Epitope-Specific IgE Profiles are Predictive of Desensitization and Remission in the IMPACT Trial.

BACKGROUND: Results from the IMPACT trial suggest that initiation of peanut oral immunotherapy (pnOIT) before age 4 years can increase chances of achieving desensitization and remission. OBJECTIVE: We sought to assess sequential (linear) epitope-specific (es-)IgE and es-IgG4 profiles over the course of pnOIT and determine whether they can predict desensitization and remission outcomes. METHODS: Participants in the IMPACT trial (NCT03345160) were randomized to pnOIT or placebo for 134 weeks. Desensitization and remission endpoints were assessed by oral food challenges to 5,000mg of peanut protein at 134 and 160 weeks, respectively. This study includes data from 93/96 (96.9%) participants from the peanut OIT group and 47/50 (94%) from the placebo group. Specific IgE and IgG4 levels to peanut, component proteins, and 64 allergenic epitopes were measured. Machine learning was used to develop predictive models for desensitization and remission. RESULTS: PnOIT was associated with an overall decrease in es-IgE and increase in es-IgG4 levels. Younger subjects (<2.3 years of age) had lower baseline es-IgE binding and lower fold-change in es-IgE and es-IgG4 binding during pnOIT. Participants who achieved desensitization had lower baseline es-IgE levels compared to those who did not achieve desensitization. A machine-learning model that included 9 es-IgE antibodies could predict remission with an overall performance of: accuracy 88.2%, AUC 88.2%, sensitivity 83.3%, and specificity 90.0%; this predictive performance was comparable to, but not superior to, models based on peanut IgE. CONCLUSIONS: Baseline epitope IgE profiles can predict remission outcome for children undergoing pnOIT. Age and baseline peanut IgE remain important factors across models. Notably, pnOIT prevented the epitope spreading of es-IgE observed in placebo-treated children, suggesting a treatment effect on the breadth of the allergic response that may be especially relevant in young children. These profiles may help identify patients who are more likely to benefit from pnOIT.