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.

Core Outcome Set for IgE-mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study 'COMFA'.

BACKGROUND: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. METHODS: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS. RESULTS: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes. CONCLUSION: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes.

Age-Related Food Aversion and Anxiety Represent Primary Patient Barriers to Food Oral Immunotherapy.

BACKGROUND: Although oral immunotherapy (OIT) for food allergy is a reasonable treatment option, barriers to this procedure's implementation have not been extensively evaluated from a patient perspective. OBJECTIVE: We evaluated the barriers patients face during OIT administration, including anxiety and taste aversion, and the role of health care professionals, especially dietitians. METHODS: A survey in Canada and the United States involved families currently enrolled in food OIT programs. RESULTS: Of responses from 379 participants, fear of reaction was the most common barrier to OIT initiation, with 45.6% reporting it being a "very significant" barrier with other fears reported. However, taste aversion represented the prominent obstacle to continuation. Taste aversion was associated with a slower buildup (P = .02) and a reduction in dose (P = .002). Taste aversion was a strongly age-dependent barrier for initiation (P < .001) and continuation (P < .002), with older children over 6 years of age reporting it as a very significant barrier (P < .001). Boredom was reported as a concern for specific allergens such as peanut, egg, sesame, and hazelnuts (P < .05), emphasizing the need for diverse food options. Notably, 59.9% of respondents mixed OIT foods with sweet items. Despite these dietary concerns, dietitians were underutilized, with only 9.5% of respondents having seen a dietitian and the majority finding dietitian support helpful with greater certainty about the exact dose (P < .001). CONCLUSIONS: Taste aversion and anxiety represent primary patient-related barriers to OIT. Taste aversion was highly age dependent, with older patients being more affected. Dietitians and psychology support were underutilized, representing a critical target to improve adherence and OIT success.

SQ sublingual immunotherapy tablets for children with allergic rhinitis: A review of phase three trials.

AIM: To provide paediatricians with a summary of efficacy and safety of SQ sublingual immunotherapy (SLIT) tablets from phase three, randomised, double-blind, placebo-controlled trials in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. METHODS: PubMed searches were conducted and unpublished data were included if necessary. RESULTS: Of the 93 publications, 12 were identified reporting 10 trials. One trial was excluded as paediatric-specific efficacy data were unavailable. The nine eligible trials evaluated grass, house dust mite, ragweed and tree SLIT tablets. Consistent reductions in allergic rhinitis or rhinoconjunctivitis symptoms and medication use were observed with SQ SLIT tablets versus placebo. In a five-year trial, sustained reduction of allergic rhinoconjunctivitis symptoms, asthma symptoms and medication use were observed with SQ grass SLIT tablet versus placebo. The number-needed-to-treat to prevent asthma symptoms and medication use in one additional child during follow-up was lowest in younger children. SQ SLIT tablets were generally well tolerated across trials. CONCLUSION: Evidence supports use of SQ SLIT tablets in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. Long-term data demonstrate disease-modifying effects of SQ grass SLIT tablet and suggest the clinical relevance of initiating allergy immunotherapy earlier in the disease course.

Flex-IT! Applying "Platform Trials" Methodology to Immunotherapy for Food Allergy in Research and Clinical Practice.

There is an increasing trend in the management of food allergy toward active treatment using allergen immunotherapy (AIT). Although AIT is efficacious, treatment-related adverse events are common, particularly with oral immunotherapy in those with high levels of allergen-specific IgE sensitization. In clinical practice, these adverse events inevitably create challenges: clinicians and patients routinely face decisions whether to alter the dose itself, the frequency of dosing, and the pace of escalation, or indeed discontinue AIT altogether. Flexibility is therefore needed to adapt treatment, particularly in clinical practice, so that participants are "treated-to-target." For example, this may entail a significant change in the dosing protocol or even switching from one route of administration to another in response to frequent adverse events. We refer to this approach as flexible immunotherapy. However, there is little evidence to inform clinicians as to what changes to treatment are most likely to result in treatment success. Classical clinical trials rely, by necessity, on relatively rigid updosing protocols. To provide an evidence base to optimize AIT, the food allergy community should adopt adaptive platform trials, where a "master protocol" facilitates more efficient evaluation, including longer-term outcomes of multiple interventions. Within a single clinical trial, participants are able to switch between different treatment arms; interventions can be added or dropped without compromising the integrity of the trial. Developing platform trials for food AIT may initially be costly, but they represent a significant opportunity to grow the evidence base (with respect to both treatment outcomes and biomarker discovery) at scale. In addition, they could help understand longitudinal disease trajectories that are difficult to study in clinical trials for food allergy due to the time needed to demonstrate changes in efficacy. Finally, their adoption would achieve greater collaboration and consistency in approaches to proactive management of food allergy in routine clinical practice. As a community, we need to actively pursue this with funders and established research collaborations to deliver the very best outcomes for our patients and their families.

