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- [00:02]
Kai Rysdal
Everybody has a hot take on the economy. And whether you're curious about inflation, trade wars or the markets, what you need is reporting you can trust. Hi, I'm Kai Rysdal, the host of Marketplace. Our award winning reporters talk to everybody from CEOs to farmers to help you understand how the economy takes shape in the real world. You'll be smarter every time you listen and these days that's priceless. Listen to Marketplace on your favorite podcast app.
- [00:30]
Shankar Vedantam
I'm Shankar Vedantam, here to tell you about a great mystery. That mystery is you. As the host of a podcast called Hidden Brain, I explore big questions about what it means to be human. Questions like where do our emotions come from? Why do so many of us feel overwhelmed by modern life? How can we better understand the people around us? Discover your hidden brain. Find us wherever you get your podcasts.
- [01:01]
Dr. Kevin Dean
We knew a lot about rheumatoid arthritis from people who walked in the door with swollen joints. And that's what we studied for years. But now we think if that disease actually starts five to 10 years before that, getting the data from that earlier time period to help inform us, that's going to be the next step. AR is going to help us with that, but we still have to work on what I'm going to call natural history or longitudinal studies of walking through people in those early stages so we understand what's really important.
- [01:27]
Kathy Werzer
A lot of people live with some form of arthritis. There's osteoarthritis, stiff swollen joints because of aging and overuse. There's another, more serious form of arthritis. It's called rheumatoid arthritis. And while it causes stiff, swollen joints, it can also affect other parts of the body. RA is tough to diagnose, and right now there is no cure. But what if the future means catching autoimmune illnesses like rheumatoid arthritis before they disrupt lives? That's what we're talking about on this episode of Tomorrow's cure, a podcast from Mayo Clinic that brings the future of medicine to the present. I'm Kathy Werzer. It's great to have you with us. Joining me to talk about new ways to diagnose and treat rheumatoid arthritis are Dr. John Davis from Mayo Clinic. He's the chair of the rheumatology division at Mayo Clinic. Also with us is Dr. Kevin Dean from the University of Colorado's Anschutz Medical Center. Good to have you both here.
- [02:21]
Dr. John Davis
Hello. Hello, Kathy.
- [02:22]
Kathy Werzer
From the reading that I've done and from the individuals who I'VE talked to who have ra. It's a tough disease. I mean, folks who have it say it feels like they've been hit by a truck every day. And it can be more than just joint pain. So I'm wondering what's happening in the body to Spark Radio, Dr. Dean well.
- [02:43]
Dr. Kevin Dean
Rheumatoid arthritis has the name arthritis because the inflammation is primarily focused in the joints. That's why people feel joint pain, stiffness and swelling. But it's a systemic problem where the immune system has gone haywire throughout the body. If I can step back, the immune system, normally we want it to work very well to help us fight off infections, clear cancers, heal wounds up. But when the immune system turns on itself and starts to recognize it's the own body as its target, that's what we call autoimmune disease. So rheumatoid arthritis is not immune disease. Again, the arthritis is the primary thing. But the inflammation from the immune system in rheumatoid arthritis can cause a lot of what we call systemic effects. That's where people feel fatigued, slogged out, mental fog. That's all that inflammation. People sometimes can recall having the bad flu. That's what people feel like with rheumatoid arthritis all the time because that immune system is always ramped up and again attacking the joints, but also around the.
- [03:34]
Kathy Werzer
Body because of the systemic inflammation. Dr. Davis I can imagine that if not taken care of, if not treated properly or fast, it could really do some damage to the body.
- [03:46]
Dr. John Davis
It can do a great deal of damage. Kathy first of all, with chronic inflammation in the joints, it can lead to erosions forming where divots in the bone occur. And also cartilage can be degraded. And especially when that happens, we start seeing deformities. So joints that are normally well aligned, you look at your hand and everything looks normal. But you can really start to see deformities occurring. And when that begins to happen, we lose function in our joints. And when you talk to people with who have rheumatoid arthritis, trying to get through daily tasks can be exceptionally difficult. So we take for granted our hands and our other joints when they're working well and we're not experiencing chronic inflammation of joints, that is arthritis. And when inflammation is allowed to persist over months and years, structural damage can occur, and that's your reversible. Additionally, we can see damage in other organ systems. And Dr. Dean has done some great research on actually disease occurring in the lungs and others in our group here in Mayo Clinic, Rochester Chronic inflammation in the lungs can lead to scarring. And when the lungs scar, they can't exchange gas and they bring oxygen into the body, which is the critical function of the lungs. And so this is a major problem that we see. We can also see damage to the heart and a higher risk of heart failure in patients with chronic rheumatoid disease who are also getting older. And so these are examples of other sorts of damage that we see due to the effects of this chronic autoimmune disease.
