Epicutaneous immunotherapy for the treatment of peanut allergy.

Peanut allergy treatment options remain limited, but novel approaches are being studied, including epicutaneous immunotherapy (EPIT). EPIT uses the cutaneous immune system to promote tolerance to food allergens. Viaskin™ Peanut, an approach to EPIT in late-stage clinical development uses an occlusive patch with a condensation chamber that enables natural epidermal water loss to solubilize dry antigen on the patch, which is then absorbed and captured by skin Langerhans cells. This form of EPIT does not require disruption of the skin barrier, thus avoiding a proinflammatory cytokine response by targeting the nonvascularized epidermis and limiting systemic allergen exposure. Extensive preclinical research suggests that Viaskin Peanut has a distinct mechanism of desensitization, including the potential for disease modification, driven by a unique population of regulatory T cells. Numerous clinical studies of Viaskin Peanut have demonstrated desensitization and reductions in reaction severity, particularly in children aged 1 through 11 years, as well as a favorable safety profile with mostly mild-to-moderate skin reactions that were observed to decrease over time. EPIT with Viaskin Peanut may be a potential therapeutic option for peanut allergy that is clinically practical with long-term efficacy and tolerability.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Psychometric parameters of food allergy quality of life during an allergen immunotherapy trial.

BACKGROUND: The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) is a commonly used patient-reported outcome measure in food allergy (FA) research. It was developed before FA treatment clinical trials were commonplace and is used as a secondary outcome measure in pivotal FA treatment trials. We examined the psychometric properties of the FAQLQ-PF and its relevance to children with peanut allergy engaged in an epicutaneous immunotherapy (EPIT) clinical trial. METHODS: Analysis was performed on 26 universally answered items of the FAQLQ-PF, from assessments undertaken during the phase 3 PEPITES study (baseline, Month 12), which examined the safety and efficacy of EPIT for children with peanut allergy aged 4-11 years. Item response theory (IRT) was used to assess psychometric parameters of the FAQLQ-PF (i.e., discrimination, difficulty, and information). Confirmatory factor analysis was also employed; reliability was assessed using McDonald's omega (ω) and Cronbach's alpha (α). RESULTS: A total of 23 of 26 items presented very high discrimination levels (>1.7), and all 26 fell within the recommended difficulty threshold (between -1.5 and 1.5). The items contributed a reasonable information level for their respective factors/subdomains. The measure also presented a marginally acceptable model fit for the 3-factor structure (e.g., comparative fit index = 0.88, Tucker-Lewis index = 0.87) and good reliability levels across time points (ω and α > 0.90). CONCLUSIONS: Herein, we present a novel reanalysis of the FAQLQ-PF items using IRT. The longitudinal performance of individual items and subscales was corroborated, and items with the highest discrimination were identified, showing that the tool is suitable for longitudinal measurements in FA treatment trials.

Peanut cross-contamination in randomly selected baked goods.

BACKGROUND: The current standard of care for managing peanut allergy includes avoidance of peanut and use of injectable epinephrine; however, strict avoidance is difficult and accidental ingestion is common with potentially serious consequences. Despite vigilance and efforts to minimize the risk of accidental exposure, peanut protein cross-contamination continues to occur in a variety of foods, including baked goods. OBJECTIVE: To assess and quantify the presence of peanut protein contamination in certain baked goods. METHODS: Randomly selected baked goods were collected from bakeries in the New York and Miami metropolitan areas that sold a variety of ethnic cuisines. A second set of samples from the same bakeries was collected at least 1 week after to evaluate between-batch variability. Samples were sent to the Food Allergy Research and Resource Program to analyze peanut contamination by enzyme-linked immunosorbent assay. Consumption estimates were based on 2003 to 2010 National Health and Nutrition Examination Survey survey data. RESULTS: Of 154 samples from 18 bakeries, 4 (2.6%) had detectable peanut contamination with peanut protein levels ranging from 0.1 mg/100 g to 650 mg/100 g. Consumption estimates for single occasion ingestion of a contaminated item ranged from 0.07 mg to 832 mg of peanut protein. CONCLUSION: In this study, unintended peanut protein was present in a small, but not insignificant, proportion of baked goods, with the potential to trigger a reaction in individuals with peanut allergy. Some products contained high levels of unintended peanut protein. The current data support the potential for accidental exposure to peanut protein with its associated risk.

Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results.

BACKGROUND: The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 µg, daily epicutaneous peanut protein; DBV712 250 µg). OBJECTIVE: We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study. METHODS: Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 µg, subjects who had received DBV712 250 µg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment. RESULTS: Of 213 eligible subjects who had received DBV712 250 µg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%). CONCLUSIONS: These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

Commercial claims costs related to health care resource use associated with a diagnosis of peanut allergy.

BACKGROUND: Peanut allergy (PA) affects approximately 1.6 million US children. The current standard of care is strict avoidance and prompt reaction treatment. Peanut allergy health care costs and health care resource utilization (HCRU) are poorly understood. OBJECTIVE: To estimate PA health care costs and HCRU using a nationally representative commercial payer database. METHODS: The IBM MarketScan Commercial Claims and Encounters Database was examined for PA diagnosis/reaction codes between January 2010 and October 2016 in patients 64 years of age or younger, with age cohort-matched controls. Outcomes were measured 12 months before and after the first claim date. Health care costs and HCRU were compared using Student's t tests and χ2 tests. RESULTS: Patients with a PA-related diagnostic code (n = 41,675) incurred almost double all-cause health care costs vs controls ($6436 vs $3493, P < .001), mainly from inpatient and outpatient medical costs ($5002 vs $2832, P < .001). More than one third of the PA group patients (36%) had a code indicative of an anaphylactic reaction during follow-up. Mean PA or reaction-related code costs per visit totaled $7921 for hospitalizations and $1115 for emergency department (ED) visits. Costs were 30% lower in patients with asthma codes without PA codes vs those with both codes ($5678 vs $8112, P < .001); all-cause ED costs were more than double in patients with atopic dermatitis codes with PA codes vs those without PA codes ($654 vs $308, P < .001). CONCLUSION: National commercial payer claims data indicate a significant health care burden associated with a PA-related code, including over $6400/patient in annual all-cause costs and increased health care utilization.

Unmet needs of children with peanut allergy: Aligning the risks and the evidence.

BACKGROUND: Peanut allergy is a potentially severe and lifelong allergy, with few effective treatments or preventive measures. OBJECTIVE: To convene an expert panel of allergists, pediatricians, and advocates to discuss and highlight unmet needs in the prevention and management of peanut allergies. METHODS: Literature searches of PubMed were performed. The panel evaluated published data on the prevention of peanut allergy, treatment of existing peanut allergy, and management of reactions after unintentional peanut exposures. RESULTS: The following key unmet needs in the prevention and management of peanut allergy were identified: (1) enhancing and optimizing implementation of early peanut introduction as a means of preventing the development of peanut allergy, (2) developing knowledge translation strategies regarding the safety and efficacy data for current and emerging immunotherapies for peanut-allergic children to support their use in clinical practice, and (3) promoting understanding of true exposure risk in allergic individuals and ensuring access to epinephrine for unintentional exposures that provoke severe reactions. Practitioners should help educate caregivers about the actual risks associated with peanut allergy and its prevention and management so that treatment decisions can be evidence based rather than fear based. Support tools are needed to help address caregiver goals, expectations, and psychological barriers, as well as identify facilitators for prevention and treatment strategies. CONCLUSION: There are significant unmet needs in our understanding of peanut allergy; addressing these needs will help to enhance understanding of how to most effectively prevent and treat peanut allergy, as well as educate the food-allergic and nonallergic community regarding current evidence-based practices.

Evaluation of daily patch application duration for epicutaneous immunotherapy for peanut allergy.

