Omalizumab for the Treatment of Multiple Food Allergies.

BACKGROUND: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. METHODS: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. RESULTS: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. CONCLUSIONS: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

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

BACKGROUND: Prior studies of peanut sublingual immunotherapy (SLIT) have suggested a potential advantage with younger age at treatment initiation. OBJECTIVE: We studied the safety and efficacy of SLIT for peanut allergy in 1- to 4-year-old children. METHODS: 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 36 months of treatment. Participants desensitized to at least 443 mg peanut protein discontinued therapy for 3 months and then underwent DBPCFC to assess for remission. Biomarkers were measured at baseline and longitudinally during treatment. RESULTS: 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 in 1- 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. CONCLUSION: Peanut SLIT safely induces desensitization and remission in 1- to 4-year-old children, with improved outcomes seen with younger age at initiation.

Associations between cord blood acetaminophen biomarkers and childhood asthma with and without allergic comorbidities.

BACKGROUND: Previous studies have linked prenatal acetaminophen use to increased asthma risk in children. However, none have explored this association while differentiating between asthma cases with and without other allergic conditions or by employing objective biomarkers to assess acetaminophen exposure. OBJECTIVE: To evaluate whether the detection of acetaminophen biomarkers in cord blood is associated with the subgroups of asthma both with and without allergic comorbidities in children. METHODS: Acetaminophen biomarkers, including unchanged acetaminophen and acetaminophen glucuronide, were measured in neonatal cord blood samples from the Boston Birth Cohort. Asthma subgroups were defined on the basis of physician diagnoses of asthma and other allergic conditions (atopic dermatitis and allergic rhinitis). Multinomial regressions were used to evaluate the associations between acetaminophen biomarkers and asthma subgroups, adjusting for multiple confounders, including potential indications for maternal acetaminophen use such as maternal fever. RESULTS: The study included 142 children with asthma and at least 1 other allergic condition, 55 children with asthma but no other allergic condition, and 613 children free of asthma. Detection of acetaminophen in cord blood, reflecting maternal exposure to acetaminophen shortly before delivery, was associated with 3.73 times the odds of developing asthma without allergic comorbidities (95% CI: 1.79-7.80, P = .0004). In contrast, the detection of acetaminophen in cord blood was not associated with an elevated risk of asthma with allergic comorbidities. Analysis of acetaminophen glucuronide yielded consistent results. CONCLUSION: In a prospective birth cohort, cord blood acetaminophen biomarkers were associated with an increased risk of childhood asthma without allergic comorbidities, but were not associated with childhood asthma with allergic comorbidities.

Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation.

BACKGROUND: Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. OBJECTIVE: Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma. METHODS: We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/µL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV1 value over 12 months of follow-up. RESULTS: In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV1 comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab. CONCLUSIONS: Among patients with asthma and eosinophil counts of at least 150 cells/µL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV1 value than omalizumab and mepolizumab.

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

BACKGROUND: Studies on the efficacy of peanut sublingual immunotherapy (SLIT) are limited. The durability of desensitization after SLIT has not been well described. OBJECTIVE: We sought to evaluate the efficacy and safety of 4-mg peanut SLIT and persistence of desensitization after SLIT discontinuation. METHODS: 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). A novel 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. RESULTS: 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. CONCLUSIONS: 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.

Indoor environmental exposures and obstructive lung disease phenotypes among children with asthma living in poor urban neighborhoods.