- [05:13]
Kathy Werzer
Do we know who's at risk and why, Dr. Dean?
- [05:16]
Dr. Kevin Dean
We do to some extent. It's a bit challenging because basically people of any age can get rheumatoid arthritis. It gets a little tricky because if you're under the age of 16, the, the arthritis looks quite a bit different and we classify that differently and call that juvenile idiopathic or juvenile inflammatory arthritis. Basically any age can get it. The peak age is around the age of 50 and in women. So of all the people who get rheumatoid arthritis, three quarters are women, only about a quarter is men. So you might say, well, age around 50 and women are the highest risk. But again, lots of people, all sexes, all ages can get it. That makes it challenging and probably tells us that the disease is what we call heterogeneous, which is not one exact disease. And there's probably lots of pathways by which you get it. That doesn't help you with the question of who we can tell is going to get it. All that said, we still know some risk factors. There's a few things in the environment like cigarette smoking is a big risk factor. There's some environmental pollutants that can be a big risk factor. We now know that healthy diet and exercise are protective. So the flip side of that would be that not healthy diet and maybe carrying around a bit too much weight and obesity are actually risk factors. The most powerful risk factors we have though are blood markers now that we can tell if your immune system has gone bad, if I can use that term, and started to generate what we're going to call auto antibodies, which are markers that say your body's now immune, reacting to yourself. Those are detectable on average three to five years before the arthritis sets in. Those are probably our most powerful risk.
- [06:55]
Kathy Werzer
Factors, given the potential severity of the disease. Then, Dr. Davis, let's talk about early prediction. Mayo's center for Individualized Medicine has published on AI driven disease prediction using blood samples, which is pretty interesting. And that kind of goes a little bit to what Dr. Dean was talking about, can you explain that a little bit for our listeners?
- [07:14]
Dr. John Davis
I think this is where we need to go. I don't think it's fully developed or implemented yet, but this is part of our broad vision here at Mayo Clinic with the precure, which is the notion of trying to put together a lot of data that we can digitize about an individual. Their health, their risk factors, their health behaviors, even data that we could collect from them that might say something about their health status, even things like, you know, activity levels and other variables that we can collect using wearable technologies and then their health records. We collect a lot of data about people. We have a lot of routine blood tests, a lot of information in radiographs that we could glean over time. These are basically X rays that we take on people that may have important data that if we analyze using an AI algorithm, that could really learn a lot about the individual and may be able to identify people who could be at risk, even, you know, far ahead of when they come down with any symptoms. Right now, what we have are the antibodies. Dr. Dean talked a lot, and he has really been the pioneer at this, along with colleagues at the University of Colorado and other centers in Europe and around the United States and world, that identifying people who have positive antibodies to situate the proteins. So this test that is commercially available called anti ccp, is one way to do that. Or rheumatoid factor, which is another, older test, is a bit less specific. But, you know, identifying those antibodies really says a lot, as Dr. Gein said, about measuring risk. Genetic factors are important. And, you know, increasingly people are getting their genome analyze and learning, you know, all about their genes and what variations they have from normal. And I think one of the next steps is identifying different sort of genetic risk scores, being able to identify all the variants that might be able to predict if a person is at greater risk of rheumatoid arthritis, and trying to also quantify that, because one of the key next steps in this field is being able to accurately identify who is at risk and really be able to put a number on that in terms of what is the risk over, say, five years that someone could progress to develop rheumatoid arthritis. That type of information is really critical. If we're going to be enrolling groups of people who have high enough risk that they're going to develop rheumatoid arthritis over a short period of time that it's worth putting them on medications to try to prevent development of the disease, which is, you know, a big field that's that we're developing now.