Updates in Food Allergy Prevention in Children.

Although significant evidence exists that feeding early has a role in the prevention of food allergy, this intervention in isolation may not be sufficient. Recent evidence highlights that early introduction of peanut specifically has had no significant impact on the populational prevalence of peanut allergy. Other factors that may contribute to food allergy prevention include regularity of ingestion once an allergen is introduced and consideration to the form in which the allergen is introduced (such as baked versus cooked egg). There are also many practicalities to early feeding and some discrepant viewpoints on these practicalities, which has led to poor implementation of early feeding strategies. In general, preemptive screening before food introduction is not recommended by most international allergy societies. Although there is little guidance to inform early introduction of allergens other than milk, egg, and peanut, the mechanism of sensitization is thought to be similar and there is no harm to early introduction. In terms of frequency and duration of feeding, there is little evidence to inform any concrete recommendations.

Varying Approaches to Management of IgE-Mediated Food Allergy in Children Around the World.

Food allergy is a chronic disease that affects individuals of all ages and is a significant public health problem globally. This narrative overview examines clinical management strategies for IgE-mediated food allergy in children around the world to understand variations in practice. Information was drawn from clinical practice guidelines, recent research, the websites of professional and governmental bodies with expertise in food allergy, and clinical experts from a broad cross-section of geographical regions. The structure and delivery of clinical services, allergen avoidance and food labeling, and resources to support the management of allergic reactions in the community are discussed in detail. The adoption of emerging food immunotherapies is also explored. Wide variations in clinical management of food allergy were apparent across the different countries. Common themes were continuing issues with access to specialist care and recognition of the need to balance risk reduction with dietary and social restrictions to avoid unnecessary detrimental impacts on the quality of life of food allergy sufferers. Findings highlight the need for standardized presentation of practice and priorities, and may assist clinicians and researchers when engaging with government and funding agencies to address gaps.

Minimization of ragweed allergy immunotherapy costs through use of the sublingual immunotherapy tablet in Canadian children with allergic rhinoconjunctivitis.

BACKGROUND: Allergy immunotherapy (AIT), in the form of subcutaneous immunotherapy (SCIT) with alum-precipitated aqueous extracts, SCIT with a modified ragweed pollen allergen tyrosine adsorbate (MRPATA; Pollinex®-R), or a sublingual immunotherapy (SLIT)-tablet are options for the treatment of ragweed pollen allergic rhinoconjunctivitis (ARC) in Canadian children. A cost minimization analysis evaluated the economic implications of the use of the ragweed SLIT-tablet vs SCIT in Canadian children with ragweed ARC. METHODS: A cost minimization analysis was conducted comparing the short ragweed SLIT-tablet, 12 Amb a 1-U, preseasonally with preseasonal ragweed SCIT, annual ragweed SCIT, or MRPATA. The analysis was conducted over a time horizon of 3 years from a public payer perspective in Ontario and Quebec. Resources and costs associated with medication and services of healthcare professionals were considered for each treatment. The resource and cost input values for the model were obtained from published literature and validated by Canadian clinical experts in active allergy practice. A discount rate of 1.5% was applied. Several scenario analyses were conducted to determine the impact of many of the key base case assumptions on the outcomes. RESULTS: Over the total 3-year time horizon, the ragweed SLIT-tablet had a potential cost savings of $900.14 in Ontario and $1023.14 in Quebec when compared with preseasonal ragweed SCIT, of $6613.22 in Ontario and $8750.64 in Quebec when compared with annual ragweed SCIT, and $79.62 in Ontario and $429.49 in Quebec when compared with MRPATA. The ragweed SLIT-tablet had higher drug costs compared with the other AIT options, but lower costs for healthcare professional services. The lower costs for healthcare professional services with the ragweed SLIT-tablet were driven by the need for fewer office visits than SCIT. Scenario analysis indicated that costs were most impacted by including societal costs (e.g., costs associated with patient/caregiver travel and time lost). The potential cost savings of the ragweed SLIT-tablet versus SCIT and MRPATA was maintained in most scenarios. CONCLUSIONS: In this cost minimization analysis, the ragweed SLIT-tablet provided estimated cost savings from a public payer perspective for the treatment of ragweed ARC in Canadian children compared with SCIT or MRPATA.

An allergist's approach to food poisoning.

Foodborne illnesses represent a significant global health concern. These preventable diseases lead to substantial mortality and morbidity worldwide. Substantial overlap with food allergy exists with similar clinical presentations and symptom onset. Knowledge of the typically implicated microorganisms and toxins can help properly identify these diseases. A thorough history is essential to differentiate between these 2 disorders. The types of food implicated may be similar including milk, egg, fish, and shellfish. The timing of symptom onset may overlap and lead to misdiagnosis of disorders such as food protein-induced enterocolitis syndrome. Classically, histamine-related food poisoning is also typically confused with true food allergy and may be seen as related to fish and cheese. Knowledge of epidemiology, patterns, and etiology of allergic conditions and foodborne illness may help the allergist differentiate among these common diseases.

