Oral Immunotherapy...Just The Facts (Part One)

The fact that Aaryn and I are huge believers in Oral Immunotherapy is no secret at this point.  We have both publicly shared our story in an attempt to put a human face to a often debated topic.  Today, Aaryn and I are excited to introduce Part One of a Four Part Series on Oral Immunotherapy...Just The Facts.

Earlier this summer, Aaryn and I reached out to the greater allergy community and asked "what are the fears, myths, or questions you have/have heard about OIT?".  Foolishly, I posted this question before heading to bed, thinking we would get a few questions.  The next morning, I woke up to several dozen notifications.  When all was said and done, we had over 50 questions! That list was reviewed, and 20 questions remained (for those wondering about the other questions, some were combined, others will be saved for a less fact-focused, more experience centered article).  We reached out to none other than the renowned (and much loved) Dr. Richard Wasserman of The Dallas Food Allergy Center.  We are thrilled that he agreed to answer our (fairly long) list of questions!

PART ONE: The Basics

OrAAA: What does your protocol look like? What is the ultimate goal? 

Dr. Wasserman: We begin with a very low dose, no patient has ever reacted to our first dose. On day one we give several doses over a several hour period. After the first day, we do dose increases weekly. The target dose is a full portion of the food. Our goal is normal life. For most patients, the goal is to freely incorporate the food into their diet. Not all patients are able to do that. Some families decide that they want to continue to avoid the problem food even after they complete OIT.

OrAAA: Can you explain the concept of OIT and how it differs from the peanut patch, a pill, or the FAHF-2 work of Dr. Li? 
Dr: Wasserman: OIT, sublingual and the patch all work on the principles of desensitization that introduce progressively increasing doses of allergen over time to alter the allergic response. This approach has been used by allergists for more than 100 years. The mechanism of action of FAHF-2 is still being worked out.

OrAAA: Many of us have kiddos with several issues going on at once...how do other diseases impacts the process (Environmental allergies, asthma, Mast Cell Activation Disorder/Syndrome, EOE, FPIES)?  Are there any absolute "no's"? 

 

Dr. Wasserman: Whenever a patient begins OIT, there will always be a question of whether the symptom was caused by the OIT food. Therefore, other allergy related problems need to be well controlled before OIT is started. This applies to allergies, asthma and eczema. We have no experience with OIT in patients with mast cell activation syndrome or idiopathic anaphylaxis and would be reluctant to try in those cases because it would be hard to differentiate a food reaction from other problems. The understanding of EoE and FPIES is limited and the risks of introducing a food known to cause a reaction are unknown but those problems are difficult enough without adding the potential complications of OIT. We would not begin OIT in a patient with EoE or FPIES.

OrAAA: What are the odds that my kiddo will develop EOE/FPIES/a new food allergy/exercise induced anaphylaxis?

 

Dr. Wasserman: We believe that about 3-5% of our OIT patients develop clinical symptoms suggestive of EoE. Some groups have seen a higher incidence. Early on, when these symptoms occurred (vomiting hours after the OIT dose), we stopped OIT. Based on the work of our colleague, Dr. Katz in Israel, we now reduce the dose until symptoms resolve, hold at the lower dose for several months, and then increase again. This works for most patients. 

Food/exercise anaphylaxis has been known for many years. Exercise too soon after doing is a significant risk for a reaction. We require a two hour waiting period after dosing before athletic activity.

OrAAA: There seems to be a lot of different protocols out there (rest periods, bite proof vs. unlimited consumption, once or twice a day, etc.).  Do you know why this is? 

Dr. Wasserman: Each allergist develops the approach that he or she believes will work the best. Each OIT study can only tell us how well that protocol seems to work. The only way to know if one is better than another would be to do a study comparing them in a controlled fashion. It is unlikely that such a study will ever be done. The protocol that we use today has been modified several times based on review of our experience. We collected detailed information about the experience of each OIT patient and review that information at least annually. Based on what we see in the compiled data we modify our approach to make it safer or better tolerated. Among those who have reported their experience, the results are pretty much the same.

OrAAA: Bite proof or unlimited...which is the better goal?

 

Dr. Wasserman: It depends on the individual patient. We aim for unlimited incorporation of the food into the diet. Very few children are so difficult to treat that they can't reach the target dose but it does happen. So children really hate the taste of the food, especially peanut. For those children it doesn't really make sense to push to the full dose. The right goal is the goal that is right for the individual child and family.

