>>I guess I’m going to start with Jane while people think about their questions.
It's a long journey since the 1994 first meeting on lupus genes, so I'm wondering what your
thoughts are, we have come a long way in terms of disparity of lupus genes.
So where do you think we're going next?
>> I think the growth in knowledge in lupus genetics has been extraordinary and has informed
many other diseases.
The infrastructure that was created by funding through NIAMS with collaborations initially
in the United States, but more broadly, globally, has enabled our advancement in understanding
lupus genes, and I think what also is becoming clear is they're overlap genes that convey
risk to all of autoimmunity, so the collaborations between the NIH’s different institutes,
as well as the foundations, are really poised now to develop new targets.
I think what the genetic studies have given us is targets for treatment.
>>Ok, thank you…is there a question?
>>So, John, you talked about the importance of the specificity in terms of treatment now
that one has a real good idea of what that antibody is directed to.
[IN PEER STUDIES?]
[INAUDIBLE] Is there – what is the prospect of -- getting even greater specificity in
terms of targets, targeted to greater specificity rather than just the B cell?
>> Yes.
That's the ultimate goal.
It depends on the fact that the antibodies from different patients have the same structure
so you can develop something that works in one patient will work in another patient.
And in cloning those antibodies from different patients, there are commonalities in the antibodies.
So theoretically, it is possible, but the question is do we have the platforms yet to
develop drugs that can interfere with antibody binding or destroy B cells with that antibody,
just that antibody and their surface?
It may have to await those types of advances in research.
The other issue is, we have found in patients they only have a few of these clones of B
cells abnormal.
They don't have new ones coming out all the time.
Something happened to them that made them maybe five clones of these bad B cells.
So, if you can get rid of those, they're not going to come back.
They don’t continue to come back.
And that's why rituximab works so well.
Before we can target the original antibodies, I think we'll find maybe if we treat patients
early and get rid of those clones, we can cure the disease.
>>Microphone 2
>> The question relates to the rheumatoid factor and the anti-phospholipid antibodies.
Is there regulation or is it one of the antibodies in the [INAUDIBLE] that induces its complications?
>> Anti-phospholipid antibodies are a broad range of antibodies that actually are misnamed.
They don't react to anti-phospholipids.
They don't react to phospholipids, they react to protein structure changes when they stick
to phospholipids.
I don't think there's a lot of cross reactivity in terms of rheumatoid patients.
I think from the standpoint of immunology of pregnancy, what's really interesting in
rheumatoid arthritis is that about 30% of patients with rheumatoid arthritis go into
remission during their pregnancy.
So that's a natural biological remission.
If we can understand the immunology of that remission, we may really expand our knowledge
of targets for intervening in RA.
>> So your question -- your answer for this is that it suppresses to some aspects of rheumatoid
factor –the pregnancy—but the pregnancy itself carries exposure to a huge number of
genes from the sperm.
So how does it relate to some of the issues?
>> What pregnancy is doing, in essence, it has to be selective immunosuppression and
tolerance.
The fundamental -- a fundamental immunologic defect in rheumatoid arthritis is a break
in tolerance.
So pregnancy corrects that transiently in a subset of patients.
>> Leslie Crawford, rheumatologist, University of Kentucky.
Jane, we were talking about this at lunch, so I thought I would bring this up at this
panel.
We have made tremendous advances in basic science, but the way we conduct clinical trials
really hasn't changed that much as we developed more ways to target or specifically target
therapies.
Would you care, or any of the other panelists care, to make comments how we might think
about science in clinical trials or take advantage of the advances in targeted therapies?
>> An important philosophical question.
I guess I come to things by building teams, and we need teams of methodologists, patient
advocates, careful phenotypers, molecular biologists and people who understand study
design.
We can't underestimate the value of precise phenotyping because one thing to think about
in terms of failed trials may be who were enrolling in them and how we define whom to
enroll.
I believe we can move forward with targeted therapies, but the idea is how do you figure
out who to target?
That's the challenge.
That's what team building requires.
>> For the patient community to get involved with the clinical research, the concept of
patient registries is an important concept to get across to the public.
