Novel baseline predictors of adverse events during oral immunotherapy in children with peanut allergy

Abstract

Background: Though peanut oral immunotherapy (OIT) is a promising investigational therapy, its potential is limited by substantial adverse events (AEs), which are relatively understudied.

Objective: A retrospective analysis was conducted, pooling data from 3 pediatric peanut OIT trials, comprising the largest analysis of peanut OIT safety to date.

Methods: We pooled data from 104 children with peanut allergy from 3 peanut OIT studies. We catalogued AEs from parental reports, daily symptom diaries, and dose escalations. We included events that were considered likely related to OIT and identified potential baseline predictors of higher AE rates using generalized linear regression models.

Results: Eighty percent of subjects experienced likely related AEs during OIT (72% during buildup and 47% during maintenance). Of these AEs, over 90% occurred while at home. Approximately 42% of subjects experienced systemic reactions, and 49% experienced gastrointestinal symptoms. Twenty percent of subjects dropped out, with half (10% of the overall group) due to persistent gastrointestinal symptoms. Baseline allergic rhinitis (AR) and peanut SPT wheal size were significant predictors of higher overall AE rates. SPT wheal size predicted increased gastrointestinal AEs, and AR predicted increased systemic reactions. Over the course of OIT, 61% of subjects received treatment for likely related AEs, 59% with antihistamines and 12% with epinephrine.

Conclusions: Peanut OIT is associated with frequent AEs, with rates declining over time, and most graded mild. However, systemic reactions and intolerable gastrointestinal AEs do occur and are significantly associated with AR and peanut SPT wheal size, respectively. Further study is needed of predictive biomarkers and the overall risks and benefits of OIT.

Keywords: Peanut allergy; adverse events; oral immunotherapy; safety.

Fig 1

Consort Diagram of Study Population

Fig 2

Frequency of AEs by Symptoms Reported over Buildup and Maintenance

Fig 3

Distributions of AEs by Month By Allergic Rhinitis Status.

Fig 4

Frequency of AEs resulting in Epinephrine Use. (A) Patterns of use of epinephrine concurrently with administration of antihistamines, albuterol, oral steroids, or an emergency department visit. (B) Patterns of epinephrine use in response to specific symptoms (cough, wheeze, hives, abdominal pain, or vomiting). Overlap of AEs with two or more given symptoms (ex: cough and wheeze) may be present.

Fig 4

Frequency of AEs resulting in Epinephrine Use. (A) Patterns of use of epinephrine concurrently with administration of antihistamines, albuterol, oral steroids, or an emergency department visit. (B) Patterns of epinephrine use in response to specific symptoms (cough, wheeze, hives, abdominal pain, or vomiting). Overlap of AEs with two or more given symptoms (ex: cough and wheeze) may be present.