Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Shared decision-making in food allergy: Navigating an exciting era.

OBJECTIVE: Shared decision-making (SDM) is increasingly used in food allergy. We review its use in the areas of prevention, diagnosis, and management. DATA SOURCES: PubMed and online SDM resources. STUDY SELECTIONS: Studies and reviews relevant to SDM and areas in food allergy that decision-making may be applied were selected for discussion. RESULTS: Food allergy represents an area with multiple opportunities for SDM. Patients, on one hand, need to obtain the necessary information and understanding of existing options from the allergist. The allergist, on the other hand, needs to understand "where the patient is coming from," their needs, preferences, and values, so that jointly they can reach a decision that is responsive to these. Benefits of SDM include a better understanding of disease by patients, improved compliance with medication, better health outcomes, decreased health care costs, and improved ability of patients to manage their disease and make informed choices. CONCLUSION: In food allergy prevention, diagnosis, and management, multiple preference-sensitive options exist for patients where SDM may be used during allergy consultations, alongside decision aids. Decision aids are tools that assist and support patients during the SDM process, by supplementing the patient-physician interaction.

A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

A Review of Shared Decision-Making, Published Protocols, and Post-desensitization Strategies in Oral Immunotherapy (OIT).

PURPOSE OF REVIEW: The aim of this review is to highlight key published oral immunotherapy (OIT) protocols and post-desensitization strategies for the major food allergens and to cover important concepts to consider when evaluating OIT for food-allergic patients. Shared decision-making should help identify patient and family values which will help influence the type of evidence-based protocol and maintenance strategy to use. RECENT FINDINGS: With food OIT emerging as a treatment option, there is a pressing need for patients, physicians, and other providers to have a nuanced understanding of the management choices available to them. There are now randomized controlled trials (RCT) of OIT for peanut, egg, milk, and wheat, and reports of cohorts of patients who have undergone OIT for tree nuts and sesame clinically. The current published protocols contain significant diversity in terms of starting dose, build-up schedule, maintenance dose, and even the product used for desensitization. Emerging data can help direct the long-term maintenance strategy for patients on OIT. Based on patient and family values elicited through the shared decision-making process, an OIT protocol may be selected that balances the level of desensitization, potential side effects, frequency of clinic visits, and potential to induce sustained unresponsiveness, among other factors. Once maintenance dosing is reached, most patients will need to maintain regular exposure to the food allergen to remain desensitized. The option to transition to commercial food products with equivalent amounts of food protein as the OIT maintenance dose would simplify the dosing process and perhaps improve palatability as well. Less frequent or decreased OIT dosing can provide practical benefits but may affect the level of desensitization and safety for some patients.

Evaluation and Modification of a Shared Decision-Making Tool for Peanut Allergy Management.

PURPOSE OF REVIEW: Based on shared decision-making (SDM) principles, a decision aid was previously developed to help patients, their caregivers, and physicians decide which peanut allergy management approach best suits them. This study refined the decision aid's content to better reflect patients' and caregivers' lived experience. RECENT FINDINGS: Current standard of care for peanut allergy is avoidance, although peanut oral immunotherapy has been approved by the Food and Drug Administration for use in patients 4-17 years old. An advisory board of allergy therapy experts (n = 3) and patient advocates (n = 3) informed modifications to the decision aid. The revised tool underwent cognitive debriefing interviews (CDIs) among adolescents (12-17 years old) with peanut allergy and caregivers of patients 4-17 years old with peanut allergy to evaluate its relevance, understandability, and usefulness. The 20 CDI participants understood the information presented in the SDM tool and reported it was important and relevant. Some revisions were made based on participant feedback. Results support content validity of the Peanut Allergy Treatment SDM Tool.

The future of food allergy: Challenging existing paradigms of clinical practice.

