Oral Immunotherapy Research Articles

Nanoparticles in Allergen‐Delivery Systems for Allergen‐Specific Immunotherapy

AbstractAllergen‐specific immunotherapy (AIT) has demonstrated its ability to induce desensitization, resulting in reduced allergen‐specific immunoglobulin E (sIgE) accompanied by increased clinical thresholds. However, ensuring safety during therapy, especially with oral immunotherapy, and achieving long‐term tolerance continue to be significant challenges. To address these issues, a concept of nanoencapsulation of allergens has emerged. This paper reviews biodegradable and non‐biodegradable nanoparticles as an allergen‐delivery system, as well as adjuvants for the improvement of the efficacy of AIT. Of all the nanoparticles reviewed, polymethyl methacrylate (PMMA) and chitosan are the most popular nanoparticles for encapsulating macromolecular allergens for oral immunotherapy. Although poly(lactic‐co‐glycolic acid) (PLGA) demonstrates higher stability in the gastrointestinal environment and allergen‐loaded PLGA attenuates the sIgE antibody binding in a murine model, it has inconsistent loading capacity and is difficult to reproduce. Studies on biodistribution, pharmacokinetics, and pharmacodynamics of nanoparticles, however, should be highlighted to ensure the long‐term safety profile of utilizing nanoparticles in immunotherapy. In this regard, encapsulation efficiency and release behavior of allergens from nanoparticles are important components in predicting the safety and efficacy of treatments. The stability, reproducibility, and scalability of encapsulated allergens should also be considered for the translation to clinical applications.

Recent developments in immunotherapy approaches for allergic rhinitis.

Allergic rhinitis (AR) poses a significant global health burden, with the potential to progress to asthma, thereby impacting patients' quality of life. Immunotherapy has demonstrated effectiveness in mitigating clinical symptoms by altering the underlying disease mechanisms of AR. This article provides a thorough review of the current state of immunotherapy for AR, encompassing various facets of immunotherapeutic strategies, elucidating their mechanisms and clinical implications. By presenting a nuanced understanding of the present landscape of immunotherapy for AR, this review aims to serve as a valuable reference for informing clinical treatment strategies. The subsequent analysis of diverse immunotherapeutic pathways offers a comprehensive understanding of their mechanisms and clinical implications. A meticulous examination is conducted on subcutaneous immunotherapy, sublingual immunotherapy, oral immunotherapy, intralymphatic immunotherapy, and innovative intravenous gold-induced autologous serum injection therapy. Each pathway is systematically elucidated, with its distinctive features and potential contributions to managing AR emphasized. In conclusion, synthesizing epidemiological insights, immunotherapeutic nuances, and pathway-specific analyses encapsulates a profound understanding of immunotherapy for AR.

Zéro allergie research clinic: a clinical and research initiative in oral immunotherapy for managing IgE-mediated food allergy

Background and methodsThe Zéro allergie research clinic (Saguenay, Canada) is a clinical and research initiative in oral immunotherapy (OIT) for managing IgE-mediated food allergy (FA). A total of 183 children with FA and 27 non-allergic siblings were recruited to date in the Zéro allergie cohort (ZAC) to better understand biological mechanisms underlying FA and OIT prognosis. The primary aims are to (a) better understand the genetic, epigenetic, transcriptomic, metabolomic, and microbial diversity associated with FA; (b) establish the multi-omics and microbial diversity profiles of children following OIT to identify predictive prognosis biomarkers, (c) make OIT more accessible to the population of the Saguenay–Lac-Saint-Jean region, and (d) build a biobank of data and biological material.ResultsThe ZAC constitutes a unique and rich biobank of biological samples (blood, buccal swabs, microbiota samples [intestinal, buccal, nasal, and cutaneous]) combined with clinical data and more than 75 phenotypic characteristics.ConclusionsThis represents an innovative interdisciplinary initiative by researchers, allergists, and paediatricians to make FA care accessible to a greater number of children with IgE-mediated FA. Ultimately, it will contribute to provide more accessible treatment options with greater chances of success through a better understanding of the biological nature of FA and OIT.

