Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy

Abstract

Background Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy. Objective Our primary objective was to determine whether peanut OIT can induce sustained unresponsiveness following withdrawal of OIT. Methods We conducted a pilot clinical trial of peanut OIT at two U.S. centers. Subjects aged 1–16 were recruited and treated for up to five years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg peanut protein/day. Blood was collected at multiple time points. Clinical endpoints were measured with 5000 mg double-blinded, placebo-controlled food challenges once specific criteria were met. Results Of the 39 subjects originally enrolled, 24 completed the protocol and had evaluable outcomes. 12/24 (50%) successfully passed a challenge one month after stopping OIT and achieved sustained unresponsiveness. Peanut was added to the diet. At baseline and the time of challenge, such subjects had smaller skin tests as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2, and lower ratios of peanut-specific:total IgE, compared to subjects not passing. There were no differences in peanut IgG4 levels or functional activity at end-of-study. Conclusions This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated up to five years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin tests and lower allergen-specific IgE levels were predictive of successful outcome.

Oral Immunotherapy for Food Allergy

“…The potential efficacy of food OIT depends on the defined endpoints, including the ability to tolerate the treatment, the induction of a transient state of desensitization, and/or the development of a more durable state of clinical tolerance, which is often referred to as sustained unresponsiveness (SU) [13,14]. Desensitization is defined as a temporary increase in the threshold for reactivity, with maintenance of the desensitized state requiring continued consumption of the allergenic protein to prevent the reappearance of reactivity.…”

“…The first study of SU following peanut OIT was published in 2014 [14]. Twenty-four patients aged 1 to 16 years completed OIT with maintenance dosing of 4000 mg of peanut protein for up to 5 years.…”

“…Studies have consistently demonstrated specific immunologic changes, including increases in food-specific IgG4 and decreased basophil and mast cell responsiveness [13,14,18,56]. Some studies have shown alterations in the binding pattern of antigen to antigen-specific IgE, either by reduction in the diversity of epitope recognition or altered IgE affinity [57].…”

Safety, Clinical and Immunologic Efficacy of a Chinese Herbal Medicine (FAHF-2) for Food Allergy

“…Data from oral immunotherapy studies also indicate that longer treatment durations are likely to be more effective for well-established food allergy. [20,21] Animal studies also suggest that concurrent allergen exposure may be necessary for efficacy of FAHF-2. In the murine experiments, the mice were exposed to allergen monthly throughout the study.…”

Oral immunotherapy for the treatment of food allergy

“…Vickery et al and Syed et al both studied maintenance doses of 4000mg of peanut protein. 34 In Vickery's group, subjects underwent OIT and maintained for a total of 5 y, followed by 1 mo of avoidance, at the end of which 31% were tolerant to a 5g challenge. In comparison, the Syed cohort underwent OIT and maintenance for a total of 2 y and after avoiding for 3 mo, 30% were still tolerant to 4g.…”