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Background: The pivotal phase 3 EPITOPE trial, a 12-month, double-blind, placebo-controlled study of epicutaneous immunotherapy with the VIASKIN® patch containing 250 μg peanut protein (VP250) previously reported significant treatment response vs placebo in peanut-allergic toddlers aged 1-through-3 years., Objective: To assess interim efficacy and safety of VP250 from the first year of the EPITOPE open-label extension (OLE) study., Methods: Eligible participants enrolled in the OLE study for up to 3 years of total treatment with annual double-blind, placebo-controlled food challenges (DBPCFC) and safety assessments; here we report the first year OLE (Year 2) results., Results: 266 EPITOPE participants enrolled in the OLE study; 244 underwent Month 24 DBPCFC (n=166 VP250; n=78 placebo). After 24 months of VP250, 81.3% reached an eliciting dose (ED) ≥1000 mg, 63.8% reached an ED ≥2000 mg, and 55.9% completed the DBPCFC (cumulative dose: 3444 mg) without meeting stopping criteria. No treatment-related anaphylaxis or serious treatment-related adverse events occurred during Year 2 in this treatment arm. Local application-site reactions occurred less frequently in Year 2 vs Year 1. In placebo-treated EPITOPE participants, outcomes after 1 year of open-label VP250 were consistent with EPITOPE treatment results: 62.7% reached an ED ≥1000 mg, 36.5% reached an ED ≥2000 mg, and 28.4% completed the DBPCFC without meeting stopping criteria; and there was 1 treatment-related anaphylaxis event., Conclusions: Two years of VP250 in young peanut-allergic children demonstrated continued treatment effect increases without new safety signals. This supports the potential of VP250 as a safe and effective treatment for peanut allergy in young children., (Copyright © 2025. Published by Elsevier Inc.)

Omalizumab was recently approved by the US Food and Drug Administration for treatment of any single food allergy or multiple food allergies in children aged 1 year and older and adults. There is currently no formal guidance regarding recommended best practices for omalizumab use in food allergy, including patient selection, anticipated goals and outcomes of therapy, procedure for monitoring patients who elect to start omalizumab therapy, and ways in which omalizumab can be incorporated into the landscape of food allergy management and daily clinical practice. This work group report was developed by the food allergy therapies subcommittee of the Adverse Reactions to Foods Committee within the American Academy of Allergy, Asthma & Immunology. Consensus, evidence-based guidance regarding experts' recommendations for using omalizumab to treat children and adults with food allergy was developed by using modified Delphi methodology. In iterative fashion, a total of 8 statements regarding how to use omalizumab to treat patients with food allergy were developed by 16 clinical experts. This guidance provides the clinician with a suggested approach to patient selection, initiation of therapy, monitoring of efficacy, and long-term follow-up care. The role of preference-sensitive care is emphasized, with most statements offering care recommendations relevant to the culture and values of a particular practice setting., Competing Interests: Disclosure statement Disclosure of potential conflict of interest: A. Anagnostou reports institutional funding from Novartis; advisory board service for of Genentech, Novartis, Bryn, and Ready, Set, Food!; and consultation/speaker fees from ALK, Adelphi, Bryn, Novartis, Genentech, Medscape, Food Allergy Research and Education (FARE), MHJ, and EPG Health. J. A. Bird reports consultancy for Allergenis, DBV Technologies, FARE, Genentech, Hanimmune Therapeutics, HAL Allergy, Infinant Health, Novartis, Nutricia, and Parexel, as well as research for Aimmune, DBV Technologies, Genentech, the National Institute of Allergy and Infectious Diseases (NIAID), Novartis, Regeneron, and Siolta. S. Chinthrajah receives grant support from the Consortium for Food Allergy Research (CoFAR), NIAID, and FARE and is an advisory board member for Alladapt, Novartis, Allergenis, IgGenix, Intrommune Therapeutics, Phylaxis, and Genentech. T. E. Dribbin has received funding and is supported by NIH (K23 AI175525). D. M. Fleischer has received research support from ARS Pharmaceuticals and DBV Technologies; serves as an unpaid advisory board member for the Food Allergy and Anaphylaxis Connection Team and the National Peanut Board; receives royalties from UpToDate; and has received personal fees as a consultant to Aquestive, ARS Pharmaceuticals, Bryn Pharma, DBV Technologies, Genentech, and Nasus outside the submitted work. E. Kim reports grants to his institution from NIAID and FARE; personal fees from ALK, Ukko, Cellergy Pharma, DBV Technologies, Genentech, Hanimumme Therapeutics, Novartis, Phylaxis, Revolo Biotherapeutics; and safety review board service for Allergy Therapeutics. A. Nowak-Wegrzyn receives research support from NIAID, DBV Technologies, and Siolta Therapeutics; speaking fees from Nestle, Danone, Medscape, and Genentech; and royalties from UpToDate. In addition, A. Nowak-Wegrzyn serves as an associate editor for the Annals of Allergy, Asthma and Immunology; as director of the AAAAI board; and as chair of the medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association. M. S. Shaker is a member and cochair of the Joint Task Force on Practice Parameters, serves on the editorial board of The Journal of Allergy and Clinical Immunology: In Practice, is an associate editor of Annals of Allergy, Asthma & Immunology, and serves on the board of directors of the AAAAI (all views expressed are his own). W. Shreffler reports grants to his institution from NIAID, the Food Allergy Science Initiative, and FARE; contract research support to his institution from Genentech, DBV, Allergy Therapeutics, Aravax, Novartis; personal consulting fees from Aimmune, DBV, Novartis, ALK, Allergy Therapeutics, FARE; and royalty payments from UpToDate. S. Sicherer reports royalty payments from UpToDate and Johns Hopkins University Press; grants to his institution from tNIAID, FARE, and Pfizer; and personal fees from the AAAAI as deputy editor of the Journal of Allergy and Clinical Immunology: In Practice outside of the submitted work. B. P. Vickery reports grants from Alladapt, AstraZeneca, Genentech, NIAID, and Siolta; personal fees from Allergenis, Aravax, Reacta Biosciences, and Sanofi Regeneron; both grants and personal fees from Aimmune, DBV, FARE, Novartis, and Regeneron; and stock options from Moonlight Therapeutics outside the submitted work. J. Wang is a member of the Joint Task Force on Practice Parameters; receives research support from NIAID, Aimmune, DBV, and Siolta; and receives consultancy fees from ALK-Abelló, DBV, and Novartis. M. Greenhawt is a consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Takeda, Griffols, Nutricia, Novartis, Aquestive, Allergy Therapeutics, AstraZeneca, ALK-Abelló, Bryn, Genentech, and Prota; is a speaker for Genentech; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein–Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma, and Immunology; and is member of the Joint Taskforce on Allergy Practice Parameters. In addition, J. Wang has received honoraria for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, Kaplan, Food Allergy Research and Education, and multiple state and local allergy societies. