Prevention of peanut allergy in children: understanding the LEAP Study Q&A for the peanut industry

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1 Prevention of peanut allergy in children: understanding the LEAP Study Q&A for the peanut industry What is LEAP? Learning Early about Peanut Allergy (LEAP) is a randomised and controlled five-year clinical intervention trial based in London, UK, which reported initial results in The results were published in the New England Journal of Medicine on 26 February 2015 as Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy with an accompanying editorial Preventing Peanut Allergy through Early Consumption Ready for Prime Time? In the same issue there is a short video explaining the study and its results in graphic form. This material is in the public domain and can be freely downloaded at What is LEAP s key finding? The study s bottom line is the cause and effect demonstration that consumption of a snack containing peanut protein (Bamba) or peanut butter by infants who are at high risk for developing peanut allergy prevents the subsequent development of allergy in a very high percentage. Put another way, early dietary exposure to peanut allergen was shown to promote the development of tolerance to peanuts by the child s developing immune system and is highly effective in preventing allergic reactions to peanuts in later life for this high risk group. The intervention used in LEAP was safe, well-tolerated and, most important of all, highly effective. At age 5, peanut consumption was associated with an 86% reduction in peanut allergy among children testing negative for peanut sensitisation when the study began and with a 70% reduction in peanut allergy among those who had had positive skin-prick test results at study entry. Lead investigator Prof Gideon lack, King s College London, said: For decades allergists have been recommending that young infants avoid consuming allergenic foods such as peanut to prevent food allergies. Our findings suggest that this advice was incorrect and may have contributed to the rise in the peanut and other food allergies. This is an important clinical development and contravenes previous guidelines. Whilst these were withdrawn in 2008 in the UK and US, our study suggests that new guidelines may be needed to reduce the rate of peanut allergy in our children." Has the US peanut industry supported peanut allergy research including LEAP? Yes. National Peanut Board President and CEO Bob Parker said, Research like LEAP, which demonstrates there are ways to reduce the risk of a child developing a peanut allergy, brings hope to families everywhere. That is why U.S. peanut farmers through the National Peanut Board have contributed more than $12 million toward independent food allergy research, education and outreach worldwide over the past 15 years, and plan to continue to be part of the solution. Some online comments have expressed concern that the peanut industry was involved in the LEAP funding. This support was fully disclosed in the study itself and the industry s role has

2 been put into perspective by a statement from FARE (Food Allergy Research and Education) making it clear that the industry had no influence over the outcome:.the vast majority of the study s funding came from the National Institutes of Health and FARE. The National Peanut Board, a minority funder, was contractually prohibited from influencing any aspect of the study design or interpretation of the results. A complete list of funders can be found at end of the LEAP study itself published in NEJM. Does LEAP mean peanut allergy has been cured? No. The study was about prevention of peanut allergy not curing existing allergy in a selected group of infants under 12 months of age who were at high risk of developing peanut allergy later in life because they had risk factors such as eczema and egg allergy. The study children were included because of these risk factors. Children without these risk factors or in whom it was thought peanut allergy had probably already developed because of the degree of their sensitisation to peanut, were excluded from the study. LEAP is not a treatment or a cure for existing peanut allergy in children. The findings are not applicable to adults. Dr Andrew Clark, paediatric allergy specialist at Addenbrooke s Hospital, Cambridge said: [LEAP] challenges the way we think about first introduction of foods. In the past there was a lack of studies telling us what the best way was to avoid children having allergies. It was thought best you shouldn't give children allergenic foods. That's the whole dogma this study challenges. In a positive way I think it could mean we can improve the way we feed infants to reduce the number of food allergies in the future." Did consuming peanut protein work for all of the children in the LEAP study? No, but it did create tolerance (known as unresponsiveness ) to peanut protein in a high percentage of at risk infants. Of those avoiding peanut during the trial, about 17% had become peanut allergic by age five. However, of the group eating peanut every week, only 3% were allergic to peanut by age five. It is important to remember that these were all high risk infants, not the general population. LEAP was a very well designed and safe intervention. Ninety-eight percent of the children remained in the study until the end when they were five years old. Only one child needed epinephrine (adrenalin) and any reactions which did occur were mild to moderate. It has to be stressed that these are prevention outcomes. LEAP was not a study looking at treatment of children with peanut allergy and its results have nothing to say about a cure for peanut allergy or the treatment of anyone who has had prior allergic reactions to peanuts. Could the approach used in the LEAP study be used to treat peanut allergy? As LEAP is refined for clinical practice, it may be possible to identify and build up tolerance to peanut in high risk young children by introducing peanut products such as peanut butter into their diet from an early stage. This is primary prevention. For those already with established peanut allergy, there are experimental treatments which may become available in the future. These include oral immunotherapy (OIT) and skin patch technology (epicutaneous immunotherapy), both of which have been shown to create tolerance in some individuals by introducing increasing doses of peanut allergen.

