Episode #5: Prevention of Autoimmune Diseases with Dr. Kevin Deane

Foresight Medicine Episode #5Prevention of autoimmune diseasesIf you enjoy this interview and want to learn more about the frontier of prevention for autoimmune disease, including how you can become involved in a study of prevention for rheumatoid arthritis, please visit the website of the Autoimmune Disease Prevention Center of the University of Colorado, directed by my guest, Dr. Kevin Deane: https://medschool.cuanschutz.edu/centers/adpcRobert Rogers: I’m Robert Rogers, host of the Foresight Medicine Podcast at the Foresight Medicine Substack, where we are envisioning the future of preventive healthcare as a comprehensive, whole-body framework for leveraging new technologies to maintain health for as long as possible.In this podcast series, I interview leading experts at the forefront of prevention and early intervention across medical specialties. And today, we will be talking about autoimmune diseases. I’m very honored to have as our guest Dr. Kevin Deane. Dr. Deane is Professor of Medicine in the Division of Rheumatology at the University of Colorado. He is a leading researcher in the field of rheumatoid arthritis, where his many high-impact publications, bridging immunology, epidemiology, and clinical trials, have helped define the concept of preventing or intercepting rheumatoid arthritis and other autoimmune diseases before significant damage occurs. Dr. Deane was the principal investigator of the STOP-RA trial, a landmark rheumatoid arthritis interception study that tested whether treatment in high-risk individuals could prevent or delay the development of clinically apparent rheumatoid arthritis. And he’s a major contributor to guidelines on the identification, risk stratification, and management of people at high risk of rheumatoid arthritis. Listeners should note that we are recording this on Thursday, May 7th, 2026, and this conversation is for general informational purposes only, and does not constitute individual medical advice. Kevin, welcome. Thanks so much for joining me today. Really excited to be chatting with you.Kevin Deane: Great, Robert, thanks for the invitation, and happy to be here.Robert Rogers: So, you know, to kick things off here, this is one of the conversations that I’ve been most excited to have, because I feel like it’s one of the furthest out there frontiers for preventive healthcare. There’s a cadre of people who call themselves preventive cardiologists, preventive neurologists. I think there’s many primary care physicians and others who would consider themselves to be quite conversant in screening and early detection of cancer. But it’s not too many people who call themselves preventive rheumatologists, and I think you’re probably one of the leading people who might be able to change that. And so, first question I always just like to start off with is,how did you become interested in this field, in autoimmune disease and rheumatoid arthritis, but specifically this idea of early detection, intervention, and as you’ve termed it, interception?Kevin Deane: Good, good question. I think part of it was my own personal belief that I’d like to catch people before they get too sick. And I think that underpins a lot of my philosophy now and where I’ve gone with trying to help prevent rheumatoid arthritis. In a bunch of autoimmune diseases, in particular the rheumatic diseases, things like rheumatoid arthritis and lupus, we oftentimes wait until people get quite sick before we even see them for the first time in a rheumatologist’s office and initiate treatment. I got tired of seeing that. I thought, why can’t we get to these people earlier?There was another line of evidence, if you will, as I started my training about 20 years ago, that was coming to the forefront, where blood tests for our autoimmune diseases got a lot better, and in particular, a test came on the market, something called the anti-CCP antibody for rheumatoid arthritis, it was highly accurate for disease. That sort of acted as a game changer, because rheumatologists had a phrase, and they still do to some extent, oh, don’t just treat a lab test. And I get that, but when you have really good lab tests, it may indicate that somebody has not only got a disease now, or maybe at high risk for disease, that can change the game.So, and quick summary of that. My personal belief, let’s try and catch people before they get sick, and then some advances in the field where in rheumatic disease, we had really good blood-based biomarkers that could be predictive of future disease. That got me going down the pathway to prevention. I’ll add one other thing to that.Robert Rogers: That’s so super interesting about how the discovery and really the identification of the anti-CCP antibodies as a really powerful diagnostic tool really leveraged your career in this direction, because I sort of take for granted that blood test has existed. As long as I’ve practiced, it’s always something we send when we’re suspecting rheumatoid arthritis in the workup, but as you said, it really, really opened up this field in a very different way.Kevin Deane: Yeah. And the other line of evidence along those… For years, the disease entity type 1 diabetes has been working on early risk identification and prevention. They’re well ahead of us