Diana Oh

IR-2/11AP
Turn in Number:10
12/11/17
Interview #1
Interviewee: Kim Mudd
Name of WorkPlace: Johns Hopkins University Pediatric Allergy
Title: Senior Research Nurse/Program Coordinator
Date of Interview: December 8​th​, 2017

There is an exchange of basic greetings and a brief discussion about the Thanksgiving holiday for
about

DO: When I started my research i looked at the biological pathway of the allergy and looked
at it and never got any concrete information on what exactly happens.

KM: And as far as what happens during oral immunotherapy?

DO: I’ve been looking through and getting very vague answers or strange answers with a lot
of letters that I tried to understand but was not working

KM: So interestingly enough, the answer to that question is that we have no idea. There is a
project in the process as we speak that identifies a lot. In the whole of 150 kids, all under
4 years old when they came in and they had a challenge to peanuts and reacted to less
than 400 milligrams which is a pretty small amount of peanuts. We knew these were
very allergic kids. They were randomized to either peanuts or oral immunotherapy (OIT)
or placebo built up to a pretty hefty dose of 2 milligrams a day, kept them on that dose
for a year and a half, which is a long period of time to do a maintenance and then did a
set of challenges. Regardless of the outcome of that set of challenges, everyone stopped
dosing for 6 months and came back for another set of challenges. So the question we are
trying to answer with this project is (a. Can you induce “desensitization in a very allergic
group of kids.”), and the answer for the most part is yes.

Next question is if you stop dosing every day, for a period of 6 months, can you come
back and challenge these kids again and find out they’ve retained their ability to tolerate
peanuts. That would be called tolerance or sustained unresponsiveness. And the answer
to that question would be not so much. Along the way, these kids, oh my god, the
amount of blood, urine, and poop, and spit and everything that came out of them we
collected in trying to answer the question you’re asking. Which is “What is
desensitization?” “What is sustained unresponsiveness or tolerance?” And if we could
answer that question with this population, then we will be much closer to knowing who
this would work for because there are clearly kids in this population who did not achieve
 desensitization. They either dropped out because they were having symptoms or we got
them to the 2000 mg and left them there for a year and a half, but they did not do well
with the challenge at the end of treatment, so they were not completely desensitized.

Why? We don’t know what is different about those kids compared to their peers. So, the
vast majority of the kids made it. A hand full of kids dropped out, and another handful of
kids did not get all the way to the desensitization goal that we had set up. Well why not?
And it's nothing simple, it's not like we can say it was decided at the skin test when we
started. It’s the level of the IgE (immunoglobulin E) to the peanut when we started, its
the ARH2. I mean there are all these things we can look at and have looked at and it isn’t
any of those. So it's something in the immunology of these kids that make them prone to
either succeeding or not succeeding with the desensitization. So the question, it is a good
one, we don't have any answer for it because we don't really know at a molecular level or
a cellular level what we are doing. But it is a really interesting question.

DO: I don't know because I was looking for in the begin with and I was not getting any
answers.

KM: No, well the question you are asking is a valid question, but is clinically and hugely
relevant because before this OIT is something that is going to be used outside of clinical
trial, so before this is something that allergist are going to use in their office. You have
to be able to look at the patient and say “ok you are going to succeed in this” because
when you do the OIT treatment, there is always a risk.

DO: Yes.

KM: Everyone has symptoms. They do. Somewhere in the process, some people have
symptoms with every time you updose them, they have symptoms for a few days and
they kind of taper off, some people have symptoms that every dose they took of their
OIT, people have had out of the blue, rocking symptoms that required Epi (Epinephrine)
. We’ve had a lot of out of the blue anaphylaxis of kids who have been tolerating a dose
forever and ever, and sudden symptoms from thursday night, and they have a reaction.
This is not a risk free process. And before you put someone in that position to take on
that risk, i think you have to say to somebody “ you are going to be one of those people
who if you can keep up with this, and get through this, on the other end, you are going to
be someone who is going to be desensitized and retain it with milk and peanuts, and
whatever it is, and be protected against certainly accidental injections, but also maybe be
someone that can integrate that food into your diet.
 So that is the majority of the people and that is the group of the goal. There are two
groups in there. One group is where they can probably get through the desentiviation
process, and work from 1 to 5 to 10, and build yourself up to something that is clinically
relevant. But they are the kind of kids where there is something in their immune system,
and if they miss a couple of days of doses, “I don't want to do it, I have a stomach ache,
and I'm not going to do it, everyone in the house will get sick” because you don’t want
to throw peanut on someone that's already barfing. Those kids in that brief period of time
being off dosing, lose massive amounts of ground. They were tolerating 500 mg on
thursday, they cant dose Fri, sat, sun. because the whole house is barfing and everyone is
sick, and on monday they try to do 500 mg and react all over the place. And those kids
we have to take back down to 250 or 150 and rebuild. So, the desensitization is not
sticking very well for that kid. And we have a lot of those kids in our study.

And there is a third group. The third group is the desensitization process, trying to get
them to take the dosage every single day, induces symptoms with every dose. And they
aren’t doing it. They are not tolerant and cant be desensitized. Now i taper both kids all
look the same, for everything we know to measure. So, we have to figure out how to sort
them before we start. And you can give that information to people before you do that.
So, that is the application of the question that you’re asking.

