A growing number of studies have shown encouraging results with omalizumab (OMA) as monotherapy and as an adjunct to oral immunotherapy (OMA+OIT) in patients with single/multiple food allergies.

To evaluate the efficacy and safety of OMA or OMA+OIT in patients with IgE-mediated food allergy.

An extensive literature search (inception-December 31, 2020) was performed to identify randomized, controlled, and observational studies that assessed OMA as monotherapy or OMA+OIT in patients with IgE-mediated food allergy.

Increase in tolerated dose of foods, successful desensitization, sustained unresponsiveness, immunological biomarkers, severity of allergic reactions to food, quality of life (QoL), and safety. A P < 0.05 was considered significant.

In total, 36 studies were included. OMA monotherapy (vs pre-OMA) significantly increased the tolerated dose of multiple foods, increased the threshold of tolerated dose for milk, egg, wheat, and baked milk, improved QoL, and reduced food-induced allergic reactions (all P < 0.01). OMA+OIT significantly increased the tolerated dose of multiple foods (vs placebo and pre-OMA), desensitization (vs placebo+OIT and pre-OMA) (all P ≤ 0.01), and improved QoL (vs pre-OMA) and IgG4 levels (both P < 0.01). No major safety concerns were identified.

In IgE-mediated food allergy, OMA can help patients for consumption of multiple foods and allow for food dose escalation. As an adjunct to OIT, OMA can also support high-dose desensitization and higher maintenance doses. Further studies are warranted to empirically evaluate the effect of OMA and confirm these findings.

Innate immune cells experience long lasting metabolic and epigenetic changes after an encounter with specific stimuli. This facilitates enhanced immune responses upon secondary exposition to both the same and unrelated pathogens, a process termed trained immunity. Trained immunity-based vaccines (TIbV) are vaccines able to induce innate immune memory, thus conferring heterologous protection against a broad range of pathogens. While trained immunity has been well documented in the context of infections and multiple immune-mediated diseases, the role of innate immune memory and its contribution to the initiation and maintenance of chronic allergic diseases remains poorly understood. Over the last years, different studies attempting to uncover the role of trained immunity in allergy have emerged. Exposition to environmental factors impacting allergy development such as allergens or viruses induces the reprogramming of innate immune cells to acquire a more pro-inflammatory phenotype in the context of asthma or food allergy. Several studies have convincingly demonstrated that prevention of viral infections using TIbV contributes to reduce wheezing attacks in children, which represent a high-risk factor for asthma development later in life. Innate immune cells trained with specific stimuli might also acquire anti-inflammatory features and promote tolerance, which may have important implications for chronic inflammatory diseases such as allergies. Recent findings showed that allergoid-mannan conjugates, which are next generation vaccines for allergen-specific immunotherapy (AIT), are able to reprogram monocytes into tolerogenic dendritic cells by mechanisms depending on metabolic and epigenetic rewiring. A better understanding of the underlying mechanisms of trained immunity in allergy will pave the way for the design of novel trained immunity-based allergen vaccines as potential alternative strategies for the prevention and treatment of allergic diseases.

Health-related quality of life (HRQoL) is significantly and substantially reduced in individuals with peanut allergy due to many factors associated with unanticipated or potentially fatal reactions. Further insight on the impact of peanut oral immunotherapy in managing peanut allergy on HRQoL is needed. The aim of this analysis was to assess effects of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH), a biologic drug for peanut oral immunotherapy, on HRQoL from three phase 3 and two follow-on trials of PTAH.

HRQoL assessments from participants aged 4-17 in the PALISADE (ARC003), ARC004 (PALISADE follow-on), ARTEMIS (ARC010), RAMSES (ARC007), and ARC011 (RAMSES follow-on) trials were included in this analysis. Responses on the Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) were evaluated by age group and respondent (self or caregiver proxy). Data were analyzed with descriptive statistics and Student t tests.

Baseline FAQLQ and FAIM total scores appeared comparable between PTAH- and placebo-treated participants. Self and caregiver proxy-reported total scores on the FAQLQ for PTAH-treated participants generally improved at trial exit versus baseline; FAIM total scores improved throughout all trials. The tendency for improvement in FAQLQ total scores from baseline for PTAH appeared larger in self versus caregiver proxy-reports. Between treatment groups, PTAH was generally favored in the PALISADE and ARTEMIS trials; differences varied in the RAMSES trial based on age and respondent types.

