In a recent study published in The New England Journal of Medicinea group of researchers evaluated the efficacy and safety of omalizumab as a stand-alone treatment in increasing allergen tolerance in individuals with multiple food allergies.
Study: Omalizumab for the treatment of multiple food allergies. Image source: Dejan Stanisavljevic / Shutterstock
Record
Food allergies affect a significant portion of the United States (US) population, leading to a high demand for vigilance and adversely affecting individual well-being and health care costs. The only Food and Drug Administration (FDA)-approved treatment, oral immunotherapy for peanut allergies, is complex and can cause side effects. Omalizumab, an immunoglobulin-E (IgE)-targeting monoclonal antibody approved for other allergic conditions, shows potential in the management of multiple food allergies by improving allergen tolerance, reducing reactions, and improving quality of life. However, further research is needed to confirm the long-term safety, efficacy, and best dosage of omalizumab for the treatment of various food allergies in different demographics.
About the study
Omalizumab as monotherapy and as add-on therapy to multiallergen oral immunotherapy (OIT) in food allergic children and adults (OUtMATCH)
The OUtMATCH trial, a multistage, double-blind, placebo-controlled study at ten US centers, is investigating the efficacy of omalizumab 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 the Johns Hopkins University review board. After completing its initial phase, the trial moves on to assess long-term outcomes and re-introduction of nutrition after treatment.
Participants, aged 1 to 55 years and allergic to peanuts and at least two other specified foods, underwent thorough screening and challenges to determine eligibility. The initial phase consisted of 2:1 randomization to either omalizumab or placebo, followed by re-evaluation via dietary challenges. An interim analysis, prompted by the impact of the 2019 coronavirus disease (COVID-19) pandemic on enrollment, confirmed the potential of omalizumab, leading to an adjusted final sample size.
Statistical analysis used a two-sided Fisher’s exact test to assess treatment efficacy by comparing the proportion of participants who could consume target food doses without adverse symptoms. To address multiple comparison issues, gatekeeping and sequential testing strategies were used, ensuring a familywise error rate below 0.05. Interim analysis, indicating positive results, led to discontinuation of enrollment. Secondary endpoints are presented with 95% confidence intervals, focusing specifically on the pediatric cohort, which constituted the primary analysis group.
Study results
In the overall evaluation spanning September 2019 to November 2022, the trial tested 435 children and adolescents for eligibility. Of these, 177 were randomized to either the omalizumab or placebo group, with the majority of exclusions stemming from inadequate allergic responses to the test foods. The demographic composition of participants was predominantly male, with a median age of seven years. These subjects were highly atopic, suffered from conditions such as asthma, atopic dermatitis and allergic rhinitis, and had a median total IgE level of 700 IU per milliliter. The basic food challenge tests showed similar maximum tolerated doses in all areas for the allergens in question.
The omalizumab group of the trial saw a significant percentage (67%) of participants consume at least 600 mg of peanut protein without dose-limiting symptoms, in stark contrast to only 7% in the placebo group. This efficacy was extended to other designated foods, demonstrating the potential of omalizumab to significantly increase allergen tolerance levels among recipients. Dosage varied between participants, with considerable variation in frequency of administration based on individual requirements.
Further within-trial analysis assessed participants’ ability to ingest one, two, or three of the specified allergens in varying doses without adverse effects. Results from the omalizumab group were promising, showing significant capacity for increased allergen consumption. An open-label extension of the trial aimed to investigate the duration of omalizumab’s effectiveness 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, showed no significant change by the end of the baseline phase of the trial. However, improvements were made during the open label extension. Safety profiles were similar in both groups, with the exception of more frequent injection site reactions among omalizumab recipients. One serious adverse event was reported, which is considered possible but unlikely to be related to omalizumab.
The trial faced challenges due to the COVID-19 pandemic, which temporarily halted participant recruitment and treatment delivery. In addition, mold contamination in some food challenge products necessitated a brief pause in testing, although subsequent analyzes confirmed that these issues did not affect the overall test results.
conclusions
In summary, omalizumab significantly increased tolerance to multiple food allergens, including peanuts, cashews, eggs, and milk, among subjects aged 1 year and over 16 weeks. The majority of those treated with omalizumab could safely ingest amounts of allergen well in excess of typical accidental exposure levels, indicating its potential as an effective monotherapy for food allergies. The treatment also showed the ability to simultaneously protect against reactions from multiple allergens. Prolonged treatment at a 24-week follow-up showed prolonged tolerance.