in, actually, rheumatic diseases, but they’ve been using autoantibodies that are related to type 1 diabetes for years, have had for years very good predictive models, but had really advanced their understanding of how you can use antibodies to predict future disease, about the same time I came along into the career of rheumatology, and I was working with people who had a foot in the epidemiology world of type 1 diabetes, and also knew about rheumatoid arthritis and other autoimmune diseases. So that coming together, the knowledge from type 1 diabetes really informed my thinking. And so those three lines of evidence, me wanting to prevent disease, the new tests in rheumatic diseases, and the work that had been done in type 1 diabetes, all those things came together.Robert Rogers: Yeah, there’s a couple of threads you mentioned there that I really want us to go with here, and I think it’s interesting that you’ve brought up early in our conversation, kind of comparing some autoimmune diseases, and as you mentioned, type 1 diabetes is perhaps, among all the autoimmune diseases, the one where the paradigm of prevention is the farthest advanced, in the sense that there’s actually an approved therapy, and I’ll just say briefly for our listeners, you know, for patients who are at have a family member who’ve had type 1 diabetes, and they have the antibodies that are highly suggestive they’re going to get it, there is actually a therapy that can delay the onset of them getting to the point where they actually have full-blown diabetes and need insulin. And you could imagine, especially for a mostly juvenile disease, when you’re dealing with children, being able to delay for a few years when they might need that level of intervention is hugely, hugely valuable.And I’m glad you brought up that comparison, because I don’t want us to go too deep on this right now, but, you know, when we say… when we think of, for example, preventive cardiology, right, we’re talking mostly about, say, coronary artery disease, atherosclerotic cardiovascular disease, and maybe a few other diseases now we can get into nowadays with the valves and stuff. But when we talk about autoimmune disease, I mean, it is so many diseases, right? I mean, medical textbooks will say there’s about 100 of them, and, you know, there’s probably 10 to 15 that constitute the vast majority of what you see in your clinical practice. And I don’t really want to spend a huge amount of time, because I think it’s a really complicated and time-consuming topic. People can do a little of their own self-education with their own LLM of choice, of sort of, you know, how we describe and classify and group together the many different autoimmune diseases. But since we are going to focus on rheumatoid arthritis, I’m just curious. where do you place RA? And we can… maybe we’ll start using that, introduce that abbreviation so people… we don’t have to keep saying all the time, RA. Where do you place RA in terms of the spectrum of autoimmune diseases, in terms of how preventable or intervenable it might be?Kevin Deane: So, yeah, as you state, there’s a bunch of autoimmune diseases. If you look at each one of them, they’re all, as an individual disease, pretty rare. Like, for example, rheumatoid arthritis affects about 1% of the population. Type 1 diabetes actually affects 1 in 300, so, quite rare, but still very impactful. Lupus is about 1 in 1,000. But when you lump them all together, about 1 in 6 people actually have an autoimmune disease. This is counting them all up. Thyroid disease, some of the things I talked about, RA, or lupus, or type 1 diabetes, you lump them all. So that’s a pretty substantial, substantial portion of the population has some form of autoimmune disease. At a very high level, autoimmune diseases are when your own immune system, which should normally help you fight infections, heal wounds, help clear cancers, goes bad, if I can use that term, and starts attacking you. They can either do it in a very targeted way, like, for example, type 1 diabetes, it attacks the cells in your pancreas that make insulin. Only those cells are attacked, but boy, when those are gone. you’re out of luck, because you don’t have any insulin, and you need insulin. Rheumatoid arthritis, on the other hand, is where your immune system attacks, as the name implies, your joints and causes arthritis. It can also affect other things, including the lung, but the joints are the primary target.Other diseases, such as lupus, can affect almost any organ in the body. Another one that’s a little bit more targeted is thyroid disease, where the autoimmune system will just attack the thyroid gland. But anyway, so rheumatoid arthritis in that context. It is quite common in terms of diseases, like 1 in 100 is a little bit more than some other autoimmune disease, so that’s why we sort of focused on that. It’s something we want to first look at in prevention and rheumatic diseases. Once we figure out some things there, we’ll probably work to the more rare conditions.Robert Rogers: Great, so you know, there’s a lot of autoimmune diseases. Collectively, they represent a pretty significant portion of disease, but each one of them is so complicated, each one of them has so much of its own biology, there’s going to have to be so many, disease-specific details for