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.).

Evaluation of clinical outcomes of efficacy in food allergen immunotherapy trials, COFAITH EAACI task force.

Food allergy is a global public health problem that until recent years lacked any aetiological treatment supported by academy, industry and regulators. Food immunotherapy (AIT) is an evolving treatment option, supported by clinical practice and industry trial data. Recent AIT meta-analyses have highlighted the difficulty in pooling safety and efficacy data from AIT trials, due to secondary heterogeneity in the study. An EAACI task force (CO-FAITH) initiated by the Paediatric Section was created to focus on AIT efficacy outcomes for milk, egg and peanut allergy rather than in trial results. A systematic search and a narrative review of AIT controlled clinical trials and large case series was conducted. A total of 63 manuscripts met inclusion criteria, corresponding to 23, 21 and 22 studies of milk, egg and peanut AIT, respectively. The most common AIT efficacy outcome was desensitization, mostly defined as tolerating a maintenance phase dose, or reaching a particular dose upon successful exit oral food challenge (OFC). However, a large degree of heterogeneity was identified regarding the dose quantity defining this outcome. Sustained unresponsiveness and patient-reported outcomes (e.g. quality of life) were explored less frequently, and to date have been most rigorously described for peanut AIT versus other allergens. Change in allergen threshold assessed by OFC remains the most common efficacy measure, but OFC methods suffer from heterogeneity and methodological disparity. This review has identified multiple heterogeneous outcomes related to measuring the efficacy of AIT. Efforts to better standardize and harmonize which outcomes, and how to measure them must be carried out to help in the clinical development of safe and efficacious food allergy treatments.

Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy.

BACKGROUND: Food allergy is a leading cause of anaphylaxis worldwide. Allergen-specific immunotherapy is the only treatment shown to modify the natural history of allergic disease, but application to food allergy has been hindered by risk of severe allergic reactions and short-lived efficacy. Allergen-derived peptides could provide a solution. PVX108 comprises seven short peptides representing immunodominant T-cell epitopes of major peanut allergens for treatment of peanut allergy. METHODS: Pre-clinical safety of PVX108 was assessed using ex vivo basophil activation tests (n = 185). Clinical safety and tolerability of single and repeat PVX108 doses were evaluated in a first-in-human, randomized, double-blind, placebo-controlled trial in peanut-allergic adults (46 active, 21 placebo). The repeat-dose cohort received six doses over 16 weeks with safety monitored to 21 weeks. Exploratory immunological analyses were performed at pre-dose, Week 21 and Month 18 after treatment. RESULTS: PVX108 induced negligible activation of peanut-sensitised basophils. PVX108 was safe and well tolerated in peanut-allergic adults. There were no treatment-related hypersensitivity events or AEs of clinical concern. The only events occurring more frequently in active than placebo were mild injection site reactions. Exploratory immunological analyses revealed a decrease in the ratio of ST2+ Th2A:CCR6+ Th17-like cells within the peanut-reactive Th pool which strengthened following treatment. CONCLUSION: This study supports the concept that PVX108 could provide a safe alternative to whole peanut immunotherapies and provides evidence of durable peanut-specific T-cell modulation. Translation of these findings to clinical efficacy in ongoing Phase 2 trials would provide important proof-of-concept for using peptides to treat food allergy.

[Inflammatory Polyp due to Peanut Aspiration, Needed to Differentiate from Malignant Tumor: Report of a Case].

The patient was in his 70s. He was addmitted to our hospital because of obstructive pneumonia for 3 months. Chest computed tomography( CT) showed a nodule at the base of the right B8, obstructing the basal branch, with consolidation of the peripheral lung. Bronchoscopy revealed the right basal trunk obstruction by a tumorous lesion. FDG-PET showed heterogeneous FDG uptake at the right hilum and the lower lobe suggesting malignancy, and a thoracoscopic right lower lobectomy was performed. Pathology showed a granulation-like nodule and a brown oval foreign body incarcerated in the peripheral bronchus, which was later revealed to be a peanut, and no obvious malignant findings were observed.

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.).

Environmental Exposure to Foods as a Risk Factor for Food Allergy.

PURPOSE OF REVIEW: Many factors have been reported to contribute to the development of food allergy. Here, we summarize the role of environmental exposure to foods as a major risk factor for developing food allergy. RECENT FINDINGS: Peanut proteins are detectable and biologically active in household environments, where infants spend a majority of their time, providing an environmental source of allergen exposure. Recent evidence from clinical studies and mouse models suggests both the airway and skin are routes of exposure that lead to peanut sensitization. Environmental exposure to peanut has been clearly associated with the development of peanut allergy, although other factors such as genetic predisposition, microbial exposures, and timing of oral feeding of allergens also likely contribute. Future studies should more comprehensively assess the contributions of each of these factors for a variety of food allergens to provide more clear targets for prevention of food allergy.

