Long-term outcomes of probiotic and peanut oral immunotherapy (the PPOIT-002 study).

Background: Probiotic and peanut oral immunotherapy (PPOIT) induced long-term sustained unresponsiveness (SU) in a proof-of- concept Phase 2a randomized trial. This open-label study (PPOIT-002) aimed to confirm the tolerability and long-term effects of PPOIT in children with peanut allergy aged 1-12 years. Method(s): 20 children aged 1-12 years with double-blind placebo-controlled food challenge (DBPCFC)-confirmed peanut allergy received 18 months of PPOIT. DBPCFC (cumulative 4950mg peanut protein) were performed at end-of- treatment, 8-weeks post-treatment and 3-years post-treatment to assess for desensitisation, SU and long-term SU, respectively. Immunologic measures, peanut skin prick test (SPT) and specific IgE (sIgE), were evaluated at screening, end-of- treatment and 3-years post-treatment. Continuous outcomes for peanut SPT and sIgE were compared between timepoints using paired t-tests and paired Wilcoxon signed rank test, respectively. Result(s): Sixteen children (75%) completed study treatment. Intention-to- treat analysis showed desensitisation and 8-week SU rates of 75% (15/20) and 60% (12/20), respectively. 10 of the 12 children who achieved 8-week SU at the end-of- treatment consented to the 3-year long-term 8-week SU challenge, with 6 (60%) maintaining long-term SU. PPOIT was associated with decreased peanut SPT and sIgE levels, with significant reductions persisting at 3-years post-treatment (p =0.0022 and p =0.0012, respectively). 17 of 20 (85%) of children reported treatment-related adverse events (AE) (total 176 events). The majority of AEs (164; 93%) were mild. There were no serious AEs. Conclusion(s): This open label study demonstrated that 18 months of PPOIT induced high rates of desensitisation and 8-week SU, with persistence of SU at 3-years post-treatment in the majority of initial responders. PPOIT led to long-lasting reduction in peanut sIgE, suggesting modulation of the underlying allergic response to peanut.