Peanut OIT Research Articles

Racial and Socioeconomic Disparities Exist in Patients Pursuing Peanut Oral Immunotherapy

BackgroundOral immunotherapy (OIT) is a promising treatment for food allergy. Prior studies demonstrate significant differences among food allergic individuals across race, ethnicity, and socioeconomic groups. Disparities in OIT have not been evaluated. ObjectiveWe assessed disparities in the use of OIT in patients with peanut allergy based on race, ethnicity, and socioeconomic status at a single academic medical center. MethodsWe identified 1028 peanut allergic patients under 18 years of age receiving care in the University of Michigan food allergy clinics. 148 patients undergoing peanut OIT (treatment group) were compared to the 880 patients avoiding peanut (control group). Pertinent demographic and socioeconomic characteristics were compared. ResultsThere were no differences in gender or ethnicity between the OIT and control groups. However, Black patients comprised 18% of the control group but only 4.1% of the OIT treatment group (p<0.0001). The proportion of patients with private insurance was significantly higher in the treatment group compared to control group, 93.2% vs 82.2% (p=0.0004). Finally, the Neighborhood Affluence Index, a Census-based measure of the relative socioeconomic prosperity of a neighborhood, was significantly higher in the OIT group vs. the control group (0.51±0.18 vs 0.47±0.19) (p=0.015), while the Neighborhood Disadvantage Index, a Census-based measure of the relative socioeconomic disadvantage of a neighborhood, was significantly lower (0.082±0.062 vs 0.10±0.093) (p=0.020). ConclusionSignificant racial and economic disparities exist at our institution between peanut allergic individuals who receive OIT and those who do not. Efforts to understand the basis for these disparities are important to ensure patients have equitable access to OIT.

Probiotics and other adjuvants in allergen-specific immunotherapy for food allergy: a comprehensive review.

This review delves into the potential of manipulating the microbiome to enhance oral tolerance in food allergy, focusing on food allergen-specific immunotherapy (FA-AIT) and the use of adjuvants, with a significant emphasis on probiotics. FA-AIT, including oral (OIT), sublingual (SLIT), and epicutaneous (EPIT) immunotherapy, has shown efficacy in desensitizing patients and achieving sustained unresponsiveness (SU). However, the long-term effectiveness and safety of FA-AIT are still under investigation. Probiotics, particularly strains of Lactobacillus, play a crucial role in enhancing immune tolerance by promoting regulatory T cells (Tregs) and modulating cytokine profiles. These probiotics can induce semi-mature dendritic cells, enhance CD40 expression, inhibit IL-4 and IL-5, and promote IL-10 and TGF-β, thus contributing to mucosal defense and immunological tolerance. Clinical trials combining probiotics with FA-AIT have demonstrated improved desensitization rates and immune tolerance in food-allergic patients. For example, the combination of Lactobacillus rhamnosus with peanut OIT resulted in a significantly higher rate of SU compared to the placebo group, along with notable immune changes such as reduced peanut-specific IgE and increased IgG4 levels. The review also explores other adjuvants in FA-AIT, such as biologic drugs, which target specific immune pathways to improve treatment outcomes. Additionally, nanoparticles and herbal therapies like food allergy herbal formula 2 (FAHF-2) are discussed for their potential to enhance allergen delivery and immunogenicity, reduce adverse events, and improve desensitization. In conclusion, integrating probiotics and other adjuvants into FA-AIT protocols could significantly enhance the safety and efficacy of FA-AIT, leading to better patient outcomes and quality of life.

Interaction Between Baseline Participant Factors and Treatment Effects Following Peanut Oral Immunotherapy

