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Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

Egg allergy is a common and difficult pediatric problem. In this trial, the investigators found that oral treatment with escalating doses of egg protein enabled about one in four children with known egg allergy to eat egg without allergic symptoms. In the United States, 4% of children have a food allergy, 1 which affects health and quality of life. 2 Egg allergy has a cumulative prevalence of approximately 2.6% by 2.5 years of age, 3 with allergic reactions varying in severity from mild urticaria to systemic anaphylaxis. Severe allergic reactions can occur with a single bite of cooked egg (approximately 70 mg of egg protein). Children with egg allergy are placed on egg-free diets, but total avoidance of egg is difficult. Avoidance places a constant responsibility on patients and caregivers, leaves patients vulnerable to unintentional ingestion and anaphylaxis, and influences quality of life. . . .

GA2LEN and EFA propose minimum specifications for all industrialised countries/regions to work towards to support students with food allergies in educational settings. We reviewed research and legislation and gained feedback from over 100 patient and professional groups. We built shared expectations around: 1. training all school staff about what food allergy is, the symptoms of allergic reactions, what to do in an emergency, and when and how to use and store devices that laypeople can use to administer adrenaline (epinephrine). 2. preventing allergic reactions by using clear labelling on school menus and prepacked and non‐prepacked foods and regular cleaning where students eat. 3. preparing for serious allergic reactions, with written emergency action plans for every student with food allergies, legislation allowing schools to store adrenaline for anyone who needs it in an emergency (not just those prescribed it), and training and legal safeguards for staff administering adrenaline. 4. including affected students by discussing food allergy in the curriculum, raising awareness among all students and caregivers and reviewing school processes regularly. It is time for national and international action at the policy level. Patient groups, education networks and professional societies all play a role in campaigning for shared next steps.

This Anaphylaxis Manifesto calls on communities to prioritise 10 practical actions to improve the lives of people at risk of serious allergic reactions. The Global Allergy and Asthma European Network and the European Federation of Allergy and Airways Diseases Patients' Associations (EFA) compiled patient‐centric priorities. We used qualitative consensus methods, research evidence and feedback from over 200 patient groups, stakeholder organisations and healthcare professionals. We encourage healthcare, education and food organisations to collaborate with people at risk of serious allergic reactions to tackle safety, anxiety and financial burdens for individuals and societies. Key priorities for prevention include awareness‐raising campaigns for the public and professionals, school and workplace initiatives and mandatory precautionary allergen labels on food. Priorities for improving immediate and long‐term management include educating healthcare professionals, patients and schools about when and how to use adrenaline, funding two approved adrenaline devices for everyone at risk, and facilitating access to allergy specialists. Integrated care pathways should include clinical and non‐clinical management options such as individualised risk assessment and quality of life assessment, self‐management plans, dietetic and psychosocial support and peer support. Organisations around the world are committing to work together towards these priorities.

A peanut-derived protein product, AR101, used in an oral desensitization protocol in children and adolescents with severe peanut allergy increased the amount of oral peanut protein tolerated in approximately two thirds of participants who received AR101, as compared with 1 of 25 controls.

No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).

Purpose of ReviewTo review current and future treatment options for IgE-mediated food allergy.Recent FindingsRecent years have seen major developments in both allergen-specific and allergen-non-specific treatment options, with the first FDA-approved peanut oral immunotherapy (OIT) product becoming available in 2020. In addition to OIT, other immunotherapy modalities, biologics, adjunct therapies, and novel therapeutics are under investigation.SummaryFood allergy is a potentially life-threatening condition associated with a significant psychosocial impact. Numerous products and protocols are under investigation, with most studies focusing on OIT. A high rate of adverse events, need for frequent office visits, and cost remain challenges with OIT. Further work is needed to unify outcome measures, develop treatment protocols that minimize adverse events, establish demographic and clinical factors that influence candidate selection, and identify patient priorities.

Marc Rothenberg, John Harley and colleagues present the results of a genome-wide association study of eosinophilic esophagitis. They discover an association with variants near CAPN14 and show that CAPN14 is expressed specifically in the esophagus and is upregulated in esophageal biopsies of individuals with active disease. Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replicating association of the 5q22 locus (meta-analysis P = 1.9 × 10 −16 ), we identified an association at 2p23 spanning CAPN14 ( P = 2.5 × 10 −10 ). CAPN14 was specifically expressed in the esophagus, was dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to interleukin (IL)-13, and was located in an epigenetic hotspot modified by IL-13. Genes neighboring the top 208 EoE-associated sequence variants were enriched for esophageal expression, and multiple loci for allergic sensitization were associated with EoE susceptibility (4.8 × 10 −2 < P < 5.1 × 10 −11 ). We propose a model to explain the tissue-specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13–inducible esophageal response involving CAPN14.

There is no approved therapy for food allergies, which affect 12 million people in the United States and millions more worldwide. In the last few years, our research team at Duke has begun to develop protocols to treat peanut and other food allergies. Two distinct therapies are being developed. Oral immunotherapy (OIT), which relies on ingestion of increasing amounts of the allergenic food, has been used to successfully desensitize more than 50 peanut allergic subjects. Sublingual immunotherapy (SLIT) involves placing small quantities of peanut allergens under the tongue and has shown promise in our initial placebo-controlled clinical trial. Immunologic changes associated with OIT and SLIT include reduction in mast cell reactivity as determined by skin prick test size, decreased basophil responses, decreased specific-IgE, increased IgG4, and induction of regulatory T cells. Development of these immunotherapy strategies has generated much excitement in the food allergy community; however, further studies are needed before these approaches are ready for clinical use.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by immune hypersensitivity to food. Herein, we tested whether genetic risk factors for known, non-allergic, immune-mediated diseases, particularly those involving autoimmunity, were associated with EoE risk. We used the high-density Immunochip platform, encoding 200,000 genetic variants for major auto-immune disease. Accordingly, 1214 subjects with EoE of European ancestry and 3734 population controls were genotyped and assessed using data directly generated or imputed from the previously published GWAS. We found lack of association of EoE with the genetic variants in the major histocompatibility complex (MHC) class I, II, and III genes and nearly all other loci using a highly powered study design with dense genotyping throughout the locus. Importantly, we identified an EoE risk locus at 16p13 with genome-wide significance (Pcombined=2.05 × 10−9, odds ratio = 0.76−0.81). This region is known to encode for the genes CLEC16A, DEXI, and CIITI, which are expressed in immune cells and esophageal epithelial cells. Suggestive EoE risk were also seen 5q23 (intergenic) and 7p15 (JAZF1). Overall, we have identified an additional EoE risk locus at 16p13 and highlight a shared and unique genetic etiology of EoE with a spectrum of immune-associated diseases.