- [09:32]
Kathy Werzer
Dr. Dean, do you want to build on what Dr. Davis was saying?
- [09:35]
Dr. Kevin Dean
Absolutely. So Dr. Davis mentioned these blood tests. They're called autoantibodies. The two big ones that we have are something called anti CCP antibody, and the other one is rheumatoid factor. Those are quite good. But just those tests alone will only accurately predict that 30% of people with those abnormal blood tests will get rheumatoid arthritis within the next three or five years. That's quite powerful prediction. But if you look at the other way, that means 70% of people won't get rheumatoid arthritis. As Dr. Davis pointed out, that might not be enough risk to give somebody a powerful medication to try and stop them from progressing. So we want to increase that ability to predict. And because so many factors can play a role in who gets rheumatoid arthritis, as Dr. Davis talked about, and I mentioned earlier too, diet, exercise, medical history, other biomarkers or other blood tests, all that, I think this is perfectly poised for AI to really help us take the next step to be able to predict who's actually going to get rheumatoid arthritis. Because again, as Dr. Davis mentioned, the rubber meets the road here. We want to be sufficiently convinced someone's going to get rheumatoid arthritis that we feel confident and comfortable giving them an intervention or a drug to be able to help prevent them from going on to get rheumatoid arthritis. Because I think ideally, I think we may all agree it would be great to prevent rheumatoid arthritis rather than wait for it to just start and somebody to have arthritis and then wind up being on drugs forever. Because that's how RA is treated now. You know, you wait till you get the joint inflammation and then basically most people are on drugs forever to try and control that. If we catch it earlier, we really hope we can actually stop the process and prevent it from going on and maybe even be off of drugs completely and have a reset to the immune system.
- [11:14]
Kathy Werzer
Is that what you were trying to do with the Stop RA trial, where you were identifying people at risk for future RA through a blood test and then investigate whether treating them with a drug could delay or prevent future disease?
- [11:26]
Dr. Kevin Dean
Yes, that's what we were trying to do. So I'll step back and tell you about that story. So we had a study called Stop Ra, and Dr. Davis participated several sites around the country. It was funded by the nih. We took people who have an elevated blood marker of one of these tests called anti ccp, higher than the normal cutoff. We estimated that meant about 30 to 50% of those people would get rheumatoid arthritis over three years. We gave them a drug that's already been used for years in rheumatoid arthritis Called hydroxychloroquine. And it's a pill. It's got some risk, but it's overall quite safe. It's relatively inexpensive and very well tolerated. We thought, what a perfect drug to give to people who are poised to get rheumatoid arthritis but don't have it yet to see if we can stop disease. And back to your point, we thought we would take a shoot the moon approach where we give them a drug for a year and stop and then follow them after that, Hoping that that drug would reset their immune system. Well, it turns out that drug didn't work at all. So even while they were taking it, There was no reduction in rates of getting rheumatoid arthritis, and there was no benefit after they stopped the drug. It's an important finding because this was a drug we all wanted to use, and some of us actually have been trying to use it on an ad hoc basis to try and prevent rheumatoid arthritis. But I think it proved sufficiently robustly enough that this drug doesn't work, and we need to look for other ways to prevent rheumatoid arthritis.
- [12:50]
Kathy Werzer
Interesting though, as a researcher, Were you disappointed?
- [12:54]
Dr. Kevin Dean
Heartbroken, because we really thought it was a great idea. There's a lot of time and effort that goes into this. And you know, we had people who put themselves forward, right? They got tested for this blood marker. They had to go through all the rigmarole roll of a study to participate and come to 11 visits over three years. And we did it through Covid. So anyway, a lot of effort went into it. It didn't work. So that said, it's still good that a drug we wanted to use and thought would work doesn't work. And that is an important finding. I will add there's been other studies Now, I think there's seven studies internationally to try and prevent rheumatoid arthritis. They've tried several drugs. Some have not worked as well, But a couple of drugs have a unique finding that while people are taking the drug, they actually have much decreased rates of getting rheumatoid arthritis. Now, those effects don't seem to last, but that gives us great hope that if we use the right drug at the right time, we can alter the course of rheumatoid arthritis for people. Now I think we're going to have to refine those and I think the next the next round of prevention studies in rheumatoid arthritis, we're going to have to refine what drugs we use and how long we use them. But it is encouraging that at least some drugs have worked. So I think it's going to pave the way for future studies, especially if we can get back to what Dr. Davis was talking about. Use a variety of factors, including AI, to help predict better who's going to get rheumatoid arthritis.