The Probiotic Peanut Oral Immunotherapy-003 multicenter randomized trial found that both probiotic peanut oral immunotherapy (PPOIT) and peanut OIT alone (OIT) were effective compared with placebo in inducing clinical remission after 18 months of treatment, and improving health-related quality of life (HRQL) at 12 months after treatment. Understanding treatment effect modifiers can optimize outcomes through precision care. This post hoc study examined baseline clinical and demographic participant factors that modified treatment effects. The study sample included 201 children (aged 1-10 years) with challenge-confirmed peanut allergy. Exposure variables were baseline clinical and demographic factors. Outcomes were remission (double-blind, placebo-controlled food challenge, cumulative 4,950-mg peanut protein at 8 weeks after treatment) and HRQL (change in Food Allergy Quality of Life Questionnaire-Parent Form score). Interactions between baseline factors and treatment effects on remission and HRQL were explored with regression models. A higher degree of peanut sensitivity (large peanut skin prick test, high peanut specific IgE, and low reaction-eliciting dose at study entry challenge) and other concurrent allergic conditions (multiple food allergies, asthma, or wheeze) were associated with the decreased likelihood of attaining remission after both PPOIT and OIT treatment. History of anaphylaxis was associated with the reduced likelihood of remission after PPOIT compared with OIT. For the HRQL outcome, there was evidence that sex, history of anaphylaxis, and age modified treatment effects. Baseline participant factors modify PPOIT and OIT effects on remission and HRQL. Considering modifiers of treatment effect during participant selection may optimize treatment success and clinical trial design toward specific outcomes, such as the achievement of remission.

Comparing the risk of anaphylaxis requiring epinephrine in oral immunotherapy and subcutaneous immunotherapy: Areview of recent Canadian real-world literature.

The safety of pediatric food oral immunotherapy (Ped-OIT) has been depicted by some as less favorable than subcutaneous immunotherapy (SCIT) owing to the increased number of serious adverse events requiring epinephrine. Areview of real-world data comparing Ped-OIT and SCIT safety is necessary to guide shared decision making. Our aim was to compare the safety and adverse event profiles of peanut Ped-OIT and SCIT using Canadian real-word literature. We performed a retrospective review of recent Canadian real-world literature on peanut Ped-OIT and SCIT safety and adverse events. The incidences of systemic reactions requiring epinephrine were 11 in 270 patients (4.07%) and 12 in 41,020 doses (0.029%) in a multicenter study in British Columbia, Alberta, Manitoba, and Nova Scotia studying 270 preschool-age children treated with peanut OIT. Similarly, a multicenter study in South-Western Ontario examining 160 patients between the ages of 1 and 17 years who were treated with peanut OIT showed that the incidences of systemic reactions requiring epinephrine were 5 in 160 patients (3.1%) and 8 in 52,751 doses (0.015%). Asingle-center retrospective review of 380 patients receiving aeroallergen SCIT showed that the incidences of systemic reactions requiring epinephrine were 28 in 380 patients (7.4%) and 1 in 1047 injection visits (0.095%). These findings are comparable to those of a review of 860 patients in Ontario who received either aeroallergen or venom SCIT, in which the incidence of systemic reaction requiring epinephrine was 10 in 4242 injections (0.24%). Despite differences in the OIT protocols used and age groups studied, recent real-world data suggest that the safety of preschool peanut OIT or peanut OIT using a slower buildup schedule is comparable to that of SCIT.

The Likelihood of Sustained Unresponsiveness Following Peanut Oral Immunotherapy is Linked to The Frequency of Granzyme B+ Memory CD8+ T Cells

Participants successfully desensitized to peanut through the 2-year-long peanut OIT trial POISED were classified as sustained unresponsive (SU) vs. desensitized alone (DS) based upon oral peanut challenge outcome following a 3-month peanut avoidance period post-OIT. Mass cytometry-based phenotyping of PBMCs from these participants showed that a lower frequency of naïve CD8+ T cells positively associates with sustained unresponsiveness. We further probed CD8+ T cells from SU and DS participants to understand molecules and pathways influencing peanut tolerance.

Real-world Peanut OIT in Infants May be Safer than Noninfant Preschool OIT and Equally Effective

Real-world Peanut OIT in Infants May be Safer than Noninfant Preschool OIT and Equally Effective

Eight tips for the implementation of the first licenced peanut allergy oral immunotherapy into clinical practice