If you look in Sweden, you are part of the data registry.
In the United States, you have to be captured or paid or be incentivized to participate
in some sort of registry.
Therein lies a huge difference.
I myself, would love to see where anybody with any kind of NIAMS disease readily volunteers
and the mechanisms by which they enroll in a patient registry was -- would be easier.
That will help in terms of getting the data together to move toward targeted therapies.
>> John, did you want to comment on that?
>> My hope is if we really have targeted therapies that are effective for groups of patients,
they'll be so effective we don't have to run huge clinical trials to find their effectiveness.
You’ll only compare 10 patients in a disease that we know most patients, 99% of patients
don't go into remission.
That will make a huge difference in the cost and effectiveness and clinical trials, but
that depends on finding very effective therapies.
>> Dave Bornsteen from Washington D.C.
Amye, I want to ask you a question.
If you could expand about the pain aspect of what you talked about.
We’ve made great advances in immunology, we understand our diseases a bit more.
But one thing that seems to stand out is that these are painful conditions and how much
has that affected how you felt about your disease and though the disease maybe controlled,
how much the pain aspect still remains a problem that we need to face as physicians and as
patients.
>>David, thank you for asking that question.
It is an important subject when you live with someone with these types of diseases for which
pain is a present factor and for those of us who have these diseases.
Though I'm in remission, I still encounter pain on a regular basis.
The question becomes, what degree of pain?
Can I reach my high cabinet?
Can I put a dish away?
Can I go out of the house twice a day versus once a day?
We who have these diseases over a period of time learn to become resilient, and that word,
Joan, I think you brought up the idea of resilience.
Something when you have these conditions for any length of time -- either you die or you
become resilient.
Most become resilient in some way, shape or another.
How pain affects many of us is when we yell ‘woof’ if you will, to go to the doctor,
go to the rheumatologist, yell ‘woof’ to get help in by our family or by our friends,
yell ‘woof’ to not go to school or go to school.
Yell ‘woof’ to talk to our employer about whether you have to carry those books from
one end of the building to another.
Or thankfully, in the United States, because of the Americans with Disabilities Act, can
hopefully be equipped with a cart if you speak up loud enough.
Pain is an overriding factor in terms of my ability to function, but like many patient
advocates in this room, we actually exceed our pain tolerance.
We feel it when we get home tonight.
We'll certainly feel it tomorrow.
But we feel the price, it's worth it to be here and participate.
So there's that balance.
I would love to see more integrative research done in pain as it relates to our ability
to get the kind of help we need.
Why someone who has got the arthritis that actually affects the same joints that maybe
it does in me, that person will be very much in pain and I would not be.
So there's a lot more questions and answers, but thank you for bringing that up.
It's a great issue for further investigation.
>> In relation to pain, the joints I was wondering, I notice that -- I know that in arthritis
there is one of the response to pain and perhaps other things, as well, is joint replacement
and knee replacement and hip replacement so forth, is this the way of the future for arthritis
and pain or arthritis and -- just arthritis and joints, or are there other research things
going to, in some way, replace replacement?
That's one part of the question.
The second part, what is the standardization of the kind of joints they're replace something.
I read in the Times Business section all the time different joints have not -- have failed
or have not proven to be as effective as other makers or companies that make joints.
So I'm sure the FDA or somebody is doing this standardization of these replacement joints.
Is there some answer to that or is that just too big a question?
>> I’ll start it from a patient advocate perspective.
Joint replacement is why I was -- I would not recommend that to most people to go through
joint deterioration to the point where that becomes your only option.
Today, with the new treatments in rheumatoid arthritis, RA is not the only reason for joint
replacement, but in rheumatoid arthritis treatment, with the advent of the newer treatment particularly
biologics, one example is the Juvenile Arthritis Conference with the Arthritis Foundation.
When I was chair of the Juvenile Arthritis organization, part of the Arthritis Foundation,
we had to accommodate a high percentage of children and young adults in wheelchairs.
Today, the Juvenile Arthritis conferences really have nobody in chairs, and that's the
testament to the therapies.
