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 IgG4 ( 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 : FoxP3intermediate 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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 after withdrawal of OIT. Methods We conducted a pilot clinical trial of peanut OIT at 2 US centers. Subjects age 1 to 16 years were recruited and treated for up to 5 years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg/d peanut protein. Blood was collected at multiple time points. Clinical end points 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. Twelve (50%) of 24 successfully passed a challenge 1 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 test results, as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2 and lower ratios of peanut-specific IgE/total IgE compared with subjects not passing. There were no differences in peanut IgG4 levels or functional activity at the end of the study. Conclusions This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated for up to 5 years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin test results and lower allergen-specific IgE levels were predictive of successful outcome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Methods Subjects (median age 9 years) with allergy to walnut and another tTN (pecan, cashew, hazelnut, pistachio) received open label WOIT after completing 38-weeks of blinded, placebo-controlled ...treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Methods Fourteen subjects (median age 9 years) with allergy to walnut and another test tree nut (pecan, cashew, hazelnut, pistachio) were randomized (2:1) to receive WOIT or placebo OIT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Conclusions Oral allergy symptoms and pollen sensitization are common in multi-tree nut allergic subjects participating in a WOIT trial and complicate clinical assessment during OFC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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