Lab Testing for Overlapping Rheumatic Diseases: A Comprehensive Approach

QUEST WEBINAR:

Lab Testing for Overlapping Rheumatic Diseases: A Comprehensive Approach

Presenter: Ann Salm

Salm, Ann E   0:03
Wonderful. Thank you. Thank you, Jen.
So again, Doctor Salm, I'm here on behalf of Quest Diagnostics, medical affairs, to talk about our auto immune testing with specific focus on lab testing for overlapping rheumatic diseases. Especially in the primary care space, we're looking for a way to provide or facilitate a comprehensive approach to testing in primary care. To improve that qualified referral.

I've been working with Quest for going on 8 years now. Have been functioning both in the infectious disease and immunology space and of course, while infectious disease, aside from the pandemic, is pretty well elucidated in terms of what pathogens infect humans, we do know that in autoimmune, in the autoimmune space, there's still a lot of research going on in this space. And is a much more evolving market in innovative market for taking care of patients in this space.

So I'm really happy to be here to talk to you guys about this.
And so let's go ahead and get started with slides and we'll have Q&A at the end.

Certainly feel free to use the Q&A function.
To provide any questions that you may have as we go through and we will address those at the end. Alright. Oops, hold on.

Alright, so when we're looking at the diagnosis of rheumatic diseases, there's a category, you know, that has been sort of outlined called undifferentiated rheumatic diseases or overlap disease, wherein patients that are being seen often times in the primary care space don't really fit neatly in terms of their clinical symptoms into specific rheumatic disease characteristic criteria. So when we're looking at that diagnostic or or characterizing criteria early Renaud's phenom or RP patients, you know usually have specific symptoms that fit into that criteria. If they're being seen in primary care though they might have subclinical or ambiguous symptoms, so this is something that is a challenge in the primary care space. When we're looking at early inflammatory polyarthritis, they don't fit neatly into the RA clinical criteria. So what is a primary care physician to do in cases where they're seeing patients in this particular demographic?

And then we also have. You know there are multiple when you look beyond just RA or renon's phenomenon or lupus there are, you know over 100 different phenotypes for rheumatic diseases and how might we be able to narrow in or you know on the diagnosis of one of those many, many you know potential rheumatic diseases, or how might we be able to qualify that referral and help a rheumatologist? More make an informed decision on how to diagnose and treat a patient.

So the other piece to this is we see an uptick in interstitial pneumonia, you know which can be autoimmune derived. And so when a patient shows, you know, a sort of pulmonary symptoms that you really can't you know, you've ruled out infectious disease. You think it might be auto immune? What are some tests that we can do to sort of refer those patients?

So the challenge though is that in primary care you don't want to. Under diagnose, you don't want to miss something, but you also don't want to over diagnose.
And because you're using immunomodulatory drugs, you really want to be careful about not over diagnosing.
And so how might we be able to facilitate as a national reference lab quest?
Ways in which we can offer tests that help qualify that referral and help those rheumatologists make informed decisions and minimize that overall time to diagnosis. So that's really what we're here to talk to you guys about today.

All right, so ANA testing it, it is highly sensitive.
Certainly, especially when run through, you know IFA testing methodology.
But it can also be just not adequate in terms of how best to move forward with that patient.

So, when it comes to autoimmune diseases, ANA is not enough to diagnose.
And you can have a positive result, but you need to follow up with testing.
You need to go beyond on the ANA, to do other autoimmune antibody testing to really understand if this is truly an auto immune disease or if it's just a weak positive due to something that may not be autoimmune at all. It could be just an osteoarthritis.

The other piece is that we know that as time has gone on, we've got, you know, fewer and fewer board certified rheumatologists in the country.
You know, there have been estimates of roughly 5600 active rheumatologist in the country, but even those rheumatologists within the country that are practicing, they've estimated even fewer than that.

So that's sort of a a liberal estimate and certainly when we're looking at that rheumatology referral, a follow up rheumatology visit or referral can take six weeks at minimum and many months beyond depending on the region or locale.
And so how might we be able to reduce that referral, that time to referral and and give those rheumatologists a more comprehensive beyond just ANA sort of results lab result report?

We also know that it in prior, you know years single Rheumatic disease diagnosis was enough.
So diagnosing someone with RA or Lupus maybe was enough and you know, clinicians rarely looked beyond that.
But we know that research, you know, recent publications in the last decade - decade and a half have really shown an uptick in overlapping rheumatic diseases.

That is to say, just because someone has RA does not mean that that's the only rheumatic disease they may have.
It also has been shown to be an increased likelihood of developing secondary and tertiary rheumatic diseases.