The use of biologics in food allergy management.

Patients and families living with food allergy may experience significant burdens, including social isolation, impaired quality of life, and anxiety. Allergists/immunologists play a critical role in educating families living with food allergies about risk, particularly with regard to the rarity of fatal food allergy. Appropriate risk framing can greatly decrease the fear-based burden of disease. In 2024, an increasing complex fabric of food allergy treatments has emerged that includes oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and omalizumab, with the promise of additional treatments, including epicutaneous immunotherapy and oral mucosal immunotherapy in the near future. Younger children may be most likely to benefit from OIT and SLIT, with some evidence that suggests the possibility of an immunomodulatory effect. Omalizumab, approved in 2024 for use in conjunction with strict avoidance, increases the threshold of reactivity before a moderate-to-severe reaction for many, but not all, patients. There is no evidence to date that omalizumab has an immunomodulatory effect, and young children treated with omalizumab monotherapy may bear a lost opportunity cost from possible immunomodulation would they have been treated with OIT or SLIT instead; however, within a shared decision-making paradigm, beyond label use of omalizumab may include treatment with OIT or SLIT. Fortunately, the co-evolution of shared decision-making with modern food allergy treatments will facilitate the critical preference-sensitive care that must be characteristic of all decisions surrounding active food allergy management.

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

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

Epitope profiling of cow's milk allergen-specific antibodies with determining IgE content in epitopes-ALL, a 14-epitopes mixture

Allergen-specific antibodies (Abs), IgE, and IgG4 increase during the early phase of oral immunotherapy (OIT) of allergen food in patients; subsequently, IgE levels decrease and specific IgG4 levels increase after successful OIT treatment. The detailed profile of these Abs during OIT remains largely unclear. We developed a diagnostic tool to assess the OIT efficacy and extent of responsiveness based on a profiling method by identifying epitopes recognized by the Ab classes of IgE or IgG4.A peptide microarray followed by microplate analysis using synthetic peptides was used to identify 14 epitopes widely recognized by IgE and/or IgG4 in the serum samples of patients with OIT among the amino acid sequences of five major cow's milk allergens. The set of defined 14 epitopes clarified different epitope profiles of allergen-specific IgE and IgG4 in each patient's serum samples. Moreover, the total signal of Abs recognizing all 14 epitopes was equal to the sum of all individual epitope-specific Abs. It was further observed that the quantitative value of IgE concentrations of 14 epitopes-ALL correlated with the ImmunoCAP IgE value.These findings strongly imply that the quantity of IgE and IgG4 recognizing epitopes-ALL may easily be used to measure allergy severity. To investigate this potential, we developed an immunochromatographic method that can detect IgE and IgG4 levels in patient samples.This study clearly demonstrated the usefulness of the defined 14 epitopes and their mixture, “epitopes-ALL,” and that the simple and reliable methods of immunochromatography and microplate analyses demonstrating the epitope profile of allergen-specific Abs are applicable for diagnostic use at multiple disease stages and the OIT-treatment course in patients with cow's milk allergy.

The multiple facets of cow’s milk allergy

Cow’s milk allergy (CMA) is one of the most common food allergies in early childhood. CMA has varied presentations and multiple facets. A detailed clinical history is key for classification. In IgE-mediated CMA skin prick testing and serum specific IgE testing are useful in the diagnosis, but an oral food challenge (OFC) may still be necessary if there is doubt or to assess tolerance. Non-IgE-mediated CMA presentations include food protein-induced allergic proctocolitis (FPIAP), food protein-induced enterocolitis syndrome (FPIES), and eosinophilic esophagitis (EoE). The diagnosis of FPIAP and FPIES is based on the clinical history. An esophageal biopsy is required for the diagnosis of EoE. Atopy patch testing, IgG or IgG4 testing are not helpful in any CMA evaluation. Children with CMA (except those with FPIAP) are at risk for poor growth and a nutritional evaluation should be part of routine care. Extensively hydrolyzed formulas are the recommended first choice alternative formula for CMA. For IgE-mediated CMA, alternative approaches to traditional strict avoidance include oral immunotherapy (OIT) and omalizumab (both as monotherapy and as an adjunct to OIT). Multiple international guidelines have addressed evaluation and management of CMA providing key information, support and guidance for clinicians in daily practice.