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Food allergy management has greatly evolved in the last several years, moving from passive approaches, such as strict food allergen avoidance, to more active treatments, including regulatory approval of the first specifically indicated immunotherapy product (for peanut) in 2020. In 2024, a second therapy, omalizumab, received regulatory approval for the treatment of 1 or more IgE-mediated food allergies, providing clinicians with multiple treatment options to offer patients and families. With this expanded armamentarium of food allergy treatment options, the practicing clinician requires detailed knowledge of benefits and risks of omalizumab, how omalizumab fits into the management landscape, and how to use shared decision-making to optimize therapy. This yardstick aims to provide the clinician with a review of data leading to omalizumab's food allergy indication and an evidence-based expert opinion approach regarding on how best to use this and other therapies available to optimize patient management., Competing Interests: Disclosures Dr Anagnostou reports receiving institutional funding from Novartis; serving as advisory board member of Genentech, Novartis, Bryn, and Ready. Set. Food!; and receiving consultation/speaker fees from ALK, Adelphi, Novartis, Genentech, Medscape, FARE, MHJ, and EPG Health. Dr Greenhawt is a consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Takeda, Griffols, Nutricia, Novartis, Aquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, Bryn, Genentech, and Prota; is a speaker for Genentech; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma & Immunology; and is member of the Joint Taskforce on Allergy Practice Parameters. He has received honorarium for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, Kaplan, Food Allergy Research and Education, and multiple state/local allergy societies. Dr Shaker is a member and co-chair of the Joint Task Force on Practice Parameters, serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice, is an associate editor of Annals of Allergy, Asthma & Immunology, and serves on the board of directors of the American Academy of Allergy, Asthma & Immunology (views expressed are his own). Dr Vickery reports receiving grants from Alladapt, AstraZeneca, Genentech, National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH), and Siolta; personal fees from Allergenis, Aravax, Reacta Biosciences, and Sanofi Regeneron; both grants and personal fees from Aimmune, DBV, FARE, Novartis, and Regeneron; and stock options from Moonlight Therapeutics outside the submitted work. Dr Wang is a member of the Joint Task Force on Practice Parameters; receives research support from NIAID, Aimmune, DBV, and Siolta; and receives consultancy fees from ALK-Abello, DBV, and Novartis., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Objective: To characterize the awareness of, adherence to, and barriers to the 2017 National Institute of Allergy and Infectious Diseases (NIAID) peanut allergy prevention guidelines among the pediatrics health care workforce., Study Design: Pediatricians, family physicians, advanced practice providers (APPs), and dermatologists who provide care for infants were solicited for a population-based online survey, administered from June 6, 2022, through July 3, 2022. The survey collected information about NIAID guideline awareness, implementation, and barriers as well as concerns related to the guidelines., Results: A total of 250 pediatricians, 250 family physicians, 504 APPs, and 253 dermatologists met inclusion criteria. Self-reported guideline awareness was significantly higher for pediatricians (76%) compared with dermatologists (58%), family physicians (52%), and APPs (45%) (P < .05). Among participants who were aware of the guidelines, most reported using part or all of the guidelines in their clinical practices. Reported practice patterns for peanut introduction in 6-month-old infants were variable and did not always align with guidelines, particularly for infants with mild-to-moderate atopic dermatitis., Conclusions: Although pediatricians have the highest self-reported level of NIAID guideline awareness, awareness was suboptimal irrespective of provider type. Education for all pediatric clinicians is urgently needed to promote evidence-based peanut allergy prevention practices., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to develop an outcome measure for caregivers of children with food allergy., Methods: A community-informed measure development process was utilised to generate a novel parent-reported outcome tool for caregivers of children with food allergy. We conducted focus groups with parents and caregivers of food-allergic (n = 18) children, following which a team of coders identified themes and generated an initial set of candidate items. These items were reviewed by content-area experts (n = 10) using content validity indices. We then conducted a series of cognitive interviews with parents of children with food allergy (n = 12) validating the instrument draft., Results: We describe the results of these development steps as well as future steps to produce the final, validated form of the measure. The resultant 91-item measure is intended for parents of children ages two to 12 years., Conclusion: This measure fills a unique need in the field by leveraging key stakeholders' perspectives to develop and subsequently validate a novel parent-reported measure of parent and family food allergy impacts of children ages two to 12 years old., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

In February 2024, omalizumab was approved by the U.S. Food and Drug Administration for the treatment of food allergy, based on data from the landmark phase 3 clinical trial, Omalizumab as Monotherapy and as Adjunct Therapy in Children and Adults (OUtMATCH). In this Rostrum, OUtMATCH investigators share their perspectives on the trial results, the implications for translation into daily practice, and on remaining gaps in the field. The study met its primary and key secondary end points, demonstrating a large effect size in multiallergen desensitization compared with placebo; yet there were some participants who did not respond, and the percentage of responders tolerating all 3 food allergens was lower than that for single foods. Clinicians are likely to have many questions about appropriate patient selection, monitoring for treatment responsiveness, and how to manage off-label considerations such as dietary incorporation or cotreatment with oral immunotherapy. Additional research is needed to answer these remaining questions and ensure that the translation of omalizumab in real-world practice leads to high-quality outcomes., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Food allergy (FA) is associated with poor health-related quality of life and high levels of psychological distress. Psychological support is extremely important but not always available. As part of the Global Access to Psychological Services for Food Allergy (GAPS) study, we aimed to assess psychological distress and service use among adults, caregivers and children with FA in a global survey., Methods: Participants (n = 1329 adults with FA; n = 1907 caregivers of children with FA) from >20 countries were recruited through patient organisations, social media advertisements and online survey panels to complete an online survey. Surveys were available in six languages., Results: A total of 67.7% of adults and 77.2% of caregivers reported direct experience, and 51.6% of caregivers said their child had experienced FA-related psychological distress. The most commonly reported issue was anxiety about having an allergic reaction. Less than 20% had been assessed for FA-related psychological distress. There were significant differences across countries for levels of distress, screening for distress, seeing a mental health professional and being diagnosed with a FA-related mental health disorder (all p < .001). The United Kingdom, Australia and Brazil had the highest number of participants reporting distress. The most commonly reported barrier to seeing a mental health professional was cost., Conclusions: FA-related distress is common across