Friday, March 13, 2015

Your Burning Questions about the LEAP study...answered!


In case you have not heard, last month, a lot of new research was released at the American Academy of Allergy, Asthma, and Immunology's 2015 conference. While much of the research has brought food allergies in to the eye of the media (in a much bigger way than we have seen before/anticipated), none of the research has created more  (often heated) conversation than the LEAP study.  We reached out to you and asked for your questions and concerns and asked Dr. David Stukus, Assistant Professor of Pediatrics in Allergy/Immunology at Nationwide Childrens' Hospital in Columbus, Ohio (and Chair of the Medical Advisory Team for Kids With Food Allergies) to answer some of your most burning questions about the study!


OrAAAA:  While I am sure that most folks have heard of the LEAP study by now, can you tell us exactly what the study is and what the goals of the research were/are?

Dr. Stukus: LEAP was designed to study whether onset of peanut allergy could be prevented through early introduction. It has been known that food allergies have been on the rise for 10+ years and that some groups (ie, Israeli infants) do not have as high rate of allergy as others. Many hypotheses, but few answers. Most recent research has focused on treatment of existing food allergy…LEAP was born to try and approach prevention. They recruited over 600 infants all 4-11 months old in the United Kingdom between 2006-09 who ALL had a history of severe eczema and egg allergy. This was a high risk group, more likely to develop peanut allergy compared with other children. Each child underwent skin prick test to peanut AND physician supervised oral challenge. 10% had too + of a skin test to proceed and 13% failed food challenge and could also not proceed (great reasons to NOT try this at home). They were separated into skin test negative and mildly positive (1-4 mm wheal), then randomized to either eat peanut snack (Bamba) 3 times/week for 4 years vs. complete avoidance. Primary outcome was development of peanut allergy at 5 years of age, determined by oral challenge. It was not 100% successful, as 2% of skin test neg and 11% of mild positive skin test still developed peanut allergy even by eating it regularly. There was, however, a 86% reduction in peanut allergy for negative skin test and 70% reduction in mildly positive skin test between those that ate vs. those that avoided peanut. Pretty remarkable.

OrAAAA: There have been lots of concerns expressed about the design of this study.  Also, several members of the food allergy community have expressed concerns about funding sources for this research (and the possibility that they could influence results).  Can you talk to us about the design of this study?

Dr. Stukus: The assessment of eligibility/safety for inclusion and outcome measures were as good as it gets (in my opinion). They really did a great job of using a good, consistent protocol and excellent assessment of allergy (gold standard = oral food challenge). In regards to bias from funding source, full disclosures are made by all authors involved, considered by the journal that publishes the article, and these authors went the extra mile as they have made ALL of their results available for the world to see and conduct their own analyses. This study is not subject to additional bias from funding more so than any other study ever conducted through funding. The peer reviewed process on the path to publication is rigorous for a reason.

OrAAAA: To clarify, was there any part of the research that included a double-blind? I see the most questions surfacing around how an allergy was diagnosed at the oral challenge (which was, admittedly, different than the initial criteria), and, depending on the criteria used, potentially having influence if the researcher and patient were aware?

Dr. Stukus: Yes, excellent point. Every challenge at 5 years of age was double blind, placebo controlled. As clean as you can possibly make it. 

OrAAAA: There has been quite a bit of feedback about the results of this research, particularly from parents of food allergic children.  What do you think is causing much of this push back? Do you think the widespread publicity of this research has had a positive or negative impact?

Dr. Stukus: Great question – some of it was anticipated, but a lot was more of a surprise. This was as big as it gets in regards to publicity. Major journal publication coordinated to the minute with the presentation of results at the preeminent international allergy conference followed immediately by a press conference with major news organizations…I’ve never seen anything like this! I think the publicity has hurt the impact based upon the terrible headlines that misinterpret the study results. Let’s face it, many subsequent opinions by ill informed individuals have been based only upon reading some of these headlines, all designed solely to get more clicks or readers. (Yes, I’m frustrated by this).

In regards to push back, I think that this is hard news for the millions of individuals living with food allergy as this has nothing to do with treatment or a cure. Not to mention that dietary recommendations have changed dramatically over the last 15 years, so parents who followed the advice of the ‘experts’ and avoided peanut are now hearing that they may have been able to prevent their child’s peanut allergy. Tough news to swallow. There’s a lot more to it than that, but could easily be perceived that way.

OrAAAA: Can you talk to us about some of the limitations of this study?

Dr. Stukus: Major limitation is the infants studied – predominantly white and all had eczema and egg allergy. No inclusion of other food allergies, history of wheezing, or older children. Makes it tough to extrapolate results to other populations.

OrAAAA: There are some parents who have said that this seems like (for lack of a better phrase) OIT before the fact.  Is there any truth to that?