So this is something that we want to keep an eye on and are really promoting an education and awareness building campaign around.

So so looking at that overlap disease or secondary rheumatic disease?
Our scientific publications group has looked at multiple peer reviewed publications to try and get a better handle on what likelihood when we're looking at a patient with an autoimmune disease, what are the chances that they're gonna develop a secondary rheumatic disease?

So this is a consolidated study. This slide is depicting a consolidation of studies wherein we're looking at 897 patients with one autoimmune disease.
So this is a pooled, you know, sort of report or table showing that in those 897 patients with one autoimmune disease, those that had SLE., so on the X axis, you've got systemic lupus, rheumatoid arthritis, gilgren or anti phospholipid. And then on the Y axis, this is a histogram or bars showing percentages of patients with that primary autoimmune disease and the percentage of them that have developed a secondary autoimmune disease.

So, uh. In layman's terms, lupus patients with people with primary lupus, 38% of them developed a secondary autoimmune disease.
Rheumatoid arthritis 30% of patients with rheumatoid arthritis developed a secondary autoimmune disease. Sjogren's patients primary Sjogren's patients, 52% of them developed a secondary autoimmune disease and for those patients with Antihospholipid syndrome, this would be an autoimmune autoimmune coag disease, 43% developed a secondary auto immune disease.

So we're looking at, you know, it seems like a not a very high end number and and of 897 may not seem like much, but that's part of the problem with autoimmune research is that these, you know autoimmune syndromes are are not as wide distributed as maybe infectious disease sort of cases and so you know you deal with smaller sample sizes, smaller positivity rates.

And pooling really helps us sort of derive that increased N and better understand in a larger subset you know if you take several smaller sample size studies and sort of pool them, it gives you a better idea in a larger respect.
So. So that's really what we're trying to do here is better understanding a larger you know, sample size, population.

What. What are we seeing here in terms of the propensity or the likelihood of patients with primary autoimmune disease developing a secondary?

All right. So the other piece in terms of quest, you know work towards shining a spotlight on what are the diagnostic criteria for autoimmune diseases and what do our tests sort of do to address?
Running lab tests that are part of that diagnostic criteria for the various autoimmune diseases.
So in this table this is something that's widely available in Quest literature. We have an autoimmune interpretation guide that outlines this table, so I've inserted it into this deck.
And what you see across the column heads are the more common autoimmune diseases.

So starting from column B.
Systemic lupus, mixed connective tissue, systemic sclerosis.
Sjogren's, polymyositis dermatomyositis, antiphosolipid, antithyroid. And then in these last two columns, RA in this would be for RA patients in early RA and in all RA patients.
So we've sort of bifurcated or segmented out RA patients to early and then all and then finally, the healthy individuals column, which is something new.

We've done a table of this nature years ago, but we've added this healthy individuals column because I think in the work of primary care, there are times when you run autoimmune tests and you find that they may be positive, but you you're not sure clinically if their, symptoms fit into an autoimmune disease, at least in your head space.
And so we've added this healthy individuals column to say, hey, some of these autoimmune antibodies can be positive in healthy populations.
Specifically in noteworthy, and I'll talk about this further in the presentation, the ANA patient patients, healthy individuals with a positive ANA 20 to 30% can be positive.
So this is noteworthy.
This is something that, and you know, one lab test isn't really the magic bullet to diagnose an autoimmune disease.
You really want to look at that overall clinical picture, and whether that patient meets criteria beyond just the lab result.

I think before I advance sorry, I'm kind of getting ahead of myself.
I think the other important piece to you know, calling out on this table is that we have green highlighted values and the common perception in tables like this one, a highlight of value is highlighted is that it means that this is a high positivity rate. You know the the title of the piece is antibody prevalence, narrative and related diseases.
But, but I want to make sure that the group understands that it's not just that these are high positivity rates because some of the rates are quite small. When you think of like polymyositis dermatomyositis 15 to 30% positivity for Jill, one doesn't seem like a very high POS prevalence. But these highlights are really about outlining what are the diagnostic criteria for these particular rheumatic diseases?
So for anti phospholipid the B2, the beta 2 glycoprotein, and the cardiolipin. This is kind of right in the middle APS column, right in the middle.
Those are diagnostic criteria. Those are lab results that are incorporated into guidelines for anti phospholipid syndrome.

When we look at like lupus in the very first column, systemic lupus, ANA beta 2, glycoproteins, C3 and C4.
These values are highlighted because they are part of the diagnostic criteria for systemic lupus erythematosus.
So. So that's really what these highlights are about.
It's not about high positivity prevalence, it is more about whether these analytes in each row fit into the the diagnostic criteria for these rheumatic diseases.