The field of food allergy has seen tremendous change over the past 5-10 years with seminal studies redefining our approach to prevention and management and novel testing modalities in the horizon. Early introduction of allergenic foods is now recommended, challenging the previous paradigm of restrictive avoidance. The management of food allergy has shifted from a passive avoidance approach to active interventions that aim to provide protection from accidental exposures, decrease allergic reaction severity and improve the quality of life of food-allergic patients and their families. Additionally, novel diagnostic tools are making their way into clinical practice with the goal to reduce the need for food challenges and assist physicians in the-often complex-diagnostic process. With all the new developments and available choices for diagnosis, prevention and therapy, shared decision-making has become a key part of medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments as well as the evolution of the field of food allergy in the next decade.

Management of Anaphylaxis During Peanut Oral Immunotherapy.

BACKGROUND: Peanut oral immunotherapy (POIT) has emerged as an active management option for peanut allergy, with an FDA-approved product now available for therapy. Allergic reactions, including anaphylaxis, can occur during therapy and their management is key in optimizing this treatment and patient outcomes. PURPOSE OF REVIEW: In this manuscript, we will review the rates of allergic reactions and anaphylaxis in seminal peanut oral immunotherapy research studies. We will examine factors that can alter the risk of anaphylaxis and describe various strategies, including adjunct therapies, that have the potential to mitigate anaphylaxis risk based on published evidence. RECENT FINDINGS: Rates of anaphylaxis and epinephrine administration vary in different research studies, but there is consensus that most POIT-related allergic reactions are mild or moderate and not severe. Certain external factors (for example, tiredness, exercise, viral illness) as well as uncontrolled allergic co-morbidities (asthma, allergic rhinitis) have been shown to increase the risk of anaphylaxis during OIT. The search of biomarkers who may predict who is at risk for severe allergic reactions is ongoing. Adjunct therapies have shown promise, but further studies are required to optimize their use alongside POIT. Our understanding of anaphylaxis during POIT has increased in recent years, resulting in better management strategies. However, future plans will need to involve all stakeholders, including physicians, patients and families, researchers, public health authorities, and the food, hospitality, and catering industries.

Asthma outcomes in pediatric patients with 30-day follow-up after an asthma hospitalization in a Medicaid-managed care program.

BACKGROUND: National asthma guidelines recommend an outpatient follow-up after hospitalization for asthma. Our aim is determine if a follow-up visit within 30 days after an asthma hospitalization impacts risk for re-hospitalization and emergency department visits for asthma within the following year. METHODS: This was a retrospective cohort study of claims data of Texas Children's Health Plan (a Medicaid managed care program) members age 1 to <18 years and hospitalized for asthma between January 1, 2012, and December 31, 2018. Primary outcomes were days to re-hospitalization and emergency department visit between 30 days and 365 days following the index hospitalization. RESULTS: We identified 1,485 children age 1 to <18 years hospitalized for asthma. Comparing those with a 30 day follow-up to those without, there was no difference in days to re-hospitalization (adjusted hazard ratio 1.23, 95% Confidence Interval (CI) 0.74-2.06) or emergency department visit for asthma (aHR 1.08, 95% CI 0.88-1.33). Inhaled corticosteroid and short acting beta agonist dispensing were greater in the group completing the 30 day follow-up (means of 2.8 and 4.8 respectively for those with follow-up, 1.6 and 3.5 respectively for those without, p < 0.0001). CONCLUSION: Having a follow-up outpatient visit within 30 days of an asthma hospitalization is not associated with a decrease in asthma re-hospitalization or emergency department visit in the 30-365 day period following the index hospitalization. Non-adherence to regular use of inhaled corticosteroid medication was high in both groups. These findings suggest need for improvement in the quality and quantity of post hospital asthma follow-up.

Participant characteristics and safety outcomes of peanut oral immunotherapy in the RAMSES and ARC011 trials.

