An oral treatment for one of the most deadly allergies, to peanuts, is still effective four years after it was administered, a study has found, an Australian study has found. Lead researcher Professor Mimi Tang said: ‘This is a major step forward in identifying an effective treatment to address the food allergy problem in Western societies.’
Allergy immunotherapy company Prota Therapeutics Pty Ltd (Prota) has announced the results of a follow up study of the probiotic and peanut immunotherapy (PPOIT) treatment which it has licensed from the Murdoch Children’s Research Institute (MCRI), demonstrating long-lasting tolerance effects of treatment more than four years after the original study ended.
According to a News-Medical report, Prota believes that this follow-up study data provides the strongest evidence yet that a cure may be possible for peanut allergy and holds important implications for attacking the modern food allergy epidemic. Peanut allergy is the commonest cause of anaphylaxis, a life-threatening allergic reaction, and one of the commonest causes of death from food allergy.
Chief Scientific Officer and lead researcher Professor Mimi Tang, who pioneered the PPOIT treatment, followed children four years after they completed the initial trial. Children in the original PPOIT randomised trial were given either a combination of the probiotic, Lactobacillus rhamnosus, together with peanut protein in increasing amounts, or a placebo (56 children in total, randomised equally), for 18 months, to assess whether children would become tolerant to peanut.
Outstandingly, more than 80% of children who received the combination probiotic peanut oral immunotherapy treatment were able to tolerate peanut at the end of the trial, compared to less than four percent in the placebo group. Children who developed tolerance to peanut in the first trial were instructed to introduce peanut as part of their normal diet after the study ended; whereas children who remained peanut allergic were advised to continue peanut avoidance according to current care.
The latest follow up study investigated whether the benefits of the oral treatment were maintained four years later.
Tang said this study showed that the majority of PPOIT-treated children who tolerated peanut at the end of the original trial were still eating peanut essentially without reactions four years later.
“Of the PPOIT-treated participants who achieved short term tolerance at the end of the original trial, 80% were still eating peanut without symptoms and 70% had long-lasting challenge-proven tolerance four years after stopping treatment,” Tang said.
“These children had been eating peanut freely in their diet without having to follow any particular program of peanut intake in the years after treatment was completed. Over half were consuming moderate to large amounts of peanut on a regular basis, others were only eating peanut infrequently. The importance of this finding is that these 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.”
The majority (83%) of participants treated with PPOITin the original trial reported no allergic reactions to either intentional or accidental peanut ingestion in the four years post treatment. Of critical importance, amongst the few that reported allergic reactions to peanut following intentional peanut intake since stopping treatment, none reported anaphylaxis.
Dr Suzanne Lipe, CEO of Prota Therapeutics, said the results of the investigation, demonstrating such a high proportion of subjects still continuing to be tolerant four years later, was extremely promising and if confirmed in a larger Phase III study, would represent a paradigm shift in the way peanut allergy is managed.
“Rather than using therapy that protects against accidental ingestion, Prota’s products aim to provide sustained long-term effects and the ability to include peanut in the diet. For the first time, we could have products on the market that provide meaningful and long-lasting treatment benefits, which allow sufferers to eat peanut products without thinking about it, as part of a regular diet just like unaffected people.”
“The MCRI and Prota’s success will be a major achievement on a global scale and making this vital treatment available is what drives the team to accelerate the development programme through the US Food and Drug Administration (FDA) approval process.”
“It also suggests the exciting possibility that tolerance is a realistic target for other food allergy treatments, opening a potential pipeline of products for the company.”
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.
Kuang-Chih Hsiao, Anne-Louise Ponsonby, Christine Axelrad, Sigrid Pitkin, Mimi L K Tang