Baseline Epitope-Specific IgE Profiles are Predictive of Sustained Unresponsiveness or High Threshold One-Year Post OIT in the POISED Trial.

Abstract

Background: Results from the POISED trial suggest that discontinuation of peanut oral immunotherapy can increase the risk of regaining clinical reactivity to peanut.

Objective: We sought to determine whether those who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific (es-) IgE profiles than those who achieved transient desensitization (TD).

Methods: Subjects in the POISED trial (NCT02103270) were randomized to peanut (n=95) or placebo (n=25) for 24 months. OIT-desensitized subjects were then assigned to no peanut (PN-0, n=51) or 300mg (PN-300, n=30) for 12 months. SU and SHT were determined by those in PN-0 and PN-300, respectively, passing 4000mg peanut oral challenge. Specific IgE and IgG4 levels to peanut, Ara h 1-3 proteins and 64 allergenic epitopes were measured. We developed machine learning glmnet models with bootstrap simulations using baseline data to predict SU/SHT.

Results: Eighty (84%) subjects were desensitized to peanut. Of those, 13% (n=8) and 37% (n=13) achieved SU/SHT in PN-0 and PN-300. Decreases in epitope-and protein-specific IgE levels and increases in IgG4 levels were observed during 2 years of OIT. At baseline, patients with SU in Peanut-0 but not Peanut-300 had lower es-IgE and protein-sIgE levels compared to the TD group. A machine-learning model with 12 baseline es-IgEs and age could predict SU/SHT with an accuracy of 94%, AUC 0.97, Sensitivity 1.00, Specificity 0.91.

Conclusions: Patients who achieved SU/SHT have different baseline protein-and epitope-specific IgE profiles than those with TD. These profiles may help identify patients with an increased likelihood of achieving SU/SHT.