Peanut Oral Immunotherapy Research Articles

PATIENTS WITH HIGH PEANUT IGE COMPONENT LEVELS LESS LIKELY TO COMPLETE PEANUT ORAL IMMUNOTHERAPY UP-DOSING

PATIENTS WITH HIGH PEANUT IGE COMPONENT LEVELS LESS LIKELY TO COMPLETE PEANUT ORAL IMMUNOTHERAPY UP-DOSING

Baseline Epitope-Specific IgE Profiles are Predictive of Sustained Unresponsiveness or High Threshold One-Year Post OIT in the POISED Trial

BackgroundResults from the POISED trial suggest that discontinuation of peanut oral immunotherapy can increase the risk of regaining clinical reactivity to peanut. ObjectiveWe sought to determine whether those who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific (es-) IgE profiles than those who achieved transient desensitization (TD). MethodsSubjects in the POISED trial (NCT02103270) were randomized to peanut (n=95) or placebo (n=25) for 24 months. OIT-desensitized subjects were then assigned to no peanut (PN-0, n=51) or 300mg (PN-300, n=30) for 12 months. SU and SHT were determined by those in PN-0 and PN-300, respectively, passing 4000mg peanut oral challenge. Specific IgE and IgG4 levels to peanut, Ara h 1-3 proteins and 64 allergenic epitopes were measured. We developed machine learning glmnet models with bootstrap simulations using baseline data to predict SU/SHT. ResultsEighty (84%) subjects were desensitized to peanut. Of those, 13% (n=8) and 37% (n=13) achieved SU/SHT in PN-0 and PN-300. Decreases in epitope-and protein-specific IgE levels and increases in IgG4 levels were observed during 2 years of OIT. At baseline, patients with SU in Peanut-0 but not Peanut-300 had lower es-IgE and protein-sIgE levels compared to the TD group. A machine-learning model with 12 baseline es-IgEs and age could predict SU/SHT with an accuracy of 94%, AUC 0.97, Sensitivity 1.00, Specificity 0.91. ConclusionsPatients who achieved SU/SHT have different baseline protein-and epitope-specific IgE profiles than those with TD. These profiles may help identify patients with an increased likelihood of achieving SU/SHT.

Immunomodulatory metabolites in IgE-mediated food allergy and oral immunotherapy outcomes based on metabolomic profiling.

The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown. To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT. Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes. Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10-20) and linoleic acid derivatives (q = 3.8 × 10-5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10-8), eicosanoids (q = 7.9 × 10-7), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU. We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.

Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral Immunotherapy in Infants and Toddlers in a Real-World Setting

Oral immunotherapy (OIT) for food allergy has been largely studied in older children within the context of clinical trials, and its availability has historically been limited for younger patients with food allergy. Data has shown that the most impact may actually be seen with the use of OIT in younger infants and toddlers. To evaluate the safety and feasibility of OIT in subjects younger than 24 months in a real-world setting using commercially available food products. This was a retrospective study of subjects 24 months and younger initiated on OIT for peanut, tree nut, or sesame allergy within the Scripps Clinic allergy department. Medical records were reviewed for data regarding initial oral food challenges (OFCs), OIT, and adverse outcomes. Fifty-two subjects under 24 months of age were initiated on OIT. Most subjects (84.6%) were on single food OIT, some (15.4%) were on multi-food OIT. No increased adverse outcomes were observed on multi-food OIT. Of the 59 initial OFCs, objective reactions occurred during 42 challenges, the majority being low grade reactions. During initial OFCs, 86.1% of peanut allergic children tolerated 1/8 of one Bamba stick with no reaction. The majority (73.1%) of subjects up-dosed at home and most (51.9%) had no reactions while up-dosing. Some had low grade cutaneous reactions, none requiring epinephrine or emergency evaluation. OIT in infants is safe and feasible to perform in a real-world setting using commercially available food products with at home up-dosing, thus increasing the availability of OIT for patients.

Peanut allergen characterization and allergenicity throughout development.