countries, but with substantial country-to-country variability. Allergy providers are encouraged to routinely assess families for psychological distress and provide access to appropriate mental health resources. Development and implementation of evidence-based, patient-informed accessible, affordable FA interventions in multiple languages is urgently needed., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Food allergy (FA) affects around 5.6 million children in the United States, conferring risk for negative impacts on growth and psychosocial functioning. While evidence suggests a higher prevalence of feeding difficulties in children with FA, the link between FA and feeding dysfunction remains unclear., Objective: To investigate feeding problems in children with parent-reported IgE-mediated FA and/or pediatric feeding disorder (PFD) compared with healthy children in a community-based sample and explore factors associated with feeding problems in children with FA., Methods: A matched cross-sectional cohort study used survey data from 352 parents of children aged 6 months to 7 years who reported a diagnosed IgE-mediated FA and/or PFD (50 with FA only, 67 with FA and PFD, and 235 with PFD only). Healthy children were matched based on age, sex, race, and socioeconomic factors. Feeding problems were assessed using the Pediatric Eating Assessment Tool. Matched-pairs generalized linear regressions compared each cohort and explored factors associated with feeding problems in children with FA., Results: Children with FA exhibited significantly higher feeding problems compared with healthy children. Children with a diagnosed PFD had more severe feeding problems, irrespective of comorbid FA. Factors linked with feeding problems in children with FA included older age, non-White race, increased medical comorbidity, and limited dietary variety., Conclusions: This study adds to evidence indicating a higher prevalence of feeding problems in children with FA. Clinicians treating FA patients should routinely screen for feeding and growth concerns and consider referral to multidisciplinary feeding programs as needed., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

AMCP convened a panel of clinical and managed care experts to identify insights regarding the prevalence, clinical manifestations, and management approaches for immunoglobulin E-mediated food allergies. This article aims to summarize expert perspectives on health care system challenges and areas of agreement concerning the management of food allergies, and to advance payers' understanding of their role in supporting health care for patients with food allergies. Food allergy management requires dietary modification and is associated with significant patient and caregiver burdens. Emerging therapies provide hope for those living with food allergies but will likely lead to a rise in health plan pharmacy expenses. In considering the value of new treatments, it is important to consider the total cost of care and the value of preventing anaphylaxis and enhancing the patient's quality of life. Several challenges remain in identifying the appropriate patient population for treatment with newer agents and in optimizing treatment outcomes. Addressing health disparities will require standardized clinical protocols, better access to specialized allergy care, and management of comorbid conditions.

Competing Interests: Declaration of Competing Interest B.P. Vickery reports grants and personal fees from Aimmune, grants from Alladapt, personal fees from Allergenis, personal fees from Aravax, grants from AstraZeneca, grants and personal fees from DBV, grants and personal fees from FARE, grants from Genentech, stock options from Moonlight Therapeutics, grants from NIH-NIAID, grants and personal fees from Novartis, personal fees from Reacta Biosciences, grants and personal fees from Regeneron, personal fees from Sanofi, grants from Siolta, outside the submitted work. The remaining authors reported no conflicts of interest.

Background: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process., Objective: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form., Methods: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed., Results: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form., Conclusion: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To review current and future treatment options for IgE-mediated food allergy., Recent Findings: 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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Effective asthma self-management requires that children recognize their asthma symptoms when they occur. However, some children have altered symptom perception, which impairs their ability to respond to their asthma symptoms in a timely manner., Objective: To characterize the prevalence and features of altered symptom perception in children aged 5 to 18 years. We hypothesized that children with altered symptom perception would have more features of uncontrolled asthma, more health inequity, and poorer longitudinal asthma outcomes over 12 months., Methods: Children (N = 371) completed an outpatient research visit for clinical characterization. Altered symptom perception was defined by discordance between child responses on the 6-item Asthma Control Questionnaire and medical provider-elicited symptoms. Electronic medical records were reviewed for 12 months for the occurrence of an asthma exacerbation treated with systemic corticosteroids and an asthma exacerbation prompting an emergency department visit., Results: Approximately 15% of children had altered symptom perception and their asthma features were similar to those of children with uncontrolled asthma. Children with altered symptom perception were uniquely distinguished by non-White race and more severe prior exacerbations. These children also resided in ZIP codes with the poorest childhood opportunity (ie, poorest education, health and environmental features, and socioeconomic features). Outcomes of children with altered symptom perception were equally disparate with approximately 2-fold higher odds of a future exacerbation and approximately 3-fold higher odds of an emergency department visit for asthma., Conclusions: Altered symptom perception is present in a small but significant number of children with asthma and is related to poorer childhood opportunity and other health inequities that require additional intervention., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy., Methods: 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., Results: 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., Conclusions: 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.