International Peanut Allergy Prevention, 6 Years After the Learning Early About Peanut Study.

Six years ago, the Learning Early About Peanut (LEAP) trial findings helped fundamentally shift the paradigm of peanut allergy prevention. Although the results of LEAP are well accepted, policy-makers, caregivers, and clinicians struggle with how best to implement and apply the study's key findings in clinical practice. Differences in guidelines highlight issues related to peanut allergy prevention implementation, including caregiver acceptability, cost, fidelity, feasibility, appropriateness, and adoption. The goals of this rostrum are to review how the LEAP study has informed international peanut allergy prevention policy, as well as to review the strengths and ongoing controversies in peanut allergy prevention implementation.

Rupatadine to prevent local allergic reactions to sublingual allergy immunotherapy: a case series.

BACKGROUND: Sublingual immunotherapy tablets (SLIT-T) are an effective treatment for allergic rhinitis (AR), but some patients experience local allergic reactions (LAR) in the first few weeks of treatment that can lead to treatment discontinuation. Although oral antihistamines are recommended for the treatment and pretreatment of LAR associated with SLIT-T, there are no clinical trial data to support this recommendation. Rupatadine is an H1 antihistamine that also inhibits platelet activating factor activity. The objective of this case series is to describe real-world clinical situations in which rupatadine was used to treat or mitigate SLIT-T-related LAR. CASE PRESENTATIONS: Five cases are presented by the managing allergist and off-label use of rupatadine is their expert opinion only. Patients in all 5 cases were treated with a SLIT-T (e.g. ragweed, tree, grass, or house dust mites) for the management of allergic rhinitis and experienced bothersome LAR with the first SLIT-T administration. In 3 cases, rupatadine 10 mg was administered for the immediate treatment of LAR (either in-office with the first SLIT-T dose or for subsequent LAR experienced at home) and the symptoms resolved. In 3 cases, pretreatment with other second-generation H1 antihistamines was unable to prevent LAR and the patients discontinued the SLIT-T. In these 3 cases, switching to pretreatment with rupatadine allowed the patients to restart and tolerate SLIT-T treatment with minimal or no LAR. In these patients with an established history of LAR, proactive pretreatment with rupatadine in subsequent seasons or with initiation of a different SLIT-T mitigated the previously experienced LARs. CONCLUSIONS: In the cases presented, treatment with rupatadine resolved LAR associated with SLIT-T treatment and rupatadine pretreatment appeared to mitigate subsequent LAR. Rupatadine may be an option to treat or improve the tolerability of the SLIT-T, potentially improving early treatment persistence.

The Importance of a Timely Second Dose of the 2021 COVID-19 mRNA Vaccine Depends on the Protection Afforded by a First Dose and Subsequent Risk of Anaphylaxis.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents our greatest hope to combat the devastating coronavirus disease 2019 (COVID-19) pandemic. Amid ongoing global vaccination efforts, rare cases of severe allergic reactions to COVID-19 mRNA vaccines have received significant attention. Although the exact nature of these reactions may be heterogeneous, various approaches exist to engage with patients, communities, public health departments, primary care providers, and other clinicians in a multidisciplinary approach to advance population health. Whereas it is optimal for patients to receive COVID-19 vaccination as outlined in emergency use authorizations, second-dose deferral of mRNA vaccines may be a consideration within a shared decision-making paradigm of care in select circumstances characterized by high durable first-vaccine-dose protection and significant elevations of vaccine anaphylaxis risk. Still, the durability of protection afforded by a single dose of a COVID-19 mRNA vaccine is uncertain, and alternative approaches to complete vaccination, including precautionary use of a COVID-19 viral vector vaccine, also remain patient-preference-sensitive options. There is an urgent need to define correlates of COVID-19 immunity and the level of longer-term protection afforded by COVID-19 vaccination.

An Approach to the Office-Based Practice of Food Oral Immunotherapy.

Oral immunotherapy (OIT) provides an active treatment option for patients with food allergies. OIT may improve quality of life and raise the threshold at which a patient with food allergy may react to an allergen, but it is a rigorous therapy that requires a high degree of commitment by the clinician, patients, and families. Recent guidelines from the Canadian Society for Allergy and Clinical Immunology have provided a framework for the ethical, evidence-based, and patient-oriented clinical practice of OIT, and the European Academy of Allergy, Asthma, and Immunology guidelines have also recommended that OIT can be used as a potential treatment. The recent Food and Drug Administration approval of an OIT pharmaceutical has accelerated the adoption of OIT. This review provides a summary of the recent Canadian Society for Allergy and Clinical Immunology guidelines and a consensus of practical experience of clinicians across the United States and Canada related to patient selection, office and staff preparation, the general OIT process, OIT-related reaction management, and treatment outcomes.