PTAH for the management of peanut allergy in children appeared to have a beneficial effect on HRQoL in trials. Improvements were seen despite rigors of trial participation.

Over the last years, we have learned that the metabolic phenotype of immune cells is closely connected to the cell's effector function. Understanding these changes will allow us to better understand allergic disease pathology and improve allergy treatment by modulating immune metabolic pathways. As part two of a two-article series, this review reports on the recent studies investigating the metabolism of the cell types involved in allergies and discusses the initial application of these discoveries in allergy treatment.

The cell types involved in allergic reactions display pronounced and highly specific metabolic changes (here discussed for epithelial cells, APCs, ILC2s, mast cells, eosinophils, and Th2 cells). Currently, the first drugs targeting metabolic pathways are tested for their potential to improve allergy treatment. Immune-metabolic changes observed in allergy so far are complex and depend on the investigated disease and cell type. However, our increased understanding of the underlying principles has pointed to several promising target molecules that are now being investigated to improve allergy treatment.

Dietary advancement therapies (DAT) constitute a continuum spanning extensively heated item ingestion, progressive milk/egg ladders, and oral immunotherapy (OIT). These represent an evolution in food allergy management from strict avoidance to an active therapy that may modulate the immune system to develop tolerance to particular forms of the allergen. Many egg or milk individuals are tolerant to baked egg/milk at baseline, and regular consumption (at home ingestion) of baked milk or egg is a safe process with potential quality of life and immunologic benefit. Milk and egg ladders, developed for non-IgE mediated allergy, are being increasingly adapted to IgE-mediated allergy as a potentially safe at-home option for gradual dietary advancement. However, data are limited regarding how safe and effective these approaches are, or what patient is best suited for which DAT. It is also unclear if extensively heated allergen consumption and ladders are susceptible to the same patient-specific factors which affect day-to-day tolerance and safety in OIT. Several recent events involving near-fatal or fatal reactions to milk or egg products (all amongst patients with asthma) have highlighted that DATs are not risk-free, and that physician guidance in these therapies is essential. Such guidance may include obtaining informed consent prior to starting any DAT, and instituting the same safe dosing rules for OIT across any form of DAT. This rostrum discusses practical concerns about the safety of DAT, and considerations how clinicians can maximize patient protection while defining the safety and efficacy of real-world implementation of these concepts.

Peanut allergy can result in severe, sometimes fatal hypersensitivity reactions that place a considerable burden on the lives of patients. This article reviews the first approved immunotherapy for the mitigation of allergic reactions following accidental peanut exposure, peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Palforzia®, Aimmune Therapeutics).

This article highlights the unmet need for patients with peanut allergy, describes the therapeutic landscape, and reviews the development of and clinical data for PTAH.

PTAH offers a standardized preparation of peanut allergen, with a tolerability and efficacy profile clearly defined through its robust clinical development and trial program. In children 4-17 years old, PTAH provides a standardized, approved product that many clinicians sought prior to initiating oral immunotherapy. PTAH reduced the likelihood of more severe reactions following exposure to peanut protein; although peanut avoidance remains essential, PTAH will enable more individuals with peanut allergy to participate in activities of daily life with less anxiety.

The impact on health-related quality of life (HRQL) plays a key role for patients suffering from allergies and anaphylaxis. In this narrative review we review the HRQL in allergic patients suffering from food and venom allergy, both being the most frequent elicitors of severe allergic, potential life threatening reactions and provide an overview on the current knowledge and identified gaps. The data show that for food and venom allergy standardized assessment tools to measure HRQL are available and have been successfully applied. Our analysis shows that multiple factors can modulate HRQL in these patient groups. These include sociodemographic data like patients' age and sex, fear of accidental reactions but also external factors like the social environment and the appreciation of the seriousness of the condition by others. External factors may have a significant impact on HRQL and should be considered in patient-related outcome assessments to avoid biased measurements possibly affecting the results. The assessment of the quality of life in the context of specific immunotherapy should consider lifestyle factors and ideally, the individual change in HRQL should be measured. Although there are many data indicating a negative impact on HRQL in food allergic children and their caregivers, limited data are existing from adults with food allergy and venom allergic patients from all age groups. Also, the use of standardized questionnaires should be extended to allow for a better comparability of results between studies. Therefore, translation to additional languages is necessary. Taken together, the eliciting allergen, the severity of the allergic disease but moreover multiple external factors impact the outcome in HRQL and should be considered in HRQL assessment.