Certainly that would not be the end all be all.
For me it was.
I would defer to orthopedic surgeons here in this room to answer the second part of
your question Priscilla.
>> Yes.
We have someone -- >> I'm not here to talk about joint replacement.
My name is Lynn Gerber from George Mason University.
I would like to build on something that Dr. Bornsteen raised.
That is taking an umbrella approach, rehab and function.
There are many symptoms that people with rheumatic diseases face day in and day out.
Fatigue is one that is extremely important whose understanding we need to reach out to
establish a better conceptual framework in order to get better basic science.
My question to the panel and Dr. Salmon, especially, is, is there a place for basic research in
better understanding of symptomology, such as fatigue?
If so, how do you see that as integrated?
It's not disease or diagnostically driven necessarily, but certainly represents a huge
burden to the patient population.
I think they’re people in the audience who can comment better about the question you
asked.
But certainly they’re physiologic bases for alterations in pain perception that are
driven by cytokines and there's no question that one element in why TNF inhibitors are
so effective in rheumatoid arthritis is a sense of well being that goes far beyond changes
in cytokine profiles, SYNOVIUM, fibroblast and so on.
So I think though we may be using the right drugs, we may not understand the extent of
the pathways they're affecting and if we think of the pathways individually, we may be able
to target them more effectively.
>> Would you like to address the issue of joint replacement --
>> I'm Regis O’Keefe from Rochester.
I’m an orthopedic surgeon.
On airplanes when they need a doctor, I'm very reluctant to come forward, but I can
come forward in this audience as an orthopaedic surgeon.
That's my first disclosure to this group.
Wonderful meeting.
But as Amye experiences, we go back many years together, one great innovation of the 20th
century is total joint arthroplasty.
Between 1991 and 2004, there was a threefold increase in total knee orthroplasties in the
United States, between 2005 and 2003 with the aging population, we're not expecting
a sevenfold increase in arthroplasties.
So within that time, 40, 50 years, that's a 21 fold increase in arthroplasty.
One challenge we face is doing them better.
Although the length of staining is less and we manage pain better.
Fundamentally the procedure is the same.
And the unit cost has gone up.
When you make more computers, the cost of each goes down.
This is clearly an area where we need innovation.
While there's attempts to include biomaterials, sometimes this led to more complications and
issues.
This is an area I'm proud to say that Steve and NIAMS has been very supportive of, not
only from the standpoint of technology development, but a bigger problem of preventing the disease
much like John O'Shea said this morning.
>> Thank you very much.
We have time for a brief question.
>> Good afternoon, my name is Amy Melnick with the Arthritis Foundation.
Excellent set of panelists.
Every panel is excellent.
Especially want to comment featuring patient advocates and the story and triumph and ongoing
battle is very inspiring.
The question is if you could speak to every American in a brief 10 to 20 second description
talk about why NIAMS and NIH research is so important.
Can you share that, for the patient advocacy groups, our mission is to advocate for research,
we need better tools and we need to reach everyone with the message how important research
and advocacy is.
So share with us some nuggets, if you can talk to every single average American who
doesn't know about NIH which is a lot of people, what would you say?
>> >> In 20 seconds.
>> First let me start by saying that any of you who sat next to me in an airplane, it's
a captive audience.
I have spoken to someone for eight-and-a-half hours straight about this subject, at which
time they revealed their form of rheumatic disease to me and became an Arthritis Foundation
advocate.
But in 20 seconds, it's about function to the lay public, it's about moving, it's about
continuing a life that they have carved out for themselves, that somehow has been roadblocked
by some sort of disease.
And that NIH, in general, is the world’s leader in research.
World’s leader in research, government-funded search.
NIAMS is the world's leader in biomedical research and many musculoskeletal arthritis
and skin diseases.
That's a new twist on NIAMS, Steve.
But it's really about regaining function and who is going to do that research for us.
Unless there's strategic direction, mindful attention of the best minds in the world coming
together in an interdisciplinary kind of way that's not 20 seconds, you can cull that down
anyway you want it.
>> Thank you very much to the panel.
>> It was a great discussion.