S.K. Carlisle

A randomized controlled study of peanut oral immunotherapy: Clinical desensitization and modulation of the allergic response

BACKGROUND Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials. OBJECTIVE To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind, placebo-controlled study. METHODS In this multicenter study, children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge (OFC) at approximately 1 year. Titrated skin prick tests (SPTs) and laboratory studies were performed at regular intervals. RESULTS Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study because of allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (n = 16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), whereas placebo subjects (n = 9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg; P < .001). In contrast with the placebo group, the peanut OIT group showed reductions in SPT size (P < .001), IL-5 (P = .01), and IL-13 (P = .02) and increases in peanut-specific IgG(4) (P < .001). Peanut OIT subjects had initial increases in peanut-specific IgE (P < .01) but did not show significant change from baseline by the time of OFC. The ratio of forkhead box protein 3 (FoxP3)(hi): FoxP3(intermediate) CD4+ CD25+ T cells increased at the time of OFC (P = .04) in peanut OIT subjects. CONCLUSION These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance.

265 THE NATURAL HISTORY OF FOOD ALLERGIES IN CHILDREN: AN EVALUATION OF CLINICAL TOLERANCE AND SEVERITY OF REACTIONS TO FOOD CHALLENGES

Purpose To compare food-specific IgE levels and age of passed or failed oral food challenges (FC) and examine the severity of failed FC. Methods We performed a retrospective review of food allergic patients who underwent milk, egg, soy, wheat, and peanut FC (January 2000-June 2004) based on known predictive IgE levels. Food-specific IgE and age were determined for those who passed or failed challenges. System involvement and treatment of failed challenges were analyzed. Results One hundred sixty-three FC were performed in 106 patients (67% male; 83% Caucasian; 66% atopic comorbidities). 56% of FC were blinded, 43% open. Negative challenges occurred in 97/163 (60%) - milk 47%, egg 61%, peanut 66%, soy 61%, and wheat 63%. Median age (years) of those passing challenges was: milk 3.2; egg 4.5; peanut 5.1; soy 2.3; wheat 3.6. For failed challenges median age was milk 2.0; egg 4.4; peanut 4.0; soy 4.6; and wheat 4.0. Median food-specific IgE levels (kUA/L) for passed FC were milk 1.6; egg 0.7; peanut 0.7; soy 0.7; and wheat 6.7. IgE levels for failed challenges were milk 4.5; egg 0.7; peanut 1.4; soy 20; and wheat 7.5. For failed challenges, 80% had cutaneous involvement, 32% upper respiratory, 23% lower respiratory, and 32% gastrointestinal. Positive challenges were successfully treated with antihistamines (80%), bronchodilators (8%), charcoal (2%), epinephrine (11%), and fluids/corticosteroids (2%), while 8% required no treatment. Conclusions For patients with low food-specific IgE levels approaching 95th% negative predictive value, FC can be performed safely, with minimal symptoms and with the majority of patients showing clinical tolerance.