Wasun Chantratita: Good afternoon, everyone. Last year, I was
here and then the other global leader and they probably had identified a pharmacogenomics
is a flat shape of the meeting. If you would like to -- and today I will focus on implementation
rather than talking about the research and how the best I have the pharmacogenetic testing
in our hand because without proper implementation you’re going to cause a lot of nightmare
when you deal with the Stevens-Johnson syndrome. And I can tell you, the implementation that
genomic in practice [unintelligible] pharmacogenomics and if pharmacogenomics -- if you are talking
about Stevens-Johnson and TEN risk areas screening test, it might be the low-hanging fruit in
pharmacogenomics.
In Thailand, we interview many who suffer and to survive Stevens-Johnson syndrome and
TEN. They feel like they are burning alive. Their eye like someone poured [unintelligible]
into their eyes, the pain is so sore. Extreme, they would like to die but they cannot because
the doctor won't let them. Okay? In Thailand, pharmacogenomics project started in 2004 with
the HIV pharmacogenomics. The first draft is Nevirapine-induced Stevens-Johnson and
TEN with Ramathibodi Hospital Thailand’s Center Excellence for Life Science and Ministry
of Science and Technology. However, with regard to Thai government reimbursement program for
routine pharmacogenomics screening to prevent induced Stevens-Johnson and TEN, Carbamazepine
was the first drug of choice to implement nationwide 2014. Ten years later and the Ministry
of Public Health Thai FDA University Hospital Thai universal health care coverage program.
So in Thailand who paid for pre-genetic screening? The government.
So during the last 10 years with corroboration firmly with the Ramathibodi Hospital where
I'm working, the factory of pharmacy [unintelligible] University, Thai Ministry of Public health,
Thai -- which includes Thai FDA, Thailand Center Excellence for Life Science, paneling
with the [unintelligible] Center for [unintelligible] medicine from the former, the director [unintelligible]
and present director [unintelligible] helping out a lot to do what we call the genome by
association and HIV genotyping. There are more than 3000 cases in control, so that's
why we realize that in Thailand and in Southeast Asia we have a very high frequency of ADR-related
gene or alleles.
And you can see the Carbamazepine of a located in Asia or in Southeast Asia. Allopurinol,
well, that’s the same. Carbamazepine, that great may be Europe take care of it, and then
for the Nevirapine is an antineuroviral drug and again in Southeast Asia. D-40, which is
also an antineuroviral drug, in Asia, too. So because of we have a lot of drugs that
the -- have these are top 10 drug-induced Stevens-Johnson and TEN in Thailand with the
-- during the past probably can say that our scientists and in many hospital and institution
could work out to get the genetic marker that had been finally utilized for [unintelligible].
So these are I like to show the interim A B come up with the prototype of our molecular
polyp care for our pharmacogenomics screening as a for Naropin rash. You can see that we
not only focus on HIV-AIDS because you know with Asian Health Institute to find the two
other positive [unintelligible]. So maybe when you might wonder why the HIV-AIDS is
not so accurate. Because there are other [unintelligible] that would help to complete [unintelligible].
And for the HIV I’ll rather say that it is a quite typical the target is moving. I
spend -- we -- our team spent too much time to find the marker and to try to implement
it -- implement it with the government. It turns out that we didn't have in five years
-- Thailand at first Naropin-based enter it to where it's have been changed to [unintelligible]
so the target is keep moving. So if you would like to do research and try to implement it
to, you have to make it fast.
That's why the -- now for the HIV instead of focus on Naropin we have to focus on others
like [unintelligible] D-40 and also bacteria [unintelligible]. That's why we have the award
-- the Thailand award innovation for 2011 for what we call this service and the diagnosis
of the assay HIV ADR all in one. And in 2010, we decided HIV there is a brainstorming to
pharmacogenomics and its use to avoid [unintelligible] adverse reactions, cutaneous drug reaction,
this time organized by the Department of Medical Science, Ministry of Public Health, 2010.
Three of these people now in this room, and also at the time we invited Prof. Shuen from
Taiwan to be our keynote speaker at that time. And four years later, the government [unintelligible]
induced Stevens-Johnson [unintelligible] was the first drug of choice for the government
reimbursement nationwide, under the Ministry of Public Health Thai FDA, University Hospital,
and universal health care coverage team.
Let's go back to where I'm working the Ramathibodi hospital. We manage to have the -- what do
you call -- the pharmacogenomics lab, and it is my colleague [unintelligible] who invented
[unintelligible] pre- and post- pharmacogenomics counseling program warning and monitoring
system. And [unintelligible] assay routinely support the hospital. Every time that the
patient have the HIV-positive or [unintelligible] positive [unintelligible] adverse reaction
has been clearly shown in the prescription. This -- the folder that be always handed to
the person who have the blood tested. And is a report and is a [unintelligible] that
Teri mentioned earlier. At first we -- during last year we I hesitate to show you the cart
because my colleague said that is just simply the paper -- why people were fascinated about.
In U.S., the EMR is quite effective, but it turned out to be -- I don't know why -- they
are still like it okay [laughs].
But all this a fool-proof way that we could prevent and eradicate genetically mediated
Stevens-Johnson/TEN is in Thailand. From the time being right now, sadly said no -- may
not be able to save our life if we do not implement it completely. Usually, if you have
a pre-genetic counseling, fine. Your doctor will order a blood test; if you tested positive
then the post-genetic counseling would be in place, and then it wiser to take other
drug instead. Okay? And the PGX cart should be provided. But the nightmare that would
happen -- it occurred to me that if in no pre-counseling to have her blood test for
positive because of PGX screenings assays [unintelligible] 30 U.S. dollar in Thailand,
it easily to implement rather than warning system. So for the second doctor, she may
[unintelligible] prescribing her with the Carbamazepine because there is no post-counseling,
no warning system, no patient cart provided. And she will go back home, and then take the
medication, no monitoring following. And she may die because [unintelligible] within a
few days later. Okay?