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

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

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

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

EAACI guidelines on the management of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes.

Development of Cashew and Pistachio Ladders through a Food-Processing Approach.

Following successful oral immunotherapy (OIT) for peanut allergy using boiled peanuts (BOPI trial), this study investigated the potential of wet-thermal-processing-induced allergen modification, specifically soaking and boiling (1-4 h) to reduce the allergenicity of cashew and pistachio allergens. In addition, this study provides a foundation of understanding for developing safer forms of cashew/pistachio administration for application in OIT by gradual exposure to increasing doses of modified allergens with reduced potency as an "allergen ladder". An SDS-PAGE analysis and an intrinsic-fluorescence spectroscopy revealed altered tertiary structures of the allergens, leading to their denaturation and even degradation. Notably, the reduction in both allergen-specific polyclonal IgG and human-specific IgE (sIgE) binding correlated with the treatment time, with the most significant decrease observed after 4 h of boiling. In contrast, shorter soaking treatments showed negligible effects on the IgE-binding capacity of these nuts, therefore indicating a further need for optimization. These findings indicate that extended boiling effectively reduced the amounts of the highly potent allergenic component Ana o 3 in cashew and Pis v 1 in pistachio, as confirmed by ELISA using polyclonal anti-Ana o 3 antibodies, and an immunoblot showed decreased IgE epitope binding in cashew and pistachio allergens, which further modified their allergenic profiles. This approach shows promise as a viable method for offering a safer therapeutic option for cashew/pistachio allergy.

The Relationship Between Asthma and Food Allergies in Children

Asthma and food allergy are two complex allergic diseases with an increasing prevalence in childhood. They share risk factors, including atopic family history, atopic dermatitis, allergen sensitization, and T2 inflammatory pathways. Several studies have shown that in children with a food allergy, the risk of developing asthma, particularly in early childhood, is high. Food allergen intake or the inhalation of aerosolized allergens can induce respiratory symptoms such as bronchospasm. Patients with both conditions have an increased risk of severe asthma exacerbations, hospitalization, and mortality. The current management of clinical food hypersensitivity primarily involves the dietary avoidance of food allergens and the use of self-injectable adrenaline for severe reactions. Poorly controlled asthma limits the prescription of oral immunotherapy to foods, which has emerged as an alternative therapy for managing food allergies. Biological therapies that are effective in severe asthma have been explored for treating food allergies. Omalizumab improves asthma control and, either alone or in combination with oral immunotherapy, increases the threshold of allergen tolerance. Understanding the interplay between asthma and food allergy is crucial for developing successful treatment approaches and ameliorating patient results.

Safety and adherence of early oral immunotherapy for peanut allergy in a primary care setting: a retrospective cross-sectional study

BackgroundPeanut allergy is a common food allergy with potentially life-threatening implications. Early oral immunotherapy for peanut allergy (P-EOIT) has been shown to be effective and safe in research and specialty clinic settings. Provision of P-EOIT in primary care would make it available to more patients. We sought to assess the safety of P-EOIT in a primary care setting by documenting the rates of peanut-related allergic reactions leading to emergency department (ED) visits and use of epinephrine. We also examined adherence by assessing the percentage of patients reaching maintenance phase and continuing ingestion after one year of P-EOIT.MethodsThis retrospective study included all patients aged less than 36 months who started P-EOIT at a primary care allergy clinic in New Brunswick, Canada, from 2016 to 2020. The population included patients who (1) had a history of an allergic reaction to peanuts with a positive skin prick test or positive peanut specific IgE level (ps-IgE) or (2) no history of ingestion and a baseline ps-IgE ≥5 kU/L. Patients had biweekly clinic visits with graded increases in peanut protein up to a maintenance dose of 300 mg of peanut protein daily. A blinded retrospective review of paper charts and electronic medical records was conducted along with phone interviews regarding ED visits and epinephrine use.ResultsAll 69 consented patients reached maintenance dose over a median of 29 weeks, and 66 patients (95.7%) were still regularly consuming peanut protein after 1 year of maintenance. One patient had a peanut ingestion-related ED visit requiring epinephrine during the escalation phase of peanut protein dosing (1.4%). During the first year of maintenance phase, no patients had peanut ingestion-related ED visits nor required epinephrine.ConclusionEarly oral immunotherapy for peanut allergy in a primary care setting appears to be safe and our findings suggest that it does not lead to an increased burden of emergency department visits. Our population had high adherence rates, with the majority achieving maintenance dose and staying on this dose for one year.

