Background: Few Randomized Controlled Trials (RCTs) have evaluated oral immunotherapy effects on quality of life (QoL). We previously reported that probiotic peanut oral immunotherapy (PPOIT) significantly improved QoL compared with placebo, with improvement linked to achieving sustained unresponsiveness (SU). Objective: We examined whether PPOIT-induced QoL improvement is maintained at 4 years post-treatment. Methods: Subjects in the PPOIT-001 RCT (n=57) completed Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) and Food Allergy Independent Measure (FAIM) at pre-treatment, end-of-treatment, and 3-months, 12-months and 4-years post-treatment. Paired group t-test analyses were conducted separately for PPOIT and Placebo groups at each time point. Repeated-measures mixed ANOVAs were used to examine overall changes from pre-treatment to 4-years post-treatment, controlling for potential confounders. Results: N=38 (19 Placebo/19 PPOIT) completed FAQLQ at ALL time-points. PPOIT-treated subjects had significantly improved FAQLQ compared with placebo at 3-months, 12-months and 4-years post-treatment. FAQLQ and FAIM scores improved significantly for PPOIT group from pre-treatment to 4-years post-treatment (both p=0.001). Multivariate analysis (controlling for age, sex, SU) confirmed findings, with a very large effect size [partial eta squared=0.56]. A ‘large’ amount of peanut ingestion predicted greater improvement in FAQLQ score, compared with avoidance, small or moderate ingestion. No changes from baseline in FAQLQ or FAIM were shown for placebo. Conclusions: PPOIT induced substantial improvement in FAQLQ that persisted to 4-years post-treatment. Greatest benefit was observed in subjects ingesting large amounts of peanut. This is the first study demonstrating long-lasting improvement in QoL with a food allergy treatment.

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.