prevention for each, and so let’s go with one of them that’s more common and more defined, and so that’s why you want to zero in on RA. So let’s lay a little bit more foundation for our listeners about the disease, before we get into the idea of preventing it. So you mentioned, really, what RA is, but talk us through a little bit what the current treatment options are, what the current treatment paradigm is. Patient comes to your office with a new diagnosis of RA.Kevin Deane: Yeah. So, usually, by the time somebody gets to the specialist or the rheumatologist, they’ve had probably 6 to 12 months in common care pathways in the United States of aches and pains, stiffness, pain, feeling of swelling in their joints. Their primary care will often see them maybe one or two times, finally recognize that rheumatoid arthritis is driving these symptoms, maybe with blood tests, maybe noticing a swollen joint, then they’ll get to rheumatologist. At that point, we make a diagnosis of rheumatoid arthritis based on what we see on physical examination, whether someone has swelling in a joint that looks to us like that joint is inflamed. We do blood tests that help confirm that. Tests such as the anti-CCP antibody, another commonly used test as a rheumatoid factor, help us confirm that.Then, we initiate treatment, which, because of the immune nature, the inflammatory nature of rheumatoid arthritis, our drugs are basically all some form of an immunomodulatory agent that we try and knock back the immune system so it stops damaging the joints. And typically, once somebody gets their first swollen joint and rheumatoid arthritis, that disease for them is forever, i.e, they’ll be on some immune drug to modulate that for the rest of their lives. Now, whether that’s one drug or two or three kind of depends on the course that they’ll take, but once we get the diagnosis, immune modulation typically for life, to help knock back that inflammation, which is very important, and we do a pretty good job in most people with rheumatoid arthritis now, in dampening down the inflammation and keeping them functional and happy and not destroying their joints.But we’d argue that about half the people who get RA never feel as good as they did before they got rheumatoid arthritis, and certainly meds and all the visits you gotta do to manage disease is painful for people, so that’s why… another reason why rheumatoid arthritis has been something we’ve put at the forefront for prediction and prevention. One of the keys, also, for rheumatoid arthritis, it does have good blood tests. I think I mentioned this earlier. CCP test that is highly accurate for rheumatoid arthritis, to put some numbers on that, it’s about 95-98% specific for rheumatoid arthritis, so if you have arthritis and that blood test, we’re very confident that you have rheumatoid arthritis.That test has also given us insights, because it typically shows up in the blood three to five years before you actually get your first swollen joint. We can then use that to predict fairly accurately who’s going to get disease in the future. And I’ll stop there.Robert Rogers: No, no, that’s great, and there’s a lot of really interesting things that I want to follow up on. Since you started talking about having a good blood test, then that’s going to just be an absolutely essential prerequisite for any kind of, you know, screening or early prevention program in autoimmune disease. So tell us, so the anti-CCP is very helpful. It’s very specific for rheumatoid arthritis. How sensitive is it?Kevin Deane: So, that’s a good question. We guess it’s about 80% sensitive, so of 100 people with rheumatoid arthritis, about 80 will be positive for the anti-CCP test. In the old days, i.e. a few years back we actuallyclassified rheumatoid arthritis as two subtypes. One is what we call seropositive, where they have an autoantibody, and the other group is seronegative. The field is moving towards we’re actually probably going to break RA into subsets. And that there’s maybe more than we want to delve into here. But of the subset that’s seropositive, i.e. there’s a blood test positive, like the CCP, that’s the one that’s particularly prime for early identification and even prediction for the future, and also prevention. The subset of rheumatoid arthritis where there’s no blood markers makes it more challenging to predict who’s going to get it in the future. And that actually informs a lot of autoimmune diseases. Lots of autoimmune diseases, some of them have really good blood tests that are… I think those are the key ones that the field is working towards as the first in line to get prevention. That’s why type 1 diabetes is advanced, because they have very accurate blood tests, and I think they have data, like, if you’re under the age of 25 and you have two blood markers for type 1 diabetes, I think the risk of it is about 100% that that person will get type 1 diabetes within 10 years. That’s very powerful.Robert Rogers: So it’s fair to say… it’s fair to say that among autoimmune diseases, the anti-CCP blood test for RA kind of ranks it at the top of the list, because it’s… it’s quite sensitive, it’s very specific, and like you said, it appears… it can often appear long before symptom onset, which creates this window of opportunity. And so we’ll get into all of that in