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Journal ArticleDOI

Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults

TL;DR: Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks, with the highest responses among younger children, and when coupled with a high adherence and retention rate and significant changes in immune pathways, supports further investigation of this novel therapy.
Abstract: Background Peanut allergy is common, life-threatening, and without therapeutic options We evaluated peanut epicutaneous immunotherapy (EPIT) by using Viaskin Peanut for peanut allergy treatment Objective We sought to evaluate the clinical, safety, and immunologic effects of EPIT for the treatment of peanut allergy Methods In this multicenter, double-blind, randomized, placebo-controlled study, 74 participants with peanut allergy (ages 4-25 years) were treated with placebo (n = 25), Viaskin Peanut 100 μg (VP100; n = 24) or Viaskin Peanut 250 μg (VP250; n = 25; DBV Technologies, Montrouge, France) The primary outcome was treatment success after 52 weeks, which was defined as passing a 5044-mg protein oral food challenge or achieving a 10-fold or greater increase in successfully consumed dose from baseline to week 52 Adverse reactions and mechanistic changes were assessed Results At week 52, treatment success was achieved in 3 (12%) placebo-treated participants, 11 (46%) VP100 participants, and 12 (48%) VP250 participants ( P = 005 and P = 003, respectively, compared with placebo; VP100 vs VP250, P = 48) Median change in successfully consumed doses were 0, 43, and 130 mg of protein in the placebo, VP100, and VP250 groups, respectively (placebo vs VP100, P = 014; placebo vs VP250, P = 003) Treatment success was higher among younger children ( P = 03; age, 4-11 vs >11 years) Overall, 144% of placebo doses and 798% of VP100 and VP250 doses resulted in reactions, predominantly local patch-site and mild reactions ( P = 003) Increases in peanut-specific IgG 4 levels and IgG 4 /IgE ratios were observed in peanut EPIT-treated participants, along with trends toward reduced basophil activation and peanut-specific T H 2 cytokines Conclusions Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks, with the highest responses among younger children This, when coupled with a high adherence and retention rate and significant changes in immune pathways, supports further investigation of this novel therapy
Citations
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Journal ArticleDOI
TL;DR: This review provides general information to serve as a primer for those embarking on understanding food allergy and also details advances and updates in epidemiology, pathogenesis, diagnosis, and treatment that have occurred over the 4 years since the last comprehensive review.
Abstract: This review provides general information to serve as a primer for those embarking on understanding food allergy and also details advances and updates in epidemiology, pathogenesis, diagnosis, and treatment that have occurred over the 4 years since our last comprehensive review. Although firm prevalence data are lacking, there is a strong impression that food allergy has increased, and rates as high as approximately 10% have been documented. Genetic, epigenetic, and environmental risk factors are being elucidated increasingly, creating potential for improved prevention and treatment strategies targeted to those at risk. Insights on pathophysiology reveal a complex interplay of the epithelial barrier, mucosal and systemic immune response, route of exposure, and microbiome among other influences resulting in allergy or tolerance. The diagnosis of food allergy is largely reliant on medical history, tests for sensitization, and oral food challenges, but emerging use of component-resolved diagnostics is improving diagnostic accuracy. Additional novel diagnostics, such as basophil activation tests, determination of epitope binding, DNA methylation signatures, and bioinformatics approaches, will further change the landscape. A number of prevention strategies are under investigation, but early introduction of peanut has been advised as a public health measure based on existing data. Management remains largely based on allergen avoidance, but a panoply of promising treatment strategies are in phase 2 and 3 studies, providing immense hope that better treatment will be imminently and widely available, whereas numerous additional promising treatments are in the preclinical and clinical pipeline.

938 citations

Journal ArticleDOI
01 Apr 2018-Allergy
TL;DR: Patients and their families should be provided with information about the use of FA‐AIT for IgE‐mediated food allergy to allow them to make an informed decision about the therapy.
Abstract: Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

353 citations


Cites background from "Epicutaneous immunotherapy for the ..."

