Peanut-allergic Children Research Articles

Epicutaneous Immunotherapy vs Placebo for Peanut Protein Ingestion Among Peanut-Allergic Children

Epicutaneous Immunotherapy vs Placebo for Peanut Protein Ingestion Among Peanut-Allergic Children

An update on the controversy around offering oral immunotherapy to peanut-allergic children outside of research

An update on the controversy around offering oral immunotherapy to peanut-allergic children outside of research

B Cell Responsiveness to IL-10 in Peanut-Tolerant and Peanut-Allergic Children

B Cell Responsiveness to IL-10 in Peanut-Tolerant and Peanut-Allergic Children

Tolerance Induction Program Effect Explains Variation in Wheal Size, sIgE, and IgG4 in Peanut Allergic Children

Background: Tolerance induction oral immunotherapy, unique to our centre and termed the Tolerance Induction Program (TIP), has shown promise as a safe form of treatment in peanut allergic children. Evaluations of emerging treatments for peanut allergy typically report from a population average perspective. Our study sought to compare rate of decline in peanut-skin prick testing wheal size and sIgE following one year of high dose, weekly peanut immunotherapy using the standard population average approach to findings that account for subject variation in intercepts and slopes. Methods: This is a descriptive study in 51 peanut allergic children who underwent TIP at the Translational Pulmonary and Immunology Research Centre in Long Beach, California. Post intervention reductions in peanutwheal size and sIgE were assessed using Wilcoxen signed rank test and mixed effects modelling procedures. Results: The population average approach estimated reduction in wheal size to 29% of baseline value (p<0.001), compared to 41% after adjustment for random intercepts and slopes, p<0.001. Reduction in sIgE to 30% of baseline value using the population average approach (p<0.001), compared to 46% in the random intercepts model (p<0.001), and 44% in the random intercepts and slopes model (p=0.064). Conclusions: Tolerance induction oral immunotherapy significantly reduced peanut-SPT wheal size and sIgE in peanut allergic children. The subject specific approach produced more conservative effect estimates than observed using the standard population average approach.

Efficacy, Safety, and Quality of Life in a Multicenter, Randomized, Placebo-Controlled Trial of Low-Dose Peanut Oral Immunotherapy in Children with Peanut Allergy

Only 2 small placebo-controlled trials on peanut oral immunotherapy (OIT) have been published. We examined the efficacy, safety, immunologic parameters, quality of life (QOL), and burden of treatment (BOT) of low-dose peanut OIT in a multicenter, double-blind, randomized placebo-controlled trial. A total of 62 children aged 3 to 17 years with IgE-mediated, challenge-proven peanut allergy were randomized (1:1) to receive peanut OIT with a maintenance dose of 125 to 250 mg peanut protein or placebo. The primary outcome was the proportion of children tolerating 300 mg or more peanut protein at oral food challenge (OFC) after 16 months of OIT. We measured the occurrence of adverse events (AEs), immunologic changes, and QOL before and after OIT and BOT during OIT. Twenty-three of 31 (74.2%) children of the active group tolerated at least 300 mg peanut protein at final OFC compared with 5 of 31 (16.1%) in the placebo group (P < .001). Thirteen of 31 (41.9%) children of the active versus 1 of 31 (3.2%) of the placebo group tolerated the highest dose of 4.5 g peanut protein at final OFC (P < .001). There was no significant difference between the groups in the occurrence of AE-related dropouts or in the number, severity, and treatment of objective AEs. In the peanut-OIT group, we noted a significant reduction in peanut-specific IL-4, IL-5, IL-10, and IL-2 production by PBMCs compared with the placebo group, as well as a significant increase in peanut-specific IgG4 levels and a significant improvement in QOL; 86% of children evaluated the BOT positively. Low-dose OIT is a promising, effective, and safe treatment option for peanut-allergic children, leading to improvement in QOL, a low BOT, and immunologic changes showing tolerance development.

ECONOMIC OUTCOMES OF IMMEDIATE ACTIVATION OF EMERGENCY MEDICAL SERVICES AFTER EPINEPHRINE USE FOR PEANUT-INDUCED ANAPHYLAXIS

