Baseline epitope-specific IgE profiles are predictive of sustained unresponsiveness or high threshold 1-year post oral immunotherapy in the POISED trial.

Abstract

Results from the POISED trial suggest that discontinuation of peanut oral immunotherapy can increase the risk of regaining clinical reactivity to peanut. We sought to determine whether patients who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific IgE profiles than patients who achieved transient desensitization. Subjects in the POISED trial (NCT02103270) were randomized to peanut (n = 95) or placebo (n = 25) for 24 months. Oral immunotherapy-desensitized subjects were then assigned to no peanut (PN-0) (n = 51) or 300 mg peanut (PN-300) (n = 30) for 12 months. SU and SHT were determined by subjects in PN-0 and PN-300, respectively, passing 4000-mg peanut oral challenge. Specific IgE and IgG₄ levels to peanut; Ara h 1, Ara h 2, and Ara h 3 proteins; and 64 allergenic epitopes were measured. We developed machine learning models with bootstrap simulations using baseline data to predict SU/SHT. Of 80 (84%) subjects who were desensitized to peanut, 13% (n = 8) and 37% (n = 13) achieved SU/SHT in PN-0 and PN-300 groups. Decreases in epitope-and protein-specific IgE levels and increases in IgG₄ levels were observed during 2 years of oral immunotherapy. At baseline, patients with SU in PN-0, but not PN-300, group had lower epitope-specific IgE and protein-specific IgE levels compared with the transient desensitization group. A machine learning model with 12 baseline epitope-specific IgEs and age could predict SU/SHT with accuracy of 94%, area under the curve 0.97, sensitivity 1.00, and specificity 0.91. Subjects who achieved SU/SHT had different baseline protein- and epitope-specific IgE profiles than subjects with transient desensitization. These profiles may help identify patients with an increased likelihood of achieving SU/SHT.