ten U.S. centers, explores omalizumab's efficacy against food allergies. Developed in collaboration with the Consortium for Food Allergy Research and pharmaceutical giants, its protocols ensure rigorous evaluation and safety, overseen by Johns Hopkins University's review board. After completing its initial phase, the trial progresses to assess long-term outcomes and dietary reintroduction post-treatment.
Participants, ranging from 1 to 55 years old and allergic to peanuts and at least two other specified foods, underwent thorough screening and challenges to ascertain eligibility. The initial phase involved a 2:1 randomization to either omalizumab or placebo, followed by reevaluation through food challenges. An interim analysis, prompted by the coronavirus disease 2019 (COVID-19) pandemic's impact on enrollment, affirmed omalizumab potential, leading to an adjusted final sample size.
The statistical analysis utilized a two-sided Fisher's exact test to assess the efficacy of the treatment by comparing the percentage of participants who could ingest targeted food doses without adverse symptoms. To address multiple comparison issues, gatekeeping and sequential testing strategies were employed, ensuring a family-wise error rate below 0.05. The interim analysis, indicating positive outcomes, led to the cessation of enrollment. Secondary endpoints are presented with 95% confidence intervals, specifically focusing on the pediatric cohort, which constituted the primary analysis group.
Study results
In the comprehensive evaluation spanning from September 2019 through November 2022, the trial screened 435 children and adolescents for eligibility. Of these, 177 were randomized to either the omalizumab or placebo group, with the majority of exclusions resulting from insufficient allergic responses to the tested foods. The demographic makeup of participants was predominantly male, with a median age of seven years. These individuals were notably atopic, suffering from conditions such as asthma, atopic dermatitis, and allergic rhinitis, and had a median total IgE level of 700 IU per milliliter. Baseline food challenge tests showed similar maximum tolerated doses across the board for the allergens in question.
The trial's omalizumab group saw a significant percentage (67%) of participants able to consume at least 600 mg of peanut protein without dose-limiting symptoms, starkly contrasting with only 7% in the placebo group. This efficacy extended to other specified foods, demonstrating omalizumab's potential to significantly raise allergen tolerance levels among recipients. The dosage varied among participants, with a notable division in administration frequency based on individual requirements.
Further analysis within the trial assessed the capability of participants to ingest one, two, or three of the specified allergens in varying doses without adverse effects. Results from the omalizumab group were promising, showing a substantial capacity for increased allergen consumption. An open-label extension of the trial aimed to investigate the durability of omalizumab's efficacy over a more extended period (40 to 44 weeks), revealing that most participants maintained or improved their allergen tolerance levels.
Quality of life assessments for both participants and caregivers, conducted via validated questionnaires, indicated no significant change by the end of the initial trial stage. However, improvements were noted during the open-label extension. Safety profiles were similar across both groups, with the exception of more frequent injection-site reactions among omalizumab recipients. One serious adverse event was reported, considered possible but unlikely related to omalizumab.
The trial faced challenges due to the COVID-19 pandemic, which temporarily disrupted participant recruitment and treatment administration. Additionally, mold contamination in some food challenge products necessitated a brief pause in testing, although subsequent analyses confirmed that these issues did not impact the trial's overall results.
Conclusions
To summarize, omalizumab significantly raised the tolerance threshold for multiple food allergens, including peanuts, cashews, eggs, and milk, among individuals from as young as 1 year old over 16 weeks. A majority of those treated with omalizumab could safely ingest quantities of allergens far exceeding typical accidental exposure levels, indicating its potential as an effective monotherapy for food allergies. The treatment also demonstrated the ability to simultaneously protect against reactions from multiple allergens. Extended treatment in a 24-week follow-up showed sustained tolerance.
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