Background: Epicutaneous immunotherapy is a potential novel immunotherapy that utilizes unique cutaneous immunologic properties. In a phase III, randomized, double-blind, placebo controlled clinical trial, an epicutaneous patch (DBV712) with 250 µg of peanut protein applied once daily for 12-months was statistically superior to placebo in desensitizing children with peanut allergy (ages 4-11 years) (N = 356). Objective: To assess the relationship between the hours of daily application time and the efficacy of DBV712 250 µg. Methods: DBV712 250 µg was applied to 30 nonallergic volunteers for various durations from 2 to 24 hours and then assayed for residual peanut protein. Patch application data from the phase III clinical trial were analyzed post hoc according to prespecified responder rates and changes in the eliciting dose (ED), as measured by the geometric mean (GM) ED ratio (12 months/baseline). Results: Following application, there was a marked decrease in peanut protein on the patches from 2 to 12 hours. After 12 hours, the median peanut protein recovered was below quantification limits. The median daily patch application duration in subjects from the phase III clinical trial was 21.1 hours (DBV712 250 µg) and 22.4 hours (placebo). Ninety-five percent of the treated population achieved >10 hours per day mean application. Response rates and GM ED ratios were similar among subjects across a range of application durations; e.g., in those with a mean duration of >10 hours, the response rate was 36.6% and the GM ED ratio was 3.8, comparable with 42.6% and 4.0, respectively, in those with a mean duration of >20 hours. In DBV712 250 µg subjects with >16 hours mean application duration (84.5% of the treated population), the response rate was 38.8% versus 13.4% for placebo (difference, 24.4% [95% confidence interval, 15.5-34.0%]; p < 0.001). Conclusion: An evaluation of residual peanut protein on patches following application and post hoc analysis of phase III data strongly suggest that allergen delivery is attained with 12-16 hours of daily patch application time, sufficient to drive clinically meaningful desensitization to peanut after 12 months.

An evaluation of factors influencing response to epicutaneous immunotherapy for peanut allergy in the PEPITES trial.

Background: Epicutaneous immunotherapy (EPIT) for peanut allergy is a potential novel immunotherapy that utilizes the unique cutaneous immunologic properties to induce desensitization. A randomized, double-blind, placebo-controlled Phase 3 trial (PEPITES) in peanut-allergic children 4-11 years demonstrated an epicutaneous patch (DBV712) with 250 µg peanut protein was statistically superior to placebo in inducing desensitization following 12 months of daily treatment. Objective: To investigate what baseline and in-study factors influenced response to DBV712 250 µg, with a focus on patch adhesion, by posthoc analysis of PEPITES data. Methods: A posthoc multivariate model built with log-transformed Month 12 eliciting dose (ED) as the dependent variable was used to assess the influence of baseline characteristics and patch adhesion. Baseline characteristics and treatment response were also evaluated by stratifying subjects into decile subgroups by patch detachment rates over the 12-month study. Results: Multivariate analysis identified higher baseline ED and lower baseline peanut-specific IgE as the variables most predictive of higher Month 12 ED, followed by mean daily patch application duration, baseline SCORing Atopic Dermatitis (SCORAD) score, and age. By decile stratification, no association between patch detachment and treatment response was identified for 80% of DBV712-treated subjects. All DBV712-treated subjects, including those with the highest patch detachment rates, demonstrated treatment benefit measured by fold-changes in geometric mean ED. Conclusion: We identified subject baseline characteristics of higher baseline ED and lower baseline peanut-specific IgE as most predictive of higher Month 12 ED. For the majority of treated subjects, patch detachment did not impact treatment response. A minority of subjects, highly sensitive to peanut at baseline, had lower prespecified responder rates and higher patch detachment rates, yet still benefited from treatment based upon fold-changes in ED.

Estimated risk reduction to packaged food reactions by epicutaneous immunotherapy (EPIT) for peanut allergy.