BACKGROUND: Air trapping is an obstructive phenotype that has been associated with more severe and unstable asthma in children. Air trapping has been defined using pre- and postbronchodilator spirometry. The causes of air trapping are not completely understood. It is possible that environmental exposures could be implicated in air trapping in children with asthma. OBJECTIVE: We investigated the association between indoor exposures and air trapping in urban children with asthma. METHODS: Children with asthma aged 5 to 17 years living in Baltimore and enrolled onto the Environmental Control as Add-on Therapy for Childhood Asthma study were evaluated for air trapping using spirometry. Aeroallergen sensitization was assessed at baseline, and spirometry was performed at 0, 3, and 6 months. Air trapping was defined as an FVC z score of less than -1.64 or a change in FVC with bronchodilation of ≥10% predicted. Logistic normal random effects models were used to evaluate associations of air trapping and indoor exposures. RESULTS: Airborne and bedroom floor mouse allergen concentrations were associated with air trapping but not airflow limitation (odds ratio 1.19, 95% confidence interval 1.02-1.37, P = .02 per 2-fold increase in airborne mouse allergen; odds ratio 1.23, 95% confidence interval 1.07-1.41, P = .003 per 2-fold increase in bedroom floor mouse allergen). Other indoor exposures (cockroach, cat, dog, dust mite, particulate matter, and nicotine) were not associated with air trapping or airflow limitation. CONCLUSION: Mouse allergen exposure, but not other indoor exposure, was associated with air trapping in urban children with asthma.

Comprehensive home environmental intervention did not reduce allergen concentrations or controller medication requirements among children in Baltimore.

OBJECTIVE: To determine if the addition of home environmental control strategies (ECSs) to controller medication titration reduces asthma controller medication requirements and in-home allergen concentrations among children with persistent asthma in Baltimore City. METHODS: 155 children ages 5-17 with allergen-sensitized asthma were enrolled in a 6-month randomized clinical trial of multifaceted, individually-tailored ECS plus asthma controller medication titration compared to controller medication titration alone. Participants had to meet criteria for persistent asthma and have had an exacerbation in the previous 18 months. Allergen sensitization (mouse, cockroach, cat, dog, dust mite) was assessed at baseline and home dust allergen concentrations were measured at baseline, 3 and 6 months. ECS was delivered 3-4 times over the trial. Asthma controller medication was titrated using a guidelines-based algorithm at baseline, 2, 4, and 6 months. The primary outcome was controller medication treatment step at 6 months (0-6, as-needed albuterol to high-dose ICS + LABA). RESULTS: The population was predominately Black (90%), on public insurance (93%), and male (61%). The mean age was 10.1 years (SD 3.3). More than 70% were sensitized to a rodent, >50% to cockroach, and 70% were polysensitized. At 6 months, there were no differences in either treatment step (3.8 [SD 1.4] vs. 3.7 [SD 1.5]) or allergen concentrations between groups. CONCLUSION: Among this predominantly low-income, Black pediatric asthma population, the addition of ECS to controller medication titration reduced neither indoor allergen concentrations nor controller medication requirements compared to controller medication titration alone.

The year in food allergy.

Research into food allergy continues to rapidly evolve, accompanying and driving real changes in the clinical approach to these diseases. The past year has seen the rollout of the first treatment approved for active management of food allergy, more data on alternative methods of treatment, the continued evolution of strategies for prevention of food allergy, a renewed interest in phenotyping food allergy subtypes, and, importantly, key new insights into the pathophysiology of food allergy. We expect that in the coming years, the therapies that are in preclinical or early clinical evaluation now will make their way to the clinic, finally allowing the possibility of safe and effective treatments for food allergy.

Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations.

Importance: Structural racism has been implicated in the disproportionally high asthma morbidity experienced by children living in disadvantaged, urban neighborhoods. Current approaches designed to reduce asthma triggers have modest impact. Objective: To examine whether participation in a housing mobility program that provided housing vouchers and assistance moving to low-poverty neighborhoods was associated with reduced asthma morbidity among children and to explore potential mediating factors. Design, Setting, and Participants: Cohort study of 123 children aged 5 to 17 years with persistent asthma whose families participated in the Baltimore Regional Housing Partnership housing mobility program from 2016 to 2020. Children were matched to 115 children enrolled in the Urban Environment and Childhood Asthma (URECA) birth cohort using propensity scores. Exposure: Moving to a low-poverty neighborhood. Main Outcomes: Caregiver-reported asthma exacerbations and symptoms. Results: Among 123 children enrolled in the program, median age was 8.4 years, 58 (47.2%) were female, and 120 (97.6%) were Black. Prior to moving, 89 of 110 children (81%) lived in a high-poverty census tract (>20% of families below the poverty line); after moving, only 1 of 106 children with after-move data (0.9%) lived in a high-poverty tract. Among this cohort, 15.1% (SD, 35.8) had at least 1 exacerbation per 3-month period prior to moving vs 8.5% (SD, 28.0) after moving, an adjusted difference of -6.8 percentage points (95% CI, -11.9% to -1.7%; P = .009). Maximum symptom days in the past 2 weeks were 5.1 (SD, 5.0) before moving and 2.7 (SD, 3.8) after moving, an adjusted difference of -2.37 days (95% CI, -3.14 to -1.59; P < .001). Results remained significant in propensity score-matched analyses with URECA data. Measures of stress, including social cohesion, neighborhood safety, and urban stress, all improved with moving and were estimated to mediate between 29% and 35% of the association between moving and asthma exacerbations. Conclusions and Relevance: Children with asthma whose families participated in a program that helped them move into low-poverty neighborhoods experienced significant improvements in asthma symptom days and exacerbations. This study adds to the limited evidence suggesting that programs to counter housing discrimination can reduce childhood asthma morbidity.

