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.

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.