Relationship between serum allergen-specific immunoglobulin E and threshold dose in an oral food challenge.

BACKGROUND: Several studies have reported threshold doses for food allergens. However, evidence regarding potential risk factors for low threshold doses is limited. Moreover, the relationship between threshold dose and specific immunoglobulin E (sIgE) levels to causative foods remains unclear. This study examined the relationship and the risk factors for a low threshold dose. METHODS: We recruited children with food allergies and examined the risk factors for a positive oral food challenge (OFC) with a low threshold dose and anaphylaxis. RESULTS: We evaluated 2501 children with food allergies (1667 [67%] boys; median age, 4.9 years) to eggs (n = 1096), milk (n = 671), wheat (n = 370), peanuts (n = 258), walnuts (n = 65), and cashews (n = 41). Of these patients, 234 (9%) reacted to ≤30 mg protein of causative foods and 620 (25%) reacted to ≤100 mg protein of causative foods. The sIgE level to causative foods was a significant independent factor for positive OFCs with a threshold dose of ≤30 mg for milk, wheat, and peanuts; ≤ 100 mg for eggs, milk, wheat, peanuts, and cashews; and anaphylaxis from eggs, milk, wheat, peanuts, and walnuts. High sIgE levels to causative foods were associated with a lower threshold dose of the OFC and anaphylaxis during the OFC. CONCLUSIONS: Approximately 9% of patients reacted to ≤30 mg protein of causative foods. The potential risks of anaphylaxis should be considered during OFCs for patients with elevated sIgE levels.

An unexpected allergic skin reaction to peppermint oil capsules.

Peppermint oil capsules are prescribed to manage abdominal colic and distension, a common complaint in postcaesarean section patients. Arachis (peanut) oil is contained within one frequently prescribed peppermint formulation: Colpermin. This ingredient is contraindicated in patients with peanut and soya allergy; however, this is not stated in the side effects or contraindications section of the British National Formulary, or present on the medication packaging. A postpartum woman in her early 30s had an unexpected allergic reaction to the capsules, in the form of a generalised body rash, fortunately with no anaphylactic features. The patient reported the same reaction to soya in the past. After review of the patient's clinical and medication history, Colpermin capsules were thought to be responsible for the patient's symptoms. This case highlights the necessity for clearer documentation in prescribing formularies and on medication packaging to ensure patient safety.

Oral immunotherapy using boiled peanuts for treating peanut allergy: An open-label, single-arm trial.

BACKGROUND: Peanut allergy affects 1%-3% of children in Western countries. Boiling peanuts has been demonstrated to result in a hypoallergenic product that may provide a safer way of inducing desensitization in peanut-allergic patients by first inducing tolerance to boiled peanut. We aimed to assess the efficacy and safety of oral immunotherapy (OIT) using sequential doses of boiled peanuts followed by roasted peanuts for treating peanut allergy in children. METHODS: In this open-label, phase 2, single-arm clinical trial, children aged 6-18 years with a positive history of peanut allergy and positive peanut skin prick test ≥ 8 mm and/or peanut-specific IgE ≥ 15 kU/L at screening underwent OIT involving sequential up-dosing with 12-hour boiled peanut for 12 weeks, 2-hour boiled peanut for 20 weeks and roasted peanut for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily. PRIMARY OUTCOME: proportion of children passing open-label oral food challenge involving cumulative administration of 12 roasted peanuts (12 g peanuts; approximately 3000 mg peanut protein) 6-8 weeks after reaching the target maintenance dose. Secondary outcomes included treatment-related adverse events and use of medications for treating allergy symptoms. RESULTS: Between 1 July 2017 and 22 June 2018, 70 participants were enrolled and commenced OIT. Desensitization was successfully induced in 56 of 70 (80%) participants. Withdrawal due to treatment-related adverse events was infrequent (n = 3). Treatment-related adverse events were reported in 43 (61%) participants, corresponding to a rate of 6.58 per 1000 OIT doses. Medication use associated with treatment-related adverse events was infrequent, with rescue epinephrine use reported by three (4%) participants (0.05 per 1000 doses). CONCLUSION: Oral immunotherapy using boiled followed by roasted peanuts represents a pragmatic approach that appears effective in inducing desensitization and is associated with a favourable safety profile.

Management of Anaphylaxis During Peanut Oral Immunotherapy.