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Food allergies affect growth in children by decreasing the availability of nutrients through decreased dietary intake, increased dietary needs, food-medication interactions, and psychosocial burden. Guidelines on food allergy management frequently recommend nutrition counseling and growth monitoring of children with food allergies., Objective: To provide clear guidance for clinicians to identify children with food allergies who are at nutritional risk and ensure prompt intervention., Methods: We provide a narrative review summarizing information from national and international guidelines, retrospective studies, population studies, review articles, case reports, and case series to identify those with food allergy at greatest nutritional risk, determine the impact of nutritional interventions on growth, and develop guidance for risk reduction in children with food allergies., Results: Children with food allergies are at increased risk of nutritional deficiencies and poor growth. Nutritional assessment and intervention can improve outcomes. Identifying poor growth is an important step in the nutrition assessment. Therefore, growth should be assessed at each allergy evaluation. Interventions to ensure adequate dietary intake for growth include appropriately prescribed elimination diets, breast-feeding support and assessment, supplemental formula, vitamin and/or mineral supplementation, appropriate milk substitutes, and timely introduction of nutrient-dense complementary foods. Access to foods of appropriate nutritional value is an ongoing concern., Conclusion: Nutrition intervention or referral to registered dietitian nutritionists with additional training and/or experience in food allergy may result in improved growth and nutrition outcomes., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) to peanut and its components may influence the clinical reactivity to peanut. Allergen-specific immunotherapy is known for modifying both IgE and IgG4. Peanut oral immunotherapy may influence these serological parameters., Methods: Exploratory analyses of serological data from participants receiving peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) and placebo in the double-blind, randomized, phase 3 PALISADE trial were conducted to evaluate potential relationships between peanut-specific and peanut component-specific (Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, and Ara h 9) IgE and IgG4 levels and clinical outcomes., Results: A total of 269 participants (PTAH, n = 202; placebo, n = 67) were analyzed. No relationship was observed between specific IgE and IgG4 levels at screening and maximum tolerated peanut protein dose during screening or response status during exit double-blind placebo-controlled food challenge (DBPCFC). In PTAH-treated participants, no relationship was observed between IgE and IgG4 levels at screening and maximum symptom severity during exit DBPCFC. Postscreening ratios (ie, postscreening/screening) in the PTAH group were significant at the end of updosing and exit visit for most components. Postscreening changes in specific IgE levels were more pronounced with PTAH versus placebo for most components., Conclusions: Specific IgE and IgG4 levels at screening are not correlated with screening or exit DBPCFC results, and are not predictive of clinical response to PTAH. Peanut (Arachis hypogaea) allergen powder-dnfp contains the relevant and immunodominant allergens, inducing immunological changes with the treatment., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02635776., (© 2024 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

BACKGROUND: Peanut allergy is a common childhood allergy, and the only approved treatment for children 4 to 17 years of age is peanut allergen powder-dnfp (PTAH) oral immunotherapy. METHODS: For this phase 3, randomized, double-blind, placebo-controlled trial, we enrolled peanut-allergic children 1 to <4 years of age who experienced dose-limiting symptoms from ≤300 mg peanut protein during a screening double-blind, placebo-controlled food challenge (DBPCFC). Participants received PTAH or placebo, randomized in a 2:1 ratio, for approximately 12 months. At the trial conclusion, all participants underwent an exit BDPCFC. The primary end point was desensitization (i.e., tolerating a ≥600-mg single dose of peanut protein with only mild allergy symptoms). RESULTS: In the PTAH-treated group (n=98), 73.5% of participants tolerated a single dose of ≥600 mg peanut protein at exit DBPCFC compared with 6.3% in the placebo group (n=48). Most participants experienced an adverse event (98.0% of PTAH-treated and 97.9% of placebo-treated participants), which was mild or moderate in grade for 93.2% of participants (92.9% in PTAH-treated and 93.8% in placebo-treated participants). Treatment-related adverse events, which were mild to moderate, were experienced by 75.5% of PTAH-treated and 58.3% of placebo-treated participants. Three treatment-related systemic allergic reactions, none of which were severe or serious in grade, were noted in two PTAH-treated participants (2%). CONCLUSIONS: In peanut-allergic children 1 to <4 years of age treated with PTAH for approximately 12 months, the majority tolerated all peanut protein dose levels assessed. PTAH-treated patients had more treatment-related adverse events, which were mild to moderate severity. (Funded by Aimmune Therapeutics; ClinicalTrials.gov number, NCT03736447.)

Background: Social determinants of health have been inadequately studied in preschool children with wheezing and their caregivers but may influence the care received., Objective: To evaluate the symptom and exacerbation experiences of wheezing preschool children and their caregivers, stratified by risk of social vulnerability, over 1 year of longitudinal follow-up., Methods: A total of 79 caregivers and their preschool children with recurrent wheezing and at least 1 exacerbation in the previous year were stratified by a composite measure of social vulnerability into "low" (N = 19), "intermediate" (N = 27), and "high" (N = 33) risk groups. Outcome measures at the follow-up visits included child respiratory symptom scores, asthma control, caregiver-reported outcome measures of mental and social health, exacerbations, and health care utilization. The severity of exacerbations reflected by symptom scores and albuterol use and exacerbation-related caregiver quality of life were also assessed., Results: Preschool children at high risk of social vulnerability had greater day-to-day symptom severity and more severe symptoms during acute exacerbations. High-risk caregivers were also distinguished by lower general life satisfaction at all visits and lower global and emotional quality of life during acute exacerbations which did not improve with exacerbation resolution. Rates of exacerbation or emergency department visits did not differ, but intermediate- and high-risk families were significantly less likely to seek unscheduled outpatient care., Conclusion: Social determinants of health influence wheezing outcomes in preschool children and their caregivers. These findings argue for routine assessment of social determinants of health during medical encounters and tailored interventions in high-risk families to promote health equity and improve respiratory outcomes., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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.)., (Copyright © 2023 Massachusetts Medical Society.)

Standard care for the management of food allergies previously centered on allergen avoidance and the treatment of adverse reactions after allergen exposure. An increase in the development of immunotherapy treatments for food allergy has occurred over the past 2 decades, with many centers now offering immunotherapy. Previous studies mainly focused on school-age children in whom food allergies are likely to be persistent. However, there is increasing evidence that delivering immunotherapy for food allergy to preschool-age children may deliver higher rates of success, and that peanut allergen immunotherapy leads the way. Conversely, the natural resolution of food allergies occurs primarily in these younger age groups, resulting in challenges to selecting patients who will ultimately benefit from these treatments. Both immunotherapy and natural history studies reveal the inherent plasticity of the immune system in early life, which may be more amenable to intervention, but this raises a delicate yet unknown balance between the optimal timing of intervention versus waiting for natural resolution of the food allergy. Here we review the evidence for early food allergen immunotherapy in preschoolers, and present the pros and cons of this approach while acknowledging important research gaps in this age group., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The paradigm for food allergy management has been strict avoidance of the food allergen. There is literature supporting