BackgroundShared learnings from the early use of novel therapies can aid in their optimization. The recent introduction of peanut oral immunotherapy (peanut OIT; Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp]) for peanut allergy addresses a significant unmet need but also highlights the requirement for consideration of several factors by both prescribers and patients.ObjectiveTo provide guidance for prescribers of licenced peanut OIT to facilitate treatment delivery and improve outcomes.MethodsClinicians with experience of licenced peanut OIT (United States n = 6, United Kingdom n = 1) participated in a series of interviews and group discussions designed to elicit tips for successful implementation.ResultsClinicians identified 8 tips that were considered the most relevant, practical, and impactful for prescribers of Peanut (Arachis hypogaea) Allergen Powder-dnfp: (1) preparing to provide treatment, (2) assessing the medical indication for treatment and (3) shared decision making, (4) staff education, (5) establishing office processes, (6) managing patient expectations and using anticipatory guidance, (7) optimising adherence and (8) maintaining flexibility throughout the treatment process. In addition, a range of supporting materials (e.g., checklists and action plans) are provided.ConclusionThe introduction of a novel therapy often requires healthcare providers to modify or adopt practices to effectively employ the treatment. The provision of guidance based upon early real-world experiences of licenced peanut OIT may help inform clinical practice and improve treatment outcomes.

Real-world peanut OIT in infants may be safer than non-infant preschool OIT and equally effective

Early introduction of peanut reduces the risk for peanut allergy, as noted in the landmark Learning Early About Peanut Allergy study1; however, some infants fail primary prevention and still develop peanut allergy.2 There is evidence that preschoolers tend to have milder, more modifiable food allergy,3 which may make them excellent candidates for immunotherapy.4 Real-world data from our group have shown peanut oral immunotherapy (P-OIT) to be particularly safe and effective in preschoolers (aged <70 months),5,6 but there was no specific focus on infants (aged <12 months).

Emerging developments in the forefront of peanut oral immunotherapy.

Despite the COVID-19 pandemic, progress continued in the field of peanut oral immunotherapy over the past 12 to 18 months. Of importance, the first oral immunotherapy product for the treatment of peanut allergy was approved by the US Food and Drug Administration in January 2020. Suggested modifications to the practice of oral immunotherapy, some of which may have lasting impacts, were circulated as a result of the pandemic. New advances in pathophysiology, sustained unresponsiveness, quality of life, safety, and cost effectiveness were also published. During 2020, COVID-19 influenced the daily practice of allergy and immunology, with peanut oral immunotherapy being no exception. However, clinicians now have a FDA-approved treatment option for peanut allergy in children, a welcome development for a difficult disease. Future research is needed to clarify several knowledge deficits surrounding the best use of peanut OIT.

A198 EOSINOPHILIC ESOPHAGITIS WITH STRICTURE PRESENTING SHORTING AFTER INITIATION OF ORAL PEANUT IMMUNOTHERAPY

Abstract Background Oral immunotherapy (OIT) is increasingly practiced outside of research settings with reasonable success (Soller 2019). With OIT, a patient eats their food allergen daily, gradually increasing the dose, with the goal to prevent or reduce the severity of an anaphylactic reaction. One of the described adverse events of OIT is a risk of developing Eosinophilic Esophagitis (EoE), with cited frequency of 2.7% (Lucendo 2014). In addition, OIT is typically contraindicated in patients with known EoE but patients are not routinely screened for EoE prior to initiation of OIT. Aims To present a case of a 12 year old boy with peanut anaphylaxis who developed eosinophilic esophagitis and an esophageal stricture shortly after starting peanut immunotherapy Methods Patient chart review was conducted. A literature review was done using the words “eosinophilic esophagitis” and “immunotherapy”. Results A12 year old boy with asthma, allergic rhinitis and multiple anaphylactic food allergies, started peanut OIT with an allergist. Prior to OIT, the patient had no symptoms suggestive of EoE such as dysphagia, heartburn, chest pain or washing of food. Approximately 3.5 weeks into treatment, the patient developed daily vomiting. The patient was advised to stop the peanut OIT three days after symptom onset, but the vomiting continued for another 8 days. By the time of endoscopy (16 days after onset of vomiting), the vomiting had completely subsided for the previous five days. The upper GI endoscopy demonstrated signs of EoE throughout the length of the esophagus. In the mid esophagus there was resistance where the 9.8 mm gastroscope was unable to pass. A smaller gastroscope with a 5.9 mm width was easily able to pass through the stricture. Histology showed marked eosinophilia throughout the esophagus with basal cell hyperplasia, spongiosis, superficial microabscesses and stromal fibrosis consistent with EoE. The patient continued to be ‘asymptomatic’ at the time of endoscopy and after despite the presence of a stricture. After discussion, the patient was started on oral viscous budesonide (OVB) 1mg PO BID. The patient was re-scoped 4 weeks into OVB therapy with complete resolution of the stricture with neither macroscopic nor histologic findings of EoE. Patient is now off OVB for over a month, remains asymptomatic, and will undergo repeat endoscopy in the upcoming month to ensure normal histology Conclusions This is the first case describing EoE with an esophageal stricture shortly after initiation of OIT. Pediatric Gastroenterologists need to be increasingly aware that patients undergoing OIT are at an increasing risk of ‘developing’ or at least ‘unmasking’ EoE. More research is required to evaluate whether EoE screening, by symptom questionnaire or endoscopy is warranted prior to beginning OIT, and whether OIT is truly needed. Upper GI endoscopy showing signs of EoE and an esophageal stricture Funding Agencies CAG