So what we're looking at in terms of the analyzer, so this is the test that quest is offering. It streamlines the diagnosis for eight of the most common autoimmune diseases.
It includes 25 analytes, one blood sample and it can assess 8 different diseases.
So we're looking at for those eight different diseases, rheumatoid arthritis, antiphospholipid syndrome, autoimmune thyroid disease, Lupus, mixed connective tissue disease, Polymyositis, Sjogren's syndrome and systemic sclerosis.

So so this test is comprehensive and it has created I think, a groundswell of of support in the primary care space to improve those qualified referrals.
So that's really what this this webinar is about is trying to, you know, promote you know, build education and awareness around this analyzer panel.

So again, circling back to why the analyzer is important when you're looking at patients in primary care that have symptoms that are non specific, things like digestive problems, fever, fatigue, joint pain, muscle weakness or pain, rash, shortness of breath. Doing just an ANA does not exactly address all the potential autoimmune diseases that, or any of the potential autoimmune diseases that may be occurring now. Certainly in primary care, you're going to rule out anything infectious disease related.

But when you're thinking that you've ruled out all other things and you're not really sure, you think there's an autoimmune disease going on here, running an analyzer can help screen be on that ANA and, you know, help to provide a qualified referral for those for those that you would send on to us, rheumatology specialists.

So this table looks at in each row the analytes that are included in the analyzer, and then in the middle column we include what sort of autoimmune disease is considered. If there's a positive result for each of these analytes, what it might indicate in terms of predictive value for another, for a rheumatic disease.
So like the ANA screen is good for autoimmune disease in general, but also for lupus, specifically 90 to 95% of patients with a positive A and A and you know meet the clinical criteria symptom wise are suggestive of lupus.

When we're looking at the other analytes in the panel that are lupus related, the dsDNA, not just a regular ELISA but also with prithidia, or with prithidia. Not also, but we're we run ad SDNA antibody with prithidia. And then reflex to titer.

We have a compliment C3C and C4C, chromatin and Smith antibody. In terms of lupus and mixed connective tissue disease, we have the Smith RNP and the RNP antibody for rheumatoid arthritis.
The analyzer panel includes rheumatoid factor RF IgA, IgG and IgM, so multiple serotypes or isotypes for rheumatoid factor, CCP IGg and MCV, the mutated citrullinated vimentin antibody.

For children's, of course, the SSA and SSB antibodies SCL 70 for systemic sclerosis Jo, one for polymyositis centromere, protein B for Pressed syndrome. Beta two plecoprotein isotypes HIGAG&M for anti phospholipid cardiolipin antibodies.
Both all three isotypes IGAG&M.
And then the Thyroid peroxidase antibodies TPO 4 graves in Hashimoto's.
So this would be autoimmune thyroid disease?
So this would be the analyzer autoimmune test code 36378.

And when we're looking at the overall cost, you know, looking at insured patients roughly 80% just shy of 80% of patients with insurance are do not receive an out of pocket cost.
And then ultimately, 90% of quest patients nationwide are within the quest in network in terms of providers or insurance coverage, so.
Or at least were the preferred provider.

So so I think that these are two important pieces to keep in mind when in primary care, you're, you know, thinking about the patient out of pocket expense when running analyzer.

So ultimately this is the analyzer is a way to create a more comprehensive evaluation of patients.
Get them a qualified referral and improve that time to diagnosis and then of course the time to diagnosis is really going to impact the patient outcomes.

So how might we be able to get patients into that, you know, referral?
Informed referral process and diagnosed and treated quicker so that those outcomes outcomes are improved overall.
So that is the end of my presentation and I'm open to any questions that we have.

Hopefully our team can communicate those and I can address them as well as I'm fit or defer to our franchise folks for things that are more business or logistics oriented.

Jenkins, Jennifer M   22:09
Thank you so much, Doctor Salm.
I'll give you a second to catch your breath after that presentation.
Thanks so much.
I do want to point out.

Salm, Ann E   22:15
Thanks.

Jenkins, Jennifer M   22:16
Especially following you, going through the prevalence chart and and talking through some of the different analytes that are tested.
We do have some really phenomenal resources to help interpret these.
We have an interpretation guide that does cover everything that you see here, you can of course speak to your quest Rep to get a copy of that.

If you need a little instant gratification, you can go to diagnoseautoimmune.com and download a digital copy of that, and it's like we said, it's a very comprehensive guide to understanding. You know what the results could potentially mean for your patients.

So I encourage you to check that out and additionally we have our Clinical Education Center which has a wealth of resources for this test and our other test you can visit education.questdiagnostics.com to get to that and we've got, you know recordings of web.
Such as this, we have test summaries and other educational collateral that you'll find very beneficial.

