Methods: Systematic review of intervention studies, searching 11 international databases and contacting an international panel of experts. Studies were critically appraised using the Cochrane approach and meta-analysed.
Results: We identified 721 potentially relevant papers, from which we selected 16 reports of 14 eligible trials (12 randomised controlled trials and two controlled clinical trials). Eleven of these trials evaluated oral immunotherapy and the remaining three investigated sublingual immunotherapy.
Meta-analysis revealed that immunotherapy substantially reduced the average risk of persisting food allergy in patients (RR=0.24; 95%CI 0.11, 0.50). Pooling of the safety data however revealed an increased average risk of systemic adverse reactions in those receiving immunotherapy (RR=1.13; 95%CI 1.00, 1.27); the average risk of local (minor oropharyngeal/gastro-intestinal) adverse reactions was also increased in those receiving immunotherapy (RR=1.16; 95%CI 1.04, 1.30). Meta-analysis of immunological data demonstrated that allergen skin prick test wheal diameter significantly decreased in experimental groups compared to controls (mean difference -2.96mm; 95%CI -4.48, -1.45), whilst specific-IgG4 increased by an average of 19.9 µg/ml (95%CI 17.1, 22.6), however there was no change in specific IgE: -5.2 kU/L (95%CI -12.39, 1.99).
Conclusions: Oral/sublingual immunotherapy substantially reduces the risk of food allergy, this effect being mediated by immunological mechanisms. However, because of the stringent exclusion criteria used in many of the reviewed studies and the increased risk of systemic adverse events, immunotherapy cannot yet be recommended for routine clinical practice. Future research needs to focus on larger randomised controlled trials investigating long-term clinical tolerance induction, impact on quality of life and estimating the cost-effectiveness of treatment. Overall, this appears to be a promising line of potentially disease-modifying treatment for people with a range of IgE-mediated food allergies.