- [14:15]
Kai Rysdal
Are you trying to become a better human? Well, the Human Optimization Project is an exciting new podcast offering from Mayo Clinic which aims to help you do exactly that. We're all struggling to balance the need to perform and do more while simultaneously maintaining our wellness. In the Human Optimization Project, we're focusing on 10 key domains of human performance to help people achieve more, improve well being, and become the best humans they can be. If that sounds like what you're looking for, search for the Mayo Clinic Human Optimization Project on your favorite podcasting app.
- [14:54]
Dr. John Davis
Hi, I'm Dr. Bill Maurice from Mayo Clinic Laboratories. Curious to learn more about healthcare innovation.
- [14:59]
Kathy Werzer
I'm Dr. Bobbi Pritt, host of Answers.
- [15:02]
Dr. John Davis
From the Lab, a podcast that explores.
- [15:04]
Dr. Kevin Dean
Trends and innovations in laboratory testing and clinical diagnostics. New episodes drop twice a month. You can subscribe on your favorite podcast.
- [15:13]
Dr. John Davis
App or visit mayocliniclabs.com to learn more.
- [15:16]
Kathy Werzer
We were talking about that rheumatoid arthritis is an autoimmune disease. And I'm wondering, have there been advancements in other autoimmune diseases, say lupus, that might be helping your work going forward?
- [15:29]
Dr. Kevin Dean
Yes, there have been. So a lot of autoimmune diseases have a same basic principle of development where some someone's in an asymptomatic stage where they feel just fine, but they have blood markers that suggest their immune system has gone bad, so to speak, or gone autoimmune and they're heading down a pathway. We know that for lupus and we have some building predictive models for lupus, rheumatoid arthritis we've already talked about. I think one of the great examples is type 1 diabetes, which is an autoimmune disease. You have type 1 diabetes when your blood sugar is high and at that stage, basically, basically you have to take insulin for your rest of your life. So it's pretty devastating disease at that point. But we realize years before your insulin fails because of the autoimmune response, you can detect there's immune responses through autoantibodies. And a couple years ago there was a great study published in the New England Journal where a certain immune drug called teplizumab delayed progression of youngsters who have these biomarkers or blood markers for type 1 diabetes to getting disease. Now, that drug is FDA approved to help delay type 1 diabetes. So we look to that as a great example. They're a bit ahead of us in rheumatoid arthritis, but that's the kind of thing we'd like, where you can start going at a population, screening a population, identifying those who are at high risk, and then intervening to help delay or even ultimately prevent disease.
- [16:46]
Kathy Werzer
Dr. Davis?
- [16:47]
Dr. John Davis
Of course, a lot of these diseases, as we've talked about, don't start, you know, just today. They've been unfolding for years, years and probably decades. And we see a lot of people that are kind of on the on the cusp, and it's hard to decide if what they're suffering from is related to other health conditions or part of aging and alternatively, when really it's the beginning of an autoimmune disease that has not become full fledged, if you will, meeting, you know, classic criteria that helps clinicians make a diagnosis. And I think some of these insights are maybe helping us better and develop the tools to understand where that line is and maybe to better establish when disease is truly present and when should we be treating. This work comes up in some of the pre RA or trying to identify people who are at risk of ra. The other issue is when do you define disease? And I think that's something that comes up in some of the studies that are going out there where you're recruiting people who have symptoms, who may have joint pain. Some of them may actually have a disease already. You know, it's not about prevention, it's about when do we treat. And I think these are important things for us to continue to work on with developing new biomarkers, new tools for establishing an early diagnosis, not only prevention. Kevin, do you, do you agree with that?