a "high-threshold" phenotype, those who tolerate a small-to-modest amount of allergen but react to larger amounts. There is no consensus for best practice for these "high-threshold" individuals. We sought to understand management practices of "high-threshold" reactors using a survey that was distributed to a random sample of fellows and members of the American Academy of Allergy, Asthma, and Immunology. There were 89 respondents from the United States and Canada (11% response rate), with 64 (72%) answering all questions. Participants worked in private (52%) and academic practice (38%) and saw a median of 30 food allergic patients monthly. Eighty-one percent of respondents reported management strategies other than strict avoidance. When threshold was known, strategies ranged from allowing ingestion up to a specified amount (57%), proactively advising ingestion to a certain amount (56%), or oral immunotherapy (47%). Participants were more likely to choose a permissive approach for a mild reaction in a high-threshold milk-allergic patient compared with a peanut-allergic patient (83% vs 71%, p=.01). Important factors that influenced the approach included severity of reaction (52%), comfort with family/patient using emergency medications (42%), and family/patient preferences (41%). These survey results suggest that food allergy management recommendations are no longer binary in nature, with clinicians solely recommending avoidance for those who are allergic and ingestion for those who may not be., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Patients with food allergy may be advised to introduce specific foods into their diets, both to increase tolerance gradually and as next steps after completing oral immunotherapy or other therapeutic interventions. However, the safe use of retail foods depends on the ability to establish the specific allergen protein content of these foods., Objective: To develop a systematic approach to estimate the protein content of peanut, milk, egg, wheat, cashew, hazelnut, and walnut in a variety of retail food equivalents for each allergen and associated patient education materials., Method: We created an algorithm that used a multistep process with information from product food labels, nutrient databases, independent weighing and measuring of foods, and information provided by manufacturers, including certificates of analysis, and e-mail communication to estimate the allergen protein content of multiple retail foods for each of seven allergens. Once a variety of retail food equivalents for each allergen and allergen serving size was determined, we developed participant education handouts, which were reviewed by study teams at 10 food allergy centers, the National Institute of Allergy and Infectious Diseases, and the Consortium for Food Allergy Research coordinating center. After 1 year of use, multiple queries were addressed and the retail food equivalents and educational materials were reviewed and edited., Results: We identified a variety of retail food equivalents for seven allergens at six serving sizes, and created 48 unique patient education materials., Conclusion: Our results provide extensive guidance on a variety of retail equivalents for seven foods, and a method to estimate retail food protein equivalents systematically with ongoing reassessment., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Peanut allergy (PA) is a common, burdensome childhood disease that in most patients continues into adulthood and has historically been untreatable. However, peanut oral immunotherapy (POIT) is increasingly being incorporated into allergy practices, using both the first FDA-approved product, PTAH (previously AR101; Palforzia™, Aimmune Therapeutics), as well as store-bought peanut products. POIT in preschoolers continues to gain more acceptance as evidence accrues that it is a safe and feasible approach that may have distinct advantages. There are many new therapeutic interventions currently under study with a variety of different approaches and potential mechanisms. With respect to other forms of immunotherapy, none are currently approved, but the epicutaneous approach is the most well-studied and others are being actively investigated, including sublingual, subcutaneous, and intralymphatic. Biologics are gaining evidence both as adjunctive treatments to POIT and as monotherapy. Omalizumab is the most widely studied biologic for PA but others also have potential. Looking ahead to a future therapeutic landscape of choice, allergists will need to understand each patient's goal of treatment through shared decision-making and fully evaluate the risks, benefits, and alternatives of each new therapy., (© 2022 John Wiley & Sons Ltd.)

Background: Clinical trials (PALISADE [ARC003], ARTEMIS [ARC010]) proving efficacy and safety of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) have used double-blind, placebo-controlled food challenges (DBPCFCs) to screen for eligibility and to evaluate efficacy. In routine clinical practice, individuals with peanut allergy do not always undergo food challenges to confirm diagnosis or determine candidacy for treatment., Objective: To describe PTAH safety and tolerability in participants selected by clinical history and peanut sensitization parameters not undergoing DBPCFCs during trials and to compare findings with previously published data., Methods: RAMSES (ARC007) was a 6-month, phase 3, randomized, double-blind, placebo-controlled trial in children aged 4 to 17 years with physician-confirmed peanut allergy. ARC011 was the subsequent 6-month follow-on maintenance PTAH study. The primary end point for RAMSES and ARC011 was the frequency of treatment-emergent adverse events (AEs). We descriptively compared baseline characteristics and safety outcomes from RAMSES and ARC011 to participants undergoing DBPCFCs in phase 3 PALISADE and ARTEMIS trials., Results: In 506 patients randomized to study treatment, baseline characteristics appeared balanced among groups. Proportion of participants with at least 1 AE was 55% for PTAH vs 33.9% for placebo during initial dose escalation and 98.8% vs 94.0% during updosing, respectively. Most participants with AEs had mild or moderate events. The most common AEs were gastrointestinal. Comparisons to pooled PALISADE and ARTEMIS data revealed higher baseline median peanut-specific immunoglobulin E and skin prick test values for RAMSES participants. Safety outcomes during trial periods were comparable., Conclusion: Safety data from clinically selected children with peanut allergy receiving PTAH do not seem different from those in phase 3 trials requiring DBPCFC to enter trials., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Oral immunotherapy (OIT) leads to suppression of mast cell and basophil degranulation along with changes in the adaptive immune response., Objectives: This study aimed to determine how rapidly these effects occur during OIT and more broadly, the kinetics of basophil and mast cell suppression throughout the course of therapy., Methods: Twenty participants, age 4 to 12 years, were enrolled in a peanut OIT trial and assessed for desensitization and sustained unresponsiveness after 9 months of therapy. Blood was collected 5 times in the first month and then intermittently throughout to quantify immunoglobulins and assess basophil activation by CD63, CD203c, and phosphorylated SYK (pSYK)., Results: Twelve of 16 participants that completed the trial were desensitized after OIT, with 9 achieving sustained unresponsiveness after discontinuing OIT for 4 weeks. Basophil hyporesponsiveness, defined by lower CD63 expression, was detected as early as day 90. pSYK was correlated with CD63 expression, and there was a significant decrease in pSYK by day 250. CD203c expression remained unchanged throughout therapy. Interestingly, although