just a second, but I wanted to come back to this really interesting thing that you mentioned, which is… which gets to the logic of prevention and early intervention in RA. So you said that, you know, most patients will actually respond reasonably well to the immunomodulatory treatments that exist today, but about half of people will never feel as good as they did before they were ever diagnosed. Is that right? And so it sounds to me, and I want to make sure that we sort of spell out, really, what the logic of prevention here, it sounds like prevention could really have sort of two goals, and these aren’t necessarily distinct, they’re somewhat overlapping, but one is this idea that you know, if you could kind of hit the disease earlier and harder, you might, ameliorate the severity of it, so that person who, you know, was maybe destined to have disease that was really hard to control, that left them very symptomatic, well, maybe if you started a treatment earlier, their symptoms would be lower. But even perhaps more powerfully than that, is there also this idea that during maybe a distinct window of opportunity, if you hit the disease in a certain way, you could actually, prevent them from having it going forward. Are those both goals of prevention?Kevin Deane: Those are both goals. That second one you mentioned is… we call that the shoot-the-moon idea, where if you could catch somebody at that right time in the disease development, before they ever even felt sick, you could give them an intervention, like a time-limited intervention, like, here’s a few doses, or maybe 6 months of treatment, and reset their immune system so they would never develop that autoimmune disease in the future. That’s the goal. I think should strive for that. But the second point you also mentioned is also very important. What if we could just catch the disease early enough that there was no joint damage, and you could control it very easily, even if you had to take medicine for the rest of your life, but you didn’t ever have bad disease? That would still be a victory. So both of those are goals in prevention.Robert Rogers: Yeah, and you’ve, of course, been very involved in actually trying to develop strategies to achieve those goals, and I want to delve into that in just a minute, but you mentioned kind of what the general average person’s risk is of autoimmune disease in general, and rheumatoid arthritis in particular, but maybe just walk us through what are some of the environmental or genetic or other risk factors that place someone at increased risk?Kevin Deane: Yeah, I’ll try and speak broadly to autoimmune disease. I’ll then focus on rheumatoid arthritis. Yeah. So there’s a lot of different genes that are associated with getting autoimmune diseases. Turns out that there’s a couple of genes that put people at risk for lots of autoimmune diseases, and then within that, there’s a few genes that are specifically related to autoimmune diseases.The challenge with genes are there’s not one or two or even a set of genes that are strongly predictive, so we haven’t yet been able to use genetic testing alone to predict future risk for rheumatoid arthritis. Some of the closest things we get at in clinical care is if you have a family member who’s a first-degree relative, i.e. a mom, or a dad, or a sibling, or an offspring with an autoimmune disease, your personal risk can go up. But even then, the risks aren’t that high. So, for example, in rheumatoid arthritis, if you don’t know anybody in your family has rheumatoid arthritis, your lifetime risk is about a half to 1%.If you have a family member with rheumatoid arthritis, then your risk may go up to 5-7% in a lifetime, which is increased, but not that strong. So I think we need to look beyond just genes. Then we look at other things, like environment. So, of the the environmental factors, one of the strongest risks for any autoimmune disease is actually exposure to tobacco, and in the form of cigarette smoke. We think that the reasons for that is that insult to the body from cigarette smoke is what can trigger the autoimmune system, and actually drive lots of different types of autoimmune diseases. There’s a bunch of other things, too, that we’re learning more about as we go. Dietary components, other environmental exposures, like exposure to dust, can put people at risk for certain autoimmune diseases. We’re learning now that exposure to forest fire smoke, which the west coast of America now, maybe other parts too, are being exposed to, actually put people at risk for developing disease like rheumatoid arthritis, so combination of genes and environment really drive that forward. We’re trying to understand that better, so ultimately, we could get at what we think is what we call primordial prevention, where you eliminate environmental risks to get rid of disease. I think that’s going to be a ways in the future. So now, what we really do look at is biomarkers, where whatever set of genes you have, whatever environmental factors you have, if you start developing these biomarkers that means that you’ve really progressed down the pathway towards getting an autoimmune disease. That’s working pretty well now for rheumatoid arthritis, as we’ve mentioned, type 1 diabetes. Other diseases are coming around to this as well. They’ve got a good blood