Immunotherapy for foods
Allergen immunotherapy is a procedure that involves administration of an allergen on a regular basis with the intention to promote specific immune mechanisms and ultimately promote clinical tolerance to the allergen. For foods, several methods of immunotherapy have been studied including oral, sublingual, epicutaneous (patch), and subcutaneous. Subcutaneous immunotherapy for peanut has proven impractical due to risk of developing systemic allergic reaction.71 Out of all methods, OIT for nuts may be the most promising. A number of exciting studies are emerging, though long-term outcomes need to be further evaluated before this therapy is readily accepted for clinical practice. Furthermore, questions remain unanswered regarding whether protocols promote desensitization or tolerance. Desensitization is a temporary and reversible state, meaning once administration of the allergen is suspended, clinical reactivity returns. Tolerance refers to a long-term effect of unresponsiveness to the allergen.
In 2005, Enrique et al from Spain performed a randomized, double-blind placebo-controlled study for sublingual immunotherapy (SLIT) in adults with hazelnut allergy.72 During the final assessment, half of the patients in the treatment group were able to reach the highest dose of hazelnut (20 g) on OFC compared with only 9% in placebo group. Long-term efficacy was not evaluated.
While additional data on immunotherapy for tree nuts is somewhat lacking, peanut immunotherapy, specifically OIT, has emerged as a potential approach for induction of tolerance in allergic individuals. Recently, a few meta-analyses of immunotherapy for food have been published, including a Cochrane review specifically on peanut OIT.73 Overall, the analyses concluded that peanut OIT with short-term incremental doses of the allergen seems to be effective for inducing desensitization in some patients who are able to tolerate the regimen, but none of the studies showed induction of tolerance by OIT and no trials followed subjects for >2 years.74 One study published in 2014 demonstrated that 50% of subjects with peanut allergy treated with OIT for up to 5 years had sustained unresponsiveness for 4 weeks after cessation of therapy.75 Similar studies with patients followed for longer time periods after discontinuation of OIT are required to support this result. In all studies of OIT in food allergy, the rates of adverse reaction are not insignificant (up to 90%) in the treatment groups.74 Most reactions are mild, but further studies are needed to adequately assess risk and safety before recommending this treatment in clinical practice. An additional alarming statistic reported in a recent meta-analysis includes the development of eosinophilic esophagitis in up to 2.7% of patients undergoing OIT.76 This further illustrates the need for additional long-term follow-up studies on OIT in food allergy.
Other recent studies have looked at SLIT for peanut allergy, which involves incremental doses of daily peanut protein placed under the tongue.77–79 In 2013, Fleischer et al showed that after 44 weeks of therapy, 70% of subjects aged 12–40 years receiving peanut SLIT were able to tolerate a median successfully consumed dose of 5 g peanut protein (or tenfold more peanut powder than at baseline OFC) compared with only 15% of patients who received placebo.79 In 2015, Burks et al presented long-term follow-up of the same study cohort, after 2 and 3 years of peanut SLIT. Over 50% of participants discontinued therapy despite most adverse reactions being localized to the oropharynx. Of the peanut SLIT group, only 10.8% were fully desensitized to 10 g of peanut powder by the end of the 3 years, but all of those who were desensitized also achieved sustained unresponsiveness after discontinuation of SLIT for 8 weeks (as determined by an open feeding challenge with peanut butter).77 Another pilot study of peanut SLIT was published by Narisety et al in 2015. This was also a randomized, double-blind, placebo-controlled trial, but included peanut OIT as well. Twenty-one children were randomized to either receive active peanut SLIT/placebo OIT or placebo SLIT/active peanut OIT. Of the 16 children who did not discontinue therapy, all were able to tolerate over tenfold increase in their peanut challenge threshold, but this threshold was significantly greater in the active OIT group (P=0.1). Adverse reactions were mild, but more common in the active OIT group.78 All of these peanut SLIT studies show promise in inducing both clinical desensitization and sustained unresponsiveness for peanut-allergic individuals, though adherence seems that it may be an issue and more long-term follow-up is needed to fully evaluate side efficacy and potential side effects.
The newest method in prevention of peanut allergy was presented at the American Academy of Asthma, Allergy and Immunology (AAAAI) annual conference in March, 2015. In a late breaking abstract, Hugh A. Sampson, MD, FAAAAI, revealed the results of a multinational, double-blind, placebo-controlled randomized trial of epicutaneous immunotherapy for peanut allergy. After 1 year of therapy, patients treated with the highest dose peanut patch (250 μg) tolerated ten times the dose at their entry oral peanut challenge (at least 1 g of peanut protein or approximately four peanuts). Compliance was also promising at 95%, and there were no serious adverse reactions related to the therapy.80