BACKGROUND: Clinical trials (PALISADE [ARC003], ARTEMIS [ARC010]) proving efficacy and safety of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) have used double-blind, placebo-controlled food challenges (DBPCFCs) to screen for eligibility and to evaluate efficacy. In routine clinical practice, individuals with peanut allergy do not always undergo food challenges to confirm diagnosis or determine candidacy for treatment. OBJECTIVE: To describe PTAH safety and tolerability in participants selected by clinical history and peanut sensitization parameters not undergoing DBPCFCs during trials and to compare findings with previously published data. METHODS: RAMSES (ARC007) was a 6-month, phase 3, randomized, double-blind, placebo-controlled trial in children aged 4 to 17 years with physician-confirmed peanut allergy. ARC011 was the subsequent 6-month follow-on maintenance PTAH study. The primary end point for RAMSES and ARC011 was the frequency of treatment-emergent adverse events (AEs). We descriptively compared baseline characteristics and safety outcomes from RAMSES and ARC011 to participants undergoing DBPCFCs in phase 3 PALISADE and ARTEMIS trials. RESULTS: In 506 patients randomized to study treatment, baseline characteristics appeared balanced among groups. Proportion of participants with at least 1 AE was 55% for PTAH vs 33.9% for placebo during initial dose escalation and 98.8% vs 94.0% during updosing, respectively. Most participants with AEs had mild or moderate events. The most common AEs were gastrointestinal. Comparisons to pooled PALISADE and ARTEMIS data revealed higher baseline median peanut-specific immunoglobulin E and skin prick test values for RAMSES participants. Safety outcomes during trial periods were comparable. CONCLUSION: Safety data from clinically selected children with peanut allergy receiving PTAH do not seem different from those in phase 3 trials requiring DBPCFC to enter trials.

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 .).

Weighing the benefits and risks of oral immunotherapy in clinical practice.

Food allergies are common and affect 6-8% of children in the United States; they pose a significant burden on the quality of life of children with allergy and their caregivers due to multiple daily restrictions. Despite the recommended dietary avoidance, reactions tend to occur due to unintentional exposure to the allergenic food trigger. Fear of accidental ingestions with potentially severe reactions, including anaphylaxis and death, creates anxiety in individuals with food allergy. Oral immunotherapy has emerged as a form of active and potentially disease-modifying treatment for common food allergies encountered in childhood. The efficacy of oral immunotherapy is high, with the majority of participants achieving desensitization and, as a result, protection from trace exposures and improved quality of life. The main risk of oral immunotherapy consists of allergic reactions to treatment. In general, rates of allergic reactions and anaphylaxis are reported to be higher in individuals pursuing therapy options, but most subjects who undergo oral immunotherapy will likely experience mild or moderate reactions during treatment. Adverse events tend to reduce in both frequency and number in the maintenance period. The use of immune modulators alongside oral immunotherapy has been suggested, with the aim to improve efficacy and safety, and to facilitate the overall process. It is evident that the landscape of food allergy management is changing and that the future looks brighter, with different options emerging over time. The process of how to choose the appropriate option becomes a discussion between the clinician and the patient, which involves a joint review of the current medical evidence but also the patient's preference for balancing particular attributes of the treatment. By working together, providers and patients will ensure achievement of the best possible outcome for children with food allergies.

Quality of life improves significantly after real-world oral immunotherapy for children with peanut allergy.