Introduction Routine advice for food allergy management in layperson food allergy action plans suggests immediate (reflex) activation of emergency medical services (EMS) following use of personal self-injectable epinephrine for reaction management (“immediately call 911 and seek care in the nearest medical facility”); however, a lack of patient-preference sensitive decision autonomy may create a barrier to appropriate epinephrine use. Methods A Markov model was used to simulate reflex EMS activation for cohorts of peanut allergic children compared with an approach allowing context-sensitive EMS activation (“wait-and-see”) following epinephrine use to explore the health and economic benefits of reflex EMS activation to determine if such use represents a cost-effective strategy. This study was exempt from IRB approval. Results Assuming a 10-fold increased fatality risk from non-immediate EMS activation and 12% risk for biphasic reactions, a context-sensitive approach of EMS activation decreased costs with minimal absolute risk. In the setting of a food allergic reaction that resolved immediately and completely with prompt epinephrine treatment, the per-patient fatality rate was 1.2 × 10-6 vs. 1.9 × 10-6 for immediate vs context sensitive EMS activation. Reflex activation cost $142,943,447 per quality-adjusted life year and $1,349,335,651 per death prevented. Cost rose to $321,625,534 per life-year saved ($3,035,454,848 per death prevented) assuming a 5-fold increased fatality risk, but fell to $12,997,173 per life-year saved ($122,689,936 per death prevented) assuming a 100-fold increased fatality risk. Conclusions In children with immediate and complete resolution of food allergic reactions following prompt epinephrine use a context-specific “wait and see” approach to EMS activation can be considered.

PREDICTIVE DECLINE IN PEANUT SKIN TEST AND RAST AMONG PEANUT-ALLERGIC CHILDREN UNDERGOING HIGH-DOSE ORAL IMMUNOTHERAPY

Introduction Peanut immunotherapy remains a limited form of treatment for peanut allergic children. Limitations primarily stem from small study sizes, significant adverse events, unclear long-term immunological outcomes and the inability to reach tolerance. In our cohort of peanut anaphylaxis patients undergoing tolerance induction oral immunotherapy, we sought to determine the rate of decline in peanut skin prick testing (SPT) and RAST results following one year of high-dose, weekly peanut immunotherapy. Methods Extensive RAST and SPT to peanut was performed in addition to other diagnostic markers. Fifty-one patients underwent sequential food challenges to non-allergic nuts followed by desensitization of sensitized or anaphylactic tree nuts culminating with peanut desensitization. All patients passed a 10g peanut protein challenge. Patients transitioned over 4 months to pass a 30g peanut protein challenge. Patients sustained a weekly 30g peanut protein dose for one year. During any given week, patients were free to eat products with Results All patients demonstrated positive peanut allergy diagnostics in SPT, component testing and RAST before treatment; post-treatment a reduction was observed in this cohort. The rate of reduction was greatest for patients whose post-SPT value was in the lowest quartile (reduced to 22.2% of pre-SPT value which corresponded to an average drop from 7.5-2.0mm). Conclusions Peanut-specific RAST and SPT are reproducible, temporal markers when following patient response to immunotherapy. Peanut immunotherapy is effective in reducing SPT and RAST specific peanut values corroborated with intermittent, high-dose peanut protein exposure.

Selective nut‐eating in peanut or tree nut allergic children—How can molecular allergology help?

Selective nut‐eating in peanut or tree nut allergic children—How can molecular allergology help?

Understanding caregiver goals, benefits, and acceptable risks of peanut allergy therapies

BackgroundBoth oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) are emerging potential treatments for peanut allergy. Caregiver goals and expectations of these therapies are poorly defined. ObjectiveTo determine caregiver goals and expectations of food allergy therapy. MethodsTwenty-two detailed, semistructured interviews of OIT and EPIT caregivers were conducted, allowing caregivers to describe their motivations for and experiences with food allergy therapy and life with a peanut allergic child. ResultsIn this sample, caregivers of peanut allergic children enrolled in OIT or EPIT phase 3 trials expressed a primary goal for their child to develop a buffer against an unintentional peanut exposure. The perception of the buffer varied, representing a decreased reaction severity on exposure, increased time to react to allow for assessment, or increased threshold of peanut exposure tolerated. Although caregivers expressed that a buffer may increase their confidence in travel and dining outside the home, they do not anticipate this buffer would lessen their overall level of pretherapy anxiety, allergen-associated vigilance, or avoidance practices. Most of the caregivers hope the buffer will increase their and their child's perceived sense of freedom for the child's actions and social interactions, translating to quality of life improvement, while still respecting the limitations of having a severe allergy that has been partially treated. No caregiver viewed these therapies as a cure, and most viewed treatment as a supplement to their current avoidance practices. ConclusionCaregivers of peanut allergic children strongly desire that OIT and EPIT result in a buffer against an unintentional reaction, although most admitted that this would not significantly change their anxiety and family's current lifestyle.

Current Status of Potential Therapies for IgE-Mediated Food Allergy.

