November 8, 2010

Gina Clowes: Good Morning Dr. Burks. Thank you so much for talking with me today. I know our readers will be very interested to hear the latest on your research. For those who are not familiar, would you briefly explain oral immunotherapy?

Dr. Wesley Burks: Oral immunotherapy is a treatment where allergic children are fed minute amounts of the food protein and carefully increase the amounts over time in order to desensitize the child to that food protein.

Gina: And you started with egg immunotherapy first?

Dr. Burks: Yes, we did.

Gina: Then you moved onto to peanut. Of course our families are aware that peanut and tree nut account for most fatal and near fatal reactions. What were you thinking before the study began? What was that like for you?

Dr. Burks: What we hoped to do is address the unmet need that is there for development of a new treatment, or some type of specific treatment that would help the allergic disease go away.

Gina: Right. As a researcher, what happened during that study, or any of during any of the oral immunotherapy research that you've done that surprised you?

Dr. Burks: I think several things were interesting as we went through this study. One was the benefit that patients and their families receive from - they're realizing that their threshold changed if they were on the study treatment.

Before the study, they were having a reaction to certain amount that went up significantly while they were on the study.

I think the second thing that was interesting is that immunologically we saw significant changes while the patient was on the treatment.

I think another thing is that it was interesting to see the side effects of the therapy that clearly there were about 15-20 percent of the people that will not tolerate the treatment. And the types of the unanticipated safety events that we had that weren't really things that people had talked about with other types of immune therapy.

Gina: Do you want to say more about the unanticipated safety effects?

Dr. Burks: From a safety standpoint about 15-20 percent of patients when they enter the study, after the first few months, will not tolerate the treatment, most of the time for recurrent gastrointestinal effects.

The others that stay in, then there are allergic side effects related to viral infections and exercise. And I think we just barely understand the relationship between those factors and then the outcome of the allergic side effects.

Gina: When they get a viral illness during the immunotherapy, they don't go back baseline, do they? They just need to back up a little bit in the treatment before moving forward, again, is that correct?

Dr. Burks: We'll decrease the dose, and then work our way back up.

Gina: That's interesting. I understand that your colleague,

Dr. Bird in Texas, is now studying the immune system and how tree nut allergic children respond to viruses. So, hopefully, we'll hear more - or learn more about that.

Dr. Burks: Yes.

Gina: I think back to one of my son's worst reactions when we were actually in the ambulance with an anaphylactic reaction. He was sick with a viral illness at the time. Do you think there should be a general warning to parents to perhaps be a little more vigilant about reactions when your child is sick?

Dr. Burks: Well, I don't know that viral infections - how much they play a part in natural reactions. What we are talking about is just the interaction of viral infections and fever, and then immunotherapy.

Gina: Okay. Got it.

Let's talk a little about how the immunotherapy is done. Right now, whether it's milk, egg or peanut, the food is in the form of a powder. Why is it given in this form, and how is it prepared?

Dr. Burks: The powder that we are using with peanut is from a candy manufacturer. So it's powder - it's like a flour that is primarily protein, with the other parts of the peanut taken out; the oil and the fat.

And we mix that powder with other foods, so that they can ingest it. It's not mixed in liquid. We've found that if it's mixed in liquid, then you have significantly more side effects.

Gina: Really?

Dr. Burks: It's put in the food, and then the food is swallowed. And that allows it to bypass, to some degree, the esophagus and get into the stomach, and then in circulation.

Gina: All right, so it's from a candy manufacturer! Interesting. I'm sure you must be meticulous in how you measure this. How much peanut are they given at the very beginning?

Dr. Burks: Literally, we start out at about 1/1000th of a peanut. And that amount is increased over time. The top doses that we get to range anywhere from 1-15 peanuts, depending on the study.

Gina: Allergy parents are constantly watching those food specific IgE levels, hoping to spot a trend of outgrowing. But you're actually seeing the IgE levels go up, at least in the beginning, is that correct?

Dr. Burks: Yes, the IgE levels go up and then back down during the course of the study.

Gina: And the IgG4 levels go up. That's the one thing that goes up and stays up, and that's a good thing. Could you explain a little bit about that?

Dr. Burks: The IgG4 goes up while you're on the study. It stays up throughout the life of the study.

Traditionally, IgG4 was thought to be the antibody that would block the allergic reaction, so it was called a blocking antibody. Really, we don't understand how it works, and whether that's the reason that individuals get better, or it's just a byproduct of the immune system.

But in any type of traditional immunotherapy, IgG4s going up, while you're on treatment to that allergen, is a good thing, and it's been associated with an improved outcome. But whether there's a reason for the improved outcome, or just a byproduct of it, we really don't know.

Gina: Let's talk about the goals with this treatment. My understanding is that when a patient is treated with allergy shots for a venom allergy, they go through this for three, four, or five years. And then a lot of them are done for life. They're desensitized - for life, right?

Dr. Burks: Yes.

Gina: Is that a hope with immunotherapy with food? Is that possible? What are the odds that would happen with some of these children?

Dr. Burks: Well, the goals of the therapy are two-fold. One is to cause some type of desensitization. Meaning that if you're not on the treatment that your threshold is "x", and if you're on the treatment, your threshold is "x" plus "y". So it goes up significantly. But you're still in the treatment.