Rural Residence and Poverty Are Independent Risk Factors for Chronic Obstructive Pulmonary Disease in the United States.

RATIONALE: In developing countries, poor and rural areas have a high burden of chronic obstructive pulmonary disease (COPD), and environmental pollutants and indoor burning of biomass have been implicated as potential causal exposures. Less is known about the prevalence of COPD in the United States with respect to urban-rural distribution, poverty, and factors that uniquely contribute to COPD among never-smokers. OBJECTIVES: To understand the impact of urban-rural status, poverty, and other community factors on COPD prevalence nationwide and among never-smokers. METHODS: We studied a nationally representative sample of adults in the National Health Interview Survey 2012-2015, with data linkage between neighborhood data from the U.S. Census's American Community Survey and the National Center for Health Statistics Urban-Rural Classification Scheme. The main outcome was COPD prevalence. MEASUREMENTS AND MAIN RESULTS: The prevalence of COPD in poor, rural areas was almost twice that in the overall population (15.4% vs. 8.4%). In adjusted models, rural residence (odds ratio [OR], 1.23; P < 0.001) and census-level poverty (OR, 1.12; P = 0.012) were both associated with COPD prevalence, as were indicators of household wealth. Among never-smokers, rural residence was also associated with COPD (OR, 1.34; P < 0.001), as was neighborhood use of coal for heating (OR, 1.09; P < 0.001). CONCLUSIONS: In a nationally representative sample, rural residence and poverty were risk factors for COPD, even among never-smokers. The use of coal for heating was also a risk factor for COPD among never-smokers. Future disparities research to elucidate contributors to COPD development in poor and rural areas, including assessments of heating sources and environmental pollutants, is needed.

Material Hardship and Indoor Allergen Exposure among Low-Income, Urban, Minority Children with Persistent Asthma.

Traditional measures of socioeconomic status (SES) are associated with asthma morbidity, but their specific contributions are unclear. Increased exposure to indoor allergens among low SES children is an important consideration. Material hardship, a concept describing poor access to basic goods and services, may explain the relationship between low SES and indoor allergen exposure, and thereby, the increased risk of asthma morbidity. We sought to (i) describe the specific hardships experienced by low-Income, urban, minority children with asthma and indoor allergen sensitization and (ii) determine if material hardship is associated with indoor allergen exposure in this population. We conducted a cross-sectional analysis of children undergoing the baseline assessment for a clinical trial of home environmental modification. Participants were scored in five domains of material hardship. Domain scores were assigned based on caregiver responses to a questionnaire and were summed to generate a total material hardship score. Linear regression was used to examine the relationship between material hardship scores and bedroom floor concentrations of five common indoor allergens. Participants experienced high levels of material hardship in each of the five domains, with 33% not having access to a car, 35% not being able to pay utility bills, and 28% not being able to pay rent in the past year. Each one-point increase in material hardship was associated with an increase in cockroach allergen of 16.2% (95% CI 9.4%, 24.6%) and an increase in mouse allergen of 9.4% (95% CI 1.0%, 18.5%). After adjusting for traditional measures of SES, including household income, health insurance type, caregiver education, and caregiver employment status, the association between material hardship and cockroach allergen, but not mouse allergen, remained. These data suggest that a significant proportion of families of low-income, minority children with asthma may experience material hardship, and that they may be at greater risk of cockroach allergen exposure than their peers with similar income, but without material hardship.