The goal of this review is to provide the reader with an updated summary of published trial data regarding the use of oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) for treatment of IgE-mediated food allergies. Data from phase 2 trials for treatment of peanut allergy with OIT and EPIT reveal an increase in the threshold of reactivity for peanut-allergic children. Compared to EPIT, OIT promotes a greater increase in the threshold of reactivity; however, adverse events are more common with OIT. OIT, EPIT, and SLIT appear to modulate the immune response for some food-allergic individuals. Data regarding utility for treatment of food allergies regardless of modality is limited to few foods, as is investigation into treatment of food-allergic infants, young children, and adults. Future trials are likely to focus on young children, food allergies other than peanut, and treatment of multifood-allergic individuals.

A novel assessment of sustained unresponsiveness (SU) after long term sublingual immunotherapy (SLIT) in peanut allergic children: results of a 4 year phase II clinical trial

A novel assessment of sustained unresponsiveness (SU) after long term sublingual immunotherapy (SLIT) in peanut allergic children: results of a 4 year phase II clinical trial

Effect of Epicutaneous Immunotherapy on Inducing Peanut Desensitization in Peanut-Allergic Children: Topline Peanut Epicutaneous Immunotherapy Efficacy and Safety (PEPITES) Randomized Clinical Trial Results

Effect of Epicutaneous Immunotherapy on Inducing Peanut Desensitization in Peanut-Allergic Children: Topline Peanut Epicutaneous Immunotherapy Efficacy and Safety (PEPITES) Randomized Clinical Trial Results

Should Younger Siblings of Peanut Allergic Children Be Screened for Peanut Allergy?

The role of screening younger siblings of peanut allergic children with allergy testing before peanut introduction is controversial. Although certain guidelines note some value in screening this population, it is not a direct indication in the recent National Institute of Allergy and Infectious Diseases guideline. Some studies suggest that siblings of peanut allergic children are at increased risk of peanut allergy, whereas others note that delayed ingestion or mislabeling of allergy in these children may be the main factors accounting for this increased risk. The low risk of severe reaction with first ingestion and risks of pre-emptive testing must be balanced against data suggesting that families are reluctant to introduce peanut in siblings without testing. The goal of this article is to critically appraise the debated issues in this topic, providing a practical approach to this common clinical dilemma.

Introduction of Peanuts in Younger Siblings of Children With Peanut Allergy: A Prospective, Double-blinded Assessment of Risk, of Diagnostic Tests, and an Analysis of Patient Preferences

The purpose of the Finding the Risk of Anaphylaxis and Testing Rational In youngEr Siblings (FRATRIES) study was to determine the risk of anaphylaxis, the predictive values of peanut allergy tests, and parents’ preferences in the context of peanut introduction in the younger siblings of peanut-allergic children.The study cohort included 154 peanut-naïve children (median age of 23 months) who each had an older sibling with a diagnosis of peanut allergy. Participants were recruited in Canada through advertising in allergy clinics and through local food allergy web-based communities. Reference cohorts included parents of (1) peanut-naïve children from nonallergy pediatric clinics and (2) peanut-allergic children.This was a prospective cohort study. Peanut-naïve younger siblings underwent double-blind skin prick testing (SPT) followed by parent-led peanut introduction. At least 2 g of peanut protein was ingested to consider the introduction complete. Subjects were observed in a clinic for 2 hours. A phone call 24 hours later inquired about delayed reactions. Parents were then advised to introduce peanut in the younger child’s diet at least once a week. A phone follow-up occurred 1 year later. Questionnaires were dispensed prior to and up to a year after peanut introduction to investigate parental preferences with regard to peanut introduction in this subgroup.Eight participants (5.2%) had an unequivocal IgE-mediated reaction upon peanut introduction, including 5 with anaphylaxis. Peanut-allergic participants were significantly older than the rest of the cohort (median age of 4.0 vs 1.9 years, P = .04). The negative predictive values of SPT with peanut extract, peanut butter, and peanut-specific IgE were 99%, 100%, and 100%, respectively. The absolute positive predictive values of peanut extract SPT, peanut butter SPT, and specific IgE were 88%, 72%, and 62%, respectively. Peanut introduction at home without supervision was associated with high levels of parental anxiety in parents with a previously peanut-allergic child (median of 8.4 on a 10-point Likert scale), compared with introduction under supervision without testing (median of 3.8, P < .001) and home introduction after negative testing (median of 4.3, P < .001). If a provider recommended home peanut introduction without prior testing, 82% of parents would keep avoiding the food.Siblings of children with peanut allergy have an increased risk of anaphylaxis upon peanut introduction, with a potentially higher risk for older children who delayed introduction. Parents with a previously peanut-allergic child have significant anxiety regarding introducing peanut without prior skin testing or without supervision.This study supports previous studies showing that younger siblings of peanut-allergic children have a higher rate of peanut allergy. Recent NIAID guidelines for the prevention of peanut allergy recommend early introduction of peanut for high-risk children but do not make specific recommendations for siblings without other risk factors. In our practice, we do specifically recommend early and consistent peanut introduction in younger siblings of peanut-allergic patients, usually with prior testing. As highlighted in this study, parental anxiety regarding a possible reaction in the younger sibling, as well as the peanut-allergic child, is likely to impact home peanut introduction unless it is done with some level of medical supervision.