OrAAA: Will we have to dose forever? Why? 
Dr. Wasserman: We really don't know. It appears that some children develop sustained unresponsiveness with profound reductions (>98%) of the food specific IgE. These children don't have to dose daily. At this point, it seems that most OIT patient will need to dose indefinitely. The allergic response is still only partially understood. We don't know why some people develop food allergy nor why some respond to OIT better than other.

OrAAA: How can I know OIT is safe when it is not FDA approved?

 

Dr. Wasserman: There is a lot of misunderstanding of the role of the FDA in OIT, even by doctors. The FDA approves drugs and devices. It never approves treatments. It is likely that the FDA will eventually approve the peanut treatment being developed by Aimmune. I see this as a disaster for patients. I can treat many patients for a $6 bag of peanut flour. When the FDA approves peanut treatment, I expect that the peanut drug will cost thousands of dollars per patient excluding physician's fees.

OrAAA: Is there a chance that OIT can make an allergy WORSE?

 

Dr. Wasserman: I don't think that OIT can make an allergy worse. 

OrAAA: There seems to be pretty good consensus that adolescents are at risk for poor outcomes associated with anaphylaxis.  Is this biological or related to another factor? If it is biological, does that mean that it could make OIT dangerous at this age?

 

Dr. Wasserman: It is hard to know for sure but I think the problem with adolescents is that they deny early symptoms and don't carry epinephrine and therefore treatment is delayed. We do know that delay in the use of epinephrine is associated with bad outcomes.

OrAAA: Can you talk about doing OIT with children with special needs (such as kids with I/DD or Communication Disorders)?  Does this change anything with the OIT process?

 

Dr. Wasserman: Children receiving OIT need to be developmentally able to fully cooperate with the process, communicate subtle symptoms and be willing to eat a food every day as though it was a medicine. Each child should be evaluated individually before start OIT.

OrAAA:  If OIT in the private practice is safe, why is it so controversial? Why the lack of practices?

 

Dr. Wasserman: It has been argued publicly that more studies are needed before OIT can be offered by allergists outside of studies. Since that statement was made in a public forum, there have been more than 400,000 ER visits for food allergy and opponents say we still need to wait for more studies. OIT is a complex and demanding procedure for patients, their allergists and their allergists' office staffs. Not every office will be equipped or willing to undertake the effort to offer this therapy. I believe that OIT should be available but I don't believe that every allergist should offer OIT.

 

Dr. Wasserman is Medical Director of Pediatric Allergy and Immunology at Medical City Children’s Hospital and managing partner of Allergy Partners of North Texas. He served on the full time and clinical faculty in the Department of Pediatrics at the University of Texas Southwestern Medical School from 1988 to 2015.

He was raised in New York, where he graduated cum laude with Honors in Chemistry from Hobart College. He studied at Mt. Sinai School of Medicine and City University of New York Graduate School receiving his PhD in immunology from CUNY and his MD from Southwestern Medical School. He did an internship and residency in pediatrics and a fellowship in bone marrow transplantation and immunology at The Children’s Hospital of Philadelphia. After a fellowship at The Rockefeller University (Kunkel Lab) he became Chief of Pediatric Allergy and Immunology and Pediatric Program Director at Southwestern Medical School.

After six years as fulltime faculty, Wasserman started a private practice in allergy and immunodeficiency and DallasAllergyImmunology Research that has conducted more than 110 FDA approved studies.  He served as Director of the Immunology Clinic at Children’s Medical Center of Dallas for 19 years and taught immunodeficiency to medical students for more than 25 years. He is a past president of the Pediatric Society of Greater Dallas and has edited the Society Newsletter for fifteen years.  Wasserman is currently a Trustee of Hobart and William Smith Colleges and a past member of the AAAAI Board of Directors.

Wasserman has coauthored more than 100 peer-reviewed publications, case reports, book chapters and reviews and 80 International Meeting posters and presentations.

 

#Miles4Anaphylaxis...Racing to spread anaphylaxis awareness around the world!

It is hard to believe, but it is almost May! That means that Food Allergy Awareness Month is almost upon us!  Where has the time gone?

This year, Aaryn and I decided we wanted to try something new and exciting for Food Allergy Awareness Month (after all, how can you thrive if you keep doing the same thing over and over again?).  After lots of conversation, we kept finding ourselves coming back to the same question...how do we connect all of the amazing groups and advocates that we know (and admire)?

The answer was surprisingly simple.  We all work together as a team with the same goal!