BACKGROUND: Peanut oral immunotherapy (POIT) is a novel and active form of treatment for patients with peanut allergy, with multiple research studies supporting its efficacy and safety. However, there are limited data available on changes in patients' quality of life (QoL) after successful desensitization. The Food and Drug Administration in the United States recently approved the first POIT drug for commercial use. OBJECTIVE: To evaluate the QoL of patients with peanut allergy receiving POIT in a real-world academic setting. METHODS: Twenty-one patients aged 4 to 17 years with a physician-established diagnosis of peanut allergy were offered POIT. Quality-of-life scores were assessed with the use of a validated Food Allergy Quality of Life questionnaire. Changes in quality-of-life scores were measured for each patient before and after POIT. The Wilcoxon signed-rank test was used to compare the distributions of scores before and after therapy. RESULTS: We noted a statistically significant drop (reflecting improvement in the QoL) in the overall Food Allergy Quality of Life score (median 3.70 vs 2.97, P = .049) between baseline and successful desensitization to 300-mg peanut protein. In addition, the Social and Dietary Limitations subscale score (median 4.33 vs 2.89, P = .02) and the Food Allergy Independent Measure score (median 3.17 vs 2.22, P = .001) also improved significantly after therapy. CONCLUSION: We report a significant improvement in the overall QoL before and after POIT treatment, with fewer concerns about accidental exposures and severity of allergic reactions as well as fewer limitations in dietary choices and social interactions.

Quality of life in food allergic children: Results from 174 quality-of-life patient questionnaires.

BACKGROUND: Food allergies are becoming a global concern and pose a significant burden on allergic children and their family, with reported physical and emotional effects. OBJECTIVE: To investigate the effect of food allergy on patients' quality of life (QoL), to identify any characteristics associated with worse QoL, and to directly compare the effect of food allergies on the QoL of adolescents vs younger children. METHODS: Children 0 to 17 years old with a physician-confirmed food allergy diagnosis were invited to participate by completing the validated Food Allergy Quality of Life Questionnaire (FAQLQ). The FAQLQ form for children 10 to 12 years old was completed by the parent (proxy report), whereas the FAQLQ form for adolescents was completed by the adolescent (self-report). Scores were compared using the Wilcoxon rank sum test. Independent median regressions were used to test association between potential risk factors and QoL outcomes. RESULTS: In our cohort, the median FAQLQ score was significantly higher (reflecting lower QoL) in adolescents compared with children (4.7 vs 3.5, P = .007). The median social and dietary limitations score (5.2 vs 4, P = .002) and the median emotional impact score (3.8 vs 3.1, P = .02) were also higher in adolescents. Limitations in family activities because of food allergy had a negative effect on QoL. CONCLUSION: Food allergic adolescents are affected more than younger children (based on parental report) in terms of QoL, with a direct reflection on all areas of their daily life (emotional, dietary, and social). In addition, limitations in family activities because of the child's food allergy significantly worsen the QoL and well being of all family members.

Emerging triggers of food protein-induced enterocolitis syndrome: Lessons from a pediatric cohort of 74 children in the United States.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is an infrequent non-IgE-mediated gastrointestinal allergic disorder that occurs mostly in infants and young children. FPIES food triggers vary among different geographic locations, and the condition is still underdiagnosed and underrecognized. OBJECTIVE: To identify the triggers, characteristics, and management of FPIES in a pediatric US population of 74 children presenting to a tertiary center during a 3-year period. METHODS: We performed a retrospective electronic record review of all pediatric patients with a diagnosis of FPIES who presented to Texas Children's Hospital emergency centers and clinics. RESULTS: Most of our patients were white, and 65% had a positive family history of atopy. The median age at the first FPIES episode was 5 months (interquartile range, 4-6 months), and the median age at diagnosis was 11 months (interquartile range, 7-16 months). Grains (88%), cow's milk (49%), and vegetables (43%) were the most common food triggers in our cohort. Of the fruits, banana (24%) and avocado (16%) were predominantly reported. More than half of our patients experienced FPIES to multiple food triggers. CONCLUSION: In our cohort, rice (53%) was the most common individual food trigger, surpassing cow's milk and soybean, previously reported as the most prevalent FPIES triggers in the United States. Banana (24%) and avocado (16%) rates were also much higher than in other studied populations, likely a reflection of different dietary and weaning habits in our area. Time from disease presentation to diagnosis was delayed, potentially because of difficulties in disease recognition. We noted a significant percentage of multiple-food FPIES in contrast to other populations.