DO: So with a follow-up question, “so what people are doing today with oral OIT is trying to
sort the kids by some means to see how well they will take the oral OIT?”

KM: Or how well it works. At this point, what we are doing is, as we are figuring out the
desensitisation, and trying to induce this tolerance, can we figure out at a cellular level
what’s going on? So that we can take that knowledge and apply it, clinically, to answer
the question you’re asking. “Who is this treatment appropriate for?” It’s not appropriate
for everyone. We know that. Who is it appropriate for.

DO: So another question I had was “I was looking through some of the studies that were
done, and there were two ways that they increased the dosage. One way was to do it
more slowly over time and the other did it more rapidly.

KM: The rapid desensitization?

DO : Yes

KM: So we usually use a combination of those those two processes, and in a research world,
to bring somebody in and keep them for the whole day is that if you start at a small dose,
you can go up every hour or so, and desensitize as you are going. So when you start at
 these micromilligrams, doses, these doses are tiny, the goal is to get below the threshold
and keep knocking at the reaction threshold and keep pushing down the lane as far as
you can. We can do that when the kids are in hospitals, with literally a team at the
bedside, and we know that there are going to be symptoms along the way, but we are
managing those symptoms all the way to get as far as you can in a single study.

We have done that. It’s very labor intensive and harder to do with some kids. So most of
the projects and certainly any of the projects where the kids are going to be dosing it at
home, what we do is we start them out at, the initial dose escalation is the very first day
they see the protein, we start out at less than a milligram and try to get them up to
something that measurable in a research lab, 3 milligrams, 6 milligrams of protein,
which I have to tell you when you look at a little souffle cup or those little medicine
cups, 3 milligrams of protein at the bottom of the cup, and yeah, nothing’s in there.
That’s how little that is. Now we can with the behemoth expensive scale, we can weigh
out 3 milligrams of protein. At least 1 if not 2 decimal places [of a milligram]. So within
10 percent, which is hugely important, but is not even close to anything anyone could do
at home. It's off by a factor of 100 of anybody can do at home. So most of the time the
first day the kid sees the protein in the office, we start with 0.8 or a little bit lower
milligrams of proteins and build them over the day up to something around 3 to 6
milligrams and we send them home on that dose and that’s the dose they take daily for
the next 2-3 weeks. And they come back in and they take the dose from 3-6 milligrams,
so all of the dose increases are done under observation.

DO: I was wondering how that worked. I was reading the procedures and was like “This must
take forever though!”

KM: It is. It is very labor intensive. Which if you look from a fact perspective, goes back to
doing this in allergist office and always being there for treatments, the first day of
treatment is basically going to need 1 on 1 with a very experienced provider because
things can go terribly wrong, and we’re set up for it and this is what we do. But in an
office setting, it’s going to be much more challenging to do that initial day. To get them
to a dose. And this is not something you can say, “:Well you’re peanut allergic, and we
write you a prescription for 3 mg of peanut protein at home and tell us how it goes.” It’s
not going to be safe.

DO: Because even when I did a food challenge, it is pretty safe.

KM: That’s kind of what this is. If you think about it this is kind of what it is.

DO: I guess with a food challenge the numbers are more on your side
KM: But the same risk applies and the procedure wise, it is very similar to what this involves.

The interview goes on to discuss the procedures of oral immunotherapy and the ethics of allergy
treatment. The call ends on the note of another phone check in at the beginning of the new year.
 Reflection of the Interview
Overall, I believe that the interview went well. My advisor and I conversed on the phone

prior to the interview, but we talked mostly about the logistics of the project rather than content

knowledge. The atmosphere of our interview was more casual because my advisor’s personality and

the fact that we have already acquainted ourselves before this point. The interview proved to be

very useful for me because I now understand things that I read to a better degree. There were

several concepts that I read multiple times online, but I failed to understand them. My advisor

explained them much more simply, so I could understand them to high degree. She covered both a

clinical and ethical stance on oral immunotherapy, which gave me a better idea of the conflicts.

For my next interview, I may ask my interviewee to talk slower. My advisor talks quite fast,

and transcribing was very difficult. Therefore, I may ask for the interviewee to slow down ever so

slightly, so I can go back to the recording for review. Also, I may want to interject more in their

conversations. My advisor talked for majority of the time, and I felt rude to interrupt so I mainly

signaled with “yes” or nods. However, there were points where I did have questions, but thought it

was rude to interrupt her in the middle of her thought. Next time, I would like to politely speak up

and for clarification so I am not left behind.

For me, setting up the interview was the most difficult part. My advisor is a busy person,

which made it hard to find a time for both of us, but I made it work in the end. Another difficult part

was following the conversation while not interrupting for clarifications. There were points where I

had another question I happened to think of, but did not want to interrupt. But, by the time she

stopped talking the question was no longer relevant. The easiest part of my interview was the actual

talking. My advisor is very friendly and a lot of fun to talk to. She made the experience great, and I

felt very comfortable speaking with her the entire time.