Early Oral Immunotherapy in Peanut-Allergic Preschool Children is Safe and Highly Effective

BP Vickery, JP Berglund, CM Burk. J Allergy Clin Immunol. 2017;139(1):173–181.e8 To evaluate the efficacy, safety, and feasibility of early oral immunotherapy (E-OIT) for treatment of peanut-allergic children. The study included 40 infants and preschool children (9–36 months of age) with either a known peanut allergy or peanut sensitization (peanut-specific immunoglobulin E (IgE) >5kUA/L but no history of reaction). Matched data from a control cohort of 154 participants was retrospectively obtained from a database at Johns Hopkins and compared with study participants. In this randomized active treatment study, each enrolled subject underwent an open oral food challenge to 4 g of peanut protein at …

Extended Boiling of Peanut Progressively Reduces IgE Allergenicity While Retaining T Cell Reactivity

B Tao, K Bernardo, P Eldi. Clin Exp Allergy. 2016;46(7):1004–1014 To evaluate the impact of extended boiling on peanut allergenicity and T cell reactivity. Blood samples were collected from 10 peanut-allergic children ages 8 to 14 years with peanut-specific IgE ranging from 91.8 to >100 kU/L. Skin prick tests using boiled peanut extracts were performed on 20 known peanut-allergic children ages 2 to 16 years. Blood samples were collected for peanut antigen-specific T cell assays from 3 peanut-allergic patients and 3 nonallergic volunteer controls. Raw peanuts were boiled for 30 minutes, 1 hour, 2 hours, 4 hours, and 12 hours in deionized water. After …

Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial

Peanut oral immunotherapy, using a variety of approaches, has been previously shown to induce desensitization in peanut-allergic subjects, but no products have been approved for clinical use by regulatory agencies. We performed the first phase 2 multicentered study to assess the safety and efficacy of AR101, a novel oral biologic drug product. A randomized, double-blind, placebo-controlled trial was conducted at 8 US centers. Eligible subjects were 4 to 26 years old, sensitized to peanut, and had dose-limiting symptoms to ≤143 mg of peanut protein in a screening double-blind, placebo-controlled food challenge (DBPCFC). Subjects were randomized 1:1 to daily AR101 or placebo and gradually up-dosed from 0.5 to 300 mg/day. The primary endpoint was the proportion of subjects in each arm able to tolerate ≥443 mg (cumulative peanut protein) at exit DBPCFC with no or mild symptoms. Fifty-five subjects (29 AR101, 26 placebo) were enrolled. In the intention-to-treat analysis, 23 of 29 (79%) and 18 of 29 (62%) AR101 subjects tolerated ≥443 mg and 1043 mg at exit DBPCFC, respectively, versus 5 of 26 (19%) and 0 of 26 (0%) placebo subjects (both P < .0001). Compared with placebo, AR101 significantly reduced symptom severity during exit DBPCFCs and modulated peanut-specific cellular and humoral immune responses. Gastrointestinal (GI) symptoms were the most common treatment-related adverse events (AEs) in both groups, with 6 AR101 subjects (21%) withdrawing, 4 of those due primarily to recurrent GI AEs. In this study, AR101 demonstrated an acceptable safety profile and demonstrated clinical activity as a potential immunomodulatory treatment option in peanut-allergic children over the age of 4, adolescents, and young adults.

Long Term Effects of a Probiotic and Peanut Oral Immunotherapy (PPOIT) Treatment on Peanut Allergic Children

Long Term Effects of a Probiotic and Peanut Oral Immunotherapy (PPOIT) Treatment on Peanut Allergic Children

Sustained Unresponsiveness After Sublingual Immunotherapy for Peanut-allergic Children

Sustained Unresponsiveness After Sublingual Immunotherapy for Peanut-allergic Children

P270 Diagnostic associations of Ara H8 and Ara H9 components in peanut-allergic children

Component resolved diagnostics are increasingly utilized in the diagnosis of peanut allergy. Ara h2 is associated with severity of peanut allergy. Other peanut components are poorly understood in the clinical setting. In our cohort of peanut anaphylaxis patients undergoing oral immunotherapy (OIT), we sought to determine the pre treatment correlation of Ara h8 and Ara h9 with standardized peanut RAST and other peanut components.