Peanut-allergic Children Research Articles

Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy.

Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell-based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study, we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre-validated peanut allergy cohort. Hoxb8 MCs were passively sensitized with sera from peanut-allergic and peanut tolerant children and adolescents (n = 112). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose-titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT nonresponders were assessed with the Hoxb8 MAT. Hoxb8 MAT displayed a robust dose-dependent activation to peanut extract, with a cutoff value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/mL, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. Moreover, sera from BAT nonresponders were accurately classified into allergics and nonallergics by the Hoxb8 MAT. The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh whole blood-based BAT. Additionally, it demonstrated its value for accurate classification of BAT nonresponders into allergic and nonallergic individuals. Further investigations into its utility in the routine clinical setting are warranted.

Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral Immunotherapy in Infants and Toddlers in a Real-World Setting

Oral immunotherapy (OIT) for food allergy has been largely studied in older children within the context of clinical trials, and its availability has historically been limited for younger patients with food allergy. Data has shown that the most impact may actually be seen with the use of OIT in younger infants and toddlers. To evaluate the safety and feasibility of OIT in subjects younger than 24 months in a real-world setting using commercially available food products. This was a retrospective study of subjects 24 months and younger initiated on OIT for peanut, tree nut, or sesame allergy within the Scripps Clinic allergy department. Medical records were reviewed for data regarding initial oral food challenges (OFCs), OIT, and adverse outcomes. Fifty-two subjects under 24 months of age were initiated on OIT. Most subjects (84.6%) were on single food OIT, some (15.4%) were on multi-food OIT. No increased adverse outcomes were observed on multi-food OIT. Of the 59 initial OFCs, objective reactions occurred during 42 challenges, the majority being low grade reactions. During initial OFCs, 86.1% of peanut allergic children tolerated 1/8 of one Bamba stick with no reaction. The majority (73.1%) of subjects up-dosed at home and most (51.9%) had no reactions while up-dosing. Some had low grade cutaneous reactions, none requiring epinephrine or emergency evaluation. OIT in infants is safe and feasible to perform in a real-world setting using commercially available food products with at home up-dosing, thus increasing the availability of OIT for patients.

Fecal IgE Analyses Reveal a Role for Stratifying Peanut-Allergic Patients.

Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild-to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in astrointestinal PA symptoms is poorly understood. This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping. Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens. Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes. Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.

Blood stored in EDTA tubes provides accurate peanut basophil activation test results for 48 hours

BackgroundThe peanut basophil activation test (BAT) has demonstrated excellent diagnostic accuracy with heparinized blood, but its clinical utility is limited by the short stability of samples stored in this anticoagulant. ObjectiveUsing EDTA anticoagulated blood, these investigations determined if Peanut BAT sample stability can be extended to 2 days, the minimum stability requirement for diagnostic tests currently offered through American reference laboratories. MethodsPeanut non-allergic control (NAC), peanut IgE sensitized (PS), and peanut allergic (PA) children aged 6 months through 17 years were recruited from members of Kaiser Permanente Southern California. EDTA anti-coagulated blood samples were collected from participants, shipped to a centralized laboratory, and stored at 4oC for peanut BAT testing 1 and 2 days later. ResultsPeanut BAT results for 23 unblinded participants were used to establish sample rejection and interpretation criteria that were subsequently validated in a prospective double-blind study involving 112 additional children (39-NAC, 36-PS, 37-PA). Of 105 blinded blood samples tested on each study day, 88 (84%) day-1 and 90 (86%) day-2 peanut BAT results were considered interpretable, with diagnostic accuracies of 95.5% and 94.4%, respectively. Moreover, all interpretable PA results were considered positive (100% sensitivity). ConclusionUsing EDTA anti-coagulated blood samples collected remotely, 1 and 2 days before testing, study results highlight the favorable diagnostic performance characteristics of the peanut BAT and provide further evidence that the test could be readily operationalized for clinical use by interested commercial reference laboratories.