basophil activation was decreased across the cohort during OIT, basophil activation did not correlate with individual clinical outcomes. Serum peanut-specific IgG 4 and IgA increased throughout therapy, whereas IgE remained unchanged., Conclusions: Suppression of basophil activation occurs within the first 90 days of peanut OIT, ultimately leading to suppression of signaling through pSYK., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Important components of drug safety, efficacy, and acceptability involve manufacturing and testing of the drug substance and drug product. Peanut flour sourcing/processing and manufacturing processes may affect final drug product allergen potency and contamination level, possibly impacting drug safety, quality, and efficacy. We describe key steps in the manufacturing processes of peanut ( Arachis hypogaea ) allergen powder-dnfp (PTAH; Palforzia®), a drug used in oral immunotherapy (OIT) for the treatment of peanut allergy., Methods: Established criteria for source material must be met for manufacturing PTAH drug product. Degree of roasting was determined with a Hunter colorimeter. Protein/allergen content, identity, potency, safety, and quality of each batch of PTAH drug substance were assessed with a combustion analyzer, allergen-specific Western blot (immunoblotting), ELISA, and HPLC. Contaminants (ie, aflatoxin) were measured by UPLC., Results: Roasting degree beyond "light roast" was associated with variable degrees of protein allergen degradation, or potentially aggregation. Relative potency and amounts of protein allergens showed variability due in part to seasonal/manufacturing variability. Proportion of lots not meeting aflatoxin limits has increased in recent years. Up to 60% of peanut flour source material failed to meet screening selection acceptance criteria for proceeding to drug substance testing, mostly because of failure to meet potency acceptance criteria. Other lots were rejected due to safety (ie, aflatoxin) and quality. Influence of potency variation, within specification parameters, on safety/tolerability observed in trials was considered low, in part due to stringent controls placed at each step of manufacturing., Conclusions: Extensive variability in allergen potency is a critical issue during immunotherapy, particularly during OIT initial dose escalation and up-dosing, as it may result in lack of efficacy or avoidable adverse allergic reactions. Based on EU and US regulatory requirements, the production of PTAH includes manufacturing controls to ensure drug product safety, potency, and quality. For example, although PTAH contains all peanut allergens, each lot has met strict criteria ensuring consistent allergenic potency of Ara h 1, Ara h 2, and Ara h 6. The rigor of PTAH's manufacturing process ensures reliable dose consistency and stability throughout its shelf life., Competing Interests: Stephanie A. Leonard reports being a consultant for Aimmune Therapeutics, a Nestlé Health Science company, DBV Technologies, and Cour Pharmaceuticals Development Co., Inc, a member of the International FPIES Association medical advisory board, a speaker for Aimmune Therapeutics, a Nestlé Health Science company, and a site investigator for Aimmune Therapeutics, a Nestlé Health Science company, and DBV Technologies. Yasushi Ogawa is an employee of Aimmune Therapeutics, a Nestlé Health Science company. Paul T. Jedrzejewski is an employee of Aimmune Therapeutics, a Nestlé Health Science company. Soheila J. Maleki has no disclosures to report. Martin D. Chapman reports an R01 research grant on the structural biology of allergens from NIH NIAID. In addition, they report honorarium for molecular allergology symposium from Johns Hopkins University and is a co-owner and shareholder of InBio. Stephen A. Tilles is an employee of Aimmune Therapeutics, a Nestlé Health Science company. George Du Toit reports research grants to their institution and advisory board fees from Aimmune Therapeutics, a Nestlé Health Science company. S. Shahzad Mustafa reports honoraria for Aimmune program. Brian P. Vickery reports advisory board/consultant for Aimmune Therapeutics, AllerGenis, FARE, Reacta; site investigator for Aimmune Therapeutics, a Nestlé Health Science company, DBV, Genentech, Regeneron; and research grants from FARE and NIAID., (© 2022 Leonard, Ogawa, Jedrzejewski, Maleki, Chapman, Tilles, Du Toit, Mustafa and Vickery.)

Background: The PALISADE study, an international, phase 3 trial of peanut oral immunotherapy (POIT) with AR101, resulted in desensitization in children and adolescents who were highly allergic to peanut. An improved understanding of the immune mechanism induced in response to food allergen immunotherapy would enable more informed and effective therapeutic strategies. Our main purpose was to examine the immunological changes in blood samples from a subset of peanut-allergic individuals undergoing oral desensitization immunotherapy with AR101., Methods: Blood samples obtained as part of enrollment screening and at multiple time points during PALISADE study were used to assess basophil and CD4+ T-cell reactivity to peanut., Results: The absence of clinical reactivity to the entry double-blinded placebo-controlled peanut challenge (DBPCFC) was accompanied by a significantly lower basophil sensitivity and T-cell reactivity to peanut compared with DBPCFC reactors. At baseline, peanut-reactive TH2A cells were observed in many but not all peanut-allergic patients and their level in peripheral blood correlates with T-cell reactivity to peanut and with serum peanut-specific IgE and IgG4 levels. POIT reshaped circulating peanut-reactive T-cell responses in a subset-dependent manner. Changes in basophil and T-cell responses to peanut closely paralleled clinical benefits to AR101 therapy and resemble responses in those with lower clinical sensitivity to peanut. However, no difference in peanut-reactive Treg cell frequency was observed between groups., Conclusion: Oral desensitization therapy with AR101 leads to decreased basophil sensitivity to peanut and reshapes peanut-reactive T effector cell responses supporting its potential as an immunomodulatory therapy., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Food allergy is common and causes substantial morbidity and even mortality. Safe and effective treatments for food allergy would therefore be highly desirable, especially for individuals with multiple food allergies., Objectives: Our aim was to describe a phase 3 study on treatment of patients with multiple food allergies with omalizumab., Methods: The study was developed as a collaboration between the Consortium for Food Allergy Research, the National Institute of Allergy and Infectious Diseases, and 2 industry sponsors (Genentech and Novartis)., Results: The study is currently under way, enrolling participants from age 1 year to age 55 years who are allergic to peanut and at least 2 other foods (including milk, egg, wheat, cashew, hazelnut, and walnut). The study is designed to address 3 major questions. First, stage 1 will study the potential value of omalizumab for the treatment of patients with peanut allergy and at least 2 other common food allergens. Second, stage 2 will directly compare treatment of patients with multifood allergies using omalizumab as monotherapy versus treatment with omalizumab-facilitated multiallergen oral immunotherapy in which omalizumab is used as an adjunctive treatment. Third, stage 3 will address the longer-term outcomes following these treatment approaches, including the introduction of dietary forms of the study foods to induce or maintain desensitization., Conclusions: This phase 3 study will provide important information on the potential of omalizumab to treat patients with multiple food allergies., (© 2022 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.)

