Varshney, P. et al. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J. Allergy Clin. Immunol. 127, 654-660

Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 03/2011; 127(3):654-60. DOI: 10.1016/j.jaci.2010.12.1111
Source: PubMed


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.
To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind, placebo-controlled study.
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.
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.
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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    • "The investigators reported that 84% of subjects passed a final challenge of 20 peanuts, successfully ingesting 5 g of peanut protein compared with only 1 peanut or 280 mg of peanut protein (median value) ingested by the placebo subjects. The authors concluded that the degree of protection following successful immunotherapy was likely to prevent accidental peanut anaphylaxis [29]. "
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    ABSTRACT: Peanut allergy is common and can be a cause of severe, life-threatening reactions. It is rarely outgrown like other food allergies, such as egg and milk. Peanut allergy has a significant effect on the quality of life of sufferers and their families, due to dietary and social restrictions, but mainly stemming from fear of accidental peanut ingestion. The current management consists of strict avoidance, education and provision of emergency medication, but a disease- modifying therapy is needed for peanut allergy. Recent developments involve the use of immunotherapy, which has shown promise as an active form of treatment. Various routes of administration are being investigated, including subcutaneous, oral, sublingual and epicutaneous routes. Other forms of treatment, such as the use of vaccines and anti-IgE molecules, are also under investigation. So far, results from immunotherapy studies have shown good efficacy in achieving desensitisation to peanut with a good safety profile. However, the issue of long-term tolerance has not been fully addressed yet and larger, phase III studies are required to further investigate safety and efficacy. An assessment of cost/benefit ratio is also required prior to implementing this form of treatment. The use of immunotherapy for peanut allergy is not currently recommended for routine clinical use and should not be attempted outside specialist allergy units.
    09/2014; 4(1):30. DOI:10.1186/2045-7022-4-30
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    • "Ketotifen was selected as the premedication agent for its dual antihistamine and mast cell stabilizing properties; established safety record; and, to examine whether it may mitigate gastrointestinal symptoms frequently observed during food oral immunotherapy given its previously documented benefit in eosinophilic gastroenteritis. Using a previously published protocol for peanut OIT [9,23] we conducted a small randomized, single-blind, placebo controlled pilot study examining the rate and severity of adverse reactions during peanut OIT with ketotifen premedication during the initial four weeks of peanut dose escalation. "
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    ABSTRACT: Background Oral immunotherapy (OIT) has shown promise in inducing desensitization for food allergy. However, there are safety concerns regarding the frequency and severity of adverse events during food OIT. Objective To evaluate the effect of Ketotifen premedication on adverse reactions during peanut OIT. Methods A randomized single blind placebo controlled pilot study was performed. Peanut OIT was performed using a previously published protocol. Ketotifen was up-titrated to 2 mg twice daily over two weeks (week -2 to 0), followed by a peanut OIT initial escalation day (day 1). Ketotifen was administered from week 0–4 of peanut OIT; reactions to peanut OIT doses were recorded by clinic staff and subject diary. Results Six subjects (median age 10 years, peanut IgE >100kUA/L) were enrolled, 4 randomized to Ketotifen, 2 to placebo. The most common side effect of Ketotifen was fatigue (9% during up-titration). The rate of reaction per peanut OIT dose was lower for subjects on ketotifen (K) compared to placebo (P) during initial escalation on day 1 (K: 22% (8/36) vs. P: 67% (12/18)); week 0–4 build-up doses (K: 75% (3/4) vs. P: 100% (2/2)); and week 0–4 home doses (K: 50% (54/108) vs. P: 82% (27/33)). The rate of gastrointestinal symptoms per peanut OIT dose was also lower for subjects on ketotifen during initial escalation on day 1 (K: 17% (6/36) vs. P: 61% (11/18)); week 0–4 build-up doses (K: 75% (3/4) vs P: 100% (2/2)); and week 0–4 home doses (K: 46% (50/108) vs. P: 82% (27/33)). Conclusions Ketotifen premedication is well tolerated and reduces the rate of gastrointestinal symptoms during peanut OIT. These findings require confirmation in a larger study of Ketotifen premedication used throughout peanut OIT. Trial registration Clinical Trials number: NCT0162515
    Allergy Asthma and Clinical Immunology 07/2014; 10(1):36. DOI:10.1186/1710-1492-10-36 · 2.03 Impact Factor
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    • "This idea dates back to 1911 and originated from experiments where hen׳s egg protein was fed to guinea pigs, rendering them refractive to injections with the antigenic protein [22]. Recent clinical studies in the area of food allergies to eggs [23] and peanuts [24] have suggested that high-dose oral feeding regimens can induce a certain degree of desensitization. Whether this amounts to the establishment of lasting tolerance is still unclear, although the most recent egg allergy trial showed prolonged desensitization in about a quarter of patients [23]. "
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    ABSTRACT: Up to 25 per cent of the world׳s adult population may have the metabolic syndrome, a condition closely associated with central obesity. The metabolic syndrome is a major risk factor for cardiovascular disease and type 2 diabetes and therefore represents an important worldwide health problem. In addition to metabolic abnormalities such as raised fasting plasma glucose, high cholesterol and high blood pressure, there is consensus that obese subjects develop a state of low-grade chronic immune activation. This sustained pro-inflammatory response in fat tissue is thought to worsen insulin resistance and dyslipidemia. Likewise, the immune system contributes to the detrimental cascade of events leading to plaque formation in atherosclerosis. It has long been assumed that the innate arm of the immune system was the only key player, but emerging evidence suggests that there is in fact a sizeable adaptive immune component to obesity and cardiovascular disease. From a therapeutic perspective, it could be envisioned that immune modulation drugs such as cytokine inhibitors, co-stimulation blockers or anti-T cell agents could offer benefit. It is questionable, however, whether chronic treatment with for instance biologicals will have a favorable risk/benefit profile in a silent condition such as the metabolic syndrome. An attractive alternative could be the development of antigen-specific T cell therapies, not unlike those currently in various phases of development for type 1 diabetes. In this article, we will give an overview of antigen-specific treatment modalities in type 1 diabetes, followed by a review of the evidence for T cell involvement in obesity and atherosclerosis.
    Molecular Metabolism 06/2014; 3(3):275-283. DOI:10.1016/j.molmet.2013.12.005
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