Dr. Stukus: I see why it appears that way, but this is very different. OIT is administered to people who have a known history of allergic reaction to a food. It is essentially a desensitization procedure. The LEAP study did not include anyone who had peanut allergy – in fact, reactions were exclusion criteria. This was not a desensitization as allergy never existed. It was truly prevention, as best as can tell.

OrAAAA: There has been discussion of next steps for this research  Can you explain these? Will the study be repeated? Different countries? Cultures? Races/ethnicities? Health backgrounds?  

Dr. Stukus: I have no doubt that these results will now need to be replicated in other countries and all matter of backgrounds. Next steps for the authors is the LEAP-On study, during which the children who did not develop allergy will now avoid peanut for 12 months and then undergo repeat challenge – this is to better understand underlying mechanisms and better determine true prevention.

OrAAAA: Assuming the results can be replicated, what do you see the practical application of this research looking like?

Dr. Stukus: Assuming similar findings in other cohorts, this will dramatically change feeding guidelines and approach by allergists. I believe, as with any study/procedure, that children will need to be carefully selected. This should NOT be done at home – to reiterate, every single child in this study underwent BOTH skin prick and oral challenge to ensure safety. I envision a renewed approach to testing at risk infants early and then consideration for more early introduction of peanut and other allergenic foods.

OrAAAA: Should parents do anything different at this time?

Dr. Stukus: If your child already has peanut allergy, or is older than 12 months of age, the short answer is no. This does not change anything for these children, unfortunately. If your child has risk factors for development of peanut allergy (strong family history, eczema, other food allergy), then I would discuss with their allergist who may now consider skin test and oral challenge followed by putting into the diet.

OrAAAA: Do you believe that this research may eventually be able to be applied to other allergens?

Dr. Stukus: Eventually, yes. It’s only a matter of time.

OrAAAA: What do you want people to take away from this research?

Dr. Stukus: We still understand very little about all of the factors involved in the development of food allergy, natural history, and treatment. This is a landmark study unlike any other that offers some insight into actual steps we can take to try and prevent peanut allergy from ever developing for infants at risk. Treatment for those living with food allergies is everyone’s wish, but if we could prevent it in the first place, that would be revolutionary.

OrAAAA: There has been discussion about whether children who are not at high risk for developing an allergy should be avoiding allergens in infancy.  Is there research that supports giving or withholding allergens? Is there an ideal window? Does this change if a sibling has an allergy?

Dr. Stukus: Revamping of the guidelines by the American Academy of Pediatrics in 2008 acknowledged that there is insufficient evidence to suggest prolonged avoidance of major food allergens in low risk infants would prevent the development of allergic diseases. Not much research done to support giving it early (until now), but it is generally thought to be very safe and that there is a small window of opportunity to promote tolerance through early introduction (before 12 months old) whereas the old feeling was avoidance prevented allergy. Truth be told, for the 90% of people that do not have food allergies, it won’t matter when they eat foods for the first time.

Sibling with peanut allergy is a risk factor; many recommend skin prick or blood IgE for younger sibling before giving peanut.

OrAAAA: There are lots of confused parents asking for help understanding these results.  For many of us, we ate peanut products while pregnant and breastfeeding.  Is this insufficient to provide protection?

Dr. Stukus: Without a doubt, there is ZERO evidence that indicates that any parent caused their child to develop food allergy through their own dietary habits during pregnancy or breastfeeding. In fact, some research shows the opposite effect – the more you eat, the better it is. Unfortunately, this is not 100%. There is still so much we don’t understand. It is likely a very complicated combination of inherited genes and early life exposures (not just with food, also microorganisms in our gut and respiratory tract) that determine who does and does not develop food allergy.

I tell parents every chance I get that “It’s not your fault”. Way too much guilt for something that is so far outside of anyone’s control.

OrAAAA: It seems that the media coverage has caused much of the message of the research to get lost.  Is there anything else that you feel that parents should know that may have been missed in the chaos of the press coverage?

Dr. Stukus: I agree – it’s so important to read past the headlines. This was one study about possible PREVENTION of peanut allergy in young infants at risk who did not already have peanut allergy. Anyone who claims that this now allows for fewer safeguards in schools for children with peanut allergy, or that this now allows people with peanut allergy to start eating peanut…or that parents created peanut allergy in their children by refusing to give it to them simply does not understand what this research shows.


A giant thanks to Dr. Stukus  for taking the time to answer the questions from our readers!  

Dr. Stukus is an Assistant Professor of Pediatrics in the Section of Allergy/Immunology at Nationwide Children's Hospital, in Columbus Ohio. In addition to his interest in caring for families with food allergies and other allergic conditions, he also serves as Director of the Complex Asthma Clinic. He currently serves as the Chair of the Medical Advisory Team for Kids with Food Allergies and sits on the Board of Directors for the Asthma and Allergy Foundation of America. He previously completed his pediatric residency at Nationwide Children's Hospital and his fellowship in Allergy/Immunology at the Cleveland Clinic Foundation. You can follow him on twitter @AllergyKidsDoc.

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