A new era of active treatment for food allergy has arrived because patients with peanut allergy are increasingly able to access options for oral immunotherapy (OIT). This milestone is a culmination of years of clinical research and represents a major inflection point for the field because it will have dramatic impacts on allergy practice. In this review, we provide a brief review of the literature as well as practical guidance with concern for the use of U.S. Food and Drug Administration approved peanut OIT as well as shelf-bought products., Competing Interests: The remaining authors have no conflicts to report, (Copyright © 2022, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

Background: Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; previously known as AR101) is a daily oral immunotherapy approved to mitigate allergic reactions after accidental peanut exposure in peanut-allergic individuals aged 4-17 years., Objective: We sought to comprehensively summarize the PTAH safety profile for up to ∼2 years of treatment., Methods: Safety and adverse event (AE) data from participants aged 4-17 years from 3 controlled, phase 3 and 2 open-label extension trials were pooled and assessed., Results: Of the 944 individuals receiving ≥1 PTAH dose, median exposure was ∼49 weeks; most participants experienced ≥1 treatment-related AE (TRAE; n = 853; 90.4%). A total of 829 participants experienced TRAEs with a maximum severity of mild (497, 52.6%) or moderate (332, 35.2%); 24 participants (2.5%) experienced TRAEs graded as severe. Overall, 80 participants (9.5%) discontinued as a result of AEs; most experienced gastrointestinal symptoms and discontinued during the first 6 months. When adjusted for exposure, AEs and TRAEs occurred at a rate of 76.4 and 58.7 events per participant-year of exposure (PYE), respectively, during updosing; AEs and TRAEs decreased to 23.0 and 14.2, respectively, during 300 mg maintenance. Overall, exposure-adjusted rates of systemic allergic reactions were 0.12 events/PYE (mild), 0.11 events/PYE (moderate), and 0.01 events/PYE (severe [anaphylaxis])., Conclusion: The safety profile of PTAH was consistent across trials, manageable, and improved over time. AEs were predominantly mild to moderate, and all grades declined in frequency with continued treatment. These data can be used to facilitate shared decision-making discussions with patients and families considering treatment with PTAH., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Reducing the psychosocial impact of food allergy (FA) represents a top patient-centered research priority. This priority recognizes that psychosocial impact is an important outcome of current FA therapies (eg, oral immunotherapy), as well as interventions aimed at improving overall quality of life and illness adaptation. Reliable and valid measurement is a necessary prerequisite to developing and evaluating current and emerging FA therapies and potential changes in psychosocial impact., Methods: In this systematic review, we applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to evaluate available parent report measures assessing the psychosocial impact of pediatric IgE-mediated FA., Results: The systematic search yielded 64 articles involving 13 unique measures. Measures were evaluated through the lens of the Patient Reported Outcomes Measurement Information System (PROMIS) guidelines. Findings indicated that available measures show some evidence of reliability and validity; however, none completely adhere to PROMIS guidelines for measure development., Conclusion: Results highlight a continued need to dedicate research to develop a measurement approach that assesses the full range of psychosocial impact that parents and families may experience as a result of FA, as well as serve as a research outcome as the field continues to develop effective treatments, including immunotherapy., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life., Methods: We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores., Results: Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life., Conclusions: These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response., (© 2021 Aimmune Therapeutics. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Food allergies affect 32 million Americans. Restricted diets due to food allergies can be difficult to maintain especially when the household is food insecure. Food insecurity is defined as the inability to acquire food for household members due to insufficient money or resources for food. The COVID-19 pandemic has caused many people to face food insecurity for the first time with Latinx, Native American, and Black communities disproportionately affected. Because of the increase in food insecurity, this work group developed a survey regarding food insecurity screening. This survey was sent out to a random sample of American Academy of Allergy Asthma & Immunology members to assess food insecurity knowledge and practices. The majority of survey participants did not routinely screen their patients for food insecurity. The biggest barrier identified to screening was lack of knowledge of how to perform a screen and resources available when a patient screened positive. This work group report provides guidance on how to implement and perform a food insecurity screen, including federal resources and assistance programs., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Advances in oral immunotherapy (OIT) have led to recently expanded treatment options for food allergy (FA) patients. However, to inform future outreach efforts and ensure equitable access to emerging treatments, a greater understanding of current OIT-related awareness, attitudes, and experiences is needed., Objective: To characterize current OIT awareness, attitudes, and experiences among a nationally representative sample of U.S. adults with FA and parents/caregivers of pediatric patients., Methods: A probability-based sample of U.S. adults and parents/caregivers of children with FA was surveyed about OIT-related knowledge, attitudes, and experiences., Results: Surveys were completed by respondents (n = 781) from all 50 states. Overall, 72% did not know what OIT was prior to the survey. Respondents from households earning over $100,000 or with a college degree each had significantly greater odds of reporting any OIT awareness compared with lower-income (odds ratio 2.0; 95% confidence interval 1.2-3.4) and non-college-educated (odds ratio 1.9; 95% confidence interval 1.2-3.0) respondents. Among respondents familiar or unfamiliar with OIT, 54% and 34%, respectively, reported their expected treatment outcome was to obtain protection against accidental exposure. Among respondents familiar or unfamiliar with OIT, 38% and 35%, respectively, reported their expected treatment outcome to be curing the allergy. Furthermore, 55% of OIT unfamiliar respondents said they would not be comfortable initiating a conversation with their health care provider about their suitability for OIT., Conclusions: This study shows that, among a nationally representative sample of FA patients and pediatric caregivers, awareness of OIT is low, and over 95% of patients lack personal experience with OIT. Furthermore, the data suggest current OIT awareness is disproportionately elevated among wealthier, more highly educated respondents., (Copyright © 2021. Published by Elsevier Inc.)

Food allergies are antigen-driven diseases that can lead to IgE-mediated reactions of immediate hypersensitivity (eg, anaphylaxis triggered by a single food) or non-IgE reactions of delayed hypersensitivity such as eosinophilic esophagitis (eg, inability to eat multiple foods manifesting as abdominal pain, choking, dysphagia, vomiting, reflux, food impaction). Although both types of disease have their own unique set of challenges in diagnosis and management, it is a particularly vexing problem when a patient is afflicted by both conditions. This situation can happen when individuals with IgE-mediated food allergy undergo desensitization using currently available forms of oral immunotherapy. In this Grand Rounds Review, we review diagnostic approaches to oral immunotherapy-associated eosinophilic esophagitis, potential relationships between primary and secondary eosinophilic esophagitis, potential management approaches, areas of uncertainty, and upcoming research. Optimally supporting patients in their journey with food allergy requires shared decision making regarding alternative management strategies and the stimulation of robust research., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Food allergy continues to pose problems due to its increased frequency and its increasingly high severity. In this context, alongside the traditional avoidance strategies of allergenic foods and desensitization through the cautious progression of exposure to foods in the context of oral immunotherapy (OIT), alternative strategies have made their way in the last decades. We review the possibilities of intervention in food allergy with the use of biological drugs capable of interfering with the synthesis of IgE, with their mechanisms of action, or with complex biological mechanisms that lead to the establishment of a food allergy., Methods: Repeated Entrez PubMed searches using the template algorithm "Food allergy" and "biologics" or "Omalizumab" or "Dupilumab" or "milk desensitization" or "oral tolerance induction" or "oral immunotherapy" or "Etokimab" or "Tezepelumab" or "Quilizumab" or "Ligelizumab" or "Tralokinumab" or "Nemolizumab" or "Mepolizumab" or "Reslizumab" or "Benralizumab". The authors' clinical experience in paediatric allergy units of University hospitals was also drawn upon., Results: The landscape in this context has changed dramatically over the past 10 years. We have acquired knowledge mainly on the effect of different types of anti-IgE treatments in poliallergic patients with food allergy, and in patients treated with OIT. However, other mediators are being targeted by specific biologic treatments. Among them, the alarmins Il-33 and TSLP, IL-4 and IL-13, eosinophil-related molecules as IL-6, IL-8, IL-10, IL-12, and mostly IL-5, and integrins involved in the pathogenesis of eosinophilic gastrointestinal diseases (EGIDs), as SIGLEC-8., Conclusions: The ever-better knowledge of the mechanisms of food allergy allowing these developments will improve not only the perspective of patients with the most serious immediate food allergies such as anaphylaxis, but also those of patients with related diseases such as atopic dermatitis, eosinophilic esophagitis, and EGIDs. Biologics are also intended to complement OIT strategies that have developed over the years., (© 2021 John Wiley & Sons Ltd.)