3 Do the LEAP results have implications for preventing allergies to other foods? While LEAP was exclusively about peanut allergy, the approach it used is reflected in a study of early introduction of other foods called EAT Enquiring About Tolerance. This is testing the hypothesis that the introduction of six allergenic foods (fish, egg, dairy products, wheat, sesame and peanut) into the diet of infants from 3 months of age, alongside continued breastfeeding, results in a reduced prevalence of food allergies by 3 years of age. The EAT study is expected to report in September Is the tolerance to peanut allergen shown in the LEAP results permanent, or will it need topping up in these children from time to time? This is not known at the moment, but a 12 month follow-on study, called LEAP-On should have the answer in about February In LEAP-On, the participants from LEAP who ate peanut and did not become allergic will stop eating peanut completely and undergo a peanut food challenge 12 months later. This will show if the unresponsiveness lasts or not. The study talks about consuming peanut. Is this just another way of saying children eating peanuts or feeding children peanuts? No and the difference is important. Some media reports talked about babies eating peanuts or feeding peanuts to babies both of which are misleading and potentially dangerous. The LEAP trial used peanut protein contained in peanut products, such as the puffed snack food Bamba (see below) or smooth peanut butter, which were eaten in a supervised clinical setting and all the children were skin prick tested for peanut sensitivity before being enrolled in the study. That is what consuming peanut means in the context of the LEAP study. LEAP did not use whole peanuts because of the danger of very young children choking on them. Nor did it imply that consumption could be done outside of a supervised clinical setting. Some media reports are dangerously misleading by implying that LEAP gives permission for parents to start feeding whole peanuts to very young children or to introduce peanut products to high risk children who have not been screened to determine their degree of sensitivity. Dr James Baker, CEO of Food Allergy Research & Education (FARE) said, Parents should not simply hear a "consume peanut" message. We hope that parents understand this isn't something you do without consulting a physician and making absolutely sure the child is not allergic first," Some media reports about LEAP use the expression exposing children early to peanuts. What does that mean and is it an accurate description of what happened in LEAP? The phrase is ambiguous and should not be used as it does not describe what happened in the LEAP trial. It is known that exposure via direct skin contact to protein containing peanut particles or residues can result in sensitisation to peanut in very young children if the skin barrier is compromised, eg if a child has eczema. LEAP was about the consumption of peanut protein by eating it so that it was absorbed through the gut not through the skin. Exposure, therefore, is not a good word to use in connection with LEAP, but if it is used it must always be made clear that dietary exposure, ie consuming by eating, is meant. What is the snack Bamba and why was it used in the LEAP trial? Bamba is the brand name of a popular snack product in Israel, eaten by virtually everyone from an early age. It is a puffed maize snack product containing peanut butter The LEAP trial used 25g (1oz) packs of