Maternal triacylglycerol signature and risk of food allergy in offspring.

BACKGROUND: The prevalence of IgE-mediated food allergy (FA) is increasing worldwide, but the underlying mechanisms are poorly understood. OBJECTIVE: We sought to examine the role of maternal lipidomic profiles in risk of FA development in offspring and to investigate the potential modification effects by timing of first solid-food introduction. METHODS: This report included 1068 mother-child dyads from the Boston Birth Cohort. Maternal lipid metabolites in plasma were assessed by using liquid chromatography tandem mass spectrometry. Food sensitization (FS) was defined as a specific IgE level of 0.35 kU/L or greater to any of the 8 common food allergens determined by using ImmunoCAP. FA was defined based on FS, clinical symptoms, and food avoidance. Logistic regression was applied to analyze associations between maternal metabolites and risk of FS and FA in offspring and to explore potential effect modifications. RESULTS: Of the 1068 children, 411 had FS, and 132 had FA. Among the 209 metabolites, maternal triacylglycerols (TAGs) of shorter carbon chains and fewer double bonds were associated with greater risk of FA, whereas TAGs of longer carbon chains and more double bonds were significantly associated with lower risk of FA in offspring. These associations were stronger in children with delayed solid-food introduction (≥7 months of age) than those with earlier solid-food introduction (P = .010 for interaction between the maternal TAG score and timing of solid-food introduction). No significant association was found for FS. CONCLUSION: This is the first study to demonstrate a link between maternal TAGs and risk of FA in offspring and potential risk modification by timing of solid-food introduction.

Long-Term Coarse Particulate Matter Exposure Is Associated with Asthma among Children in Medicaid.

RATIONALE: Short- and long-term fine particulate matter (particulate matter ≤2.5 µm in aerodynamic diameter [PM2.5]) pollution is associated with asthma development and morbidity, but there are few data on the effects of long-term exposure to coarse PM (PM10-2.5) on respiratory health. OBJECTIVES: To understand the relationship between long-term fine and coarse PM exposure and asthma prevalence and morbidity among children. METHODS: A semiparametric regression model that incorporated PM2.5 and PM10 monitor data and geographic characteristics was developed to predict 2-year average PM2.5 and PM10-2.5 exposure during the period 2009 to 2010 at the zip-code tabulation area level. Data from 7,810,025 children aged 5 to 20 years enrolled in Medicaid from 2009 to 2010 were used in a log-linear regression model with predicted PM levels to estimate the association between PM exposure and asthma prevalence and morbidity, adjusting for race/ethnicity, sex, age, area-level urbanicity, poverty, education, and unmeasured spatial confounding. MEASUREMENTS AND MAIN RESULTS: Exposure to coarse PM was associated with increased asthma diagnosis prevalence (rate ratio [RR] for 1-µg/m3 increase in coarse PM level, 1.006; 95% confidence interval [CI], 1.001-1.011), hospitalizations (RR, 1.023; 95% CI, 1.003-1.042), and emergency department visits (RR, 1.017; 95% CI, 1.001-1.033) when adjusting for fine PM. Fine PM exposure was more strongly associated with increased asthma prevalence and morbidity than coarse PM. The estimates remained elevated across different levels of spatial confounding adjustment. CONCLUSIONS: Among children enrolled in Medicaid, exposure to higher average coarse PM levels is associated with increased asthma prevalence and morbidity. These results suggest the need for direct monitoring of coarse PM and reconsideration of limits on long-term average coarse PM pollution levels.

Advances in food allergy in 2017.