BACKGROUND: Peanut allergy is a generally persistent, sometimes life-threatening food allergy. With no treatments demonstrating the ability to cure a food allergy, the focus of drugs in development has been on providing a level of protection against accidental exposure reactions. However, no study has estimated the relative risk reduction of a food-allergic population receiving a specific immunotherapeutic treatment for their allergies. OBJECTIVE: To estimate the relative risk reduction when consuming peanut-contaminated packaged food products in a double-blind, placebo-controlled Phase 3 study population of children treated with epicutaneous immunotherapy (EPIT) for 12 months with either a patch containing 250 µg peanut protein (250-µg patch) or a placebo patch. METHODS: The probability of an allergic reaction due to the unintended presence of peanut protein in packaged food products was modeled per study group and food category combination using Monte Carlo simulations. Risks per eating occasion of a contaminated packaged food product and the number of individuals per study population predicted to react on a yearly basis were investigated. RESULTS: The population treated with the 250-µg patch demonstrated a significantly increased dose-response distribution after 12 months of treatment, which resulted in a relative risk reduction of 73.2% to 78.4% when consuming peanut-contaminated packaged food products. In contrast, no statistically significant change was observed for the placebo group at the 12-month point. CONCLUSION: Our study estimates a substantial relative risk reduction for allergic reactions among peanut-allergic children after 12 months of EPIT with the 250-µg patch, supporting the potential real-world clinical relevance of this investigational immunotherapy and its possible role as a future therapy for peanut-allergic children. ClinicalTrials.gov Identifier: NCT02636699.

Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy: The PEPITES Randomized Clinical Trial.

Importance: There are currently no approved treatments for peanut allergy. Objective: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein. Interventions: Daily treatment with peanut patch containing either 250 µg of peanut protein (n = 238) or placebo (n = 118) for 12 months. Main Outcomes and Measures: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs). Results: Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P < .001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group. Conclusions and Relevance: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-µg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined. Trial Registration: ClinicalTrials.gov Identifier: NCT02636699.

Prevalence of food allergies in South Asia.

OBJECTIVE: To evaluate the published medical literature on the prevalence and types of food allergies in South Asia. DATA SOURCES: A PubMed search was performed using the keywords India and food allergy, Asia and food allergy, and South Asia and food allergy for any period. Articles cited in selected studies were reviewed for their appropriateness of inclusion into this review. STUDY SELECTIONS: Publications were included that were original research and fit the topic of food allergy and South Asia. South Asia is defined as region inclusive of India, Pakistan, Bangladesh, and Sri Lanka. RESULTS: A total of 169 articles were initially identified, and 47 were reviewed in detail for inclusion in this review. The primary focus was placed on 10 studies that consisted of case reports of newly reported or documented food allergy, survey studies that investigated food allergy prevalence in specific demographics, and prospective and cross-sectional studies with case controls, all of which investigated food allergy prevalence by allergy testing in a selected population. CONCLUSION: The medical literature on the prevalence and types of food allergy in South Asia indicates that there is a variety of unusual and unique allergens and an overall low incidence of food allergy. There is also an association of increased food allergy prevalence in individuals who live in metropolitan regions or who migrate to communities that have adopted westernization.

Multicenter prevalence of anaphylaxis in clinic-based oral food challenges.

BACKGROUND: Although previous single-center studies report the rate of anaphylaxis for oral food challenges (OFCs) as 9% to 11%, little is known regarding the epidemiology of clinical OFCs across multiple centers in the United States. OBJECTIVE: To examine the epidemiology, symptoms, and treatment of clinical low-risk OFCs in the nonresearch setting. METHODS: Data were obtained from 2008 to 2013 through a physician survey in 5 food allergy centers geographically distributed across the United States. Allergic reaction rates and the association of reaction rates with year, hospital, and demographics were determined using a linear mixed model. Meta-analysis was used to pool the proportion of reactions and anaphylaxis with inverse-variance weights using a random-effects model with exact confidence intervals (CIs). RESULTS: A total of 6,377 OFCs were performed, and the pooled estimate of anaphylaxis was 2% (95% CI, 1%-3%). The rate of allergic reactions was 14% (95% CI, 13%-16%) and was consistent during the study period (P = .40). Reaction rates ranged from 13% to 33%. Males reacted 16% more frequently than females (95% CI, 4%-37.5%; P = .04). Foods challenged in 2013 varied geographically, with peanut as the most challenged food in the Northeast, Midwest, and West and egg as the most challenged in the South. CONCLUSION: As the largest national survey of allergic reactions of clinical open OFCs in a nonresearch setting in the United States, this study found that performing clinical nonresearch open low-risk OFCs results in few allergic reactions, with 86% of challenges resulting in no reactions and 98% without anaphylaxis.

