Effects of probiotic plus peanut oral immunotherapy sustained over 4 years
Combined probiotic and peanut oral immunotherapy (PPOIT) has sustained benefits in individuals with peanut allergy 4 years after treatment cessation, according to a recent study.
“There is intense interest in oral immunotherapy as a food allergy treatment to induce desensitization [defined as being able to tolerate the allergen while on treatment], or sustained unresponsiveness [defined as being able to tolerate the allergen weeks or months after stopping treatment],” said the researchers.
“Our findings show that combined [PPOIT] provides long-lasting clinical benefit compared with placebo … the treatment resulted in symptom-free peanut ingestion, food-challenge-proven sustained unresponsiveness, and persistent suppression of the allergic immune response to peanut 4 years after treatment cessation,” they said.
In this follow-up of the randomized, double-blind PPOIT trial, researchers used questionnaires, skin prick tests, peanut sIgE and sIgG4 concentration measurements, and peanut challenge to assess the peanut intake and adverse reactions of 48 participants of the PPOIT trial following treatment cessation (mean time postcessation, 4.2 years). Participants had previously received once-daily doses of either PPOIT (2 x 1010 colony-forming units of Lactobacillus rhamnosus CGMCC 1.3724 plus 2 g peanut protein; mean age 12.1 years, 63 percent male) or placebo (maltodextrin; mean age 11.7 years, 67 percent male) for 18 months. Those who passed the sustained unresponsiveness challenge at study end were advised to continue peanut consumption in their diet.
Participants who had been randomized to the PPOIT group had a higher likelihood of continuing peanut consumption compared with those assigned to placebo (67 percent [n=16] vs 4 percent [n=1], absolute difference 63 percent; p=0.001). [Lancet Child Adolesc Health 2017;doi:10.1016/S2352-4642(17)30041-X]
Compared with those on placebo, participants in the PPOIT group also had smaller wheals on the skin prick test (mean 8.1 vs 13.3 mm, absolute difference -5.2 mm; p=0.035) and had higher sIgG4:sIgE ratios (geometric mean 67.3 vs 5.2; p=0.031).
In the peanut challenge, conducted among 27 participants who ceased peanut consumption for 8 weeks, more participants in the PPOIT group achieved 8-week sustained unresponsiveness compared with those on placebo (58 percent [n=7] vs 7 percent [n=1]; absolute difference 52 percent; p=0.012).
“[T]hese seven PPOIT-treated patients showed true, probably lasting tolerance, meaning that they can eat peanut whenever they choose, even very infrequently, similar to a nonallergic person. For researchers, the allergic child, and their caregivers, this finding is the most meaningful change possible,” said Dr Matthew Greenhawt from the Children’s Hospital Colorado, Aurora, Colorado, US, in a commentary. [Lancet Child Adolesc Health 2017;doi:10.1016/S2352-4642(17)30042-1]
Low allergy occurrence
Allergic reactions following peanut consumption were reported in four and six participants in the PPOIT and placebo groups, respectively, though the reactions were minor and there was no incidence of anaphylaxis.
“The frequency and severity of reactions in PPOIT-treated participants were similar to those after accidental ingestion in placebo-treated participants, suggesting that PPOIT-induced sustained unresponsiveness offers an equivalent safety profile to peanut avoidance,” said the researchers.
“[The PPOIT-treated] children had been eating peanut freely in their diet without having to follow any particular programme of peanut intake in the years after treatment was completed,” said lead researcher Professor Mimi Tang from The Royal Children’s Hospital, Victoria, Australia.
“[T]hese children were able to eat peanut like children who don’t have peanut allergy and still maintain their tolerant state, protected against reactions to peanut,” she said.
The future of oral immunotherapy
“[T]he proportion of patients achieving sustained unresponsiveness at 4 years is more than double that achieved immediately after oral immunotherapy alone in most studies, suggesting that addition of the probiotic could enhance the tolerance-inducing capacity of oral immunotherapy,” said the researchers.
“Successful replication of these data could lead to broader questions of generalizability of the probiotic plus oral immunotherapy approach to other allergens and possible abandonment of oral immunotherapy without probiotic co-administration,” said Greenhawt.
The low number of participants in the peanut challenge and the single-centre design were limitations, said the researchers, who called for larger studies and meta-analyses to conclusively determine the long-term safety outcomes of PPOIT.
“[These findings] suggest the exciting possibility that tolerance is a realistic target for treating food allergy. This is a major step forward in identifying an effective treatment to address the food allergy problem in Western societies,” said Tang.