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.).

Accelerating Food Allergy Research: Need for a Data Commons.

Food allergy is a significant health problem affecting approximately 8% of children and 11% of adults in the United States. It exhibits all the characteristics of a "complex" genetic trait; therefore, it is necessary to look at very large numbers of patients, far more than exist at any single organization, to eliminate gaps in the current understanding of this complex chronic disorder. Advances may be achieved by bringing together food allergy data from large numbers of patients into a Data Commons, a secure and efficient platform for researchers, comprising standardized data, available in a common interface for download and/or analysis, in accordance with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles. Prior data commons initiatives indicate that research community consensus and support, formal food allergy ontology, data standards, an accepted platform and data management tools, an agreed upon infrastructure, and trusted governance are the foundation of any successful data commons. In this article, we will present the justification for the creation of a food allergy data commons and describe the core principles that can make it successful and sustainable.

Assessing Disparities in the Prevalence of Atopic Comorbidities Among Food-Allergic Children.

BACKGROUND: Previous studies have reported that Black children with food allergy (FA) have higher risk of atopic comorbidities than White children. OBJECTIVE: Our study sought to understand if disparities in the prevalence of atopic comorbidities among children with FA are driven by individual and community-level socioeconomic status (SES). METHODS: We analyzed data from a prospective, multicenter cohort investigating the natural history of pediatric atopy: the Food Allergy Outcomes Related to White and African American Racial Differences (FORWARD) study. A validated, multicomponent area deprivation index (ADI) percentile score was tabulated by the census block group for each subject's home address. The association of ADI with atopic comorbidities in FA was assessed via multivariable regression analysis. RESULTS: Of the 700 children in this study, the mean ADI was 37.7 (95% confidence interval: 35.6-39.7). The mean ADI was higher in children with asthma (43.3) compared with those without asthma (31.8), which remained significant after adjusting for race (P < .0001). Children with allergic rhinitis (AR) had a higher mean ADI (39.1) compared with those without (33.4) (P = .008). ADI was associated with secondhand smoking, parents' education, and household income. Black children had a higher risk for asthma after adjusting for ADI and SES-related factors. CONCLUSION: The independent association of ADI with asthma and AR, regardless of race, suggests a role of neighborhood-level socioeconomic deprivation in the development of these conditions among children with FA. Black children with FA remained at higher risk for asthma after adjusting for SES-related variables, which can indicate an independent risk for asthma in these children.

Associations of Food Allergy-Related Dietary Knowledge, Attitudes, and Behaviors Among Caregivers of Black and White Children With Food Allergy.

BACKGROUND: The increasing prevalence of pediatric food allergy (FA) in the United States has disproportionately affected non-Hispanic Black youth. However, racial and other socioeconomic disparities in FA management among caregivers of children with FA remain unclear. OBJECTIVE: To determine associations between socioeconomic, clinical, and health care factors and FA-related knowledge, attitudes, and behaviors among caregivers of Black and White children with FA. DESIGN: Cross-sectional survey analysis from the Food Allergy Outcomes Related to White and African American Racial Differences Study. PARTICIPANTS/SETTINGS: Longitudinal cohort of caregivers of 385 Black and White children with FA ages birth to 12 years residing in Chicago, Illinois, Cincinnati, Ohio, and Washington, DC from 2017 to March 2021. MAIN OUTCOME MEASURES: There were 3 primary outcomes of interest: (1) FA knowledge assessed by scores from the Knowledge Survey, (2) FA-related attitudes assessed by newly developed survey, and (3) food-related behaviors assessed by the FORWARD Diet and Purchasing Habit Surveys completed 6 months postenrollment. ANALYSES: Multivariable linear and logistic regression. RESULTS: The overall response rate to the 6-month postenrollment survey was 51.3% (385 of 751). White caregivers represented 69.4% of the participants. Black race was associated with a 1.5-point mean decrease in FA knowledge score (95% CI: -2.2 to -0.7) compared with White caregivers, and a graduate degree or bachelor's degree was associated with associated with a 1.7-point mean increase (95% CI: 0.8-2.7) and 1.1-point mean increase (95% CI: 0.2-2.0) in FA knowledge score, respectively, compared with caregivers who had less than a bachelor's degree. Multiple FAs and ever visited the emergency department for a food-related allergic reaction were also associated with higher levels of FA knowledge. Ever visited the emergency department for FA was also associated with higher odds of 2 measures of FA attitudes reflecting parental anxiety. Greater FA knowledge scores were consistently associated with lower odds of several FA-related food purchasing and eating behaviors assumed to have elevated risk of FA. Eating food prepared at school was the only FA behavior associated with race. Compared with White children, Black children were 2.5 times more likely to eat school-prepared foods (95% CI: 1.2-5.6). CONCLUSIONS: Findings from this study identified socioeconomic, racial, and clinical factors associated with caregivers' FA-related knowledge, attitudes, and behaviors, but further research is warranted to better understand these relationships.

