Community and academic allergists' perspectives on integrating biologics into food allergy care: A qualitative study.

BACKGROUND: Biologics are an important area of research and development, including for treatment of food allergy (FA). However, how allergists perceive the risks and benefits of biologics to treat FA remains largely unknown. OBJECTIVE: To explore how US-based allergists perceive the use of biologics in FA treatment. METHODS: Using a combination of purposive and snowball sampling, providers were recruited through direct solicitation by email to participate in a telephone or Zoom interview about their perceptions of the risks and benefits of current and future FA treatment options. Interviews were transcribed, deidentified, and coded to conduct a thematic analysis. RESULTS: We conducted 60 interviews with providers from 34 states working either in community practice (53.3%) or academic medical centers (46.7%). Our sample was primarily non-Hispanic White (60.0%) and men (56.7%). The plurality was in their 40s (41.7%). Our findings clustered in the following 4 main themes: (1) perceived benefits of biologics, (2) ideal use of biologics, (3) concerns about biologics, and (4) biologics as the perceived future of FA. Community and academic providers had largely similar views, but academic providers more often emphasized the benefits of biologics, and community providers were, on the whole, more supportive of using biologics as an adjunct to oral immunotherapy rather than as monotherapy. CONCLUSION: This study indicates that providers hold mixed views about the use of biologics to treat FA. However, most were enthusiastic about prescribing biologics for FA while also being highly concerned about the cost to patients and the health care system.

Epicutaneous immunotherapy for the treatment of peanut allergy.

Peanut allergy treatment options remain limited, but novel approaches are being studied, including epicutaneous immunotherapy (EPIT). EPIT uses the cutaneous immune system to promote tolerance to food allergens. Viaskin™ Peanut, an approach to EPIT in late-stage clinical development uses an occlusive patch with a condensation chamber that enables natural epidermal water loss to solubilize dry antigen on the patch, which is then absorbed and captured by skin Langerhans cells. This form of EPIT does not require disruption of the skin barrier, thus avoiding a proinflammatory cytokine response by targeting the nonvascularized epidermis and limiting systemic allergen exposure. Extensive preclinical research suggests that Viaskin Peanut has a distinct mechanism of desensitization, including the potential for disease modification, driven by a unique population of regulatory T cells. Numerous clinical studies of Viaskin Peanut have demonstrated desensitization and reductions in reaction severity, particularly in children aged 1 through 11 years, as well as a favorable safety profile with mostly mild-to-moderate skin reactions that were observed to decrease over time. EPIT with Viaskin Peanut may be a potential therapeutic option for peanut allergy that is clinically practical with long-term efficacy and tolerability.

Omalizumab Implementation in Practice: Lessons Learned from the OUtMATCH Study.

In February 2024, omalizumab was approved by the 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 endpoints, demonstrating a large effect size in multi-allergen desensitization compared to 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 co-treatment 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.

A Review of Shared Decision-Making, Published Protocols, and Post-desensitization Strategies in Oral Immunotherapy (OIT).

PURPOSE OF REVIEW: The aim of this review is to highlight key published oral immunotherapy (OIT) protocols and post-desensitization strategies for the major food allergens and to cover important concepts to consider when evaluating OIT for food-allergic patients. Shared decision-making should help identify patient and family values which will help influence the type of evidence-based protocol and maintenance strategy to use. RECENT FINDINGS: With food OIT emerging as a treatment option, there is a pressing need for patients, physicians, and other providers to have a nuanced understanding of the management choices available to them. There are now randomized controlled trials (RCT) of OIT for peanut, egg, milk, and wheat, and reports of cohorts of patients who have undergone OIT for tree nuts and sesame clinically. The current published protocols contain significant diversity in terms of starting dose, build-up schedule, maintenance dose, and even the product used for desensitization. Emerging data can help direct the long-term maintenance strategy for patients on OIT. Based on patient and family values elicited through the shared decision-making process, an OIT protocol may be selected that balances the level of desensitization, potential side effects, frequency of clinic visits, and potential to induce sustained unresponsiveness, among other factors. Once maintenance dosing is reached, most patients will need to maintain regular exposure to the food allergen to remain desensitized. The option to transition to commercial food products with equivalent amounts of food protein as the OIT maintenance dose would simplify the dosing process and perhaps improve palatability as well. Less frequent or decreased OIT dosing can provide practical benefits but may affect the level of desensitization and safety for some patients.

Omalizumab for the Treatment of Multiple Food Allergies.

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.).

Food allergies on a college campus.

There are limited data on food allergies among college students. In this article, we review the most current available studies. These self-reported surveys and qualitative interviews reported overall poor avoidance of known allergens and low rates of carrying self-injectable epinephrine among students with food allergy. College students may exhibit risk-taking food behaviors due to a number of factors, including age-appropriate risk-taking predilection, strong social influences, and lack of experience in self-advocacy. Having to disclose an otherwise invisible condition repeatedly in a new environment may also lead to "disclosure fatigue," creating an additional barrier to self-advocacy. Common themes in the narrative include hypervigilance, stigma management, and concern about others' misunderstanding of food allergy. Although there is a paucity of data in this area, it is likely that having greater support at the institution level, along with support from peers and faculty, may help improve awareness, self-injectable epinephrine carriage, and allergen avoidance. This review also discusses strategies for preparedness at school, including specific steps to maximize safety.