BACKGROUND: Peanut oral immunotherapy (POIT) has emerged as an active management option for peanut allergy, with an FDA-approved product now available for therapy. Allergic reactions, including anaphylaxis, can occur during therapy and their management is key in optimizing this treatment and patient outcomes. PURPOSE OF REVIEW: In this manuscript, we will review the rates of allergic reactions and anaphylaxis in seminal peanut oral immunotherapy research studies. We will examine factors that can alter the risk of anaphylaxis and describe various strategies, including adjunct therapies, that have the potential to mitigate anaphylaxis risk based on published evidence. RECENT FINDINGS: Rates of anaphylaxis and epinephrine administration vary in different research studies, but there is consensus that most POIT-related allergic reactions are mild or moderate and not severe. Certain external factors (for example, tiredness, exercise, viral illness) as well as uncontrolled allergic co-morbidities (asthma, allergic rhinitis) have been shown to increase the risk of anaphylaxis during OIT. The search of biomarkers who may predict who is at risk for severe allergic reactions is ongoing. Adjunct therapies have shown promise, but further studies are required to optimize their use alongside POIT. Our understanding of anaphylaxis during POIT has increased in recent years, resulting in better management strategies. However, future plans will need to involve all stakeholders, including physicians, patients and families, researchers, public health authorities, and the food, hospitality, and catering industries.

High-dimensional immune profiles correlate with phenotypes of peanut allergy during food-allergic reactions.

BACKGROUND: Food challenges carry a burden of safety, effort and resources. Clinical reactivity and presentation, such as thresholds and symptoms, are considered challenging to predict ex vivo. AIMS: To identify changes of peripheral immune signatures during oral food challenges (OFC) that correlate with the clinical outcome in patients with peanut allergy (PA). METHODS: Children with a positive (OFC+ , n = 16) or a negative (OFC- , n = 10) OFC-outcome were included (controls, n = 7). Single-cell mass cytometry/unsupervised analysis allowed unbiased immunophenotyping during OFC. RESULTS: Peripheral immune profiles correlated with OFC outcome. OFC+ -profiles revealed mainly decreased Th2 cells, memory Treg and activated NK cells, which had an increased homing marker expression signifying immune cell migration into effector tissues along with symptom onset. OFC- -profiles had also signs of ongoing inflammation, but with a signature of a controlled response, lacking homing marker expression and featuring a concomitant increase of Th2-shifted CD4+ T cells and Treg cells. Low versus high threshold reactivity-groups had differential frequencies of intermediate monocytes and myeloid dendritic cells at baseline. Low threshold was associated with increased CD8+ T cells and reduced memory cells (central memory [CM] CD4+ [Th2] T cells, CM CD8+ T cells, Treg). Immune signatures also discriminated patients with preferential skin versus gastrointestinal symptoms, whereby skin signs correlated with increased expression of CCR4, a molecule enabling skin trafficking, on various immune cell types. CONCLUSION: We showed that peripheral immune signatures reflected dynamics of clinical outcome during OFC with peanut. Those immune alterations hold promise as a basis for predictive OFC biomarker discovery to monitor disease outcome and therapy of PA.

Global systematic review and meta-analysis on prevalence and concentration of aflatoxins in peanuts oil and probabilistic risk assessment.

Exposure to mycotoxins in food is largely unavoidable, and concerns about their health effects are growing. Consumption of vegetable oils such as peanuts oil has increased, hence several studies have been conducted on concentration of aflatoxins (AFs) in peanuts oil. Search was performed in Scopus and PubMed databases on prevalence and concentration of AFs in peanuts oil from 1 January 2005 to 15 April 29, 2022. Prevalence and concentration of AFs in peanuts oil was meta-analyzed based on country and type of AFs subgroups. In addition, health risk was calculated using monte carlo simulation method. Pooled prevalence of AFB1 in peanuts oil was 47.9%; AFB2, 46.45%; AFG1, 46.92% and AFG2, 54.01%. The Overall prevalence of AFTs was 49.30%, 95%CI (35.80-62.84%). Pooled concentration of AFB1 in peanuts oil was 2.30 µg/kg; AFB2, 0.77 µg/kg; AFG1, 0.07 µg/kg; AFG1, 0.28 µg/kg. The sort of country based on mean of MOEs in the adults consumers was Japan (47,059) > China (17,670) > Ethiopia (7,398) > Sudan (6,974) > USA (1,012) and sort of country based on mean of MOEs in the children was Japan (120,994) > China (46,991) > Ethiopia (19,251) > Sudan (18,200) > USA (2,620). Therefore, adults consumers were in considerable health risk in Ethiopia, Sudan and USA and for children in USA (MOE < 10,000).