OK, I do think really quickly we can cover and this can be for you, Doctor Salm or for our product friends as well.
What is the specimen type for the analyzer test and what is the expected turn around time?

Salm, Ann E   23:38
The specimen type is Red top tube 9ML serum to my knowledge and the turn around time is 2 to three business days.
But I guess I would encourage my colleagues on the business side to sanity check, make sure that that's the current understanding.

Freeman, Anne J   24:03
Still, I can jump in real fast.
I'm Anne Freeman with our product team. With the clinical franchise at Quest.
The testing is all performed in our specialty lab in San Juan Capistrano, so we have to factor in time for the samples to get there and for all the testing to be completed.

So the turn-around time is a little longer than your typical Ana, but you get a lot more information. So it's actually 7 to 10 days from the date of collection of from the patient.
And then Dr. Salm is correct with the 9 mil of serum. But we recently validated the test off of SST tubes.
So you don't necessarily need to pour the serum over to a transport tube if you just draw 3SST tubes and centrifuge those and refrigerate them, you can send them in those tubes now, but it typically does take either 3 red tops or three SST tubes to get enough serum to complete all the testing.

Salm, Ann E   25:07
Wonderful. Thanks, Anne.
So 7 to 10 business days or.

Freeman, Anne J   25:24
No calendar days, so weekends. Yeah. Mm hmm.

Salm, Ann E   25:25
Calendar days. OK, OK. And that's upon receipt, so to our lab to SJC.
Is that right?

Freeman, Anne J   25:26
It's actually we start counting when the patient starts counting.
So from the day of collection. So yeah, so it factors in that that local time too, Yep.

Salm, Ann E   25:34
Oh great.
OK, OK. Got you.
Great. Sounds good.

Jenkins, Jennifer M   25:45
Right. We do have a question we've received in our Q&A function and doctor Salm, this one went maybe, but potentially follow up depending, but you might know, have you seen or heard I guess through you know your time here at quest of patients with MS that are also showing positive for a second diagnosis with an autoimmune condition?

Salm, Ann E   26:05
Oh that would take probably a follow up. Yeah. The MS group is, you know, that's really handled more in our Neuro franchise. So that's not something I'm Privy to. But yeah, I can.
I I'm going to need to do some internal sort of polling and networking to get that.
So yeah, I would need to follow up.
Hopefully we can get that follow up information.

Jenkins, Jennifer M   26:32
Yep, we've got contact info.

Salm, Ann E   26:35
Right. Sounds good. OK, thank you.

Jenkins, Jennifer M   26:40
I guess just another point of clarification.
You know, you showed the chart with a whole bunch of components.

Salm, Ann E   26:46
Yeah.

Jenkins, Jennifer M   26:47
And all of these components are contained in analyzer, correct?

Salm, Ann E   26:52
Yes, yes, that is correct.
So our prevalence chart.
These analytes are all so. I'm showing on the screen.
In each of the rows. These are analytes and then I've also shown this table.
These are also analytes that are included in the analyzer panel, Yep.

Jenkins, Jennifer M   27:15
And again, your quest sales Rep can give you additional literature that can go into great detail about a lot of our autoimmune testing as well, if that's something you're inclined to read.

Hey if anyone has any last minute questions please feel free to pop them into the Q&A box. We'll give it just a minute, but again, thank you so much, Doctor Salm, for for presenting this for us.
I think it was very valuable. I know we all believe strongly in the analyzer test and and how it can aid in quicker diagnosis or help identify patients with multiple autoimmune conditions, which is so important for effective treatment.

Salm, Ann E   28:07
Yeah, yeah, I agree.
And you know, I've done talks like this across the country and certainly we've had a lot of interest in the primary care space.
And also just patient care, anecdotal evidence that you know patients are getting referred you know have a qualified referral and are getting cared for quicker and more accurately, so it might not be a perfect fit for all patients.
And all networks.
Some rheumatology networks are stronger in certain geographies of the country than in others.
But where it's difficult to get into a rheumatologist, there's been specifically very strong interest in the primary care space to to use the analyzer panel and improve that time to diagnosis and and getting patients referred so I did the opportunity to talk today.

Jenkins, Jennifer M   29:07
Absolutely. So we do not have any further questions.
So I think we will end it right here and again thank you so much, Doctor Sam, and thank you everyone for your attention to us today.

Salm, Ann E   29:27
All right.

Jenkins, Jennifer M   29:20
Have a great day.

Salm, Ann E   29:21
Thank you.

Jenkins, Jennifer M stopped transcription