Risk factors associated with safety of preschool peanut oral immunotherapy.

Background: An understanding of how patient characteristics such as age, baseline peanut-specific IgE, and atopic comorbidities may influence potential safety outcomes during peanut oral immunotherapy (P-OIT) could aid in shared decision making between clinicians and patient families. Objective: This study explored the relationship between baseline patient characteristics and reactions during P-OIT using a large sample size to better understand potential risk factors influencing P-OIT safety. Methods: Data were obtained from the Food Allergy Immunotherapy (FAIT) registry, which collects real-world OIT data from community and academic allergy clinics across Canada. Multivariable logistic regression modeling was performed to examine the relationship between baseline patient characteristics and reactions during P-OIT. Multiple imputation was applied to reduce potential bias caused by missingness and to maximize the use of available information to preserve statistical power. Results: Between April 2017 and June 2021, a total of 653 eligible patients initiated P-OIT. Multivariable regression analysis showed pre-OIT grade 2+ initial reaction (odds ratio [OR] = 1.33, 95% confidence interval [CI] 1.10, 1.61), allergic rhinitis (OR = 1.60, 95% CI 1.08, 2.38), older age (OR = 1.01, 95% CI 1.00, 1.02), and higher baseline peanut-specific IgE (OR = 1.02, 95% CI 1.02, 1.03) were associated with grade 2+ reaction during P-OIT after adjusting for potential risk factors. Conclusion: Our study identified several clinically important risk factors for grade 2+ reactions during P-OIT: pre-OIT grade 2+ initial reaction, allergic rhinitis, older age, and higher baseline peanut-specific IgE. These results highlight the need for individualized risk stratification for OIT.

Real-World Safety Analysis of Preschool Tree Nut Oral Immunotherapy.

BACKGROUND: Our group previously described preschool peanut oral immunotherapy (OIT) in a real-world, multicenter setting, suggesting that this therapy is safe for most preschoolers. OBJECTIVE: To examine the safety and tolerability of tree nut (TN) OIT in preschoolers in the real world. METHODS: As part of a Canada-wide quality improvement project, TN-OIT (cashew/pistachio, walnut/pecan, hazelnut, almond, and macadamia nut) was performed in preschoolers who had (1) a skin prick test wheal diameter greater than or equal to 3 mm or a specific IgE level greater than or equal to 0.35 kU/L and a convincing objective IgE-mediated reaction or (2) no ingestion history and a specific IgE level greater than or equal to 5 kU/L. Dose escalations were performed every 2 to 4 weeks till a maintenance dose of 300 mg of TN protein was reached. Symptoms were recorded and classified using the modified World Allergy Organization Subcutaneous Immunotherapy Reaction Grading System (1, mildest; 5, fatal). RESULTS: Of the 92 patients who started TN-OIT from 2018 to 2021, 79 (85.9%) underwent single-food TN-OIT and 13 (14.1%) underwent multifood TN-OIT to 2 (10.8%) or 3 (3.3%) TNs. Eighty-nine (96.7%) patients reached maintenance, and 4 (4.3%) dropped out. Sixty-five (70.7%) patients experienced reactions during buildup: 35 (38.0%) grade 1 reactions, 30 (32.6%) grade 2 reactions, no grade 3 or 4 reactions, and 2 (2.17%) received epinephrine. CONCLUSIONS: Preschool TN-OIT in a real-world, multicenter setting appears safe and tolerable, with results comparable with our previously reported peanut OIT findings.

Revaccination and Adverse Event Recurrence in Patients with Adverse Events following Immunization.

OBJECTIVES: To estimate the risk of recurrence of adverse events following immunization (AEFIs) upon revaccination and to determine among patients with suspected vaccine allergy whether allergy skin test positivity was associated with AEFI recurrence. STUDY DESIGN: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 with AEFIs who required revaccination with the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Special Immunization Clinic physicians used guidelines to inform their recommendations. Participants were followed up after revaccination to capture AEFI recurrences. Data were transferred to a central database for descriptive analysis. RESULTS: Overall, 588 participants were assessed for 627 AEFIs; 570 (91%) AEFIs occurred in children <18 years of age. AEFIs included immediate hypersensitivity (130/627; 21%), large local reactions (110/627; 18%), nonurticarial rash (51/627; 8%), seizures (26/627; 4%), and thrombocytopenia (11/627; 2%). Revaccination was recommended to 513 of 588 (87%) participants. Among participants recommended and due for revaccination during the study period, 63% (299/477) were revaccinated. AEFI recurrence was 10% (31/299) overall, 31% (15/49) for large local reactions, and 7% (5/66) for immediate hypersensitivity. No recurrence was serious. Among 92 participants with suspected vaccine allergy who underwent skin testing and were revaccinated, the negative predictive value of skin testing for AEFI recurrence was 96% (95% CI 92.5%-99.5%). CONCLUSIONS: Most individuals with AEFIs were safely revaccinated. Among those with suspected vaccine allergy, skin testing may help determine the safety of revaccination.

Dietary exposures and allergy prevention in high-risk infants.

Infants at high risk for developing a food allergy have either an atopic condition (such as eczema) themselves or an immediate family member with such a condition. Breastfeeding should be promoted and supported regardless of issues pertaining to food allergy prevention, but for infants whose mothers cannot or choose not to breastfeed, using a specific formula (i.e., hydrolyzed formula) is not recommended to prevent food allergies. When cow's milk protein formula has been introduced in an infant's diet, make sure that regular ingestion (as little as 10 mL daily) is maintained to prevent loss of tolerance. For high-risk infants, there is compelling evidence that introducing allergenic foods early-at around 6 months, but not before 4 months of age-can prevent common food allergies, and allergies to peanut and egg in particular. Once an allergenic food has been introduced, regular ingestion (e.g., a few times a week) is important to maintain tolerance. Common allergenic foods can be introduced without pausing for days between new foods, and the risk for a severe reaction at first exposure in infancy is extremely low. Pre-emptive in-office screening before introducing allergenic foods is not recommended. No recommendations can be made at this time about the role of maternal dietary modification during pregnancy or lactation, or about supplementing with vitamin D, omega 3, or pre- or probiotics as means to prevent food allergy.

