Long-term clinical and immunological effects of probiotic and peanut oral immunotherapy after treatment cessation: 4-year follow-up of a randomised, double-blind, placebo-controlled trial

Abstract

Background: Oral immunotherapy has attracted much interest as a potential treatment for food allergy, yet little is known about its long-term effects. We aimed to assess long-term outcomes in participants who completed a randomised, double-blind, placebo-controlled trial of combined probiotic and peanut oral immunotherapy (PPOIT), which was previously shown to induce desensitisation and 2-week sustained unresponsiveness.

Methods: All participants who completed the PPOIT randomised trial were eligible to participate in this follow-up study 4 years after treatment cessation. Peanut intake and adverse reactions to peanut in the 4 years after treatment cessation were systematically documented with a structured questionnaire administered by allergy nurses. Additionally, participants were invited to undergo peanut skin prick tests, measurement of peanut sIgE and sIgG4 concentrations, and double-blind placebo-controlled peanut challenge to assess 8-week sustained unresponsiveness.

Findings: 48 (86%) of 56 eligible participants were enrolled in the follow-up study. Mean time since stopping treatment was 4·2 years in both PPOIT (SD 0·6) and placebo (SD 0·7) participants. Participants from the PPOIT group were significantly more likely than those from the placebo group to have continued eating peanut (16 [67%] of 24 vs one [4%] of 24; absolute difference 63% [95% CI 42-83], p=0·001; number needed to treat 1·6 [95% CI 1·2-2·4]). Four PPOIT-treated participants and six placebo participants reported allergic reactions to peanut after intentional or accidental intake since stopping treatment, but none had anaphylaxis. PPOIT-treated participants had smaller wheals in peanut skin prick test (mean 8·1 mm [SD 7·7] vs 13·3 mm [7·6]; absolute difference -5·2 mm [95% CI -10·3 to 0·0]; age-adjusted and sex-adjusted p=0·035) and significantly higher peanut sIgG4:sIgE ratios than placebo participants (geometric mean 67·3 [95% CI 10·3-440·0] vs 5·2 [1·2-21·8]; p=0·031). Seven (58%) of 12 participants from the PPOIT group attained 8-week sustained unresponsiveness, compared with one (7%) of 15 participants from the placebo group (absolute difference 52% [95% CI 21-82), p=0·012; number needed to treat 1·9 [95% CI 1·2-4·8]).

Interpretation: PPOIT provides long-lasting clinical benefit and persistent suppression of the allergic immune response to peanut.

Funding: Murdoch Childrens Research Institute and Australian Food Allergy Foundation.