Probiotics added to peanut oral immunotherapy have no effect on remission but reduce GI symptom burden

10th February 2022

Adding probiotics to oral peanut immunotherapy does not increase clinical remission in children but may reduce gastrointestinal symptom burden

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.

Citation
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

Peanut allergy leads to huge psychosocial burden among sufferers

A peanut allergy has been found to be associated with a huge psychosocial burden affecting the daily lives of affected individuals

Having a peanut allery places a huge psychosocial burden among sufferers according to the results of a large quantitative and qualitative European study. The Allergy to Peanuts imPacting Emotions And Life study (APPEAL) study by researchers from the School of Applied Psychology and Department of Paediatrics and Child Health,University College Cork, Cork, Ireland, set out to explore the psychological burden of living with a peanut allergy in Europe.

A peanut allergy is not uncommon and in a systematic review of food allergies in Europe, the pooled estimate of a peanut allergy among all ages was estimated to be 1.3%. Moreover, the life-long nature of a food allergy is such that the health-related quality of life is impaired in food allergic adolescents and adults, compared to the general population.

Some results from the APPEAL study have already been published and demonstrate how the presence of a peanut allergy impacts upon sufferers. For the present analysis, the researchers focused on the data obtained from participants in the UK and Ireland arm of the study. The APPEAL study had two distinct phases; an initial, online, quantitative analysis which was followed by in depth telephone or in-person interviews with children (aged 8 to 12 years), teenagers (13 to 17 years) and adults (18 to 30 years) all of whom had a self-reported diagnosis of a peanut allergy. Individuals were recruited via patient advocacy groups and specialist patient recruitment panels. For the quantitative arm of the study, participants were asked to rate the impact of their allergy on activities such as food choices when eating out or buying food, using a 5-point Likert scale, where 1 indicated a low impact and 5 to highest.

Peanut allergy and its impact daily life

A total of 284 individuals which included 160 adults with a mean age of 33.9 years (61% female) completed the online survey. The situations causing most restrictions for participants were choosing foods when eating out, for which 82% reported feeling moderately or extremely restricted, choosing where to eat (82%), eating during special occasions (76%) and when buying food from a shop (71%). Participants also reported being moderately restricted when choosing a holiday destination (68%), travelling on airplanes (68%) and in socialising with friends (64%).

Interestingly, nearly a fifth (18%) reported being frequently frustrated because of the limitations due to their peanut allergy. The psychological impact of living with a peanut allergy also had a major effect on daily living with 70% reporting at least a moderate amount of frustration because of their allergy, 71% reporting stress, 65% feeling tense and 75% feeling anxious. In fact, 86% reported a moderate level of worry in situations such as social occasions where food was involved.

During the qualitative arm of the study, over half of those interviewed reported that their allergy had a negative impact on their social activities which resulted in not going out with friends, avoiding events where peanuts might be served and having limited food options during social events. In addition, 40% reported being bullied because of their allergy. Overall, affected individuals reported on how their allergy affected social activities, relationships, emotions and work.

The authors concluded that the presence of a peanut allergy placed a huge psychosocial burden upon sufferers, highlighting an unmet need among sufferers.

Citation
Tsoumani M et al. Allergy to Peanuts imPacting Emotions And Life (APPEAL): The impact of peanut allergy on children, teenagers, adults and caregivers in the UK and Ireland. PLoS One 2022

Peanut oral immunotherapy increases desensitisation and remission in children

27th January 2022

Peanut oral immunotherapy in children has been shown in a randomised, placebo trial to increase rates of both desensitisation and remission

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.

Findings

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.

Citation

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

Analysis shows skin peanut allergy patch safe and well tolerated over 3-year period

1st December 2021

Viaskin, an epicutaneous peanut allergy patch, has been found to be safe and well tolerated when used by children over a three-year period

The use of Viaskin, an epicutaneous patch used for children with a peanut allergy appears to be safe and well tolerated according to a three-year analysis presented by at the American College of Allergy, Asthma and Immunology Conference, November 2021.

A peanut allergy is thought to affect around 2% of the general population and in a study of 3218 children, the incidence was found to be 24.8%. The presence of a peanut allergy is challenging for those affected and requires a high level of vigilance directed towards the avoidance of accidental ingestion of peanut-containing foods.

The use of viaskin represents ‘epicutaneous’ immunotherapy and according to the manufacturer, DBV Technologies, is a proprietary technology platform that enables the delivery of biologically active compounds to the immune system through the skin.

The data presented at the American College of Allergy, Asthma and Immunology Conference was based on the REALISE trial, which included children with documented histories of peanut anaphylaxis and who were randomised, 3:1, to either viaskin peanut 250mcg (which contains 1/1000th of the protein found in a single peanut) or a placebo for a period of 6 months. Once this initial phase was completed, all subjects continued to receive the active treatment in an open-label extension, for a period of three years. For the REALISE study, the primary outcome was set as adverse Events (AEs), treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) throughout the study period.

The 6-month safety data for viaskin has already been published and showed that the patch was well-tolerated.

Findings

REALISE recruited 393 children with a median age of 7 years (gender not reported) of whom, 14 (3.6%) had a history of severe anaphylaxis. Throughout the study period, most subjects experienced at least one TEAE although these were reported as being mild (97.4%) or moderate (70.4%) in severity and commonly consisted of application site erythema and pruritus which fortunately decreased over time.

Overall, 16 children experienced a total of 17 anaphylactic reactions (none severe) considered to be due to viaskin. In addition, there were 2 serious that were viakskin-related TEAEs (2 anaphylactic reactions: one leading to permanent study discontinuation). No difference in TEAEs in subjects with severe anaphylaxis history was apparent.

The authors concluded that ‘over 36-months, Viaskin Peanut was generally well tolerated, with decreasing frequency and intensity of local and systemic treatment-related AEs over time.’

The product is yet to be approved by the FDA, which has requested more data or the EMA.

Citation

Brown-Whitehorn T et al. D030 REALISE (REAL-LIFE USE AND SAFETY OF EPIT) STUDY: 3 YEAR RESULTS IN PEANUT-ALLERGIC CHILDREN. Ann Allergy Asthma Immunol 2021