Peanut-Specific IgA and IgG4 in Saliva are Modulated by Peanut OIT

Peanut-Specific IgA and IgG4 in Saliva are Modulated by Peanut OIT

ICER report for peanut OIT comes up short

ICER report for peanut OIT comes up short

Five Year Follow-Up Of Early Intervention Peanut OIT Showed Characteristics of Sustained and Prolonged Clinical Benefit

Five Year Follow-Up Of Early Intervention Peanut OIT Showed Characteristics of Sustained and Prolonged Clinical Benefit

Immunotherapy for Food Allergy: Are We There Yet?

Current clinical research focuses on food allergen-specific immunotherapy through oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. Immunotherapy relies on the delivery of gradually increasing doses of specific allergens to induce desensitization (defined as temporary antigen hyporesponsiveness that depends on regular food ingestion) and, ultimately, tolerance (defined as the ability to ingest food without symptoms despite prolonged periods of avoidance or irregular intake). Although the majority of the patients treated with OIT achieve desensitization, only a minority achieves tolerance. OIT involves higher maintenance doses of food protein (300 mg-4g) compared with SLIT (2.5-7.5 mg) and EPIT (250-500 mcg). OIT efficacy is higher compared with SLIT, but OIT is associated with higher rate of systemic adverse events compared with SLIT and EPIT. OIT is also associated with a minor risk of eosinophilic esophagitis. Combined treatment of OIT and anti-IgE monoclonal antibody has improved safety but not efficacy compared with OIT alone. Early initiation of peanut OIT in peanut-allergic infants and young children may afford superior efficacy and safety. In this review, we discuss the allergen-specific strategies currently explored for the treatment of food allergy, including immunotherapy with native and heat-modified food proteins. Additional research employs strategies to improve the safety and efficacy of allergen immunotherapy through modifications of allergen structure and addition of immunomodulatory adjuvants.

Six month course of peanut OIT leads to suppression of basophil activation which begins to wane within four weeks after OIT is stopped

Six month course of peanut OIT leads to suppression of basophil activation which begins to wane within four weeks after OIT is stopped

A new OIT protocol for severe peanut allergy

Methods Our pirmary outcome was the increase in the amount of ingested peanut protein tolerated in DBPCFC by peanut OIT. Secondarily we investigated safety of OIT. Since September 2011, peanut-sensitized patients with moderate to severe allergic reaction (1) in DBPCFC were included. Bronchial hyperreactivity, exhaled nitric oxide, and food allergy related quality of life (2, 3) were evaluated pre and post OIT. Roasted and defatted peanut flour, allergenity of which was assessed using microarray inhibition, was mixed with margarine (no milk or soy) in 3 concentrations at hospital kitchen. A teaspoonful of peanut-margarine mixture weight 1.7 g. From week 20 and on, we used real peanuts. The first dose of 0.1 mg peanut protein was taken at hospital and the same dose continued daily at home. Dose escalations occurred at home every 1 to 2 weeks. The patient returned to the hospital 7 times for dose escalation. Antihistamine was taken daily until 2 weeks from reaching the maintenance dose of 4 peanuts. As safety procedures, exercise was forbidden one hour post each dose and the day of escalation, and the patients carried adrenalin auto-injectors.

