Food allergy - Emerging treatments

Sublingual immunotherapy

Gradual oral exposure to native food proteins induces regulatory T cells early in treatment and results in immune deviation towards non-allergic Th1 responses later in therapy.[16] In one study, patients taking hazelnut sublingual immunotherapy (SLIT) were able to increase the mean threshold dose eliciting a reaction, although 50% of the patients' symptoms were limited to oral allergy syndrome at enrolment.[85] A double-blind, placebo-controlled study of peanut SLIT showed that those receiving peanut SLIT were able to tolerate 20 times more peanut protein than the placebo group.[86] A significant decrease in skin prick test wheal diameter, decreased basophil responsiveness, and significant changes in both peanut-specific immunoglobulin (Ig) E and IgG4 were detected in the treatment group compared with the placebo group. Studies investigating the utility of SLIT for other foods are ongoing, and its use is still considered investigational.

Oral immunotherapy

A food allergen is given in increasing amounts over a period of months to increase the triggering dose threshold for food-allergic patients. A number of oral immunotherapy (OIT) trials have focused on treatment of peanut allergy and have shown that the majority of children with peanut allergy can be desensitised using OIT. In one phase III trial, children and adolescents who were highly allergic to peanut were randomised to receive OIT with a peanut-derived OIT, or placebo. Children who received peanut-derived OIT were able to ingest higher doses of peanut protein without dose-limiting symptoms compared with the placebo group, and had lower symptom severity during peanut exposure at the exit food challenge.[87] Peanut (Arachis hypogaea) allergen powder is an OIT that is approved for use in patients, aged 4 to 17 years, with a confirmed diagnosis of peanut allergy. However, one systematic review and meta-analysis of OIT for peanut allergy showed that, despite effectively inducing desensitisation, peanut OIT regimes considerably increased allergic and anaphylactic reactions compared with avoidance or placebo.[88] It is important to note that most reactions experienced during OIT are mild and do not prevent participants from continuing on therapy; sustained immunological remission has not been convincingly proven when OIT is discontinued or continued at a reduced dose.[89][90][91] The latter is an important limitation of OIT since the majority of peanut-allergic individuals receiving OIT will need to ingest peanut indefinitely to maintain the protective benefit of OIT. Further research will focus on reducing adverse effects associated with therapy, and the development of surrogate biomarkers to better characterise allergic patients who will respond favourably to therapy, and those for whom other treatment options or strict allergen avoidance would be preferable. OIT to other foods, such as milk and egg, has also shown promise.[92][93][94] [ ] For example, ADP101, an IgE-mediated multi-food oral immunotherapy, has been granted fast-track designation by the Food and Drug Administration (FDA) for the treatment of single or multiple food allergies, including almonds, cashews, chicken egg, codfish, cow milk, hazelnut, peanut, pecan, pistachio, salmon, sesame seed, shrimp, soya, walnut, and wheat. One multicentre, randomised, double-blind, placebo phase I/II trial demonstrated that ADP101 has a dose-dependent, clinically meaningful desensitisation response for paediatric patients with some food allergies.[95]

Peptide immunotherapy

Numerous small peptides are presented to T-cell epitopes without IgE crosslinking. Efficacy has been shown in murine models, but translation to humans has been difficult.[16]

Chinese herbal medicine

The herbal compound (Food Allergy Herbal Formula-2 or FAHF-2) has been proven safe in adolescents and adults; however, the ability to improve tolerance to food allergens has not been demonstrated.[96] Ongoing trials are investigating the potential of FAHF-2 to improve the safety of OIT when used in combination with multi-food OIT.[97]

Omalizumab

Omalizumab, an anti-IgE monoclonal antibody, is approved by the FDA for IgE-mediated food allergy in children 1 year or older and adults for the reduction of allergic reactions (including anaphylaxis) due to accidental exposure to one or more foods. It should be used in conjunction with food allergen avoidance. Omalizumab has also been demonstrated to improve the safety of milk oral immunotherapy without affecting efficacy.[98] An ongoing clinical trial is investigating the potential of omalizumab to increase the dose-triggering threshold for a number of food allergens in multi-food allergic individuals, and to improve the safety of multi-food OIT.[99]

Epicutaneous immunotherapy

Epicutaneous immunotherapy (EPIT) involves prolonged exposure to an allergen to the skin via an epicutaneous patch. One phase III trial reported a statistically significant response to EPIT (35.3% vs 13.6% in the placebo arm) peanut-allergic children aged 4 to 11 years.[100] However, the prespecified lower bound of the confidence interval criterion for a positive result was not met.[100] Ongoing trials are investigating the efficacy of milk EPIT in milk-allergic children and peanut EPIT in peanut-allergic children 1 to 3 years of age.[101][102]