Allergen Immunotherapy and/or Biologicals for IgE-mediated Food Allergy: A Systematic Review and Meta-analysis

To investigate by a systematic review and meta-analysis whether oral allergen immunotherapy with or without biologicals or whether biologicals alone can have significant impacts on IgE-mediated food allergy.

Thirty six trials with 2126 mainly child participants were included in this study of food allergies confirmed by oral food challenge. These trials were obtained via a search strategy utilizing 6 databases: CINAHL, Cochrane Library, Embase, ISI Web of Science, Medline, and Scopus.

A task force of allergy specialists, patient representatives, primary care doctors, psychologists, other clinicians, teachers, and methodologists from 19 countries participated in the review. Study types included were randomized controlled trials for immunotherapy and biological monotherapy as well as controlled comparator trials with placebo, no intervention, or routine management without active treatment of biological monotherapy. Eligible studies included those with outcomes data on quality of life, desensitization (ability to tolerate allergen during treatment), sustained unresponsiveness (ability to tolerate allergen after discontinuing therapy), adverse reactions, severe adverse reactions, and cost-effectiveness. The GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation) was used to synthesize data about each outcome.

Oral immunotherapy resulted in a large increase in the proportion able to tolerate peanut during therapy (absolute difference 62%, risk ratio [RR] 9.9, 95%confidence interval [CI] 4.5–21.4, high certainty) with somewhat less certainty for cow’s milk (absolute difference 53%, RR 5.7, 95% CI 1.9–16.7, moderate certainty), and hen’s egg allergy (absolute difference 79%, RR 8.9, 95% CI 4.4–18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300 mg or 1000 mg peanut protein was 2. Peanut oral immunotherapy may increase the proportion of children able to tolerate peanut after stopping therapy (absolute difference 31%, RR 8.8, 95% CI 1.2–61.6, low certainty). Oral immunotherapy did not increase adverse reactions (RR 1.1, 95% CI 1.0–1.2, low certainty) or severe reaction in peanut allergy (RR 1.6, 95% CI 0.7–3.5, low certainty) but may increase mild adverse reactions in cow’s milk and hen’s egg allergy. Epicutaneous immunotherapy increased tolerance while on therapy for peanut (RR 2.6, 95% CI 1.8–3.8, moderate certainty). Results were unclear for other allergies and administration routes. There were too few trials of biologicals alone (3) or with immunotherapy (1) to provide conclusions.

Oral immunotherapy improves tolerance while on therapy and is probably safe in peanut, cow’s milk, and hen’s egg allergy when guided by an allergy specialist as was done in studies reviewed in the meta-analysis. Adverse reactions were mainly mild. With peanut and egg, about one-third may maintain tolerance after stopping therapy, at least in the short term (3 months). More research is needed about quality of life, cost, and biologicals.

This study will be used to inform Global Allergy and Asthma European Network (GA 2 LEN) guidelines and add to existing guidelines. Gains in tolerance may not be sustained after stopping oral therapy and patients will need to decide whether they are willing to continue therapy for an extended period. More trials are needed to ascertain whether other routes of administration for therapy and adding biologicals can have beneficial impacts on food allergies. A recent report by Zuberbier, et al in J Allergy Clin Immunol Pract. 2023;11(4):1134–1146 suggests that omalizumab may provide such benefit.