A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy.

BACKGROUND: Although promising results have emerged regarding oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for the treatment of peanut allergy (PA), direct comparisons of these approaches are limited. OBJECTIVE: This study was conducted to compare the safety, efficacy, and mechanistic correlates of peanut OIT and SLIT. METHODS: In this double-blind study children with PA were randomized to receive active SLIT/placebo OIT or active OIT/placebo SLIT. Doses were escalated to 3.7 mg/d (SLIT) or 2000 mg/d (OIT), and subjects were rechallenged after 6 and 12 months of maintenance. After unblinding, therapy was modified per protocol to offer an additional 6 months of therapy. Subjects who passed challenges at 12 or 18 months were taken off treatment for 4 weeks and rechallenged. RESULTS: Twenty-one subjects aged 7 to 13 years were randomized. Five discontinued therapy during the blinded phase. Of the remaining 16, all had a greater than 10-fold increase in challenge threshold after 12 months. The increased threshold was significantly greater in the active OIT group (141- vs 22-fold, P = .01). Significant within-group changes in skin test results and peanut-specific IgE and IgG4 levels were found, with overall greater effects with OIT. Adverse reactions were generally mild but more common with OIT (P < .001), including moderate reactions and doses requiring medication. Four subjects had sustained unresponsiveness at study completion. CONCLUSION: OIT appeared far more effective than SLIT for the treatment of PA but was also associated with significantly more adverse reactions and early study withdrawal. Sustained unresponsiveness after 4 weeks of avoidance was seen in only a small minority of subjects.

Suppression of the immunologic response to peanut during immunotherapy is often transient.

BACKGROUND: Studies suggest that oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for food allergy hold promise; however, the immunologic mechanisms underlying these therapies are not well understood. OBJECTIVE: We sought to generate insights into the mechanisms and duration of suppression of immune responses to peanut during immunotherapy. METHODS: Blood was obtained from subjects at baseline and at multiple time points during a placebo-controlled trial of peanut OIT and SLIT. Immunologic outcomes included measurement of spontaneous and stimulated basophil activity by using automated fluorometry (histamine) and flow cytometry (activation markers and IL-4), measurement of allergen-induced cytokine expression in dendritic cell (DC)-T-cell cocultures by using multiplexing technology, and measurement of MHC II and costimulatory molecule expression on DCs by using flow cytometry. RESULTS: Spontaneous and allergen-induced basophil reactivity (histamine release, CD63 expression, and IL-4 production) were suppressed during dose escalation and after 6 months of maintenance dosing. Peanut- and dust mite-induced expression of TH2 cytokines was reduced in DC-T-cell cocultures during immunotherapy. This was associated with decreased levels of CD40, HLA-DR, and CD86 expression on DCs and increased expression of CD80. These effects were most striking in myeloid DC-T-cell cocultures from subjects receiving OIT. Many markers of immunologic suppression reversed after withdrawal from immunotherapy and in some cases during ongoing maintenance therapy. CONCLUSION: OIT and SLIT for peanut allergy induce rapid suppression of basophil effector functions, DC activation, and TH2 cytokine responses during the initial phases of immunotherapy in an antigen-nonspecific manner. Although there was some interindividual variation, in many patients suppression appeared to be temporary.

Sublingual vs oral immunotherapy for food allergy: identifying the right approach.

The incidence of food allergy in developed countries has increased in recent years, escalating the need to find a suitable form of treatment as an alternative to current management, which includes strict avoidance and ready availability of injectable epinephrine (adrenaline). Allergen immunotherapy is currently being studied for use in the treatment of IgE-mediated food allergy to the most common foods, including peanut, tree nut, milk and egg. Two modalities, oral immunotherapy (OIT) and sublingual immunotherapy (SLIT), have shown great promise. Both OIT and SLIT have been able to desensitize subjects to varying degrees, but the two treatment methods differ in doses that can be achieved, duration of treatment, safety profile and ease of use outside the research setting, among other aspects. More research is needed to conclude which mode of treatment is more effective in inducing long-term tolerance with the least amount of serious adverse reactions. However, OIT and SLIT show great promise, and a widespread treatment for food allergy may be within reach.