This review highlights research and policy advances in food allergy that were published in 2017 in the Journal and beyond. In 2017, many important studies on the treatment of food allergy were published, bringing us ever closer to a standardized treatment for food allergy. Other important advancements included research into other management strategies, including thresholds for avoidance, management of food allergies in schools, and development of new guidelines for prevention of food allergy. There were several important epidemiologic studies helping us understand the phenotypes of allergic disease, and new hypotheses were proposed for how best to prevent food allergy. Finally, there was a welcome increased attention to non-IgE-mediated food allergies.

Urban residence, neighborhood poverty, race/ethnicity, and asthma morbidity among children on Medicaid.

BACKGROUND: Although poor-urban (inner-city) areas are thought to have high asthma prevalence and morbidity, we recently found that inner cities do not have higher prevalent pediatric asthma. Whether asthma morbidity is higher in inner-city areas across the United States is not known. OBJECTIVE: This study sought to examine relationships between residence in poor and urban areas, race/ethnicity, and asthma morbidity among children with asthma who are enrolled in Medicaid. METHODS: Children aged 5 to 19 enrolled in Medicaid in 2009 to 2010 were included. Asthma was defined by at least 1 outpatient or emergency department (ED) visit with a primary diagnosis code of asthma over the 2-year period. Urbanization status was defined at the county level and neighborhood poverty at the zip-code level. Among children with asthma, logistic models were created to examine the effects of urbanization, neighborhood poverty, and race/ethnicity on rates of asthma outpatient visits, ED visits, and hospitalizations. RESULTS: This study included 16,860,716 children (1,534,820 with asthma). Among children enrolled in Medicaid, residence in inner-city areas did not confer increased risk of prevalent asthma in either crude or adjusted analyses, but it was associated with significantly more asthma-related ED visits and hospitalizations among those with asthma in crude analyses (risk ratio, 1.48; 95% CI, 1.24-1.36; and 1.97; 95% CI, 1.50-1.72, respectively) and when adjusted for race/ethnicity, age, and sex (adjusted risk ratio, 1.23; 95% CI, 1.08-1.15; and 1.62; 95% CI, 1.26-1.43). Residence in urban or poor areas and non-Hispanic black race/ethnicity were all independently associated with increased risk of asthma-related ED visits and hospitalizations. CONCLUSIONS: Residence in poor and urban areas is an important risk factor for asthma morbidity, but not for prevalence, among low-income US children.

Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective.

BACKGROUND: Oral immunotherapy (OIT) is an effective experimental food allergy treatment that is limited by treatment withdrawal and the frequent reversibility of desensitization if interrupted. Newly diagnosed preschool children may have clinical and immunological characteristics more amenable to treatment. OBJECTIVE: We sought to test the safety, effectiveness, and feasibility of early OIT (E-OIT) in the treatment of peanut allergy. METHODS: We enrolled 40 children aged 9 to 36 months with suspected or known peanut allergy. Qualifying subjects reacted to peanut during an entry food challenge and were block-randomized 1:1 to receive E-OIT at goal maintenance doses of 300 or 3000 mg/d in a double-blinded fashion. The primary end point, sustained unresponsiveness at 4 weeks after stopping early intervention oral immunotherapy (4-SU), was assessed by double-blinded, placebo-controlled food challenge either upon achieving 4 prespecified criteria, or after 3 maintenance years. Peanut-specific immune responses were serially analyzed. Outcomes were compared with 154 matched standard-care controls. RESULTS: Of 40 consented subjects, 3 (7.5%) did not qualify. Overall, 29 of 37 (78%) in the intent-to-treat analysis achieved 4-SU (300-mg arm, 17 of 20 [85%]; 3000 mg, 12 of 17 [71%], P = .43) over a median of 29 months. Per-protocol, the overall proportion achieving 4-SU was 29 of 32 (91%). Peanut-specific IgE levels significantly declined in E-OIT-treated children, who were 19 times more likely to successfully consume dietary peanut than matched standard-care controls, in whom peanut-specific IgE levels significantly increased (relative risk, 19.42; 95% CI, 8.7-43.7; P < .001). Allergic side effects during E-OIT were common but all were mild to moderate. CONCLUSIONS: At both doses tested, E-OIT had an acceptable safety profile and was highly successful in rapidly suppressing allergic immune responses and achieving safe dietary reintroduction.