Assessing daily food allergy self-management among adolescents using a 24-hour recall interview.

BACKGROUND: Severe food allergic reactions can be life-threatening or fatal and are experienced by up to 40% of children with food allergies, with adolescents at greatest risk. There are no comprehensive measures to assess food allergy management behaviors that could prevent allergic reactions. OBJECTIVE: To describe food allergy self-management behaviors as reported by adolescents on a 24-hour recall measure and identify related factors. METHODS: Adolescents aged 10 to 14 years with immunoglobulin E-mediated food allergy completed the Food Allergy Management 24-Hour Recall as an interview. Participants answered questions on each food they ate on the previous day and food allergy self-management behaviors. RESULTS: Participants were a diverse sample (28% White) of 101 adolescents (mean age = 11.80 years; 53% male sex). Most meals and snacks (76%) were observed by adults. Epinephrine autoinjectors (EAIs) were reportedly available for almost all meals and snacks (93%). Almost all foods had been eaten before (95%) and were verified as allergen free (92%). Furthermore, 35% of the time, past experience with the food was the only method used to verify safety. Child age, number of food allergies, or time since allergic reaction was not related to self-management behavior. EAI availability and ingredient verification were most common at home and in school; adult observation was least likely in the home. CONCLUSION: Adolescents reported that EAIs were frequently available, but they relied on past experience with food to determine safety. Appropriate assessment of food safety should be a primary intervention target. The Food Allergy Management 24-Hour Recall may be a useful tool to assess and track food allergy self-management.

Characteristics of Food Allergic Reactions in United States Restaurants.

BACKGROUND: Food allergic reactions of varying severity occur in restaurants. Studies to date have shown that there are gaps in knowledge of and communication between restaurant staff and food allergic individuals. OBJECTIVE: We sought to characterize allergic reactions in restaurants to better inform the restaurant industry, food allergic individual, and allergist so that mitigation strategies can be implemented. METHODS: Data collected over a 2-year period from 2822 individuals in the Food Allergy Research & Education registry were analyzed using descriptive statistics. RESULTS: Dining out accounted for the second most common location for a food allergic reaction, after one's home, and many were severe with 28.0% requiring 1 dose and 6.2% requiring 2 doses of epinephrine. Cafes, fast food establishments, and Asian restaurants were frequently implicated sites. Peanut, tree nuts, and milk were the most common inciting allergens, and tree nuts resulted in the most common use of epinephrine. Of the allergic reactions, 53.9% occurred despite conveyance of food allergy to restaurant staff, 26.6% occurred when allergens were declared on the menu, and 13.7% occurred when allergens were declared on the menu and restaurant staff were informed of a food allergy. CONCLUSIONS: Allergic reactions in restaurants are common and can be severe. Findings presented here underscore the need for restaurant staff training and mandatory declaration of allergenic ingredients in meals. This updated knowledge will help support advocacy efforts and inform patients, allergists, and the restaurant industry on best practices for dining out to improve the quality of life for food allergic individuals.

African American Children Are More Likely to Be Allergic to Shellfish and Finfish: Findings from FORWARD, a Multisite Cohort Study.