  • ...Epicutaneous 6 immunotherapy (EPIT) is also under investigation for peanut and milk; it involves application 7 of patches containing food allergen onto the skin (17)....

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  • ...A single 27 prospective RCT of EPIT with peanut suggests a favorable safety profile (17)....

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  • ...This effect was higher in patients below 11 years of 26 age (17)....

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08 Jul 2011
TL;DR: In this article, the authors investigated the efficacy and safety of oral immunotherapy (OIT) in peanut allergy and found that OIT appeared to be safe and of some benefit in many patients with peanut allergy.
Abstract: BACKGROUND The only treatment option for peanut allergy is strict avoidance. OBJECTIVE To investigate efficacy and safety of oral immunotherapy (OIT) in peanut allergy. METHODS Twenty-three children (age, 3.2-14.3 years) with IgE-mediated peanut allergy confirmed by positive double-blind, placebo-controlled food challenge (DBPCFC) received OIT following a rush protocol with roasted peanut for 7 days. If a protective dose of at least 0.5 g peanut was not achieved, patients continued with a long-term buildup protocol using biweekly dose increases up to at least 0.5 g peanut. A maintenance phase for 8 weeks was followed by 2 weeks of peanut avoidance and a final DBPCFC. Immunologic parameters were determined. RESULTS After OIT using the rush protocol, patients tolerated a median dose of only 0.15 g peanut. Twenty-two of 23 patients continued with the long-term protocol. After a median of 7 months, 14 patients reached the protective dose. At the final DBPCFC, patients tolerated a median of 1 g (range, 0.25-4 g) in comparison with 0.19 g peanut at the DBPCFC before OIT (range, 0.02-1 g). In 2.6% of 6137 total daily doses, mild to moderate side effects were observed; in 1.3%, symptoms of pulmonary obstruction were detected. OIT was discontinued in 4 of 22 patients because of adverse events. There was a significant increase in peanut-specific serum IgG(4) and a decrease in peanut-specific IL-5, IL-4, and IL-2 production by PBMCs after OIT. CONCLUSION Long-term OIT appears to be safe and of some benefit in many patients with peanut allergy. With an increase in threshold levels and a reduction of peanut-specific T(H)2 cytokine production, the induction of tolerance may be feasible in some patients.

325 citations

Journal ArticleDOI
TL;DR: To determine that oral immunotherapy (OIT) to egg is safe and effective to desensitize patients and induce sustained unresponsiveness, a double-blind, randomized placebo-controlled study of 55 children, sensitive to egg, is conducted.
Abstract: AW Burks, SM Jones, RA Wood; Consortium of Food Allergy Research (CoFAR) N Engl J Med 2012;367(3):233–243 To determine that oral immunotherapy (OIT) to egg is safe and effective to desensitize patients and induce sustained unresponsiveness A double-blind, randomized placebo-controlled study of 55 children, 5 to 11 years of age, sensitive to egg, with 40 receiving OIT and 15 placebo Initial dose escalation and buildup, maintenance phases up to 2 g of egg protein (one-third egg) This was followed by an oral …