BSACI guidance for the implementation of Palforzia® peanut oral immunotherapy in the United Kingdom: A Delphi consensus study

AbstractBackgroundPalforzia® enables the safe and effective desensitisation of children with peanut allergy. The treatment pathway requires multiple visits for dose escalation, up‐dosing, monitoring of patients taking maintenance therapy and conversion onto daily real‐world peanut consumption. The demand for peanut immunotherapy outstrips current National Health Service (NHS) capacity and requires services to develop a national consensus on how best to offer Palforzia® in a safe and equitable manner. We undertook a Delphi consensus exercise to determine guidance statements for the implementation of Palforzia®‐based immunotherapy in the NHS.MethodsWe undertook focus groups with children and young people who had received peanut immunotherapy to assess what was important for them and their carers. Common themes from patients formed the basis of creating draft statements. A panel of 18 multi‐disciplinary professionals engaged in two rounds of anonymised voting to adapt the statements and score their importance. A final consensus workshop consolidated any variation in comments and scores to develop the final guidance statements.ResultsThe panel achieved consensus on 91% (29/32) of guidance statements, demonstrating strong consensus around pragmatic principles for assuring the integrity of consent, safety and conversion from Palforzia® to real‐world peanut products. The greatest amount of feedback was generated from three broad issues; (i) whether eligibility assessment should include compulsory peanut challenges and whether these should be designed to assess the threshold at which patients react to peanut, (ii) the governance processes to best ensure that patients' interests are prioritised and (iii) how to safely transition young people to other services, or discharge them, while they are taking daily peanut.ConclusionsThis consensus highlights the urgent need for the NHS to increase capacity for undertaking diagnostic food challenges as well as developing Palforzia® immunotherapy pathways. The voting panel agreed that families of peanut allergic children should be made aware of immunotherapy, that eligibility assessment should include how co‐morbid conditions are managed and that services should monitor for adverse effects. The finalised statements are now published online for clinical practice in the UK. These guidance statements will be adapted in the coming years as more evidence is published and as the international experience of peanut immunotherapy evolves.

Peanut oral immunotherapy using an extensively heated and baked novel composition of peanuts.

Oral immunotherapy (OIT) is an increasingly acceptable therapeutic option for peanut-allergic (PA) children, despite significant side effects. Major peanut allergenic proteins are heat-resistant and are not rendered hypoallergenic after baking or cooking. Lyophilized peanut protein-MH (LPP-MH) is a novel composition from developing peanuts, enabling cooking-induced reduction in allergenicity. We aimed to explore the safety and efficacy of OIT, with extensively heated and baked (EHEB) LPP-MH in PA children. In a single-arm, single-center, pilot study, PA children with a single highest tolerated dose of <100 mg peanut protein were placed on a 40-week OIT protocol with 300 mg daily of heat-treated LPP-MH. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6-12 months of follow-up visit. Thirty-three children with PA were enrolled, with a mean cumulative tolerated dose (MCTD) of 71.2 mg PP (95% CI 45-100 mg). After 40 weeks, 32/33 patients were able to consume more than 300 mg of natural PP, with MCTD of 1709 mg (CI 365-3675 mg). There were no severe allergic reactions requiring epinephrine, during any of the observed LPP-MH challenges or any treatment related doses at home. After 6-12 months on daily maintenance, the MCTD was 8821 mg (95% CI 1930-13,500 mg). This enabled most children age-appropriate dietary inclusion of peanuts. An OIT protocol with heat-treated LPP-MH, a novel composition from developing peanuts, seems a potentially safe and efficacious OIT modality for PA children, enabling the introduction of dietary levels of peanut proteins in highly allergic PA children. Validation in randomized controlled studies is mandated.

Real-world safety experience with Peanut (Arachis hypogaea) Allergen Powder-dnfp in 2500 children with peanut allergy

Real-world safety experience with Peanut (Arachis hypogaea) Allergen Powder-dnfp in 2500 children with peanut allergy

High Degree of Desensitization After 1 Year of Early-Life Peanut Oral Immunotherapy: Small Children Oral Immunotherapy (SmaChO) Randomized Controlled Trial

