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

Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.25). 03/2011; 127(3):654-60. DOI: 10.1016/j.jaci.2010.12.1111
Source: PubMed

ABSTRACT 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.


Available from: Amy Scurlock, May 28, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1. Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1. Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product. Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug product demonstrated at least 20 months of stability. The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine. © 2015 S. Karger AG, Basel.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Peanut allergy is an increasingly common health problem. Current treatment guidelines are based on strict avoidance. However, in the last few years, oral immunotherapy protocols have shown promising results yielding increased tolerance to peanut in allergic children. Adolescence is particularly at risk. We have designed a randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of peanut oral escalating immunotherapy in a 12- to 18-year-old population with proved allergy to peanut. Patients are selected when the threshold of peanut intake is over 100 mg and 2 cumulated g on the first double-blind, placebo-controlled oral food challenge (DBPCOFC). During the build-up placebo-controlled blinded phase, doses containing peanut or placebo will be administered by gradual up-dosing from 10 mg to 2 g with 2-weekly increments. After this first randomized phase, the desensitized participants will continue to intake native peanut in an unblinded process during 13 or 37 weeks following a second randomization. Adverse events are picked up and managed throughout the entire protocol. The main endpoint is the percentage of patients with negative DBPCOFC at the threshold of 2 g of cumulative peanut at the end of the build-up phase of 24 weeks. Secondary endpoints include: (1) desensitization 6 weeks and 6 months after the end of the maintenance phase; (2) adverse effects during the build-up phase; (3) immunological profile confirming peanut desensitization. Immunologic assays will be carried out at every DBPCOFC and at the middle of the build-up phase to evaluate the peanut immunologic profile modifications. This double-blind, placebo-controlled study will be, to our knowledge, the first evaluation of a peanut oral immunotherapy protocol in teenagers in the purpose to reduce severe reactions after unexpected intake and to improve quality of life. NCT02046083 (23 January 2014).
    Trials 04/2015; 16(1):197. DOI:10.1186/s13063-015-0717-y · 2.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of pediatric food allergy and anaphylaxis has increased in the last decades, especially in westernized countries where this emerging phenomenon was marked as a “second wave” of the allergic epidemic. Over recent years great advances have been achieved in the field of in vitro allergy testing and component-resolved diagnosis has increasingly entered clinical practice. Testing for allergen components can contribute to a more precise diagnosis by discriminating primary from cross-reactive sensitizations and assessing the risk of severe allergic reactions. The basic concept of the management of food allergy in children is also changing. Avoidance of the offending food is still the mainstay for disease management, especially in primary health care settings, but it severely affects the patients’ quality of life without reducing the risk of accidental allergic reactions. There is a growing body of evidence to show that specific oral tolerance induction can represent a promising treatment option for food allergic patients. In parallel, education of food allergic patients and their caregivers as well as physicians about anaphylaxis and its treatment is becoming recognized a fundamental need. International guidelines have recently integrated these new evidences and their broad application all over Europe represents the new challenge for food allergy specialists.
    Italian Journal of Pediatrics 12/2015; 41(1). DOI:10.1186/s13052-014-0108-0