- [18:04]
Dr. Kevin Dean
I completely agree. And if I can expand on that, in the old days, we used to diagnose rheumatoid arthritis when you had a bunch of swollen joints that we could feel with our fingers as physicians and say, aha, that joint feels squishy and swollen and inflamed. That's rheumatoid arthritis, as Dr. Davis pointed out. Now we're finding people who may not have a swollen Joint. And you can only see inflammation in that joint if you do an mri, magnetic resonance imaging, which is, you know, high resolution imaging of that. And so it's moving back where we actually think disease may start. And then that's further complicated by. Some people will actually start to develop the symptoms of rheumatoid arthritis. They may have joint pain, they may even have an MRI that shows they have joint inflammation. But all of that goes away for that person without any intervention where they regulate themselves. And so I think understanding all those pieces and parts is going to be an important part of this next step. People have known this for years in prevention. Not every nodule in the lung actually is lung cancer. This is one of the reasons why we've been very reluctant to just do lung scans on everybody in the world, because not everything that looks like cancer is cancer. And then you may wind up hurting people more by going after it and treating it. So understanding what's truly disease, when does it really start? What are the effective therapies? I think that's gonna be a challenge, I think an exciting challenge, but something we're gonna have to, we're gonna have to tackle.
- [19:26]
Kathy Werzer
Say, can I ask you both something interesting? Now, you mentioned there are some environmental factors, right? And I'm wondering. I'm fascinated with the exposome. Some of this also deals with what we're exposed to over our lives. One theory is that RA begins to develop in sites such as the intestines or lungs, for whatever reason. So might treatment and research require targeting different pathways of the body that might be exposed to Lord knows what? Is anyone looking at that, Dr. Davis?
- [19:56]
Dr. John Davis
I think a lot of people are looking at that. Part of the fundamental theory about how rheumatoid arthritis develops is that certain people are born with certain genetic factors that are risk factors, but then different exposures happen over the course of life. And a lot of people have proposed this notion of the mucosal origins, and that's a fancy technical word for that. The. It starts in right at the body surfaces that are exposed to the environment. So the airways, the lungs, the gut, you know, are all places where our body and our immune system really comes into contact with the external environment. So, and we've known that it's been supported for years with the knowledge that smoking is a major risk factor. And there is reason to think that, that it's sort of contributing to activation of the immune system in the lungs. This is a really important notion and that there is a great insight and a lot of work that's already been done that have shown that these kind of exposures at mucosal surfaces, really, that body lining surfaces are. Is an important factor in who develops rheumatoid arthritis. I don't think we've worked out well exactly what the mechanisms are, but a lot of groups are on their way. Dr. Dean has done a lot of research already on this.
- [21:01]
Dr. Kevin Dean
Dr. Tiffany is exactly right. And if I could step back. The field of rheumatoid arthritis worked for decades treating the arthritis of rheumatoid arthritis. You know, we learned from an inflamed joint what the biology is inside of that joint and try and target each one of those pieces and parts. That's led to some great advances in therapy. But we now know that the immunity or the autoimmunity of rheumatoid arthritis is present for years before that first swollen joint happens. And that's taking place as what Dr. Davis talked about. We think probably in mucosal sites. And it's not all the same mucosal sites. Some people, we think the gums may be inflamed and that could be triggering their immunity. Some of the lungs, some of the gut, but it's outside of the joints. Now we have to reframe our scientific investigations to say what are the immune problems at those sites, not just the joint, since the joint's not actually involved in this early stage, what's the immune activity there and how to target that? Because that's going to be key, I think, for the future, for treatment and prevention of disease. If you just try and target the usual suspects in the inflamed joint, that's not going to get us there. It may still be pretty good, but we got to go go deeper. And I think that's where the next few years, the scientific community is really starting to understand that and poised to investigate that more. It'll be challenging. I think it's really the way we need to look at rheumatoid arthritis in the future.
- [22:23]
Dr. Bill Maurice
Busy healthcare professionals, this one's for you. Find Mayo Clinic talks on your favorite podcasting app or visit Cell Podcasts to learn more. Every week we share succinct, relevant and practical medical insights tailored for healthcare clinicians that you can immediately apply to your practice. Each episode covers common health issues seen in a primary care practice shared by Mayo Clinic experts. Busy healthcare professionals, this one's for you. Find Mayo Clinic talks on your favorite podcasting app or visit ce mayo.edu podcasts to learn more. Every week we share succinct Relevant and practical medical insights tailored for healthcare clinicians that you can immediately apply to your practice. Each episode covers common health issues seen in a primary care practice shared by Mayo Clinic experts.
