Background: High dose rapid-escalation oral immunotherapy (OIT) with adjunct probiotic is highly effective at inducing sustained unresponsiveness (SU) of peanut allergy, but the efficacy of this approach for other food allergies is untested. This open-label study aimed to confirm the safety, tolerability and long-term effects of high dose egg and milk oral immunotherapy (OIT) with probiotic in children. Methods: Participants aged 5–17 years with egg (n=20) or milk (n=20) allergy confirmed by double-blind placebo-controlled food challenge (DBPCFC) received probiotic and either egg or milk OIT for 18 months. SU was assessed by DBPCFC performed post-treatment (after 8-weeks dietary allergen exclusion). The primary outcome was proportion completing the dose-escalation phase according to protocol. Secondary outcomes were proportion with SU, adverse events (AE) and change in health-related quality of life (HRQL). Results: Nine (45%) egg, and 7 (35%) milk completed the dose-escalation according to protocol, and 17 (85%) in both groups were able to reach maintenance phase with dose modifications. Eleven (55%) egg and 10 (50%) milk participants attained SU. Treatment-related AEs were frequent, with 9 (45%) egg and 13 (65%) milk participants reporting at least one moderate or severe event. Clinically significant improvements in HRQL were observed in both groups. Conclusion: High dose rapid-escalation OIT with adjunct probiotic is a promising treatment for egg and milk allergy which may increase the likelihood of achieving SU and shorten the required treatment period for participants. The efficacy and safety of this approach should be confirmed in later-stage placebo-controlled randomised trials.

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.

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.