288 citations

Journal ArticleDOI
TL;DR: Better understanding of the molecular mechanism governing the generation of Treg and Breg cells during allergen tolerance might well open new avenues for alternative therapeutic interventions in allergic diseases and help better understanding of other immune‐tolerance‐related diseases.
Abstract: Allergy is a major public health problem with a high socio-economic impact. The number of allergic patients is expected to reach to four billion within two decades when the World's population reaches to 10 billion. Our knowledge on the molecular mechanisms underlying allergic diseases and allergen tolerance induction had significant advances during the last years. Nowadays, it is well accepted that the generation and maintenance of allergen-specific regulatory T cells (Tregs) and regulatory B cells (Bregs) and the involvement of their suppressive cytokines and surface molecules are essential for the induction of allergen tolerance. These mechanisms play essential roles for the restoration of healthy immune responses to allergens in allergen-specific immunotherapy (AIT) and healthy immune response during high-dose antigen exposure in beekeepers and cat owners. AIT remains as the only disease-modifying and curative treatment for allergic diseases and represents a perfect model to investigate the antigen-specific immune responses in humans. A large number of clinical trials demonstrated AIT as an effective treatment in many patients, but it still faces several drawbacks in relation to efficacy, safety, long duration, and patient adherence. Novel strategies to overcome these inconveniences, such as the development of novel adjuvants and alternative routes of administration are being developed. The better understanding of the molecular mechanism governing the generation of Treg and Breg cells during allergen tolerance might well open new avenues for alternative therapeutic interventions in allergic diseases and help better understanding of other immune-tolerance-related diseases.

221 citations

References
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Journal ArticleDOI
TL;DR: The National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy, which include a consensus definition for food allergy.
Abstract: Food allergy is an important public health problem that affects children and adults and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no current treatment for food allergy: the disease can only be managed by allergen avoidance or treatment of symptoms. The diagnosis and management of food allergy also may vary from one clinical practice setting to another. Finally, because patients frequently confuse nonallergic food reactions, such as food intolerance, with food allergies, there is an unfounded belief among the public that food allergy prevalence is higher than it truly is. In response to these concerns, the National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy. These Guidelines are intended for use by a wide variety of health care professionals, including family practice physicians, clinical specialists, and nurse practitioners. The Guidelines include a consensus definition for food allergy, discuss comorbid conditions often associated with food allergy, and focus on both IgE-mediated and non-IgE-mediated reactions to food. Topics addressed include the epidemiology, natural history, diagnosis, and management of food allergy, as well as the management of severe symptoms and anaphylaxis. These Guidelines provide 43 concise clinical recommendations and additional guidance on points of current controversy in patient management. They also identify gaps in the current scientific knowledge to be addressed through future research.

2,014 citations

Journal ArticleDOI
TL;DR: Findings suggest that the prevalence and severity of childhood food allergy is greater than previously reported and that disparities exist in the clinical diagnosis of disease.
Abstract: OBJECTIVE: The goal of this study was to better estimate the prevalence and severity of childhood food allergy in the United States. METHODS: A randomized, cross-sectional survey was administered electronically to a representative sample of US households with children from June 2009 to February 2010. Eligible participants included adults (aged 18 years or older) able to complete the survey in Spanish or English who resided in a household with at least 1 child younger than 18 years. Data were adjusted using both base and poststratification weights to account for potential biases from sampling design and nonresponse. Data were analyzed as weighted proportions to estimate prevalence and severity of food allergy. Multiple logistic regression models were constructed to identify characteristics significantly associated with outcomes. RESULTS: Data were collected for 40 104 children; incomplete responses for 1624 children were excluded, which yielded a final sample of 38 480. Food allergy prevalence was 8.0% (95% confidence interval [CI]: 7.6–8.3). Among children with food allergy, 38.7% had a history of severe reactions, and 30.4% had multiple food allergies. Prevalence according to allergen among food-allergic children was highest for peanut (25.2% [95% CI: 23.3–27.1]), followed by milk (21.1% [95% CI: 19.4–22.8]) and shellfish (17.2% [95% CI: 15.6–18.9]). Odds of food allergy were significantly associated with race, age, income, and geographic region. Disparities in food allergy diagnosis according to race and income were observed. CONCLUSIONS: Findings suggest that the prevalence and severity of childhood food allergy is greater than previously reported. Data suggest that disparities exist in the clinical diagnosis of disease.

