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A peanut-derived protein product, AR101, used in an oral desensitization protocol in children and adolescents with severe peanut allergy increased the amount of oral peanut protein tolerated in approximately two thirds of participants who received AR101, as compared with 1 of 25 controls.

Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. 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. 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. 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.).

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. 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. 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. 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.).

In this issue of the Journal , Greenhawt and colleagues report the findings of the EPITOPE (Epicutaneous Immunotherapy in Toddlers with Peanut Allergy) trial, a phase 3, multinational, double-blind, randomized, placebo-controlled trial of Viaskin Peanut 250 μg, a patch that delivers peanut protein to the skin to desensitize young children with peanut allergy. 1 The trial, which involved toddlers 1 to 3 years of age, met its clinical end points, and the product, if approved, could eventually be used in this population. The primary finding is that after receiving treatment with the peanut patch for a year, 67.0% of the toddlers in . . .

Current laboratory tests are less than 50% accurate in distinguishing between people who have food allergies (FA) and those who are merely sensitized to foods, resulting in the use of expensive and potentially dangerous Oral Food Challenges. This study presents a purely-computational machine learning approach, conducted using DNA Methylation (DNAm) data, to accurately diagnose food allergies and potentially find epigenetic targets for the disease. An unbiased feature-selection pipeline was created that narrowed down 405,000+ potential CpG biomarkers to 18. Machine-learning models that utilized subsets of this 18-feature aggregate achieved perfect classification accuracy on completely hidden test cohorts (on an 8-fold hidden dataset). Ensemble classification was also shown to be effective for this High Dimension Low Sample Size (HDLSS) DNA methylation dataset. The efficacy of these machine learning classifiers and the 18 CpGs was further validated by their high accuracy on a large number of hidden data permutations, where the samples in the training, cross-validation, and hidden sets were repeatedly randomly allocated. The 18-CpG signature mapped to 13 genes, on which biological insights were collected. Notably, many of the FA-discriminating genes found in this study were strongly associated with the immune system, and seven of the 13 genes were previously associated with FA. Previous studies have also created highly-accurate classifiers for this dataset, using both data-driven and a priori biological insights to construct a 96-CpG signature. This research builds on previous work because it uses a completely computational approach to obtain a perfect classification accuracy while using only 18 highly discriminating CpGs (0.005% of the total available features). In machine learning, simpler models, as used in this study, are generally preferred over more complex ones (other things being equal). Lastly, the completely data-driven methodology presented in this research eliminates the need for a priori biological information and allows for generalizability to other DNAm classification problems.

ObjectiveTo assess the impact of anaphylaxis on health-related quality of life (HRQL) and self-efficacy in food-allergic patients undergoing in-hospital food challenge.DesignSecondary analysis of a randomised controlled trial.SettingSpecialist allergy centre.PatientsPeanut-allergic young people aged 8–16 years.InterventionsDouble-blind, placebo-controlled food challenge to peanut, with HRQL and self-efficacy assessed using validated questionnaire, approximately 2 weeks prior to and 2 weeks after challenge. Where possible, anaphylaxis was treated with self-injected adrenaline (epinephrine).Main outcome measuresChange in HRQL and self-efficacy.Results56 participants had reactions at food challenge, of whom 16 (29%) had anaphylaxis. Overall, there was an improvement in HRQL (mean 2.6 points (95% CI 0.3 to 4.8); p=0.030) and self-efficacy (mean 4.1 points (95% CI 2.4 to 5.9); p<0.0001), independent of whether anaphylaxis occurred. Parents also reported improved HRQL (mean 10.3 points (95% CI 5.9 to 14.7); p<0.0001). We found evidence of discordance between the improvement in HRQL and self-efficacy as reported by young people and that perceived by parents in their child.ConclusionsAnaphylaxis at food challenge, followed by self-administration of injected adrenaline, was associated with an increase in HRQL and self-efficacy in young people with peanut allergy. We found no evidence that the occurrence of anaphylaxis had a detrimental effect. Young people should be encouraged to self-administer adrenaline using their autoinjector device to treat anaphylaxis at in-hospital challenge.Trial registration number NCT02149719

Background Peanuts (PN) and tree nuts (TN) are among the most frequent elicitors of food allergy and can lead to life-threatening reactions. The current advice for allergic patients is to strictly avoid the offending food independently of their individual threshold level, whereas sensitized patients without allergic symptoms should frequently consume the food to avoid (re-)development of food allergy. The aim of this trial is to investigate (I) whether the consumption of low allergen amounts below the individual threshold may support natural tolerance development and (II) to what extent regular allergen consumption in sensitized but tolerant subjects prevents the (re-)development of PN or TN allergy. Methods The TINA trial consisting of (part I) a randomized, controlled, open, parallel group, single-center, superiority trial (RCT), and (part II) a prospective observational exploratory cohort study. Children and adults (age 1–67 years) with suspected or known primary PN and/or TN allergy will undergo an oral food challenge (OFC) to determine their clinical reactivity and individual threshold. In the RCT, 120 PN or TN allergic patients who tolerate ≥100 mg of food protein will be randomized (1:1 ratio) to consumption of products with low amounts of PN or TN on a regular basis or strict avoidance for 1 year. The consumption group will start with 1/100 of their individual threshold, increasing the protein amount to 1/50 and 1/10 after 4 and 8 months, respectively. The primary endpoint is the clinical tolerance to PN or TN after 1 year assessed by OFC. In the cohort study, 120 subjects sensitized to PN and/or TN but tolerant are advised to regularly consume the food and observed for 1 year. The primary endpoint is the maintenance of clinical tolerance to PN and/or TN after 1 year assessed by challenging with the former tolerated cumulative dose. Discussion This clinical trial will help to determine the impact of allergen consumption versus avoidance on natural tolerance development and whether the current dietary advice for PN or TN allergic patients with higher threshold levels is still valid. Trial registration German Clinical Trials Register; ID: DRKS00016764 (RCT), DRKS00020467 (cohort study). Registered on 15 January 2020, http://www.drks.de .