test, we’re starting to look at it for prediction and prevention. Things like lupus, which has great blood tests as well, another autoimmune disease called scleroderma. People are working in advancing that. So, a lot of things are coming along. To use blood-based biomarkers, not necessarily genetics, to predict future disease.Robert Rogers: Great, and just at the level of what might be actionable for an individual patient, mentioning both environmental and genetic risk factors, so, you know, avoiding smoking, and then you also mentioned things like avoiding forest fire smoke, but a lot of those things really require, sort of, environmental or public policy at a large scale. Are there any other specific lifestyle recommendations that are actually advisable for a patient to prevent, to lower the risk of autoimmune disease?Kevin Deane: Yeah, I left that out. So, it’s also becoming apparent for a variety of autoimmune diseases that diet and obesity and lack of exercise, those three things, diet, obesity, lack of exercise, are actually strong contributors to dysregulated immune system or autoimmunity. A few diseases are perhaps more related to that. Rheumatoid arthritis, obesity is one of the strongest lifestyle risk factors one can have for getting rheumatoid arthritis. Other autoimmune diseases, including psoriasis and psoriatic arthritis, also obesity is a big driver, so that’s a… that’s a big driver.The recommendation there, then, is to maintain a healthy body weight. So far, no one’s proven a specific diet in particular for autoimmune diseases. However, general information and population-based studies suggest that a Mediterranean-type diet, which is whole grains, fruits and vegetables, minimal meats, minimal fats, and if you want to use a fat, don’t use butter, use olive oil. Mediterranean diet is thought to help reduce risk for autoimmune diseases. And daily exercise is beneficial across the board for a lot of conditions, but also may reduce risk for autoimmune disease.Robert Rogers: Very good. And then on the genetics front, you know, as you mentioned, at a sort of interesting research or population level, we can identify, patients who are at a relatively increased risk for autoimmune disease, but the problem is that as a practical matter, for instance, telling somebody that their general risk of something goes from 1% to 5% to 7% may not be all that useful. But I’m curious, just if you’ve given this some thought, you know, we do have people who are healthy adults who are considering getting whole genome or whole exome sequencing, just to learn about their disease risk across a variety of diseases, and do you think that there’d be utility to learning about their polygenic risk for autoimmune disease, or do you think that could cause more anxiety than is actually useful, or, like many things, really apply a case-by-case basis?Kevin Deane: Yeah, I think at a high level, for most autoimmune diseases now, the broad genetic testing for risk is not right where it needs to be for this to be actionable for all people. That said, there’s a few certain genes that are at higher risk for things like type 1 diabetes, but as a general whole for autoimmune diseases, I think the genetic testing isn’t at the level it needs to be. Now, that may be changed soon, we may have different breakthroughs. But I’ll give you an example, at least for rheumatoid arthritis. The strongest risk factor, genetic risk factor, for rheumatoid arthritis is something called the shared epitope, which is, I won’t go into huge detail, but a marker on chromosome 6 that creates a certain risk. That risk factor is present in about 30-50% of the population, yet only 1% of the population or less get rheumatoid arthritis, speaking to the fact that that gene may show up on a screen as being a risk factor for rheumatoid arthritis, but very few of those people will actually go on to get rheumatoid arthritis. So it’s not quite there yet. Now, if we get better at this and understand what’s the gene, and then what’s the environmental interaction and be able to put that into more actionable prediction, that’ll be something, but we aren’t… we aren’t quite there yet.Robert Rogers: Great. So, that’s a very helpful answer, and so I’m curious, as we now kind of get into the meat and potatoes of prevention here, how much damage to joints and other organs can typically accrue before a patient will actually present clinically with symptoms? And what do we know about, sort of, how long that preclinical phase of RA disease lasts?Kevin Deane: In general from blood bank studies where we’ve been able to actually find people who develop rheumatoid arthritis and go back in time for blood they might have had fortuitously collected and stored before they got diagnosis, we think, on average, the immune markers appear in the blood for rheumatoid arthritis, this is including that CCP test, on average 3 to 5 years before they get their first swollen joint. Now, that’s a range then, right? So people can have these markers for up to 10 years or longer before they get rheumatoid arthritis. Some people have a very rapid course where their biomarkers may be abnormal, their CCP may be abnormal, and they get arthritis within a few months. But the range is 3 to 5 years.The challenge is, is that there’s not probably initially any joint involvement