So what we are currently doing at Ramathibodi hospital to make sure that the PGX should
be effectively and safely impose -- implement, sorry. One, we try to combine because we have
the EMR but not quite effective, link all the unit pre- and post- pharmacogenomics counseling,
and also PGX screening assay, and we try to emphasize to the patient and the doctor that
the PGX is the screening assay; it is not diagnostic test. So is not that accurate when
you compare. Okay?
And then after that, after they leave the hospital, they have the pulse monitoring for
the patient [unintelligible] to manually call to the after discharge making the telephone
call every two weeks in two months. We have a [unintelligible] and also, in order to educate
patient, public, and clinician, we've come up with the MP games on android and IOS. I
just heard that Teri Minchin [spelled phonetically] about in the morning that we would like to
educate the clinician. I think that I cannot wait for five years from now. I like to make
it now, today. That's why the -- I have the MP games. MP game is what it is. MP game is
the -- what do you call -- mobile pharmacogenomics game.
In last month, there is a University in the race University [unintelligible] University
of Ministry of Information and Communication Technology approach me, asked me to help to
make the education to children. I said that I may be a lot [unintelligible] God as my
creation. From my work, I just transform -- be transform all my work to be on this application.
And is it genomic medicine, particularly in pharmacogenomics, when you click you can let
them study, that is pre- and post-test, and then the game three would be make sure that
you will not miss the Stevens-Johnson anymore. Okay? I will let the Teri to test that first
and we have the English version.
So far the Southeast Asian, we have the pharmacogenomics research network, CFAM, 2012-2013 was held
in Thailand, 2014 Indonesia, 2015 will be held in Malaysia, next week. Okay? And that
the professor [unintelligible] would be -- share with you about the workshop. And this reading
matter -- if you would like to study our work in 10 years of studying from nature reviews
genetics, the book called “Genomic and Health in Developing World” and “HIV Pharmacogenomics”
and [unintelligible] movie that you can read online, free of charge. Thank you.
Steven Katz: Thank you very much.
[applause]
So education and implementation were the emphasis here. Are there questions or comments? Yes?
Female Speaker: I was wondering, you were showing one little
baby with -- affected with a disease and I was wondering if you observed that women who,
during pregnancy received Nevirapine have healthy children, yes or not? From our South
African colleagues I know that all the ladies they had that during pregnancy were given
Nevirapine because of HIV infection who developed SJS/TEN had healthy children, and that none
of the children, even though these babies received the same drug for six months after
birth, ever had SJS or TEN -- which you could expect or think it might happen. Do you have
any ideas on that?
Wasun Chantratita: I do not have any idea and then the picture
that I showed you [unintelligible] an IPT not in pharmacogenomics, all right? That doesn't
commit you to have any idea -- we never do any pharmacogenomics on the pregnant women
at all. We did some pharmacogenomics study on the Nevirapine level in pregnancy womens
and [unintelligible] one of the -- I can't remember what one of the [unintelligible]
has influenza on the [unintelligible] of the Nevirapine on pregnancy womens, but we didn’t
see that the Stevens in the children related to the matter. I think we don't have that
data.
Steven Katz: Has anyone seen? Just to broaden your question.
Has anyone seen in late pregnancy Stevens-Johnson where the baby is delivered with or without
Stevens-Johnson? If it's transmitted with granulysin one would expect something there;
of course, there may be other genes in the child.
Male Speaker: If it’s T-cell mediated, then you would
expect the fetus to be protected because it would be tolerized [spelled phonetically]
to the androgens.
Male Speaker: Right, but --
Steven Katz: The reason I raised the question --
[multiple speakers]
Steven Katz: -- Dr. Chung.
Wen-Hung Chung: Yes.
Steven Katz: Obviously no answer to that, but -- that did
you have a question?
Male Speaker: No.
Wasun Chantratita: -- but what we observe is as [unintelligible]15
-- or no 35 or 5 we see [unintelligible] Naropin-induced rash is protective breaks for [unintelligible]
in Thai populations. So the same alleles that cause rash from Naropin is actually protect
from this disease progressions in issuing re-infection. So this may explain some things.
Steven Katz: So I’d like to thank all the -- question?
Yes.
Female Speaker: Sorry, I was just going to ask along those
lines -- did you have was that your -- the Nevirapine DRESS cohort and were those B-3505's
that were protected or -- just from the previous work that’s been published, I think, from
Thailand with Nevirapine DRESS and B-3505, the ones that had protected viral loads. Those
were the B-3505’s, the ones that carried HLA-B-3505? Or --
Wasun Chantratita: The protective effect of B-3505 is not studied
in our data set, but it was studied in another data set in -- not in Thailand and in that
cohort, they observed both this drug [unintelligible] reaction and the protective effect of the
B-5505 -- B-3505 on [unintelligible] disease progressions. So it's like a [unintelligible]
cohort of our data.
Female Speaker: Thank you.
Steven Katz: Thanks, everyone. And Teri has a few announcements.
Teri Manolio: Just to remind you, we’re now going to break.
Those of you who ordered lunch in advance, it's in room nine there, so if you would just
grab it and bring it back in here where we are going to have a discussion. Those of you
who are going to make the trek down to the cafeteria, you need to take the elevator to
do that. Marc Williams has volunteered to lead you effectively and quickly down there
and back up. We will reconvene at 1:00 for discussion and we’ll see you then.
[end of transcript]