Development of Tolerance Following Peanut Immunotherapy Is Associated with Basophil Hyporesponsiveness and Low Peanut-IgE:IgG4 Ratio

RationalePeanut allergic patients can be desensitized with both oral (OIT) and sublingual (SLIT) immunotherapy, however once therapy is withdrawn only a subset of subjects will remain tolerant. We examined basophil responses and peanut-specific immunoglobulins to determine if these parameters were indicative of tolerance development.MethodsSubjects enrolled in peanut OIT or SLIT protocols underwent double-blind placebo-controlled food challenges (DBPCFCs) with peanut to assess desensitization while continuing daily therapy. Subjects passing the DBPCFC were instructed to cease daily therapy and avoid all peanut products for 4 weeks, at which time a second DBPCFC was administered to assess tolerance. Basophil activation to peanut antigens, as well as serum peanut-specific IgE and IgG4 were measured at the time of desensitization DBPCFC.ResultsTolerance was achieved in 5 of 12 (41.7%) subjects receiving SLIT, whereas 18 of 27 (66.7%) subjects were tolerant after receiving OIT. Basophil responses were significantly lower in the SLIT group that developed tolerance than in the non-tolerant SLIT group for each of 4 log-fold dilutions of peanut antigen used in the assay (p<0.05). Cumulatively 21 of 23 (91.3%) tolerant subjects had a peanut-IgE:IgG4 ratio below 0.92, while only 3 of 15 non-tolerant subjects had a ratio below 0.92; yielding an ROC curve with 91.3% specificity and 81.3% sensitivity.ConclusionsDevelopment of tolerance following abstinence from peanut immunotherapy is possible and is associated with low basophil activation profiles and peanut-specific IgE:IgG4 ratio. Mechanistically, basophil suppression and the balance of antigen-specific IgE and IgG4 may be important in the development of tolerance following peanut immunotherapy. RationalePeanut allergic patients can be desensitized with both oral (OIT) and sublingual (SLIT) immunotherapy, however once therapy is withdrawn only a subset of subjects will remain tolerant. We examined basophil responses and peanut-specific immunoglobulins to determine if these parameters were indicative of tolerance development. Peanut allergic patients can be desensitized with both oral (OIT) and sublingual (SLIT) immunotherapy, however once therapy is withdrawn only a subset of subjects will remain tolerant. We examined basophil responses and peanut-specific immunoglobulins to determine if these parameters were indicative of tolerance development. MethodsSubjects enrolled in peanut OIT or SLIT protocols underwent double-blind placebo-controlled food challenges (DBPCFCs) with peanut to assess desensitization while continuing daily therapy. Subjects passing the DBPCFC were instructed to cease daily therapy and avoid all peanut products for 4 weeks, at which time a second DBPCFC was administered to assess tolerance. Basophil activation to peanut antigens, as well as serum peanut-specific IgE and IgG4 were measured at the time of desensitization DBPCFC. Subjects enrolled in peanut OIT or SLIT protocols underwent double-blind placebo-controlled food challenges (DBPCFCs) with peanut to assess desensitization while continuing daily therapy. Subjects passing the DBPCFC were instructed to cease daily therapy and avoid all peanut products for 4 weeks, at which time a second DBPCFC was administered to assess tolerance. Basophil activation to peanut antigens, as well as serum peanut-specific IgE and IgG4 were measured at the time of desensitization DBPCFC. ResultsTolerance was achieved in 5 of 12 (41.7%) subjects receiving SLIT, whereas 18 of 27 (66.7%) subjects were tolerant after receiving OIT. Basophil responses were significantly lower in the SLIT group that developed tolerance than in the non-tolerant SLIT group for each of 4 log-fold dilutions of peanut antigen used in the assay (p<0.05). Cumulatively 21 of 23 (91.3%) tolerant subjects had a peanut-IgE:IgG4 ratio below 0.92, while only 3 of 15 non-tolerant subjects had a ratio below 0.92; yielding an ROC curve with 91.3% specificity and 81.3% sensitivity. Tolerance was achieved in 5 of 12 (41.7%) subjects receiving SLIT, whereas 18 of 27 (66.7%) subjects were tolerant after receiving OIT. Basophil responses were significantly lower in the SLIT group that developed tolerance than in the non-tolerant SLIT group for each of 4 log-fold dilutions of peanut antigen used in the assay (p<0.05). Cumulatively 21 of 23 (91.3%) tolerant subjects had a peanut-IgE:IgG4 ratio below 0.92, while only 3 of 15 non-tolerant subjects had a ratio below 0.92; yielding an ROC curve with 91.3% specificity and 81.3% sensitivity. ConclusionsDevelopment of tolerance following abstinence from peanut immunotherapy is possible and is associated with low basophil activation profiles and peanut-specific IgE:IgG4 ratio. Mechanistically, basophil suppression and the balance of antigen-specific IgE and IgG4 may be important in the development of tolerance following peanut immunotherapy. Development of tolerance following abstinence from peanut immunotherapy is possible and is associated with low basophil activation profiles and peanut-specific IgE:IgG4 ratio. Mechanistically, basophil suppression and the balance of antigen-specific IgE and IgG4 may be important in the development of tolerance following peanut immunotherapy.