Peanut allergy (PA) in children is a major concern. There is a need for better biological material for both diagnosis and oral immunotherapy (OIT) treatments. The unique state of seeds at early reproductive stages may affect the allergenicity of storage proteins, and impact clinical diagnostic and OIT protocols. The objective of this study was to evaluate the major allergen content in sequential seed developmental stages and monitor allergenicity via specific IgE binding quantification and skin prick testing. Seeds were collected from peanut plants and sorted into five developmental stages: initial (S1), developing (S2), full-size without coloration (S3), full-size with coloration (S4), and fully mature (S5) seeds. Samples were characterized by RNA-Seq, ELISA, and immunohistochemistry. Lyophilized, ground preparations were used for evaluation of skin test responses in sixty challenge-proven PA children. Gene expression, protein content, and specific IgE binding of allergenic proteins increased throughout seed maturation and development. An expression bias towards the less allergenic A-genome copy of the major allergen Ara h 2 was found in earlier stages, especially in stage S2. Immunohistochemical staining showed that Ara h 2 is more dispersed in the cell and less accumulated within organized bodies at stage S2 versus stage S4. Significant differences were found in mean wheal responses between the commercial peanut extract (equivalent to stage S5) and stages S1 and S2, but not with stage S4, upon skin prick testing in subjects with PA. The observed decrease in peanut-specific IgE binding of immature peanut seeds may be a result not only of decreased amounts of allergenic proteins, but also of profound changes in seed composition and conformation. This may be significant for developing a safer and more effective peanut OIT protocol.

Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study.

Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission). Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic). 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001). By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcome over desensitization or remaining allergic.

The use of boiled peanut oral immunotherapy in children

The use of boiled peanut oral immunotherapy in children

Insights into the clinical, immunologic, and genetic underpinnings of food allergy.

The last few decades have seen striking changes in the field of food allergy. The prevalence of the disease has risen dramatically in many parts of the globe, and management of the condition has undergone major revision. While delayed introduction of common allergenic foods during infancy was advised for many years, the learning early about peanut allergy (LEAP) trial and other studies led to a major shift in infant feeding practices, with deliberate early introduction of these foods now recommended. Additionally, the Food and Drug Administration approved the first treatment for food allergy in 2020-a peanut oral immunotherapy (OIT) product that likely represents just the beginning of new immunotherapy-based and other treatments for food allergy. Our knowledge of the environmental and genetic factors contributing to the pathogenesis of food allergy has also undergone transformational advances. Here, we will discuss our efforts to improve the clinical care of patients with food allergy and our understanding of the immunological mechanisms contributing to this common disease.

Enhanced Gut Microbiome Capacity for Amino Acid Metabolism is associated with Peanut Oral Immunotherapy Failure.

Peanut Oral Immunotherapy (POIT) holds promise for remission of peanut allergy, though treatment is protracted and successful in only a subset of patients. Because the gut microbiome is linked to food allergy, we sought to identify fecal microbial predictors of POIT efficacy and to develop mechanistic insights into treatment response. Longitudinal functional analysis of the fecal microbiome of children (n=79) undergoing POIT in a first double-blind, placebo-controlled clinical trial, identified five microbial-derived bile acids enriched in fecal samples prior to POIT initiation that predicted treatment efficacy (AUC 0.71). Failure to induce disease remission was associated with a distinct fecal microbiome with enhanced capacity for bile acid deconjugation, amino acid metabolism, and increased peanut peptide degradation in vitro . Thus, microbiome mechanisms of POIT failure appear to include depletion of immunomodulatory secondary bile and amino acids and the antigenic peanut peptides necessary to promote peanut allergy desensitization and remission.

Viral Vector Based Immunotherapy for Peanut Allergy.

Food allergy (FA) is estimated to impact up to 10% of the population and is a growing health concern. FA results from a failure in the mucosal immune system to establish or maintain immunological tolerance to innocuous dietary antigens, IgE production, and the release of histamine and other mediators upon exposure to a food allergen. Of the different FAs, peanut allergy has the highest incidence of severe allergic responses, including systemic anaphylaxis. Despite the recent FDA approval of peanut oral immunotherapy and other investigational immunotherapies, a loss of protection following cessation of therapy can occur, suggesting that these therapies do not address the underlying immune response driving FA. Our lab has shown that liver-directed gene therapy with an adeno-associated virus (AAV) vector induces transgene product-specific regulatory T cells (Tregs), eradicates pre-existing pathogenic antibodies, and protects against anaphylaxis in several models, including ovalbumin induced FA. In an epicutaneous peanut allergy mouse model, the hepatic AAV co-expression of four peanut antigens Ara h1, Ara h2, Ara h3, and Ara h6 together or the single expression of Ara h3 prevented the development of a peanut allergy. Since FA patients show a reduction in Treg numbers and/or function, we believe our approach may address this unmet need.