BackgroundThe prevalence of peanut allergy is about 2% and mostly lifelong. Studies of oral immunotherapy (OIT) with peanut – daily oral intake of an initially low and then increasing dose of peanut - often show problematic side effects but there are indications of better safety and effect in younger children compared with older children and adults. ObjectiveTo determine the safety and effectiveness of peanut OIT with a slow up-dosing strategy and low maintenance dose, in peanut allergic children 1-3 years of age, a 1-year interim analysis. MethodsIn a randomized controlled trial (2:1 ratio) 75 children with median age 31 months (IQR 23 – 40) were assigned to receive peanut oral immunotherapy (OIT) (n=50) or peanut avoidance (n=25). ResultsIn the OIT group and the avoidance group, 43/50 and 20/25 children, respectively, performed the 1-year open oral peanut challenge. A cumulative dose of 750 mg peanut protein after one year was tolerated by 72% (36/50) in the OIT-group compared to 4% (1/25) in the avoidance-group, p<0.001. Median tolerated cumulative dose was 2750 mg (IQR 275 – 5000) peanut protein in the OIT-group compared to 2.8 mg (IQR 0.3 – 27.8) in the avoidance-group, p<0.001. Of the doses administered at home during the first year of OIT, 1.4% resulted in adverse events, 79% were mild, and three doses of epinephrine were given at home to two individuals. ConclusionIn children 1-3 years of age, peanut OIT with the combination of slow up-dosing and low maintenance dose seems safe and effective after one year. ClinicalTrials.govNCT04511494

Joint transcriptomic and cytometric study of children with peanut allergy reveals molecular and cellular cross talk in reaction thresholds

BackgroundReaction thresholds in peanut allergy are highly variable. Elucidating causal relationships between molecular and cellular processes associated with variable thresholds could point to therapeutic pathways for raising thresholds. ObjectiveTo characterize molecular and cellular systemic processes associated with reaction threshold in peanut allergy and causal relationships between them. Methods105 children ages 4 to 14 years with suspected peanut allergy underwent double-blind, placebo-controlled food challenges to peanut. The cumulative peanut protein quantity eliciting allergic symptoms was considered the reaction threshold for each child. Peripheral blood samples collected at 0, 2, and 4 hours after challenge start were used for RNA sequencing, whole blood staining, and cytometry. Statistical and network analyses were performed to identify associations and causal mediation between the molecular and cellular profiles and peanut reaction threshold. ResultsWithin the cohort (n=105), 81 (77%) experienced allergic reactions after ingesting varying quantities of peanut, ranging from 43 to 9043 mg cumulative peanut protein. Peripheral blood expression of transcripts (e.g., IGF1R, FDR=5.4e-5 and PADI4, FDR=5.4e-5) and neutrophil abundance (FDR=9.5e-4) were associated with peanut threshold. Co-expression network analyses revealed that the threshold-associated transcripts were enriched in modules for FcγR-mediated phagocytosis (FDR=3.2e-3) and TLR (FDR=1.4e-3) signaling. Bayesian network, key driver, and causal mediation analyses identified key drivers (AP5B1, KLHL21, VASP, TPD52L2 and IGF2R) within these modules involved in bi-directional causal mediation relationships with neutrophil abundance. ConclusionKey driver transcripts in FcγR-mediated phagocytosis and TLR signaling bi-directionally interact with neutrophils in peripheral blood and are associated with reaction threshold in peanut allergy.

Open-Label Study of the Efficacy, Safety, and Durability of Peanut Sublingual Immunotherapy in Peanut-Allergic Children.

Open-Label Study of the Efficacy, Safety, and Durability of Peanut Sublingual Immunotherapy in Peanut-Allergic Children.