4 Bamba. 17g or 2/3 of the Bamba pack provided 2g peanut protein, and the children consumed this 3 times per week. Bamba was used because an observational study in 2008 ( found that Israeli children have lower rates of peanut allergy compared to Jewish children in the UK of similar ancestry. The Israeli children began consuming peanut-containing foods, particularly Bamba, very early in life. LEAP therefore investigated the hypothesis that the very low rates of peanut allergy in Israeli children were a result of high levels of peanut consumption beginning in infancy. The Israeli children consumed about 6-8g of peanut protein per week, so that was used as the upper limit in the LEAP study. It isn t known what would have happened if more or less than that amount had been consumed. For children in the LEAP trial who did not like Bamba, equivalent amounts of smooth peanut butter were used instead to achieve the same effect. Could putting peanut flour or smooth peanut butter into weaning foods for babies be a way to achieve this result achieved by LEAP? This has been suggested as an alternative to consuming Bamba or peanut butter, but it will depend on how the guidelines about childhood allergy and about weaning and breastfeeding are revised in the light of the LEAP findings and also the EAT study findings. Getting the dose and the feeding frequency right are important. But it is possible that new products along these lines could be developed once the revised guidelines are available. LEAP studied high-risk children living in Britain, so are the findings applicable to children in other countries? LEAP included 640 high risk infants under 12 months old. Having an egg allergy or eczema typically means a 15-20% chance of developing peanut allergy later. This number was chosen to give statistical robustness to the study. If the group had been drawn from the general population, the numbers needed for the study would have been several thousand and thus unmanageable over five years. All infants were screened using a peanut protein skin prick test to identify those already showing signs of an allergic reaction. Those with large wheals (areas of raised or reddened skin >4mm diameter) were excluded from the study because they probably already had a peanut allergy. Those with slight wheals (< 4mm) were included in LEAP, but analysed separately to those showing no skin reaction. The LEAP study children were all living in the United Kingdom and predominantly white with eczema and/or egg allergy. Geography and ethnicity must be considered before extrapolating the results to other populations, for example older children or African-American or Hispanic infants in the US or infants with multiple food allergies. However, the investigators have stated that subgroup analyses of the data of Black and Asian children in LEAP suggests that the intervention works regardless of ethnicity. Are clinical skills at the right level to identify children at high risk of developing peanut allergy so parents can be advised what steps to take? Skill levels and access to clinicians with allergy expertise are real concerns for the LEAP team. Investigator Dr George du Toit, King s College London and Guy s and Thomas NHS

5 Foundation Trust said, We believe there's an urgent need for clinicians to be skilled in identifying the at-risk population. This means a basic knowledge about atopic eczema, egg allergy, and milk allergy, which are all risk factors for peanut allergy, and then of course skinprick testing, which in the LEAP study we found to be invaluable for dissecting risk categories. Worldwide, not all patients in fact a real minority of allergic patients have access to even those basic diagnostic skills." Does the LEAP finding about preventing peanut allergy mean that educational approaches to food allergy management in schools and other settings will not be as important in future? No and in many ways these initiatives will become even more important. Encouraging as LEAP is for the future, no one should be under any illusion that LEAP s findings mean that peanut allergy is no longer a serious issue for many individuals who are already allergic. The need for allergy-safe and evidence-based management practices particularly in schools and other settings where children are present - and the provision of accurate information to food allergic consumers has not gone away because of LEAP. In many ways the need for these things will become more urgent and the American peanut industry will continue to support such initiatives. We want the 98% of the population who are not peanut allergic to be able to enjoy peanut products without food bans and restrictions while the 2% or thereabouts of the population who may have an allergy to peanuts can be safe and well-informed. What are some reliable online sources of information about LEAP and its implications? There is no substitute for reading the published study and the accompanying editorial in NEJM. In addition, LEAP team members and other leading paediatric allergy specialists and patientled bodies have discussed the findings widely. Below are links to some of online sources which are reliable and which also correct some of the misunderstandings which may develop around the study and its implications. Anaphylaxis Campaign FARE (Food Allergy Research and Education) Scientific American Huffington Post NHS Choices National Institutes of Health Medscape AsthmaAllergiesChildren.com

6 Kids with Food Allergies Massachusetts General Hospital for Children Allergic Living Compiled March 2015 by Dr Andrew Craig Health Consultant American Peanut Council Lansdowne Building (Room 222) 2 Lansdowne Road Croydon CR9 2ER Tel: + 44 (0) agcraig@peanutsusa.org.uk