Antigen-Specific IL-13 Secretion in Children with Eosinophilic Esophagitis

S U N D A Y 471 Development of Tolerance Following Peanut Immunotherapy Is Associated with Basophil Hyporesponsiveness and Low Peanut-IgE:IgG4 Ratio Michael D. Kulis, Jr, , PhD, Rishu Guo, PhD, Edwin Kim, MD, MS, Brian P. Vickery, MD, A. Wesley Burks, MD FAAAAI; University of North Carolina at Chapel Hill, Chapel Hill, NC. RATIONALE: Peanut allergic patients can be desensitized with both oral (OIT) and sublingual (SLIT) immunotherapy, however once therapy is withdrawn only a subset of subjects will remain tolerant. We examined basophil responses and peanut-specific immunoglobulins to determine if these parameters were indicative of tolerance development. METHODS: Subjects enrolled in peanut OIT or SLIT protocols underwent double-blind placebo-controlled food challenges (DBPCFCs) with peanut to assess desensitization while continuing daily therapy. Subjects passing the DBPCFC were instructed to cease daily therapy and avoid all peanut products for 4 weeks, at which time a second DBPCFC was administered to assess tolerance. Basophil activation to peanut antigens, as well as serum peanut-specific IgE and IgG4 were measured at the time of desensitization DBPCFC. RESULTS: Tolerance was achieved in 5 of 12 (41.7%) subjects receiving SLIT, whereas 18 of 27 (66.7%) subjects were tolerant after receiving OIT. Basophil responses were significantly lower in the SLIT group that developed tolerance than in the non-tolerant SLIT group for each of 4 log-fold dilutions of peanut antigen used in the assay (p<0.05). Cumulatively 21 of 23 (91.3%) tolerant subjects had a peanut-IgE:IgG4 ratio below 0.92, while only 3 of 15 non-tolerant subjects had a ratio below 0.92; yielding an ROC curve with 91.3% specificity and 81.3% sensitivity. CONCLUSIONS: Development of tolerance following abstinence from peanut immunotherapy is possible and is associated with low basophil activation profiles and peanut-specific IgE:IgG4 ratio. Mechanistically, basophil suppression and the balance of antigen-specific IgE and IgG4may be important in the development of tolerance following peanut immunotherapy.

Life with Peanut: Follow up of Tolerant Versus Desensitized Subjects After Peanut OIT

Life with Peanut: Follow up of Tolerant Versus Desensitized Subjects After Peanut OIT

2078- Immunotherapy – 2078. Allergen-specific oral immunotherapy for peanut allergy: a Cochrane systematic review

in children, and that this is associated with evidence of concurrent immune-modulation. This treatment approach was however associated with substantial risk of adverse reactions, although most of these were mild. Thus, peanut OIT cannot currently be recommended as a treatment for the management of patients with IgE-mediated peanut allergy. Larger RCTs are needed investigating the acceptability, effectiveness and cost-effectiveness of safer treatment regimens, particularly in relation to the induction of long-term immune tolerance.