- [23:45]
Kathy Werzer
There have been studies in terms of the inhalation of the particles that are getting into the lung and then causing systemic inflammation.
- [23:53]
Dr. John Davis
Yeah. So a shout out again to a lot of colleagues. Dr. Vanessa Kronz are here collaborated also with folks at the University of Nebraska and Brigham Women's Hospital and study done out of data from the VA system. So but they're able to show that using different environmental detectors that sort of measure particulate matter in the air, that exposure to certain particulate matter. It's the PM2.5, which has to do the very small size of these particles and also nitric oxides was another one that fell out. Is being associated with increased risk of rheumatoid arthritis. New cases of rheumatoid arthritis and also patients who develop the dreaded lung disease in the setting of having rheumatoid arthritis. And again, these are emanating from smoke. Those are produced by fire smoke. And with fires that are occurring with environmental change, we're seeing more of that and having times when the air turns red almost it seems in different. Different parts and can be a bit scary. Fortunately, it tended to go away and where I live in Minnesota. But I think in the future we're going to have to learn how to monitor that and to adjust our exposures to avoid those kinds of things.
- [25:03]
Kathy Werzer
Wow, that is scary. Of course, in Colorado you've had your share of wildfires as well, Dr. Dean.
- [25:08]
Dr. Kevin Dean
Correct. What's fascinating is, you know, we've known for years that cigarette smoking is a risk factor for rheumatoid arthritis as well as other diseases. But then, interestingly, very few people smoke in the United States anymore, which is good news. But we're still seeing rheumatoid arthritis. And I think this is why it's fascinating. Think. Well, there's other things that we all breathe in and certainly fire smoke and other occupational exposures. All those things. I think it's fascinating to that's sort of our next frontier.
- [25:33]
Dr. John Davis
The risks that that exposure is going to produce is still relatively small. And most people get exposed and never develop rheumatoid arthritis. But others who have these other risk factors. Right. It can lead to this beat getting expressed in terms of that risk. So it's a public health issue and something that we will have to contend with in coming decades.
- [25:52]
Kathy Werzer
Dr. Davis, can you share how gut microbiome research might predict not just the onset of ra, but also individual responses to treatment.
- [26:01]
Dr. John Davis
Yeah, we're learning a lot about this. Different gut bacteria. Different profiles of gut bacteria already are telling us something about individuals who are sick and who have chronic diseases. Across a lot of diseases, including rheumatoid arthritis, but other like diseases like cirrhosis or chronic heart disease or even neurological diseases, you can see abnormalities in what we call dysbiosis, which is, you know, kind of a profile of low bacterial diversity. Turns out that, you know, having lots of different types of bacteria tends to be healthier, in a sense, and correlated more with health. People who have chronic diseases, including rheumatoid arthritis, it contracts. But you can also see overabundance of some bacteria that may be healthy and are less frequently observed in people who are healthy. And some of those bacteria may be doing specific things and producing different metabolic factors that talks with our immune system in a way that leads to activating immunity and leading to some of the downstream consequences of turning on these autoimmune mechanisms and people who are genetically predisposed. I think a lot is being worked on that with regard to idea of prediction. You know, I think part of it is, can we use in certain people, how do we know where to look? You know, do we look in the lungs? Is it the gut? Is it the nasal passages? I wanted to mention one of my colleagues, Dr. Vanessa Kronzer, is doing some very interesting work, along with other collaborators looking at upper respiratory exposures, like just infections or even allergic diseases. It turns out those are also risk factors for rheumatoid arthritis. And so she's looking at profiles of the nasal microbiome as a future direction to try to identify people at risk. So a lot of places to look. We have done some work looking and others have done this also trying to predict who responds to methotrexate. And it turns out with about 80% accuracy, we can identify, just based on profiles of gut microbes and a couple of clinical factors, who is going to respond to methotrexate with relatively high accuracy. Part of that is the relationship with the immune system, but part of also is it turns out the gut bacteria metabolize certain medications, including methotrexate and some of that metabolism. The bacteria that metabolize methotrexate over and underabundance of those relative to other people probably has something to do with who gets better on methotrexate. And so there are probably drugs we'd like to even predict more, whether or not they're going to work that are more expensive or have greater risk. And so we need to kind of use this and learn from it and now take it to other medications like biologic medications that are injectables and can lead to some even greater responses in populations of people. So that's sort of the next frontier there.