Controlled studies on the effect of exercise on intestinal uptake of protein are scarce and underlying mechanisms largely unclear. We studied the uptake of the major allergen Ara h 6 following peanut consumption in an exercise model and compared this with changes in markers of intestinal permeability and integrity. Ten overnight-fasted healthy non-allergic men (n = 4) and women (n = 6) (23 ± 4 years) ingested 100 g of peanuts together with a lactulose/rhamnose (L/R) solution, followed by rest or by 60 min cycling at 70% of their maximal workload. Significantly higher, though variable, levels of Ara h 6 in serum were found during exercise compared to rest (Peak p = 0.03; area under the curve p = 0.006), with individual fold changes ranging from no increase to an increase of over 150-fold in the uptake of Ara h 6. Similarly, uptake of lactulose (2–18 fold change, p = 0.0009) and L/R ratios (0.4–7.9 fold change, p = 0.04) were significantly increased which indicates an increase in intestinal permeability. Intestinal permeability and uptake of Ara h 6 were strongly correlated (r = 0.77, p < 0.0001 for lactulose and Ara h 6). Endurance exercise after consumption may lead to increased paracellular intestinal uptake of food proteins.

BACKGROUND: In South East Asia, concerns exist about the acceptability of peanut-based Ready-to-Use-Therapeutic-Foods (RUTF) for the treatment of severe acute malnutrition (SAM). Therefore, an alternative, culturally acceptable RUTF made from locally available ingredients and complying with local food traditions and preferences was developed. The current study evaluated its acceptability and impact on anthropometry. METHODS: The study was a randomized, two-arm, cross-over intervention trial to test the acceptability of the local product (bar) against a commercially available, peanut-based RUTF paste (Plumpy’nut®). Children (n = 67) from two kindergartens in a rural area of North Vietnam were recruited. The age of the children was between 3 and 5 years. RESULTS: The Vietnamese RUTF was well-accepted, although overall acceptability was less than of Plumpy’nut®, with the latter scoring higher on palatability (P < 0.05). In contrast, reluctance to eat Plumpy’nut® was higher than for the Vietnamese RUTF (P < 0.05). Impact on anthropmetrical indices was similar for both RUTF. The nutritional status of the children who consumed the two RUTF over a 4 week period improved significantly, with a mean weight gain of 0.64 (SD 0.27) Kg, and increases in WHZ and HAZ z-scores of 0.48 (SD 0.30) and 0.05 (SD 0.13) respectively (P < 0.01 both). Weight gain was similar between the 2 products (0.32 kg per 2 weeks for both). CONCLUSIONS: Both the commercial Plumpy’nut® and the local produced RUTF were accepted although the harder consistency of the local product might have caused the lower overall acceptance. The promising increase in nutritional status needs to be confirmed in a controlled trial in children with SAM.

Background Peanut allergy is an increasingly common health problem. Current treatment guidelines are based on strict avoidance. However, in the last few years, oral immunotherapy protocols have shown promising results yielding increased tolerance to peanut in allergic children. Adolescence is particularly at risk. Methods/Design We have designed a randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of peanut oral escalating immunotherapy in a 12- to 18–year-old population with proved allergy to peanut. Patients are selected when the threshold of peanut intake is over 100 mg and 2 cumulated g on the first double-blind, placebo-controlled oral food challenge (DBPCOFC). During the build-up placebo-controlled blinded phase, doses containing peanut or placebo will be administered by gradual up-dosing from 10 mg to 2 g with 2-weekly increments. After this first randomized phase, the desensitized participants will continue to intake native peanut in an unblinded process during 13 or 37 weeks following a second randomization. Adverse events are picked up and managed throughout the entire protocol. The main endpoint is the percentage of patients with negative DBPCOFC at the threshold of 2 g of cumulative peanut at the end of the build-up phase of 24 weeks. Secondary endpoints include: (1) desensitization 6 weeks and 6 months after the end of the maintenance phase; (2) adverse effects during the build-up phase; (3) immunological profile confirming peanut desensitization. Immunologic assays will be carried out at every DBPCOFC and at the middle of the build-up phase to evaluate the peanut immunologic profile modifications. Discussion This double-blind, placebo-controlled study will be, to our knowledge, the first evaluation of a peanut oral immunotherapy protocol in teenagers in the purpose to reduce severe reactions after unexpected intake and to improve quality of life. Trial registration ClinicalTrial.gov: NCT02046083 (23 January 2014).