1,161 citations

Journal ArticleDOI
TL;DR: Although caution is required in comparing surveys, peanut allergy, TN allergy, or both continue to be reported by more than 1% of the US population and appear to be increasingly reported among children over the past decade.
Abstract: Background Allergy to peanuts and tree nuts (TNs) is the leading cause of fatal allergic reactions in the United States, and the prevalence appears to be increasing. Objectives We sought to determine the US prevalence of self-reported peanut, TN, and sesame allergy in 2008 and compare results with comparable surveys conducted in 1997 and 2002. Methods A nationwide, cross-sectional, random telephone survey for peanut and TN allergy was conducted with a previously used questionnaire, with additional questions about sesame. Results A total of 5,300 households (13,534 subjects) were surveyed (participation rate, 42% vs 52% in 2002 and 67% in 1997). Peanut allergy, TN allergy, or both was reported by 1.4% of subjects (95% CI, 1.2% to 1.6%) compared with 1.2% in 2002 and 1.4% in 1997. For adults, the prevalence was 1.3% (95% CI, 1.1% to 1.6%), which was not significantly different from prior surveys. However, the prevalence of peanut or TN allergy for children younger than 18 years was 2.1% (95% CI, 1.6% to 2.7%) compared with 1.2% in 2002 ( P = .007) and 0.6% in 1997 ( P P = not significant) and 0.4% in 1997 ( P Conclusions Although caution is required in comparing surveys, peanut allergy, TN allergy, or both continue to be reported by more than 1% of the US population (eg, >3 million subjects) and appear to be increasingly reported among children over the past decade. Sesame allergy is reported much less commonly.

814 citations


"Epicutaneous immunotherapy for the ..." refers background in this paper

  • ...5% to 1%(1,2) and a 3fold increase noted from 1997-2008.(2) In addition to being a key culprit in food-induced mortality, peanut allergy is associated with reduced quality of life and health economic effect....

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Journal ArticleDOI
TL;DR: Microarray data suggest a novel role for apoptosis in OIT, which induces clinical desensitization to peanut, with significant longer-term humoral and cellular changes.
Abstract: 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. Objective The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT. Methods Children with peanut allergy underwent an OIT protocol including initial day escalation, buildup, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated. Results Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12 to 18 months, whereas IgG 4 increased significantly. Serum factors inhibited IgE–peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-γ, and TNF-α from PBMCs increased over a period of 6 to 12 months. Peanut-specific forkhead box protein 3 T cells increased until 12 months and decreased thereafter. In addition, T-cell microarrays showed downregulation of genes in apoptotic pathways. Conclusion Oral immunotherapy induces clinical desensitization to peanut, with significant longer-term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT.

643 citations


"Epicutaneous immunotherapy for the ..." refers background or result in this paper

  • ...In comparison, OIT is associated with more adverse reactions, including anaphylaxis, but has been shown to induce robust changes in challenge thresholds of 5,000 to 10,000 mg.(9,11,14,21,33,34) Sublingual immunotherapy is associated with fewer adverse reactions than OIT, but changes in challenge SCD are also more modest, with our CoFAR study of a similar design demonstrating a change in SCD of approximately 500 mg....

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  • ...The immunomodulation noted with active treatment, including increases in peanut-specific IgG4 levels and IgG4/IgE ratios, is consistent with changes seen with other forms of food immunotherapy.(11,14,33-36) The trends seen in both basophil and Tcell responses suggest that exposure to peanut through intact skin might modulate TH2 responses and basophil reactivity....

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  • ...Oral immunotherapy (OIT) has been shown to induce desensitization inmost participants and sustained unresponsiveness in a minority, although adverse reactions are common.(9,11,14,20-22) Epicutaneous immunotherapy (EPIT) is an emerging modality for the treatment of food allergy....

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Journal ArticleDOI
TL;DR: These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset.
Abstract: BACKGROUND For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy. METHODS In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months. RESULTS After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in eggspecific IgG4 antibody levels were associated with passing the oral food challenge at 24 months. CONCLUSIONS These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.)

562 citations

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