Background: Although blood eosinophils are a frequently used marker of type 2 inflammation in children with asthma, their sensitivity is relatively poor. Additional markers of type 2 inflammation are needed., Objective: We hypothesized that plasma concentrations of eosinophil cationic protein (ECP), a marker of eosinophil activation, would be useful for detection of type 2 inflammation and would predict poorer asthma outcomes over 1 year., Methods: Children and adolescents 6 through 17 years (N = 256) with confirmed asthma completed a baseline visit and a follow-up visit at 12 months. A subset also underwent systemic corticosteroid responsiveness testing with intramuscular triamcinolone. Outcome measures at 12 months included uncontrolled asthma, lung function, and asthma exacerbations treated with systemic corticosteroids., Results: Plasma ECP concentrations ranged from 0.03 to 413.61 ng/mL (median, 6.95 ng/mL) and were consistently associated with other markers of type 2 inflammation. At baseline, children in the highest ECP tertile had poorer asthma control, more airflow limitation, and more exacerbations, but also had greater symptom improvement with intramuscular triamcinolone. At 12 months, associations between the highest ECP tertile and exacerbations, but not lung function or asthma control, persisted after covariate adjustment. However, the sensitivity of ECP was modest and was not markedly different from that of blood eosinophil counts., Conclusion: Plasma ECP concentrations may be a useful marker of type 2 inflammation in children and may help identify those children at highest risk for recurrent exacerbations who could benefit from corticosteroid treatment. However, additional markers may be needed to improve sensitivity for outcome detection., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents., Objective: ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals., Methods: Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics., Results: Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm., Conclusions: Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders., Methods: We undertook a mixed-methods systematic review, which involved searching 11 international biomedical databases for published studies from inception to 31 December 2019. Studies were independently screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses and, therefore, narrative synthesis of quantitative and qualitative data was performed., Results: We found 23 studies providing eligible primary data on symptom-specific severity of food allergic reactions, and 31 previously published symptom-severity scoring systems referred to food allergic reactions. There were seven studies which assessed quality-of-life measures in patients (and family members) with different food allergy severity and two studies that investigated the economic burden of food allergy severity. Overall, the quality and the global rating of all included studies were judged as being moderate., Conclusions: There is heterogeneity among severity scoring systems used and even outcomes considered in the context of severity of food allergy. No score has been validated. Our results will be used to inform the development of an international consensus to define the severity of food allergy., Systematic Review Registration: A protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42020183103 (https://www.crd.york.ac.uk/prospero/#recordDetails)., Competing Interests: The following authors declared no potential interests: Ignacio J Ansotegui; Stefania Arasi; Shahd Daher; Alessandro Fiocchi; Ulugbek Nurmatov; Stavros Petrou; Graham Roberts; Mario Sánchez-Borges; Luciana Kase Tanno; Marta Vazquez Ortiz; Gary Wing-Kin Wong. Some of the authors have professional affiliations related to the content of the systematic review as set out below: Audrey Dunn-Galvin: consultancy fee from Aimmune and DBV; Paul J Turner: grants from UK 10.13039/501100000265Medical Research Council, 10.13039/501100013342NIHR/Imperial BRC, JM Charitable Foundation and UK 10.13039/501100000354Food Standards Agency; personal fees from UK Food Standards Agency, DBV Technologies, ILSI Europe and Allergenis, non-financial support from Aimmune Therapeutics; Sayantani B Sindher: supported by 10.13039/100000002NIH grants. Involved in clinical trials with Regeneron, Aimmune Therapeutics, DBV Technologies, Adare Pharmaceuticals, Sanofi, Novartis; Ruchi Gupta: grants from The 10.13039/100000002National Institute of Health (NIH) (R21 ID # AI135705, R01 ID# AI130348, U01 ID # AI138907), Rho Inc., Stanford Sean N. Parker Center for Allergy Research, UnitedHealth Group, Thermo Fisher Scientific, Genentech, and the National Confectioners Association (NCA); is employed by Ann & Robert H. Lurie Children's Hospital of Chicago; is a Professor of Pediatrics at Northwestern University; and serves as a medical consultant/advisor for Before Brands, Kaléo Inc., Genentech, ICER, FARE, Aimmune Therapeutics, and DBV Technologies; Philippe Eigenmann: Research grants and support: Ulrich Muller Gierock Foundation, 10.13039/100011033ThermoFisher Scientific; Consultant: DBV technologies, Nesté, Danone, Novartis, Abbott; Speaking engagements: ThermoFisher Scientific, ALK, Abbott; Stock options: DBV technologies; Anna Nowak-Wegrzyn: Grant/Research/Clinical Trial Support: DBV Technologies; ITN/NIAID; 10.13039/100004324Astellas Pharmaceutical; 10.13039/100004339Sanofi-Aventis [Future therapies for food allergy]. International FPIES Association [FPIES, unpaid advisor]. Consultant/Advisory Boards: Gerber Nutrition Institute; Merck. Speaking engagements: Nestle, Thermofisher Scientific; Montserrat Fernandez-Rivas: research grants from the Spanish Government (10.13039/501100003329MINECO, ISCIII) for the project SOLMILK, ARADyAL network and PI19/01095; consultancy fees from Aimmune, DBV, Novartis, SPRIM; lecture fees from ALK, Allergy Therapeutics, Diater, GSK, HAL Allergy, Thermofisher Scientific; Brian P Vickery: Employment: Pediatric Institute of Emory University + Children's Healthcare of Atlant; Consultant/Advisor: Aimmune Therapeutics; AllerGenis, LLC; Food Allergy Research and Education (FARE); Reacta Biosciences; Grant support: NIH-NIAID; 10.13039/100006423FARE; 10.13039/100004328Genentech; Clinical investigator: Aimmune; DBV Technologies; Regeneron; Motohiro Ebisawa: lecture fees: DBV technologies and Mylan., (© 2021 The Authors.)