BACKGROUND: Despite major differences in health profiles and rates of health care utilization between African American and White children with food allergy (FA), the detailed phenotypic variables that can potentially impact these outcomes have not been thoroughly studied. OBJECTIVE: We aimed to characterize phenotypic differences such as allergies to different foods and allergic comorbidities between African American and White children with FA enrolled in the Food Allergy Outcomes Related to White and African American Racial Differences study. METHODS: Our active, prospective, multicenter cohort study is currently enrolling African American and White children aged 0 to 12 years diagnosed with FA and followed by allergy/immunology clinics at 4 urban tertiary centers in the United States. To evaluate associations between race and phenotypic variables, we used multivariable logistic regression, adjusting for important demographic and confounding factors, as well as potential household clustering. RESULTS: As of May 2020, there were 239 African Americans and 425 Whites with complete intake information enrolled in the study. In comparison with Whites, we found that African Americans had significantly higher adjusted odds of allergy to finfish (odds ratio [OR]: 2.54, P < .01) and shellfish (OR: 3.10, P < .001). African Americans also had higher adjusted odds of asthma than Whites (asthma prevalence of 60.5% in African Americans and 27.2% in Whites; OR: 2.70, P < .001). In addition, shellfish allergy was associated with asthma, after controlling for race. CONCLUSION: Among a diverse cohort of children with physician-diagnosed FA, we observed that African American children had higher odds of allergy to shellfish and finfish, and higher rates of asthma. Interestingly, having asthma was independently associated with allergy to shellfish, after controlling for race.

Continuous and Daily Oral Immunotherapy for Peanut Allergy: Results from a 2-Year Open-Label Follow-On Study.

BACKGROUND: The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. OBJECTIVE: ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. METHODS: Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. RESULTS: Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. CONCLUSIONS: Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

Enhancing practice efficiency: A key organizational strategy to improve professional fulfillment in allergy and immunology.

OBJECTIVE: To review evidence-based strategies that have been noted to improve professional fulfillment and reduce burnout by enhancing practice efficiency. DATA SOURCES: A comprehensive literature review was conducted to evaluate the strategies to improve efficiency of practice-a key driver of burnout among physicians. STUDY SELECTIONS: Studies of efficiency-enhancing practices relevant to allergy-immunology were included. RESULTS: Professional burnout is prevalent among physicians and is associated with negative outcomes affecting physicians, patients, and health care organizations. Recent surveys suggest at least 35% of US allergists-immunologists experience burnout. There are multiple drivers of professional burnout, some at the individual level and others at the organizational or practice level. Strategies to improve professional fulfillment may be conceptualized using the Stanford physician wellness framework, in which efforts target the following 3 reciprocal domains: culture, personal resilience, and practice efficiency. Organizational strategies that support physician well-being by creating a more efficient practice environment hold great promise, particularly for allergists-immunologists. The reduction of administrative burden and fostering of team-based care have been found in multiple studies to be cost-effective strategies to improve physician and patient satisfaction. CONCLUSION: To ensure the well-being of the US allergy-immunology workforce and optimize patient outcomes, both private and academic allergy-immunology institutions should prioritize the adoption and iterative evaluation and refinement of these strategies to cocreate an efficient and ideal practice environment.

Food Allergy in Restaurants Work Group Report.

Individuals with food allergy are at risk for accidental exposures, potentially resulting in allergic reactions that may cause significant morbidity and mortality. Dining out, including restaurants or take-out, account for a large proportion of severe reactions. Errors due to gaps in knowledge or miscommunication can easily occur on behalf of food-allergic individuals or restaurant staff, resulting in accidental exposures and allergic reactions. Improved legislation, training of restaurant staff, and practitioner-guided education are recommended to reinforce patient safety and prevent severe allergic reactions. This Work Group Report provides guidance with specific practices that practitioners may recommend, and that patients and restaurant staff may employ, for prevention and treatment of food-allergic reactions in restaurants.

AR101 Oral Immunotherapy for Peanut Allergy.

BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms. RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older. CONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).