- We even progressed faster to complication.
So the message is, fellows, residents, faculty,
if you have a patient who has small bowel perianal,
and whose immune responses are high in all of them,
that's not the patient that you're gonna get healing
with corticosteroids, and more reason for us
to move to a biologic therapy as first-line therapy.
So, this is just to get the idea out
that there are certain risk patients
who early intervention is basically
the most appropriate therapy.
So, in conclusion, can serologies help determine
prognosis and guide therapy?
I think we always need more data
and this is why we continue in our careers,
to try and investigate and ask more questions.
We always need better, adequately-powered,
prospective studies, that actually put all of this.
And in pediatrics, we have a thousand-patient
prospective study looking at all of this
over a three year period,
and we're already 600 patients enrolled,
so we're doing well nationwide.
However, we do have some data.
So the question is, not a question,
exclamation mark, we should consider using it.
At present we do have more of a reactive approach,
and we're doing all this research
to try and get us to be more proactive,
and I think if we're more proactive,
we can prevent complications in those
at risk of severe disease,
and obviously improve quality of life,
and I think a message to our patients
is yes, all interventions,
I'd say not including,
but mostly inaction, carry risk.
And risk benefit discussions with patients are needed,
and whether they are at high or low risk
for complicated disease, and visually,
we may be able to communicate that to our patients.
And that biomarkers and clinical parameters
can predict recurrence, more aggressive phenotypes,
and actually should guide a much more
targeted approach to therapy.
Thank you very much.
(audience applause)
Any questions?
Allen?
- That was great, I really appreciate that.
- Urologies were drawn before,
so serologies were drawn before,
but retrospect of meaning,
I went back to the chart to actually look
at their outcome and used Harvey-Bradshaw so we did,
and that was developing pilot data for my NIH grant.
I didn't realize I would,
I just thought I would have like 50 patients,
I would present it, but then I had actually
a great med student and she found 94 of them.
I had many more but I didn't have all follow-up data yet,
so I took them out, 'cause I really thought,
"Wow, we're seeing a trend in the first 50."
We went back and got another 50, it took out six.
It ended up that there were 94 patients,
and we used partial MAYO for an outcome
and Harvey-Bradshaw for the Crohn's,
because we didn't have an adequate PCDAI measurement,
'cause you needed heights and it just wasn't accurate.
So we chose Harvey-Bradshaw and we chose partial MAYO,
'cause we didn't have endoscopic outcomes.
So this was just looking back at the chart
to see what was their outcome, yeah.
- [Allen] And did you look at titers of ASCA
and did that have an impact?
- P-ANCA titer.
So, what was interesting was that we say p-ANCA yes-no,
but the strongest p-ANCA predictor
was a p-ANCA in the fourth quartile.
So if you actually think about it, zero to 25, you know,
a level of 75 to 100, for example.
So now you're really, basically,
those patients who have a p-ANCA greater than 100,
one, don't respond to Remicade,
and two, are getting pouchitis.
Fabulous, right?
Great outcome.
We really need another therapy for this.
So that's even more reason to suggest
if you can identify that patient
who you need to go,
hopefully Vedolizumab would be an opportunity,
some other pathway, like an anti-integrin,
not TYSABRI, but another pathway,
will be effective in those patients who are
not candidates for Inflixumab.
And for me, the most important decision where to use this,
is in the hospitalized, sick UC patient.
The outpatient, I really don't care,
meaning it was 50-50.
The Europeans showed that it was a 50-50
in an outpatient setting, these were not hospitalized UC.
You can flip a coin.
Now some patients say, "Listen, I don't wanna flip a coin.
"I want certainty.
"Take my col--", you know, what's more certain.
Depends on your communica--
and some patients, you may offer Prograf
instead of in the hospital.
So the point is, if you have a patient who's high p-ANCA,
you know that the probability of them responding to
anti-TNF is very low, maybe the roll of the dice
in a sick patient.
Outpatient, 50-50, hospitalized, roll of the dice.
They may respond to the first, but the chance
of them avoiding colectomy is low, right?
The question is, would you just go straight to colectomy?
Would you offer them Prograf?
Would you say I'm sorry, I'm not giving you,
you know, what's your communication gonna be?
I'll tell you that I don't even offer them
an anti-TNF therapy.
Why, what's happening with patients
who get anti-TNF who go to colectomy,
MAYO and other have shown us.
These patients are getting severe complications.
I don't think it's the biologic,
I think it's we're keeping them on Prednisone longer,
'cause we're counting the days for their next infusion,
we're keeping them on 60 milli--
When was a patient ever outside of the hospital,
still on 60 for two weeks, waiting for their next drug?
They would've been in the OR already,
had they not responded to Cyclo,
or they weren't respond, right?
So we're just keeping them on steroids, I think,
waiting for Remicade to kick in, in an out,
we'll send them home.
"Oh, you improved from 20 stools to 10, go home.
"We'll wait for another 14 days,
"we'll give you your Remicade,
"but stay on steroids until then."
So I think the studies didn't really account
for cumulative dose of steroids.
The surgeons just looked at whether
you're on Remicade, yes, no, right, so different.
So I think, for me, it's changing my practice tremendously.
And now p-ANCA has been shown multiple times,
but it's mainly the high p-ANCA.
If they're 50, I let them tell me what they want to have.
How's that, if you had to ask me what's my cut off.
When it starts to get above 50, as a serology,
I start to communicate with them,
that I think we should go a different path.
Now, if they've already failed great levels
of immunomodulators, Prograf and Cyclo
are not a bridge, right?
What am I bridging to?
If they have low levels of six MP,
to me it's like they were never on good doses,
so I'll let them try again as a maintenance.
But what do you do when a patient has already failed
60 G's of 300, they're failing,
their steroid refractory, their p-ANCA's 115,
what are you gonna do, right?
Are you gonna go to, in theory, it would be colectomy,
if we believed the data.
So now, we're doing it in a prospective, 200 patient,
using CDI, UCDAI, like the full monty,
MRNA expression, Gene expression, Cytokines,
Serologies, Hackas, everything, it's in an NIH trial,
so that's happening as we speak to validate.
Remember, this was just pilot data,
which is fun to say, "Wow, it actually is consistent."
But the more fun things about this serology,
about that study, was the GWAS.
That was really the premise and I didn't show
because of time, but to find four new genes
that predict TNF responsiveness,
only 4 out of 600,000.
Any lab can pick that up, right?
I mean, we have to validate that.
If it's validated, and we can validate those four genes,
then those are the genes
that we need to start searching for.
So it's kind of an evolution.
It's a pharmacogenetics and we're gonna do
the same thing for