Remission is the desired outcome following OIT as it allows individuals to discontinue treatment and eat the allergen freely. Early initiation of OIT in infants and toddlers has been embraced as an approach to increase the likelihood of remission. However, there is no high-quality evidence supporting younger age as an independent factor driving remission; available studies are limited by small samples of younger subjects and lack of adjustment for confounding covariates, particularly peanut-specific IgE (sIgE) levels which is closely correlated with age. This study examined relationships between peanut sIgE and age at baseline and remission, in children aged 1-10 who completed 18 months of OIT in the PPOIT-003 RCT (n=162). Remission was defined as absence of clinical reactivity to peanut after 8 weeks of allergen avoidance/treatment discontinuation. Age and sIgE were examined as continuous variables in univariate and multivariate regression models. Baseline peanut sIgE levels were significantly associated with remission, independent of age (OR 0.1 [0.05-0.22], p<0.001). Higher peanut sIgE was consistently predictive of lower likelihood of remission, independent of age. In contrast, there was no independent association between age and remission after adjusting for baseline sIgE (OR 0.94 [0.79-1.12], p=0.5). Findings do not support age as an independent predictor of remission following OIT. Additional studies examining safety and efficacy of OIT in infants and younger children are urgently needed, ahead of widespread adoption of early intervention.

This review summarises recent advances in characterising the transcriptional pathways associated with outcomes following Oral Immunotherapy. Recent technological advances including single-cell sequencing are transforming the ways in which the transcriptional landscape is understood. The application of these technologies is still in its infancy in food allergy but here we summarise current understanding of gene expression changes following oral immunotherapy for food allergy and specific signatures underpinning the different clinical outcomes of desensitisation and remission (sustained unresponsiveness). T helper 2A cells have been identified as a cell type which correlates with disease activity and is modified by treatment. Molecular features at study entry may differentiate individuals who achieve more positive outcomes during OIT. Recent findings point to T cell anergy and Type 1 interferon pathways as potential mechanisms supporting redirection of the allergen-specific immune response away from allergy towards remission. Despite these developments in our understanding of immune mechanisms following OIT, there are still significant gaps. Additional studies examining immune signatures associated with long term and well-defined clinical outcomes are required to gain a more complete understanding of the pathways leading to remission of allergy, in order to optimise treatments and gain improved outcomes for patients.

Background: Combined treatment with probiotic and peanut oral immunotherapy (PPOIT) was shown to induce sustained unresponsiveness (SU) in a proof-of-concept randomized trial. Additional data on safety and long-term outcomes are needed. This study aimed to evaluate the safety and long-term effects of PPOIT in children with peanut allergy. Methods: Open-label study of 20 children aged 1-12 years with challenge-confirmed peanut allergy; all children received 18-months of PPOIT. Efficacy endpoints were desensitization, 8-week SU, and persistence of 8-week SU at 3-years post-treatment, assessed by double-blind placebo-controlled food challenge (cumulative 4950mg peanut protein). Treatment emergent adverse events and relationship to study treatment were recorded. Immunologic measures and health related quality of life (HRQL) were evaluated at screening, end-of-treatment and 3-years post-treatment. Results: Sixteen children (75%) completed treatment. By intention-to-treat analysis, 75% (15/20) achieved desensitization and 60% (12/20) achieved 8-week SU. Ten of 12 participants with SU at end-of-treatment consented to the 3-year SU challenge; 6 (60%) had persistence of SU. PPOIT was associated with significantly reduced peanut skin prick test wheal size and serum peanut specific-IgE levels at end-of-treatment, 12-months and 3-years post-treatment. There were no serious adverse events. HRQL scores improved (exceeding the Minimal Clinically Important Difference of 0.45) at 12-months post-treatment with benefit sustained at 3-years post-treatment. Conclusions: Eighteen months of PPOIT induced high rates of desensitization and SU, and SU persisted to 3-years post-treatment in a majority of initial responders. PPOIT led to long-lasting suppression of peanut sIgE and long-lasting clinically important improvement in HRQL.