Out of this conversation, the #Miles4Anaphylaxis idea was born.  We wondered, "what if
 we could 'circle' the world, raising awareness of food allergies and anaphylaxis one step at a time?".  At first, the process seemed terrifyingly complicated (for the record, it still does...we just decided nothing ventured, nothing gained).  But conversation after conversation reinforced that while we may live on opposite sides of the world, food allergies and anaphylaxis have made us one big family!

So here is the deal...starting May 1st, we will beginning "circling the globe".  We will be raising food allergy/anaphylaxis awareness with every mile! And WE NEED YOU!!!!  You can hike, bike, run, walk, swim, ski, rollerblade (is it still a thing?), skateboard, surf, or even crawl!  No matter how you do it, each step gets us closer to the 24,901.55 miles it will take to hit our goal!  All you need to do is do your thing and email us your mileage at miles4anaphylaxis@gmail.com!While you are out getting your miles in, feel free to join us in rocking teal.  We will be rocking a teal flower every step of the way! And please use the hashtag #miles4anaphylaxis so that we can see all of your awesome work!

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.

From Poison to Peanuts

A year ago, if someone had told me that my shelves would be filled with Reces Pieces and Peanut M&M's, I would have thought you were crazy.  But today, when we stop by the drugstore, we always pick up at least one bag of both.  The conversation always goes something like this:

Cashier: "Oooohhh, that looks yummy! Are you guys having snacks tonight?"

Mary: "That's my medicine."

Cashier: "That is silly, candy can't be medicine!"

Mary: "You're wrong.  I am allergic to peanuts, but I finished OIT.  So that means I have to eat peanuts in the morning and at night.  So that is my medicine."

Cashier: (To me) "Gosh, that must be nice medicine.  I wish I had to take that for medicine!"

Mary: (Before I can speak) "No, it is a tiny bit yucky.  But it means I won't die from peanuts.  So that is okay."

Never, in my wildest dreams, could I have imagined having this conversation (none-the-less imagining my 7 year old asserting herself and educating random strangers about food allergies).

Our journey has been difficult (to say the least).  While we had suspected a peanut allergy for some time (that is another story for another time), she was officially diagnosed in 2011.  That day marked the beginning of a long, scary, traumatic journey.  Mary went into anaphylaxis minutes after her test began.  Everything after that was a blur.

Over the next couple years, we battled.  We were on guard.  We carried wipes and epinephrine everywhere.  And we kept her reaction free.  Until November 20th, 2013.  That day will be permanently etched in my mind.  Mary had been sick that day (which is likely what set the stage for her reaction).  After insane amounts of fighting, we had convinced the school to agree to whole class handwashing after meal and snack periods.  When we spelled it out for them, apparently, saying that "Ice Cream Day" was a snack period was not clear enough.  No one washed their hands, and Mary touched a surface that had peanut residue.  She had an initial delayed reaction and a biphasic reaction.

After sitting in the back of two different ambulances, in the ER, I promised myself, Mary, and God that this would never happen again.  Aaryn and I had talked about OIT before, but I was so scared.  Nothing made it less scary.  I just was more afraid of losing her.

It took a while to get Mary ready for OIT.  She has both Asthma and Mast Cell Activation Syndrome.  This means that it took a lot of work to stabilize her enough to handle OIT.  After lots of work, we scheduled our first appointment.  November 3rd, 2014.  Almost exactly one year to the date.

I was terrified.  But I refused to show it.  I completely trusted Dr. Baker and his staff, so I knew that if anything bad happened, they would know how to handle it.  I chose to not tell Mary about side effects...I did not want her to go in expecting something to go wrong.  I simply said "it may be yucky, but it is going to mean that you can be safe...no more fear of dying" (Mary had asked if peanuts would kill her multiple times by this point).

On that day, we arrived early.  I showed up with enough snacks and entertainment to keep a small army busy.  They took baseline vitals, and then started with her first dose.  I watched her so closely that I am sure she thought I was crazy.  And...nothing.  Then the next dose.  And the next.  Finally, Dr. Baker came in and said that they would call it quits for the day so we did not get sick of looking at each other! And that was it.  They sent us on our way with tiny little pieces of peanuts.  It was the craziest thing ever.

We came back week after week.  Within an amazing six short weeks, Mary hit maintenance.  And that was it.  No drama.  No chaos.  No catastrophe.  In six short weeks, our lives changed forever.  The fear was gone.

We still have to read labels (Mary is considered "Bite Proof" but does not eat above her dose).  We still carry epinephrine everywhere.  But that fear is gone.  Mary can return (safely) to school.  She can have birthday cake.  She can live....without the fear of dying.