Diagnosis and management of shrimp allergy.

Shrimp allergy, the most common food allergy in the United States, affects up to 2% of the population. Its etiology is multi-factorial with the combination of genetic predisposition and environmental exposures. This review summarizes the latest diagnosis and management strategies for shrimp allergy. Currently, the double-blind, placebo-controlled food challenge is the gold standard for diagnosis. Moreover, mainstream and experimental management strategies include food allergen avoidance, the FDA-approved omalizumab, and oral immunotherapy. Herein, we emphasize the urgent need to develop more effective diagnostic tools and therapies for shrimp allergy.

Probiotics as adjuvants to mitigate adverse reactions and enhance effectiveness in Food Allergy Immunotherapy.

In the past decades, food allergies became increasingly dominant since early childhood, leading to a lower quality of life and to increasing costs addressed by the health care system. Beside standard avoidance of specific allergens and drug treatments following allergen exposure, a great deal of research has lately focused on Food Allergy Allergen Immunotherapy (FA-AIT). SCIT and EPIT (Subcutaneous and Epicutaneous Immunotherapy), OIT (Oral Immunotherapy), and SLIT (Sublingual Immunotherapy) consist in gradual exposure to allergens to desensitize and achieve tolerance once therapy has ended. Although promising, FA-AIT may bring acute local and systemic adverse reactions. To enhance efficacy, safety and convenience of AIT, the quest of potential adjuvants to mitigate the adverse reactions becomes crucial. Immunomodulatory activities, such as that of increasing the regulatory T cells and decreasing the IgE, have been observed in specific probiotics' strains and multiple studies elucidated the role of gut microbiota as a major interplayer among the host and its immune system. In this review, the microbiome modulation is shown as potential AIT adjuvant, nevertheless the need of more clinical studies in the near future is pivotal to assess the efficacy of targeted bacterial therapies and faecal microbiota transplantation.

Real-world experience: a retrospective pediatric chart review to determine why patients and caregivers discontinue oral immunotherapy

BackgroundOral immunotherapy (OIT) is an increasingly utilized management strategy for IgE-mediated food allergy. Despite promising efficacy and effectiveness, there is still a lack of data surrounding the reasons for discontinuation of OIT. The primary reason stated in the literature for discontinuation is adverse gastrointestinal effects. Social factors contributing to OIT discontinuation have not been well reported. We hypothesize that social considerations are significant contributors to treatment discontinuation.MethodsWe completed a retrospective chart review of 50 patients treated in community pediatric allergy practices who discontinued OIT out of 507 patients who were started on OIT between October 1, 2017-October 27, 2022. Reasons for discontinuation were identified and classified into five main categories: unsafe care decisions, anxiety, adverse effects of OIT, uncontrolled comorbidity and social factors. Categories were not exclusive.Results507 patients were started on OIT, with data available for 50 patients who discontinued OIT, aged 10 months to 18 years and 2 months. The overall discontinuation rate was 9.8%, of which 40 patients (80%) discontinued during buildup, 9 patients (18%) discontinued during maintenance and one patient on two food OIT discontinued one food during buildup and one during maintenance (2%). Thirty-four patients (68%) had multiple reasons for discontinuing OIT. Social factors were the most common reason for discontinuation and were identified in 32 patients (64%). Twenty-four patients (48%) discontinued OIT due to adverse effects. Gastrointestinal symptoms were the most prevalent, while anaphylaxis contributed to discontinuation in 15 patients (30%). Anxiety led to discontinuation in 17 patients (34%).ConclusionsOur data highlights the importance of social factors and anxiety in the success of OIT completion. Our results support the need to consider not only the patient’s medical history, but also their social history and support networks when selecting patients who are good candidates for OIT to optimize the successful completion of OIT.

