Background-Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported.
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.
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.
Background
Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown.
Objective
We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow’s milk (CM) allergy.
Methods
We randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG4 levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels.
Results
Thirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P = .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG4 levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group.
Conclusion
OIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy.
Background-There are no treatments currently available for peanut allergy. Sublingual immunotherapy is a novel approach to the treatment of peanut allergy.
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