The emotional, social, and financial burden of food allergies on children and their families.

BACKGROUND: As the prevalence of food allergy has risen among children and young adults, both in the United States and around the world, investigators have become increasingly aware of the daily emotional toll on patients and their families of living with food allergy. OBJECTIVE: To review the literature regarding the emotional, social, and financial impact of food allergy on pediatric patients and their families, and to provide evidence-based suggestions for clinicians on how to most effectively address these issues. METHODS: A literature search was performed to identify relevant articles related to the emotional, social, and financial impact of food allergy. RESULTS: There is a growing body of literature that demonstrates that living with food allergy adversely affects patients and families in the domains above. CONCLUSION: Food allergy can significantly impact pediatric patients and their families in all areas of their lives. Clinicians should be aware of these issues when working with these families. Implementing a multidisciplinary approach can help families cope with emotional, social, and financial burdens.

Effect of Varying Doses of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Exposure Among Patients With Peanut Sensitivity: A Randomized Clinical Trial.

Importance: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. Objective: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. Design, Setting, and Participants: Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016). Patients (n = 221) had peanut sensitivity and positive double-blind, placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein. Interventions: Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 µg (n = 53), 100 µg (n = 56), or 250 µg (n = 56) of peanut protein or a placebo patch (n = 56). Following daily patch application for 12 months, patients underwent a double-blind, placebo-controlled food challenge to establish changes in eliciting dose. Main Outcomes and Measures: The primary efficacy end point was percentage of treatment responders (eliciting dose: ≥10-times increase and/or reaching ≥1000 mg of peanut protein) in each group vs placebo patch after 12 months. Secondary end points included percentage of responders by age strata and treatment-emergent adverse events (TEAEs). Results: Of 221 patients randomized (median age, 11 years [quartile 1, quartile 3: 8, 16]; 37.6% female), 93.7% completed the trial. A significant absolute difference in response rates was observed at month 12 between the 250-µg (n = 28; 50.0%) and placebo (n = 14; 25.0%) patches (difference, 25.0%; 95% CI, 7.7%-42.3%; P = .01). No significant difference was seen between the placebo patch vs the 100-µg patch. Because of statistical testing hierarchical rules, the 50-µg patch was not compared with placebo. Interaction by age group was only significant for the 250-µg patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-µg (n = 15; 53.6%) and placebo (n = 6; 19.4%) patches was 34.2% (95% CI, 11.1%-57.3%; P = .008); adolescents/adults showed no difference between the 250-µg (n = 13; 46.4%) and placebo (n = 8; 32.0%) patches: 14.4% (95% CI, -11.6% to 40.4%; P = .40). No dose-related serious AEs were observed. The percentage of patients with 1 or more TEAEs (largely local skin reactions) was similar across all groups in year 1: 50-µg patch = 100%, 100-µg patch = 98.2%, 250-µg patch = 100%, and placebo patch = 92.9%. The overall median adherence was 97.6% after 1 year; the dropout rate for treatment-related AEs was 0.9%. Conclusions and Relevance: In this dose-ranging trial of peanut-allergic patients, the 250-µg peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial. Trial Registration: clinicaltrials.gov Identifier: NCT01675882.

Effects on growth and tolerance and hypoallergenicity of an amino acid-based formula with synbiotics.