BSACI guidance for the implementation of Palforzia® peanut oral immunotherapy in the United Kingdom: A Delphi consensus study

AbstractBackgroundPalforzia® enables the safe and effective desensitisation of children with peanut allergy. The treatment pathway requires multiple visits for dose escalation, up‐dosing, monitoring of patients taking maintenance therapy and conversion onto daily real‐world peanut consumption. The demand for peanut immunotherapy outstrips current National Health Service (NHS) capacity and requires services to develop a national consensus on how best to offer Palforzia® in a safe and equitable manner. We undertook a Delphi consensus exercise to determine guidance statements for the implementation of Palforzia®‐based immunotherapy in the NHS.MethodsWe undertook focus groups with children and young people who had received peanut immunotherapy to assess what was important for them and their carers. Common themes from patients formed the basis of creating draft statements. A panel of 18 multi‐disciplinary professionals engaged in two rounds of anonymised voting to adapt the statements and score their importance. A final consensus workshop consolidated any variation in comments and scores to develop the final guidance statements.ResultsThe panel achieved consensus on 91% (29/32) of guidance statements, demonstrating strong consensus around pragmatic principles for assuring the integrity of consent, safety and conversion from Palforzia® to real‐world peanut products. The greatest amount of feedback was generated from three broad issues; (i) whether eligibility assessment should include compulsory peanut challenges and whether these should be designed to assess the threshold at which patients react to peanut, (ii) the governance processes to best ensure that patients' interests are prioritised and (iii) how to safely transition young people to other services, or discharge them, while they are taking daily peanut.ConclusionsThis consensus highlights the urgent need for the NHS to increase capacity for undertaking diagnostic food challenges as well as developing Palforzia® immunotherapy pathways. The voting panel agreed that families of peanut allergic children should be made aware of immunotherapy, that eligibility assessment should include how co‐morbid conditions are managed and that services should monitor for adverse effects. The finalised statements are now published online for clinical practice in the UK. These guidance statements will be adapted in the coming years as more evidence is published and as the international experience of peanut immunotherapy evolves.

Metabolomics of IgE-Mediated Food Allergy and Oral Immunotherapy Outcomes based on Metabolomic Profiling.

The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown. To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multi-ethnic cohorts and responses to OIT. Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N=384), a Costa Rican cohort of children with asthma (N=1040), and a peanut OIT trial (N=20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterwards). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes. Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q=2.4×10 -20 ) and linoleic acid derivatives (q=3.8×10 -5 ) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q=4.1×10 -8 ), eicosanoids (q=7.9×10 -7 ), and histidine pathways (q=0.015). In particular, the bile acid lithocholate (4.97[1.93,16.14], p=0.0027), the eicosanoid leukotriene B4 (3.21[1.38,8.38], p=0.01), and the histidine metabolite urocanic acid (22.13[3.98,194.67], p=0.0015) were higher in SU. We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy. - Compared with unaffected controls, children with food allergy demonstrated higher levels of bile acids and distinct histidine/urocanic acid profiles, suggesting a potential role of these metabolites in food allergy. - In participants receiving oral immunotherapy for food allergy, those who were able to maintain tolerance-even after stopping therapyhad lower overall levels of bile acid and histidine metabolites, with the exception of lithocholic acid and urocanic acid, two metabolites that have roles in T cell differentiation that may increase the likelihood of remission in immunotherapy. This is the first study of plasma metabolomic profiles of responses to OIT in individuals with IgE-mediated food allergy. Identification of immunomodulatory metabolites in allergic tolerance may help identify mechanisms of tolerance and guide future therapeutic development.

THE EFFICACY AND SAFETY OF ORAL IMMUNOTHERAPY FOR FOOD ALLERGIES IN PRESCHOOL-AGED CHILDREN

In the last two decades, food allergy (FA) has emerged as a significant concern, with a continuous rise in prevalence worldwide. Furthermore, increasing awareness about this issue in the general public has prompted rigorous efforts to find long-term solutions to FA. In the pediatric group, most cases of FA are reported during the initial 3 to 5 years. The most common FA in preschoolers include eggs, cows milk, tree nuts, and peanuts. Conventional approaches for the management of FA include mitigating adverse reactions associated with the consumption of food allergens and avoidance of that particular food allergen. However, constant avoidance remains a challenge, requiring constant due diligence. Therefore, Oral immunotherapy (OIT), an allergen-specific method for managing FA has been introduced. The present review provides an overview of the mechanisms and processes of OIT. The most common OITs studied include peanut, tree nuts, egg, and milk OITs. Furthermore, the literature search yielded significant evidence that showed the safety and efficacy of these OITs. The review also identified the gaps in the literature, which highlight the need for future investigations. Future studies should focus on conducting well-designed clinical trials with larger sample sizes, establishing standardized treatment protocols, investigating immunological mechanisms, and assessing the broader impact of OIT.