- [28:37]
Kathy Werzer
Really exciting stuff. See, I'm wondering, by the way, how does AI maybe supercharge a lot of what you both are doing?
- [28:44]
Dr. Kevin Dean
Our prior statistical analysis to identify scientific questions has been quite good and led us to a great place. However, we have a big, big problem with big data in health and disease where lots and lots of factors can play a role to a single person's ultimate outcome to getting a disease. Looking at all those bits and pieces all at once and putting the picture together is where I think AI has great promise. Where our old approaches, our standard approaches, our statisticians may get mad at me for this, but those may not be strong enough now to, to factor in everything that we already know now can affect the immune system. You mentioned the exposome, a hugely varied thing for each individual. But then if I have millions of bacteria in my gut and another hundred thousand in my mouth, all those are little pieces that are coming together. But I think AI is going to be able to help us tackle that vast amount of information and paint the right picture for the right person at the right time. And those are just, I think techniques where AI is going to really help us. And they, they already are starting to help us with that. I think we've seen it in ways such as weather prediction has gotten a lot better. Those algorithms that can tell you what ad to put up before you, that is very interesting to you to buy. That's fascinating because you may not like that approach, but what if that's going to tell you the right drug or the right intervention that you should have to prevent your rheumatoid arthritis? I think those same kind of algorithms are going to be very helpful.
- [30:10]
Kathy Werzer
And Dr. Davis, what do you want to add about this?
- [30:13]
Dr. John Davis
You know, AI is here whether we like it or not. And we have been using it for some time already really for research purposes, but I think now it's available to use clinically. When I do my clinical notes every day, it's after my voice has been recorded and a clinical note is being generated using an AI algorithm. And then of course I edit that and have to make it my own note. But you know, it's a big service to make that process happen more quickly and so part of it is about efficiency, part of it is the ability to actually analyze such high dimensional data where we're looking at, you know, millions of variables, not a hundred, like Research 1.0. Now we're in 2.0 and beyond, and we have to use these novel tools. A lot of the insights that we've gotten from looking at the gut microbiome, of course that was done using machine learning, a form of. A form of AI. And I think now the next wave is about putting together multiple types of data. So looking at genetics or what we call genomic data, looking at proteins, looking at metabolites in the blood that could be produced by bacteria or by our own cell types. So putting together multiple types of data that are going to help us make better predictions about individuals and whether or not an individual develop a disease or will an individual respond to a certain medication or not. So I think the challenge for us going forward is how do we assemble those data efficiently so we can really learn for it in real time, creating sort of digital banks of data that can go along with, you know, other types of variables that are already in the chart, other medical information. It's really going to be important for us to be able to scale and recognize and achieve this opportunity that we have with AI.
- [31:54]
Dr. Kevin Dean
I liked Dr. Davis's understanding how we're gonna have to set up data to be able to use AI. And I would say for rheumatoid arthritis, part of the challenge has been we knew a lot about rheumatoid arthritis from people who walked in the door with swollen joints. And that's what we studied for years. But now we think if that disease actually starts five to 10 years before that, getting the data from that earlier time period to help inform us that that's going to be the next step. AR is going to help us with that. But we still have to work on what I'm going to call natural history or longitudinal studies of walking through people in those early stages so we understand what's really important. If I can use an example, I think we all understand now heart disease has a lot of things that play a role into that. Smoking and high cholesterol and high blood pressure. All that was learned from these large scale longitudinal studies where they studied a city called Framingham and all the people in that and watched them over years. To kind of come up with all those core principles that we now understand about heart disease. We're going to have to start looking at a lot of diseases, rheumatoid arthritis included in that same way and applying AI to help us understand all those data.
- [33:03]
Kathy Werzer
Where do you think your field of rheumatology goes in the next five to 10 years?