Real-life studies are encouraged to evaluate the effectiveness and safety of allergen immunotherapy (AIT). In this context, a retrospective cohort study was conducted to assess the effectiveness and safety of carbamylated monomeric allergoid subcutaneous immunotherapy (MA SCIT), along with patient satisfaction.

A total of 291 patients with rhinoconjunctivitis with or without asthma with inhalant (house dust mite, grass, and pellitory) allergies were enrolled in this study. Perceived efficacy and perceived satisfaction with MA-SCIT, symptom score by VAS, ARIA classification of rhinitis, drug consumption, number of asthma worsening episodes, and asthma symptom control were evaluated by questionnaires before, after one year, at the end of treatment, and after one or two years of MA-SCIT.

The overall symptom score significantly decreased over the years of MA-SCIT, irrespective of specific sensitization (p < 0.01). There was a substantial amelioration of rhinitis severity, with a significant reduction (p < 0.01) in drug use. A significant reduction was observed in the asthma symptom VAS score and asthma-worsening episodes requiring systemic steroids. None of the patients reported any severe adverse reactions. Finally, 90% of the patients reported full satisfaction with the treatment.

The study showed that AIT with carbamylated monomeric allergoids of grass, pellitory, and mites was effective and well tolerated by patients.

Cluster schedules for subcutaneous allergen immunotherapy require significantly fewer injections, but there have been conflicting reports regarding the risk of systemic reaction.

To compare the incidence of systemic reactions during the build-up stages of multi-allergen standard versus cluster immunotherapy.

Data on systemic reactions were collected prospectively from 91 adult, urban patients who underwent either standard or cluster allergen immunotherapy at the Johns Hopkins Allergy and Asthma Center between 2014-2022. Systemic reactions were recorded during build-up phase and compared for both protocols using Pearson's chi-square, Fisher exact test, and multivariate logistic regression models.

Overall, systemic reaction rates were 21% for patients in the standard schedule and 37% for patients in the cluster immunotherapy schedule which was not statistically different (P = 0.084). However, the systemic reaction rate for each individual injection was 0.69% per injection in the standard protocol and 2.29% per injection in the cluster schedule (IRR = 3.3). 100% of all systemic reactions in both groups occurred in the second half of the build-up phase. Multivariate regression showed that the target prescription PNU and the number of allergens in the treatment vial did not influence systemic reaction rates (OR = 1.00 and 1.06 respectively).

The overall incidence of systemic reaction was not statistically different for cluster and standard allergen immunotherapy protocols. However, since cluster patients received about half the number of injections, the risk for systemic reaction per individual injection is more than 3 fold higher than that of standard immunotherapy.

Home reactions requiring epinephrine administration, a marker of their severity, restrict the widespread use of oral immunotherapy (OIT) but their risk-factors are largely unknown.

To identify risk factors for such reactions during OIT to most allergenic foods.

All patients who began OIT for peanut, tree nuts, sesame or egg allergy at the Shamir Medical Center between April 2010 and January 2020 were enrolled. Patients were instructed to use their epinephrine auto injectors during reactions consisting of severe abdominal pain, significant shortness of breath, or lethargy, or whenever in uncertainty of reaction severity. Patients with and without home epinephrine-treated reactions (HETRs) were compared.

A total of 757 OIT treatments to peanut (n=346), tree nuts (n=221; walnut n=147, cashew n=57, hazelnut n=16, almond n=1), sesame (n=115) and egg (n=75) were administered to 644 patients. Eighty-three (10.9%) patients experienced HETRs. The highest rate of HETRs was experienced during walnut (20.4%) or hazelnut (25%) OIT, followed by peanut (9.8%), sesame (6.1%), egg (6.7%) and cashew (5.3%) OIT. Risks factors for HETRs included a reaction treated in an ER (p=0.0048) before starting OIT, and a reaction treated with epinephrine during in-clinic induction (p<0.0001). Significantly less patients (73.6%) with, compared to those without (88.3%) HETRs achieved full desensitization (p=0.001), but only a few patients with HETRs (8.4%) failed treatment.

Previous reaction severity is the main predictor for HETRs during OIT. These reactions are more frequent during walnut and hazelnut OIT compared to other foods studied. Most patients experiencing HETRs achieved desensitization.