Probiotics, prebiotics and food allergy: a review.

Background. The review was structured in the following sections: 1) Cow's Milk Proteins Allergy (CMA), 2) Food Allergy to Peanuts and 3) Prevention of Food Allergy. In CMA, studies indicate that extensively hydrolyzed casein formula supplemented with Lactobacillus Rhamnosus GG aids in acquiring tolerance to cow's milk proteins, resolving gastrointestinal symptoms and preventing of other allergic manifestations. In peanut oral immunotherapy (OI), supplementation with Lactobacillus Rhamnosus CGMCC 1.3724 appears to promote sustained desensitization. However, the evidence supporting probiotics for preventing food allergies lacks robustness. Current evidence supports the use of oligosaccharides from breast milk in the first months of life for preventing atopic dermatitis, FA and asthma Methods. A PubMed/Medline search was carried out on articles published between 2011 and 2021 with the following query: ("Food Hypersensitivity"[Mesh]) AND (("Probiotics"[Mesh]) OR ("Prebiotics"[Mesh])). Subsequently, the titles and abstracts were analysed and selected according to established criteria. After full reading of these articles, 54 were included and a narrative review was performed. Results. The review was structured in the following sections: 1) Cow's Milk Proteins Allergy (CMA), 2) Food Allergy to Peanuts and 3) Prevention of Food Allergy. In CMA, studies indicate that extensively hydrolyzed casein formula supplemented with Lactobacillus Rhamnosus GG aids in acquiring tolerance to cow's milk proteins, resolving gastrointestinal symptoms and preventing of other allergic manifestations. In peanut oral immunotherapy (OI), supplementation with Lactobacillus Rhamnosus CGMCC 1.3724 appears to promote sustained desensitization. However, the evidence supporting probiotics for preventing food allergies lacks robustness. Current evidence supports the use of oligosaccharides from breast milk in the first months of life for preventing atopic dermatitis, FA and asthma. Conclusions. The potential of probiotics to be used as therapeutic adjuvants in CMA and peanut OI is promising. However, there is inconsistency regarding the type of probiotic, the dose and duration of supplementation. Further studies are needed to clarify the role of probiotics and prebiotics in FA.

Real-world adoption of peanut oral immunotherapy in infants and toddlers

Real-world adoption of peanut oral immunotherapy in infants and toddlers

Racial and Socioeconomic Disparities Exist in Patients Pursuing Peanut Oral Immunotherapy

BackgroundOral immunotherapy (OIT) is a promising treatment for food allergy. Prior studies demonstrate significant differences among food allergic individuals across race, ethnicity, and socioeconomic groups. Disparities in OIT have not been evaluated. ObjectiveWe assessed disparities in the use of OIT in patients with peanut allergy based on race, ethnicity, and socioeconomic status at a single academic medical center. MethodsWe identified 1028 peanut allergic patients under 18 years of age receiving care in the University of Michigan food allergy clinics. 148 patients undergoing peanut OIT (treatment group) were compared to the 880 patients avoiding peanut (control group). Pertinent demographic and socioeconomic characteristics were compared. ResultsThere were no differences in gender or ethnicity between the OIT and control groups. However, Black patients comprised 18% of the control group but only 4.1% of the OIT treatment group (p<0.0001). The proportion of patients with private insurance was significantly higher in the treatment group compared to control group, 93.2% vs 82.2% (p=0.0004). Finally, the Neighborhood Affluence Index, a Census-based measure of the relative socioeconomic prosperity of a neighborhood, was significantly higher in the OIT group vs. the control group (0.51±0.18 vs 0.47±0.19) (p=0.015), while the Neighborhood Disadvantage Index, a Census-based measure of the relative socioeconomic disadvantage of a neighborhood, was significantly lower (0.082±0.062 vs 0.10±0.093) (p=0.020). ConclusionSignificant racial and economic disparities exist at our institution between peanut allergic individuals who receive OIT and those who do not. Efforts to understand the basis for these disparities are important to ensure patients have equitable access to OIT.

Evaluation and Modification of a Shared Decision-Making Tool for Peanut Allergy Management.

