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10th February 2022
Addition of probiotics to oral peanut immunotherapy does not lead to a meaningful increase in the proportion of children achieving clinical remission but may reduce the gastrointestinal symptom burden. This was the conclusion of a randomised trial by researchers from the Murdoch Children’s Research Institute, Victoria, Australia.
In a study of 2848 infants, the prevalence of any sensitisation to peanut was 8.9% and there is accumulating evidence that peanut oral immunotherapy (OIT) is effective at inducing desensitisation through down-regulation of effector pathways in the allergic reaction cascade. With some evidence that ingestion of probiotic bacteria strains have anti-inflammatory properties in children with atopic eczema, the Australian team wanted to examine the additional benefit of probiotics with OIT as a means of improving clinical remission of peanut allergy. The same team had already showed that the combination of probiotics with peanut OIT was effective in inducing sustained unresponsiveness in children with a peanut allergy but their study did not employ a peanut OIT only arm and therefore it was not possible to determine the incremental benefit of probiotics compared to OIT alone.
For the present study, the Australian team included an OIT arm in addition of the probiotics and OIT group and sought to determine if adding a probiotic induced a higher level of sustained unresponsiveness (i.e., clinical remission) compared to peanut OIT alone. They undertook a multi-centre, randomised trial, the PPOIT-003 study, in children aged 1 to 10 years of age with a confirmed peanut allergy. The participants were randomised 2:2:1 to receive probiotics and peanut OIT (PP0IT group), OIT alone or placebo for a period of 18 months and were then followed-up after completion of treatment. Oral immunotherapy was gradually increased until a 2000 mg daily maintenance dose was reached and tolerated. They set the primary outcome as the proportion of participants with an 8-week sustained unresponsiveness, which was defined as passing both food challenges (i.e., no reaction) to a cumulative dose of 4950 mg of peanut protein, at both completion of treatment (i.e., 18 months) and 8 weeks after cessation of treatment.
Probiotics and sustained unresponsiveness
A total of 201 children with a mean age of 5.9 years (64% male) were randomised to PPOIT (79), OIT (83) or placebo.
A sustained unresponsiveness (i.e., remission) was achieved by 46% of those in the PPOIT group, 51% of the OIT group and 5% of those given placebo. This gave a rise difference of 40.4% (95% CI 27.4 – 53.4, p < 0.0001) for PPOIT vs placebo and and -5.03% (95% CI -20.4 – 10.34, p = 0.52) for the PPOIT vs OIT groups. In other words, there was no significant difference between the PPOIT and the OIT groups.
The researchers then assessed the exposure-adjusted incidence rate of adverse effects, which is a better measure of the burden of adverse effects, since it takes account of differences in the follow-up duration between treatment groups. Using this measure, the incidence was significantly lower in the PPOIT group compared to the OIT group (p = 0.042). This was seen for the incidence of abdominal pain, vomiting and allergic cough, allergic respiratory and respiratory adverse events.
The authors concluded that while addition of probiotics to the OIT had no noticeable effect on the level of sustained unresponsiveness, it did appear to reduce the burden of gastrointestinal symptoms and systemic reactions. They called for future studies to confirm this preliminary findings.
Lake P et al. Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial Lancet Child Adolesc Health 2022
27th January 2022
The use of peanut oral immunotherapy in children is associated with an increase in the proportion who achieve desensitisation and remission. This was the conclusion of a randomised, placebo-controlled trial by researchers from the Department of Paediatrics, Arkansas, USA.
Peanut allergy (PA) currently affects approximately 2% of the general population and commonly affects children as revealed in one study which how among 3218 children identified with food allergy, 24.8% reported a peanut allergy. Although allergy avoidance is the best strategy, in recent years, peanut oral immunotherapy has become more widely available and one product, Palforzia has been approved for use in the EU. Trial data shows that oral immunotherapy with Palforzia (known as AR101 in the study) in children and adolescents results in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at an exit food challenge compared to placebo. Nevertheless, whether use of oral immunotherapy can induce both desensitisation (i.e., a higher allergic reaction threshold) and remission, in other words, non-responsiveness after discontinuing therapy, is unclear.
For the present study, the US team undertook a randomised, placebo trial in children aged 12 years and younger and who were found to react to 500 mg or less or peanut protein, during a double-blind, placebo-controlled food challenge (DBPCFC). They randomised children 2:1 to peanut oral immunotherapy or placebo for a total of 134 weeks and which was equivalent to giving 2000 mg of peanut protein per day. This was followed by 26 weeks of no treatment and then re-assessment at week 160. The DBPCFC used a dose of 500 mg of peanut protein at week 134 and at week 160. At week 134, those who passed the DBPCFC challenge were considered to be desensitised and those who passed the challenge at week 160, deemed to be in remission. The primary endpoint was the proportion of children desensitised after 134 weeks of oral immunotherapy and the main secondary outcome was the proportion who were defined as in remission at week 160.
A total of 146 participants with a median age of 39.3 months (32% girls) were enrolled and 96 assigned to peanut oral immunotherapy.
At week 134, 71% of those receiving oral immunotherapy and 2% of those given placebo, met the primary outcome of desensitisation (risk difference, RD = 69%, 95% CI 59 – 79, p < 0.0001). The median tolerated peanut protein dose was 5005 mg (roughly 16 peanuts) for those given immunotherapy compared to 5 mg in the placebo group (p < 0.0001).
After discontinuation of immunotherapy, 21% of those previously receiving treatment and 2% of the placebo group, met the remission criteria (RD = 19%, 95% CI 10 – 28%, p = 0.0021) at week 160, although the tolerated dose of protein was lower at 755 mg for those who had immunotherapy but 0 mg for the placebo arm.
The authors concluded that peanut oral immunotherapy before age 4 increased both desensitisation and remission and called for future studies to focus on aged-defined benefits and risk to define the most appropriate window of opportunity to induce remission.
Jones SM et al. Efficacy and safety of oral immunotherapy in children aged 1 to 3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study Lancet 2022