First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy.

BACKGROUND: We previously described safety of preschool peanut oral immunotherapy (P-OIT) in a real-world setting; 0.4% of patients experienced a severe reaction, and 4.1% received epinephrine, during build-up. OBJECTIVE: To determine the effectiveness of preschool P-OIT after 1 year of maintenance. METHODS: Preschoolers (9-70 months) with at least 1 objective reaction to peanut (during baseline oral food challenge (OFC) or P-OIT build-up) received a follow-up OFC to cumulative 4000 mg protein after 1 year on 300 mg peanut daily maintenance. Effectiveness of desensitization was defined as proportion of patients with a negative follow-up OFC. Symptoms and treatment at follow-up OFC were recorded. RESULTS: Of the 117 patients who successfully completed 1 year of P-OIT and subsequently underwent a cumulative 4000-mg follow-up OFC, 92 (78.6%) had a negative OFC and 115 (98.3%) tolerated a cumulative dose of greater than or equal to 1000 mg. For the 25 (21.4%) who reacted, their threshold increased by 3376 mg (95% CI, 2884-3868) from baseline to follow-up; 17 (14.5%) patients experienced grade 1 reactions, 7 (6.00%) grade 2, and 1 (0.85%) grade 3. Two patients (1.71%) received epinephrine associated with P-OIT, and 1 (0.85%) went to the emergency department. CONCLUSIONS: Our data demonstrate that real-world preschool P-OIT is effective after 1 year of maintenance for those who received a follow-up OFC. For those who reacted, their threshold increased sufficiently to protect against accidental exposures. P-OIT should be considered for preschoolers as an alternative to current recommendations to avoid peanut.

First Real-World Safety Analysis of Preschool Peanut Oral Immunotherapy.

BACKGROUND: In 2017, a clinical trial of 37 subjects demonstrated that preschool peanut oral immunotherapy (P-OIT) was safe, with predominantly mild symptoms reported and only 1 moderate reaction requiring epinephrine. OBJECTIVES: We sought to examine whether these findings would be applicable in a real-world setting. METHODS: As part of a Canada-wide quality improvement project, community and academic allergists administered P-OIT to preschool-age children who had (1) skin prick test wheal diameter greater than or equal to 3 mm or specific IgE level greater than or equal to 0.35 kU/L and history of reaction and/or positive baseline oral food challenge, or (2) no ingestion history and specific IgE level greater than or equal to 5 kU/L. Over 16 to 22 weeks, patients had biweekly clinic visits for updosing, and consumed the dose daily at home between visits. Target maintenance dose was 300 mg peanut protein. Symptoms were classified using a modified World Allergy Organization Subcutaneous Immunotherapy Reaction Grading System (1 mildest, 5 fatal). RESULTS: Of 270 patients who started P-OIT in the period 2017 to 2018, 243 reached maintenance, and 27 dropped out (10.0%); 67.8% of patients experienced reactions during buildup: 36.3% grade 1, 31.1% grade 2, and 0.40% grade 4. Eleven patients (4.10%) received epinephrine (10 patients received 1 dose, 1 patient received epinephrine on 2 separate days), representing 2.23% of reactions (12 of 538) and 0.029% of doses (12 of 41,020). CONCLUSIONS: We are the first group to describe preschool P-OIT in a real-world multicenter setting. The treatment appears to be safe for the vast majority of patients because symptoms were generally mild and very few reactions received epinephrine; however, life-threatening reactions in a minority of patients (0.4%) can still occur.

Impact of primary food allergies on the introduction of other foods amongst Canadian children and their siblings.

BACKGROUND: Food-allergic children frequently avoid other highly allergenic foods. The NIAID 2010 guidelines state that individuals with an IgE-mediated food allergy should avoid their specific allergens and physicians should help patients to decide whether certain cross-reactive foods also should be avoided. Patients at risk for developing food allergy do not need to limit exposure to foods that may be cross-reactive with the major food allergens. The purpose of this study was to determine if parents of food-allergic children are given advice regarding introduction of allergenic foods; if these foods are avoided or delayed; if there is anxiety when introducing new foods; and if introducing other allergenic foods leads to any allergic reaction. The study also determined if there was a similar pattern seen amongst younger siblings. METHODS: An online survey was administered between December 2011 and March 2012 via Anaphylaxis Canada's website, available to Canadian parents and caregivers who are registered members of the organization and who have a child with a food allergy. RESULTS: 644 parents completed the online survey. 51% of families were given advice regarding the introduction of other allergenic foods. 72% were told to avoid certain foods, and 41% to delay certain foods. 58% of parents did avoid or delay other highly allergenic foods, mainly due to a fear of allergic reaction. 69% of children did not have an allergic reaction when these foods were subsequently introduced. 68% of parents felt moderate or high levels of anxiety when introducing other foods. A similar pattern was seen amongst the younger siblings. CONCLUSIONS: Canadian parents and caregivers of children with food allergies receive varied advice from health care professionals regarding the introduction of new allergenic foods, and feel moderate to high levels of anxiety. A similar pattern may be seen amongst younger siblings. While the majority of children in our study did not have an allergic reaction to a new food, a significant proportion of children did react. A more consistent approach to the advice given by health care professionals may decrease parental anxiety. Further research to support the 2010 NIAID guidelines may be necessary to clarify recommendations.