Based on shared decision-making (SDM) principles, a decision aid was previously developed to help patients, their caregivers, and physicians decide which peanut allergy management approach best suits them. This study refined the decision aid's content to better reflect patients' and caregivers' lived experience. Current standard of care for peanut allergy is avoidance, although peanut oral immunotherapy has been approved by the Food and Drug Administration for use in patients 4-17 years old. An advisory board of allergy therapy experts (n = 3) and patient advocates (n = 3) informed modifications to the decision aid. The revised tool underwent cognitive debriefing interviews (CDIs) among adolescents (12-17 years old) with peanut allergy and caregivers of patients 4-17 years old with peanut allergy to evaluate its relevance, understandability, and usefulness. The 20 CDI participants understood the information presented in the SDM tool and reported it was important and relevant. Some revisions were made based on participant feedback. Results support content validity of the Peanut Allergy Treatment SDM Tool.

Neutralizing IgG4 antibodies are a biomarker of sustained efficacy after peanut oral immunotherapy

BackgroundClinical efficacy of oral immunotherapy (OIT) has been associated with the induction of blocking antibodies, particularly those capable of disrupting IgE-allergen interactions. Previously, we identified monoclonal antibodies (mAb) to Ara h 2 and structurally characterized their epitopes. ObjectiveWe investigated longitudinal changes during OIT in antibody binding to conformational epitopes and correlated the results with isotype and clinical efficacy. MethodsWe developed an indirect inhibitory ELISA using mAbs to block conformational epitopes on immobilized Ara h 2 from binding to serum immunoglobulins from peanut-allergic patients undergoing OIT. We tested the functional blocking ability of mAbs using passive cutaneous anaphylaxis (PCA) in mice with humanized FcεRI receptors. ResultsDiverse serum IgE recognition of Ara h 2 conformational epitopes are similar before and after OIT. Optimal inhibition of serum IgE occurs with the combination of two neutralizing mAbs (nAbs) recognizing epitopes 1.2 and 3, compared to two non-neutralizing mAbs (non-nAbs). Post-OIT, IgG4 nAbs, but not IgG1 or IgG2 nAbs, increased in sustained compared to transient outcomes. Induction of IgG4 nAbs occurs after OIT only in those with sustained efficacy. Murine PCA after sensitization with pooled human sera is significantly inhibited by nAbs compared to non-nAbs. ConclusionsSerum IgE conformational epitope diversity remains unchanged during OIT. However, IgG4 nAbs capable of uniquely disrupting IgE-allergen interactions to prevent effector cell activation are selectively induced in OIT-treated individuals with sustained clinical efficacy. Therefore, the induction of neutralizing IgG4 antibodies to Ara h 2 are clinically relevant biomarkers of durable efficacy in OIT.

High Degree of Desensitization After 1 Year of Early-Life Peanut Oral Immunotherapy: Small Children Oral Immunotherapy (SmaChO) Randomized Controlled Trial

BackgroundThe prevalence of peanut allergy is about 2% and mostly lifelong. Studies of oral immunotherapy (OIT) with peanut – daily oral intake of an initially low and then increasing dose of peanut - often show problematic side effects but there are indications of better safety and effect in younger children compared with older children and adults. ObjectiveTo determine the safety and effectiveness of peanut OIT with a slow up-dosing strategy and low maintenance dose, in peanut allergic children 1-3 years of age, a 1-year interim analysis. MethodsIn a randomized controlled trial (2:1 ratio) 75 children with median age 31 months (IQR 23 – 40) were assigned to receive peanut oral immunotherapy (OIT) (n=50) or peanut avoidance (n=25). ResultsIn the OIT group and the avoidance group, 43/50 and 20/25 children, respectively, performed the 1-year open oral peanut challenge. A cumulative dose of 750 mg peanut protein after one year was tolerated by 72% (36/50) in the OIT-group compared to 4% (1/25) in the avoidance-group, p<0.001. Median tolerated cumulative dose was 2750 mg (IQR 275 – 5000) peanut protein in the OIT-group compared to 2.8 mg (IQR 0.3 – 27.8) in the avoidance-group, p<0.001. Of the doses administered at home during the first year of OIT, 1.4% resulted in adverse events, 79% were mild, and three doses of epinephrine were given at home to two individuals. ConclusionIn children 1-3 years of age, peanut OIT with the combination of slow up-dosing and low maintenance dose seems safe and effective after one year. ClinicalTrials.govNCT04511494

The Future of Food Allergy Management: Advancements in Therapies.

To review current and future treatment options for IgE-mediated food allergy. Recent 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. Food 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.