Another goal of any type of immunotherapy would be to treat someone for a period of three, four, or five years. And at that point, hopefully, you can stop the therapy, and they are tolerant. So they're tolerant of whatever that food or allergen, or insect venom.

So that's the ultimate goal is can you treat someone for a period of time, stop the treatment, and they're clinically tolerant. They can eat it without worrying about it.

Gina: What is the longest you've followed a patient who's gone this oral immunotherapy for any food?

Dr. Burks: For 5+ years...

Gina: Do these patients still have to keep the food in their diet, daily?

Dr. Burks: We have some patients that have been treated for a period of time, that are off the therapy, and they're eating peanuts in their diet. We have some other patients that have been on the therapy for an equal amount of time and haven't been able to stop the therapy.

Gina: Of the children who are considered tolerant, have any of those children had an adverse reaction out of the blue?

Dr. Burks: No, they have not.

Gina: Are there any generalizations that you can make that about kids that tolerate the immunotherapy verses those who don't?

Dr. Burks: No, we really can't.

Gina: Can you say how often children who are undergoing immunotherapy end up with EE (EoE)?

Dr. Burks: No, as I said earlier, about 15-20 percent of kids cannot tolerate the therapy. And, predominately, those side effects are in the gastrointestinal tract.

Gina: Let's talk about what's on the horizon. Will you be doing oral immunotherapy for tree nuts, and if so, do you foresee any kind of a tree nut mix for those children who have multiple tree nut allergies?

Dr. Burks: The studies are broadening in nature. There are investigators studying milk and egg, tree nuts, shellfish, fish.

There's not any reason to think that if it works for a peanut, that it wouldn't work for any other foods. The side effects might be different, and that's what we need - and others, need to find out about before we feel like it might be a possibility.

I think one of the other concepts that you talked about is the use of one tree nut if you're multiple tree nut allergic. And, again, that is being studied, and we don't know the answer to it, yet.

Gina: You're saying that perhaps if you desensitize someone to one tree nut, it might affect some of the other tree nut allergies?

Dr. Burks: Yeah, we don't know that, but that's an idea that is being studied.

Gina: That would be lovely!

Dr. Burks: Yes, it is under investigation but we don't know the answer.

Gina: Looking at other research, we see children who are desensitized using baked egg or baked milk, and they go on to consume different forms of cooked milk or egg. Eventually, most of them go on to all forms of cooked egg and even unheated milk.

Since we know that boiled peanuts are less allergenic than dry roasted peanuts, has anyone ever looked at trying to desensitize kids using boiled peanuts? Have we looked at this?

Dr Burks: Various investigators have suggested this idea and some are beginning to study it.

Gina: Let's talk about the future of immunotherapy and when it might be widely available.

You're aware that other allergists are offering oral immunotherapy in their offices. You published an article earlier this year basically saying that we're not ready to offer oral immunotherapy just yet. Would you explain why?

Dr. Burks: For oral immunotherapy currently, we only know that it causes desensitization. We don't know that it causes long-term tolerance. And we know that individuals that are on the therapy their threshold likely goes up, but they are still unknown and unanticipated allergic side effects that can be quite significant and can be systemic in nature. And we don't that the individuals treated will truly become tolerate tolerant long-term.

The side effects are not all known yet, so it is important to know these before beginning to treat everyone. There are a number of clinical trials ongoing now and when those are completed we will have a better idea of the dose that might cause desensitization and also when it might occur.

Gina: I hear what you're saying. I take it very seriously, I do. I appreciate you sharing your thoughts on this issue. So just to clarify, even with all of your experience with this, you do not offer immunotherapy for food to your patients?

Dr. Burks: Yes, that is correct.

Gina: Parents are so anxious for treatment. Realistically - what is the timeframe for this? What do you foresee as the best-case and worst case scenario?

Dr. Burks: If you look at all the different treatment options investigators are studying internationally for peanut allergies, there are several in larger studies. Chinese herbal medicine, oral immunotherapy. sublingual immunotherapy, reengineered proteins and epicutaneous immunotherapy are all in clinical trials.

So, of all those things, then probably the first thing that could be available would be the Chinese herbal medicine because it's being studied as a supplement and it goes through a different regulatory process.

So if it's effective, and it's being studied now, it might be available in two to four years.

And then you look the next group of studies, those need five-year studies done to look at tolerance. And they are just now beginning to being designed.

Gina: On a more personal level, why do you do what you do? You're putting yourself out there when you're doing this research. I have to believe there's a little bit of trepidation.

Dr. Burks: The reason that we, and a lot of others, started this a long time ago is that we knew there were a lot of kids that had food allergy, a rising number that had peanut allergy, and we really didn't have a good treatment option for them.

Gina: One last question. We obviously want to see more research from you, but at the end of your career, what would have happened that you would retire and say, "I did what I set out to do"?

Dr. Burks: That's an interesting question. I think mine is not related to a specific project, but just more with the people that I work with and the people that are training. I'd want to know that they can learn from what all of us are doing, and that they will continue, and make it better.

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A. Wesley Burks, MD is the Kiser-Arena Professor and Chief of the Division of Pediatric Allergy and Immunology at Duke University Medical Center in Durham, North Carolina.

For general information on Clinical Trials at Duke, click here.

For information about the Duke Food Allergy Initiative, click here.

For more information about Dr. Wesley Burks, or to schedule an appointment at the Duke Children's Center, click here.