Oral immunotherapy improves the quality of life of adults with food allergy

BackgroundOral immunotherapy (OIT) has become the standard of care for children with food allergy (FA) and has substantially improved their quality of life. The effect of OIT on the quality of life in adults, however, has been studied to a much lesser degree.MethodsPatients with food allergy aged ≥ 18 years who underwent OIT at Shamir Medical Center completed the Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) before and at the end of treatment. Adults with FA not undergoing OIT who completed the FAQLQ-AF at 2 time points, served as controls.ResultsA total of 44 adults, median age 23.4 years, who underwent OIT for milk (n = 19), egg (n = 2), peanut (n = 9), sesame (n = 6), and tree nuts (n = 8), and 11 controls were studied. The median OIT starting dose was 23.8 mg protein. 33 patients (75%) reached full desensitization within a median of 10.3 months. The FAQLQ-AF baseline scores were comparable between the study and control groups for all items except for Food Allergy related Health (FAH) item in which the study group had a significantly better score (p = 0.02). At the second time point, the study group had significantly better scores in all items (Allergen Avoidance and Dietary Restrictions (AADR), p = 0.02; and Emotional Impact (EI), Risk of Allergen Exposure (RAE), FAH and the Total Score, p < 0.01). The change in scores for the study group was significantly better, statistically and clinically, in AADR, p = 0.04; EI, p < 0.01; RAE, p = 0.01, and in the total score, p = 0.01.ConclusionsOIT significantly improves quality of life of adults with FA. This finding adds important support for providing OIT in this population.

Anaphylaxis Management in Paediatric Patients Undergoing Milk Oral Immunotherapy.

Anaphylaxis Management in Paediatric Patients Undergoing Milk Oral Immunotherapy.

Immunotherapeutic potential of collagen V oral administration in mBSA/CFA-induced arthritis.

We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 μg/300 μL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 μL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.

Food allergy in children: treatment challenges and outcome standardization

Relevance. Food allergy (FA) is an important public health concern, particularly among children, with an increasing prevalence. It is associated with a significant decrease in the quality of life for patients and their families due to the need to avoid allergens and the risk of severe allergic reactions, such as anaphylaxis. Despite active research, the primary treatment remains elimination diets, which limit patients’ options and highlight the need for new therapeutic solutions.Aim of the review. This review aims to summarize the current treatment methods for food allergy, discuss the challenges in evaluating the effectiveness of interventions, and highlight the importance of standardizing outcomes in clinical trials to improve comparability and practical relevance.Content. The review discusses modern therapeutic approaches for food allergy, such as oral, epicutaneous, and sublingual immunotherapies, which have shown positive results in achieving tolerance to allergens. Special attention is given to safety concerns, particularly for children, emphasizing the need for further research. The potential use of biological agents, such as omalizumab, in food allergy treatment is also explored. The review addresses challenges in choosing and standardizing endpoints in clinical trials, where most focus on desensitization and immunological markers, while patient-centered outcomes, such as quality of life, remain under-researched. The implementation of “core outcome sets” is highlighted as an important step toward improving data comparability and forming a more objective basis for clinical recommendations.Conclusions. The review emphasizes significant progress in food allergy treatment but notes the need for further research to ensure the safety of new therapies, particularly for children. Standardizing outcomes in clinical trials plays a key role in improving the quality and comparability of research, which will, in turn, help develop more effective clinical guidelines and improve patients’ quality of life.