Oral Immunotherapy for Peanut Allergy in Children 1 to Less Than 4 Years of Age

BackgroundPeanut allergy is a common childhood allergy, and the only approved treatment for children 4 to 17 years of age is peanut allergen powder-dnfp (PTAH) oral immunotherapy.MethodsFor this phase 3, randomized, double-blind, placebo-controlled trial, we enrolled peanut-allergic children 1 to <4 years of age who experienced dose-limiting symptoms from ≤300 mg peanut protein during a screening double-blind, placebo-controlled food challenge (DBPCFC). Participants received PTAH or placebo, randomized in a 2:1 ratio, for approximately 12 months. At the trial conclusion, all participants underwent an exit BDPCFC. The primary end point was desensitization (i.e., tolerating a ≥600-mg single dose of peanut protein with only mild allergy symptoms).ResultsIn the PTAH-treated group (n=98), 73.5% of participants tolerated a single dose of ≥600 mg peanut protein at exit DBPCFC compared with 6.3% in the placebo group (n=48). Most participants experienced an adverse event (98.0% of PTAH-treated and 97.9% of placebo-treated participants), which was mild or moderate in grade for 93.2% of participants (92.9% in PTAH-treated and 93.8% in placebo-treated participants). Treatment-related adverse events, which were mild to moderate, were experienced by 75.5% of PTAH-treated and 58.3% of placebo-treated participants. Three treatment-related systemic allergic reactions, none of which were severe or serious in grade, were noted in two PTAH-treated participants (2%).ConclusionsIn peanut-allergic children 1 to <4 years of age treated with PTAH for approximately 12 months, the majority tolerated all peanut protein dose levels assessed. PTAH-treated patients had more treatment-related adverse events, which were mild to moderate severity. (Funded by Aimmune Therapeutics; ClinicalTrials.gov number, NCT03736447.)

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

Prior studies of peanut sublingual immunotherapy (SLIT) have suggested a potential advantage with younger age at treatment initiation. We studied the safety and efficacy of SLIT for peanut allergy in 1- to 4-year-old children. 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 36monthsoftreatment. Participants desensitized to at least443mg peanut protein discontinued therapy for 3 months and then underwent DBPCFC to assess for remission. Biomarkers were measured at baseline and longitudinally during treatment. 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 in1- 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. Peanut SLIT safely induces desensitization and remission in 1- to 4-year-old children, with improved outcomes seen with younger age at initiation.

Association of Reaction Symptoms and Eliciting Dose With Health-Related Quality of Life in Children With Peanut Allergy.

Food allergy adversely affects the health-related quality of life (HRQoL) of patients. It is unclear whether factors such as the reaction eliciting dose (ED) and the nature of allergic reaction symptoms affect HRQoL. To explore associations between reaction ED or the nature of allergic symptoms and HRQoL among children with peanut allergy. This study was a secondary analysis of baseline data from the PPOIT-003 randomized trial in 212 children aged 1 to 10 years with challenge-confirmed peanut allergy. Children's past reaction symptoms were collected by clinicians during screening. Associations between variables of interest and parent-reported child-proxy HRQoL were examined by univariable and multivariable linear regression. Mean age of study participants was 5.9 years; 63.2% were male. Children with a low reaction ED of 80 mg peanut protein had significantly poorer HRQoL (β= -0.81; 95% CI, -1.61 to -0.00; P= .049) compared with children with a high ED of 2,500 mg peanut protein. Gastrointestinal symptoms (β= 0.45; 95% CI, 0.03-0.87; P= .037), lower airway symptoms (β= 0.46; 95% CI, 0.05-0.87; P= .030), multisystem involvement (β= 0.71; 95% CI, 0.25-1.16; P=.003), or anaphylaxis (β= 0.46; 95% CI, 0.04-0.87; P= .031) during a previous reaction were associated with worse HRQoL. Peanut-allergic children with a lower allergen reaction threshold experienced a greater negative HRQoL impact compared with children with higher reaction thresholds. In addition, specific past allergic reaction symptoms were associated with comparatively worse HRQoL. Children experiencing these symptoms and those with lower reaction ED require increased clinical support to manage the food allergy and are likely to benefit from interventions that can improve HRQoL.

No evidence of isotretinoin sensitization in peanut-allergic children: a cross-sectional study.

The European Medicines Agency (EMA) advises that all medicines containing soya-derived excipients should be labelled as contraindicated in peanut-allergic individuals. This is despite evidence of very little cross-reactivity between soya and peanut allergies. It is highly unlikely that patients with peanut allergy are at risk of a cross-reactive soya oil-based allergic reaction to soya protein in isotretinoin. This cross-sectional study has demonstrated the absence of IgE-sensitization to isotretinoin in peanut-allergic children and adolescents. Isotretinoin does not need to be avoided by peanut-allergic patients and we would encourage the EMA to alter their advice regarding soybean oil-containing medications to reflect this.

Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children.

Epicutaneous immunotherapy with investigational Viaskin™ Peanut 250 μg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear whether serologic biomarkers predict response. Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE-Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge. Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p< 0.001) and had highest area under the curve (AUC) for predicting ED ≥300 mg and ≥1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE >20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kUA /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg). Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.