- [33:08]
Dr. John Davis
I do think that we're going to have a lot more data. We're going to have to get comfortable managing. I think that we will be doing, you know, broader panels of antibody tests as we learn about newer markers, you know, as opposed to the days when we had, you know, basically two tests, there's rheumatoid factor and ccp. And I think that we'll learn there's a broader range of both antibody tests and other types of markers that can help with establishing a diagnosis or identifying people who are at risk. I think that we will be doing a lot more prediction. I think we'll gain tests that will help us individualize treatments better. Maybe not saying what is the exact best test for an individual, but but saying, you know, you're in the group of patients that are more likely to respond to this versus that and using evidence and data to make better predictions about what drugs are best for a person.
- [33:56]
Kathy Werzer
Dr. Dean, what do you think?
- [33:58]
Dr. Kevin Dean
I also think one of our challenges will be how, as healthcare providers, to interpret that data and provide it to people who are sitting in front of us as patients in a sensical way. Actually, I have great hope that AI is going to help us do that. Interpretation what we know into a digestible format where people can actually take that information and make it meaningful themselves. Because if we can't do that, it becomes silly to have all this fancy data and whatnot if we can't communicate well. I think the other great promise is that not only are advances in data and how we interpret data going to help us in predicting who's going to go on to get disease. I'm excited to think it's going to actually give us novel ways to actually treat disease, because the data now is showing us things about how disease develops that give us brand new ideas for targets and giving us new ways to think about things. Kind of back to your exposome. Like if we could really understand what it is in the environment that's driving something, that's not only going to help us identify who's at risk for disease, but also help us target something to prevent disease. And there's fascinating issues now where people can understand the biology of certain proteins and understand how medications can target those proteins even better to make more effective therapies. So I think a lot of that's quite exciting. That used to take years in experiments, but now AI can design a drug for you quite quickly and maybe even interpret how that's going to work and maybe avoid some of the bad side effects that might come up.
- [35:19]
Dr. John Davis
I think right now a lot of rheumatology practices hands on that is that we really feel most comfortable when we can examine the joints. And I think what we've been talking about is increasing when we're diagnosing people at a stage in which there's not as much swelling to see on an end joint examination. And I think additionally consumers are looking for easier ways to access care and needing to do it more digitally, more virtually where we have less opportunity in some ways to examine the joints. So I, I see care in the future becoming, you know, more digital, more virtual and what we're have to rely on increasingly tests to help us know what's going on that are a bit more accurate than just physical exam, which may be important. And I'm not saying we're going to get away from that entirely. I'm too traditional in some senses. But on the other hand, I think a lot of factors are going to be driving us to using data that are in digital forms and that's how we're making decisions about, about care for patients.
- [36:18]
Kathy Werzer
Now that's interesting and I wonder if that helps folks say in rural areas.
- [36:22]
Dr. John Davis
It's part of the disparity, right? I mean they can't come access us in Colorado, where Kevin is, or me in Rochester, Minnesota. I think rheumatology is also known for rheumatologists in the United States to meet the demand. And probably the same thing can certainly be said around the world. People are going to need to access this more virtually and we're going to have to find ways to deliver care that's safe and effective and reliable and patients who are much farther away than just our local site, so. Exactly, that's how it's going to happen.
- [36:51]
Dr. Kevin Dean
I would just second that. And I'm just reflecting back. The summertime is great in Colorado for people to get to our clinic and get seen. But we're coming up on whether I just was at clinic this morning and scheduling someone and they would be having to come back in January and we were said, oh shoot, that's normally a six hour drive but in January it could actually be impossible and just that kind of thing, just access to care. I think that's going to be an important way forward.
- [37:17]
Kathy Werzer
Well, Dr. John Davis and Dr. Kevin Dean, it's been a real pleasure talking with you both. Thank you for your good work.
- [37:23]
Dr. John Davis
Thank you Kathy, it's been a pleasure being here with you and Kevin today.
- [37:26]
Dr. Kevin Dean
Yes, thank you. Thank you. Thanks for the opportunity.
- [37:28]
Kathy Werzer
We've been talking to Dr. John Davis of Mayo Clinic. He's the chair of the rheumatology division at Mayo Clinic. Also with us, Dr. Kevin Dean of the University of Colorado Anschutz Medical Campus. Tomorrow's Cure is a production of Mayo Clinic with production help from the podglomerate. Be sure to follow Tomorrow's Cure wherever you get your podcasts. I'm Kathy Werzer. Thank you so much for listening.
- [37:52]
Dr. John Davis
Sa.