Desensitization and remission after peanut sublingual immunotherapy in 1- to 4-year-old peanut-allergic children: A randomized, placebo-controlled trial.

BACKGROUND: Prior studies of peanut sublingual immunotherapy (SLIT) have suggested a potential advantage with younger age at treatment initiation. OBJECTIVE: We studied the safety and efficacy of SLIT for peanut allergy in 1- to 4-year-old children. METHODS: Peanut-allergic 1- to 4-year-old children were randomized to receive 4 mg peanut SLIT versus placebo. Desensitization was assessed by double-blind, placebo-controlled food challenge (DBPCFC) after 36 months of treatment. Participants desensitized to at least 443 mg peanut protein discontinued therapy for 3 months and then underwent DBPCFC to assess for remission. Biomarkers were measured at baseline and longitudinally during treatment. RESULTS: Fifty participants (25 peanut SLIT, 25 placebo) with a median age of 2.4 years were enrolled across 2 sites. The primary end point of desensitization was met with actively treated versus placebo participants having a significantly greater median cumulative tolerated dose (4443 mg vs 143 mg), higher likelihood of passing the month 36 DBPCFC (60% vs 0), and higher likelihood of demonstrating remission (48% vs 0). The highest rate of desensitization and remission was seen in 1- to 2-year-olds, followed by 2- to 3-year-olds and 3- to 4-year-olds. Longitudinal changes in peanut skin prick testing, peanut-specific IgG4, and peanut-specific IgG4/IgE ratio were seen in peanut SLIT but not placebo participants. Oropharyngeal itching was more commonly reported by peanut SLIT than placebo participants. Skin, gastrointestinal, upper respiratory, lower respiratory, and multisystem adverse events were similar between treatment groups. CONCLUSION: Peanut SLIT safely induces desensitization and remission in 1- to 4-year-old children, with improved outcomes seen with younger age at initiation.

New Approaches to Food Allergy Immunotherapy.

Food allergy is an increasing public health problem in children and adults. In addition to the risk of potentially severe reactions, food allergy can have a significant burden on quality of life, nutrition, cost of living, and social activities. Traditionally, treatment has primarily included strict food allergen avoidance and use of emergency medications to treat an allergic reaction. However, in recent years, there have been significant strides in the advancement of food allergy treatment, including the approval of the first and only approved therapy (peanut oral immunotherapy) for food allergy in 2020. Clinical trials have primarily focused on food allergen immunotherapy (oral, epicutaneous, sublingual). Building off of a foundation of promising data supporting the efficacy of food oral immunotherapy and our greater understanding of the underlying mechanism of immunotherapy, newer approaches, including alternative routes of delivery, adjuncts to therapy, modified allergens, and utilization in younger patients, aim to provide safer and more effective treatment approaches to the millions of patients burdened by food allergy.

Recent advances in food allergen immunotherapy.

Food allergies can pose significant risks and profoundly impact the quality of life of children and their families, making them a major public health concern. Allergen avoidance has been the traditional mainstay of treatment; however, recent research has focused on various approaches to food allergen immunotherapy. This review summarizes the recent advancements in oral, sublingual, and epicutaneous immunotherapies, highlighting their respective advantages and disadvantages. The ultimate goal of food allergen immunotherapy is to maximize efficacy while minimizing risks, leading to the exploration of strategies such as low-dose immunotherapy and the use of biologics. When selecting candidates for immunotherapy among patients with food allergies, factors such as allergen characteristics, the likelihood of natural resolution, age, symptom severity, and impact on quality of life require consideration, and an individualized approach should be adopted to determine the most suitable treatment method.

Alanine Scanning of the Unstructured Region of Ara h 2 and of a Related Mimotope Reveals Critical Amino Acids for IgE Binding.

SCOPE: The unstructured region of Ara h 2, referred to as epitope 3, contains a repeated motif, DYPSh (h = hydroxyproline) that is important for IgE binding. METHODS AND RESULTS: IgE binding assays to 20mer and shorter peptides of epitope 3, defines a 16mer core sequence containing one copy of the DPYSh motif, DEDSYERDPYShSQDP. This study performs alanine scanning of this and a related 12mer mimotope, LLDPYAhRAWTK. IgE binding, using a pool of 10 sera and with individual sera, is greatly reduced when alanine is substituted for aspartate at position 8 (D8; p < 0.01), tyrosine at position 10 (Y10; p < 0.01), and hydroxyproline at position 12 (h12; p < 0.001). IgE binding to alanine-substituted peptides of a mimotope containing the DPY_h motif confirm the critical importance of Y (p < 0.01) and h (p < 0.01), but not D. Molecular modeling of the core and mimotope suggests an h-dependent conformational basis for the recognition of these sequences by polyclonal IgE. CONCLUSIONS: IgE from pooled sera and individual sera differentially bound amino acids throughout the sequences of Epitope 3 and its mimotope, with Y10 and h12 being most important for all sera. These results are highly significant for designing hypoallergenic forms of Ara h 2.

Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

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.).

Retail Food Equivalents for Post-Oral Immunotherapy Dosing in the Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food-Allergic Children and Adults (OUtMATCH) Clinical Trial.

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.

Structure and IgE Cross-Reactivity among Cashew, Pistachio, Walnut, and Peanut Vicilin-Buried Peptides.

Peanut and tree-nut allergies are frequently comorbid for reasons not completely understood. Vicilin-buried peptides (VBPs) are an emerging family of food allergens whose conserved structural fold could mediate peanut/tree-nut co-allergy. Peptide microarrays were used to identify immunoglobulin E (IgE) epitopes from the N-terminus of the vicilin allergens Ara h 1, Ana o 1, Jug r 2, and Pis v 3 using serum from three patient diagnosis groups: monoallergic to either peanuts or cashew/pistachio, or dual allergic. IgE binding peptides were highly prevalent in the VBP domains AH1.1, AO1.1, JR2.1, and PV3.1, but not in AO1.2, JR2.2, JR2.3, and PV3.2 nor the unstructured regions. The IgE profiles did not correlate with diagnosis group. The structure of the VBPs from cashew and pistachio was solved using solution-NMR. Comparisons of structural features suggest that the VBP scaffold from peanuts and tree-nuts can support cross-reactivity. This may help understand comorbidity and cross-reactivity despite a distant evolutionary origin.

Open-label study of the efficacy, safety, and durability of peanut sublingual immunotherapy in peanut-allergic children.

BACKGROUND: Studies on the efficacy of peanut sublingual immunotherapy (SLIT) are limited. The durability of desensitization after SLIT has not been well described. OBJECTIVE: We sought to evaluate the efficacy and safety of 4-mg peanut SLIT and persistence of desensitization after SLIT discontinuation. METHODS: Challenge-proven peanut-allergic 1- to 11-year-old children were treated with open-label 4-mg peanut SLIT for 48 months. Desensitization after peanut SLIT was assessed by a 5000-mg double-blind, placebo-controlled food challenge (DBPCFC). A novel randomly assigned avoidance period of 1 to 17 weeks was followed by the DBPCFC. Skin prick test results immunoglobulin levels, basophil activation test results, TH1, TH2, and IL-10 cytokines were measured longitudinally. Safety was assessed through patient-reported home diaries. RESULTS: Fifty-four participants were enrolled and 47 (87%) completed peanut SLIT and the 48-month DBPCFC per protocol. The mean successfully consumed dose (SCD) during the DBPCFC increased from 48 to 2723 mg of peanut protein after SLIT (P < .0001), with 70% achieving clinically significant desensitization (SCD > 800 mg) and 36% achieving full desensitization (SCD = 5000 mg). Modeled median time to loss of clinically significant desensitization was 22 weeks. Peanut skin prick test; peanut-specific IgE, IgG4, and IgG4/IgE ratio; and peanut-stimulated basophil activation test, IL-4, IL-5, IL-13, IFN-γ, and IL-10 changed significantly compared with baseline, with changes seen as early as 6 months. Median rate of reaction per dose was 0.5%, with transient oropharyngeal itching being the most common, and there were no dosing symptoms requiring epinephrine. CONCLUSIONS: In this open-label, prospective study, peanut SLIT was safe and induced clinically significant desensitization in most of the children, lasting more than 17 weeks after discontinuation of therapy.

A clinical focus on oral tolerance in the development, prevention, and management of food allergy.

Food allergy impacts up to 10 % of the population and can result in life-threatening anaphylactic reactions. The pathogenesis of food allergy is not entirely understood but the disruption in naturally occurring oral tolerance is presumed to be involved. Research has been directed not only toward prevention of food allergy but on the restoration of oral tolerance by various means including immunotherapy (oral, sublingual, and epicutaneous), as well as adjunctive therapies including biologicals and probiotics. This review paper briefly discusses the involvement of oral tolerance in the pathogenesis of food allergy and how food allergy might be prevented; however, the main focus is on the potential for restoration of oral tolerance with various treatment modalities (oral immunotherapy with and without adjunctive therapies).

Treatment for food allergy: Current status and unmet needs.

The treatment of food allergy has traditionally relied on avoidance of the offending food(s) and use of emergency medications in the event of accidental exposures. However, this long-standing paradigm is beginning to shift, as a variety of treatment approaches have been and are being developed. This report provides an overview of the past, present, and future landscape of interventional clinical trials for the treatment of food allergy. It focuses on specific issues related to participant characteristics, protocol design, and study end points in the key clinical trials in the literature and examine how differences between studies may impact the clinical significance of the study results. Recommendations are provided for the optimization of future trial designs and focus on specific unmet needs in this rapidly evolving field.