Peanut thresholds in peanut-allergic children are related to dietary composition.

There is no clear explanation for the large variation in threshold levels among peanut-allergic children. We hypothesized that diet composition can partly explain this variation in thresholds, as nutrients and foods influence the intestinal barrier function and microbiota. to explore the relationship between the threshold levels for peanut and nutritional intake and gut microbial composition in peanut-allergic children. In this explorative cross-sectional study the cumulative threshold levels for peanut were determined by oral food challenge tests. Data on nutrients and foods consumed were obtained from 3-day food diaries. Microbial composition of faeces and saliva were determined by molecular microbiota detection technique. Multivariable linear regression analysis and multiple logistic regression were used to explore the associations, adjusted for energy and senitization. Sixty-five children were included, of whom 32 (49%) (median age 50 months, IQR 28.0-96.5) had a positive oral food challenge. Significant positive associations were found between the intake of total carbohydrates, vitamin A and cumulative threshold levels for peanut, while significant negative associations were found for long-chain polyunsaturated fatty acids, linoleic acid and omega-6 fatty acids. No associations were found between threshold levels and microbial composition of faeces and saliva. However, a significant higher abundance of Proteobacteria and Bacteroidetes in saliva (p = 0.011 and 0.04, respectively) and of Proteobacteria in faeces (p = 0.003) were found in children with a positive peanut challenge compared to children with a negative peanut challenge. As a novel concept, this study showed that dietary composition is related to threshold levels for peanut.

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

Studies on the efficacy of peanut sublingual immunotherapy (SLIT) are limited. The durability of desensitization after SLIT has not been well described. We sought to evaluate the efficacy and safety of 4-mg peanut SLIT and persistence of desensitization after SLIT discontinuation. 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). Anovel 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. 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. 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.

Efficacy and safety of peanut epicutaneous immunotherapy in patients with atopic comorbidities.

Co-occurring atopic conditions are common in children with peanut allergy. As such, it is important to examine the safety and efficacy of epicutaneous immunotherapy with Viaskin Peanut 250 μg patch (VP250) in peanut-allergic children with these conditions. We sought to compare efficacy and safety of VP250 versus placebo in peanut-allergic children with/withoutongoing atopic conditions at baseline, includingasthma, atopic dermatitis/eczema, or concomitant food allergy. A subgroup analysis of peanut-allergic children aged 4 to 11 years enrolled in PEPITES (12 months) and REALISE (6 months) randomized, placebo-controlled, phase 3 trials was conducted. The efficacy outcome measure was the difference in prespecified responder rate between placebo and VP250 groups at month 12 based on eliciting dose of peanut protein using double-blind, placebo-controlled food challenge in PEPITES. Safety profiles were evaluated by baseline concomitant disease subgroup in all randomized subjects who received 1 or more dose of the study drug in PEPITES and REALISE pooled data. Responder rates were significantly (P< .05, all comparisons) greater with VP250 compared with placebo treatment regardless of whether subjects had other atopic conditions. Safety and tolerability profiles were generally similar across subgroups, with no new safety concerns detected. Atrend for both higher responder rates and rates of local reactions was observed in subjects with baseline atopic dermatitis versus those without. In subjects with concomitant food allergy at baseline, higher rates of treatment-emergent adverse events, but not study discontinuations or overall rates of anaphylaxis, were observed. The results support the safety and efficacy of VP250 for treating peanut-allergic children with or without concomitant atopic conditions.

Relevance of sensitization to legumes in peanut-allergic children

Relevance of sensitization to legumes in peanut-allergic children

Efficacy and Safety of Epicutaneous Immunotherapy (EPIT) for Peanut Allergy in Subjects Aged 1-3 Years With and Without Atopic Dermatitis in the EPITOPE Study

In a Phase 3 double-blind, placebo-controlled clinical trial of 1-3-year-old peanut-allergic children (EPITOPE), EPIT with Viaskin Peanut 250 μg patch (VP250) reduced reactivity to peanut ingestion. We explored whether treatment response or safety was influenced by baseline atopic dermatitis (AD) in this population.