BACKGROUND: To evaluate the effects of an amino acid-based formula (AAF) with synbiotics on growth and tolerance in healthy infants. The hypoallergenicity of this AAF with synbiotics was evaluated in subjects with cow's milk allergy (CMA). METHODS: Study 1: 115 full-term, healthy infants randomly received an AAF with synbiotics or a commercially available AAF for 16 wk. Subjects' weight, length, and head circumference were primary outcome measures. Stool characteristics and gastrointestinal (GI) symptoms were secondary outcome measures. Clinical examinations, dietary intake, clinical laboratory results, and adverse events were recorded. Study 2: hypoallergenicity of the AAF with synbiotics was evaluated in 30 infants and children with immunoglobulin E (IgE)-mediated CMA using a double-blind, placebo-controlled food challenge, and a 7-d feeding period. RESULTS: Study 1: comparable results in growth parameters and tolerance were observed for both groups. Minimal differences were observed in stool characteristics and GI symptoms throughout the study. Study 2: all 30 subjects with IgE-mediated CMA completed the study with no allergic reactions detected to challenges. CONCLUSION: These studies demonstrate that an AAF with synbiotics is safe and well tolerated and promotes normal growth when fed to healthy full-term infants as the sole source of nutrition and is hypoallergenic in subjects with CMA.

Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in Children With Cow's Milk Allergy: A Randomized Clinical Trial.

Importance: No approved treatment exists for allergen-specific immunoglobulin E (IgE)-mediated cow's milk allergy (CMA), a common childhood food allergy. Objective: To assess dose, efficacy, and safety of epicutaneous immunotherapy with Viaskin milk in children with IgE-mediated CMA. Design, Setting, and Participants: A phase 1/2, 2-part, randomized, double-blind, placebo-controlled dose-ranging clinical trial in children aged 2 to 17 years with IgE-mediated CMA was conducted between November 2014 through December 2017. It took place at 17 trial sites in the US and Canada. Current CMA was confirmed by double-blind, placebo-controlled food challenge at study entry. Part A assessed the short-term safety of 150 µg, 300 µg, or 500 µg of Viaskin milk; part B evaluated the efficacy and safety of the 3 doses vs placebo over 12 months of treatment. Of the 308 screened participants with physician-diagnosed CMA, 198 met eligibility criteria (including an eliciting dose 300 mg or less) and were randomized. Intervention: Safety of Viaskin milk (150-µg, 300-µg, or 500-µg doses) was evaluated over a 3-week period (part A). In part B, 180 additional participants were randomized to receive Viaskin milk at doses of 150 µg, 300 µg, or 500 µg or placebo (1:1:1:1) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of treatment responders, defined as a 10-fold or more increase in the cumulative reactive dose of cow's milk protein (reaching at least 144 mg) or a cumulative reactive dose of cow's milk protein at 1444 mg or more at the month 12 double-blind, placebo-controlled food challenge. Results: A total of 95.5% of the randomized participants (mean [SD] age, 8 [4.17] years; 124 of 198 were male [62.6%]) completed treatment. The highest response rate was observed in participants who received Viaskin milk at the 300-µg dose with 24 of 49 responders (49.0%) overall vs 16 of 53 responders (30.2%) in the placebo group (odds ratio, 2.19; 95% CI, 0.91-5.41; P = .09), highest in the 2 to 11 years age group (22 of 38 [57.9%] vs 13 of 40 [32.5%]; P = .04). Most treatment-emergent adverse events were mild or moderate application-site reactions. One participant in the 500-µg Viaskin milk dose group experienced treatment-related anaphylaxis. Conclusions and Relevance: In this randomized clinical trial, 12 months of daily epicutaneous immunotherapy with a dose of Viaskin milk at 300 µg was associated with a statistically significant treatment response in 2- to 11-year-old children with IgE-mediated CMA. Treatment-related anaphylaxis and treatment-related discontinuation rates were low. Further research is needed to explore Viaskin milk as a viable treatment option for children with IgE-mediated CMA. Trial Registration: ClinicalTrials.gov Identifier: NCT02223182.