in rheumatoid arthritis. We think that those antibodies and that autoimmunity is being triggered somewhere else in the body. There’s growing insights into that might be in the lung, that might be in the gut, it might be in the cervical vaginal tract in some individuals, maybe the gums and others. So it’s not an arthritic condition at first, but the autoimmunity gets developed, circulates in the body, and then ultimately then targets the joints. Once that joint gets targeted, this is pretty variable, at least in rheumatoid arthritis. You can have some individuals who have explosive onset of disease, where they’ll go from basically no joint symptoms to multiple joints are painful and swollen, and they’re having a difficult time doing daily activities within a week or two of the onset of disease. Some people may have a much slower course, where they have one joint that flares up, and then it settles down, and then another one flares up, and they slowly accumulate. So the range is pretty wide.The other challenge, though, is any kind of joint inflammation can start to damage the joint. And that’s why we’re ultimately going to try and develop ways that we can find people before those joint symptoms even first start, because even once the joint symptom starts, even if it’s mild, damage can occur. And then over time, even if you shut that inflammation off, if that small bit of damage has occurred that can then progress and become disabling for a person down the road, even though the original disease process is shut down.Robert Rogers: Do we have data that suggests that, if you start treatment with our current therapies at an earlier point in the disease, that the chance of success is actually higher, or the chance of getting control of disease and having minimal amounts of symptoms is actually higher? I imagine that’s a very hard thing to study, because, you know, people come in when they come in, and we don’t let them say, well, let’s… you wait a while before we start treatment, so it has to be mostly observational data. But from the observational data that exists, what do we know about that?Kevin Deane: Yeah, so we do know that the earlier you catch rheumatoid arthritis, once it’s crossed that threshold to being what we’re going to call full-blown disease where you have inflammation, the earlier you catch it and start treatment, the better those people do, and the lessmedicine they need, ultimately, to control disease. So, at the very least, the field needs to find people in an earlier stage of active disease and get treatment started then. We think of it, it’s probably akin to, like, a fire. You have a match that’s lit, let’s say that’s a little bit of inflammation. You can have a campfire that’s a bit more inflammation, and you can have a full-blown forest fire. It’s much easier to control a match being lit. You can pinch that with your fingers and shut it off. Harder to put out a campfire, and almost impossible to put out some big forest fires. So it’s the same thing for rheumatoid arthritis. Catch it early, it’s easier to treat, easier to shut it down, and there’s less damage. So that’s… at the very least, we can catch itat an early stage, that’s gonna be beneficial for the people.Robert Rogers: And that really adds to how compelling the logic is of prevention, because that we already know that if we treat at an earlier point in the course of symptomatic disease, that we have a higher chance of success. It makes sense that if you could extend that back in time, you might have even greater success.Kevin Deane: Yeah, and you mentioned that term, it’s a great term, window of opportunity, which can mean different things, but in rheumatoid arthritis and other autoimmune disease, we think that there’s a window of opportunity even before any damage occurs, where the immune system has become dysregulated, and that’s the time to strike, to helpfully stop it from ever damaging an organ, or even hit the reset, those two branches of what we think would be success and prevention that we talked about earlier.Robert Rogers: And I think that’s a great segue into something that I really want to go a little bit deep with you on, which is the trial that you led, the STOP-RA trial, to really inform what we know in that area. So tell us about that. Tell us about the trial, its rationale, its design, and all its details, because we’re actually quite curious.Kevin Deane: Yeah, so I’ll build on some of the things we’ve talked about already. So, we know that blood markers for rheumatoid arthritis can appear, on average 3 to 5 years before a person gets their first swollen joint. In particular, the anti-CCP antibody is quite accurate for rheumatoid arthritis. I’ll give you some harder numbers for that. If somebody has an elevation of a blood marker for anti-CCP in general, that person has a 30-50% chance of developing rheumatoid arthritis within 3 to 5 years. So we use the CCP test as the anchor inclusion factor, or identification factor, for our study. To put people in the trial. So the requirements were you had to have an anti-CCP test elevated in the blood.We picked a higher level than just your average positive test, because we wanted to make sure that we weren’t getting any false positives in there, so we picked a level that was 2 times the normal cutoff. I won’t go into great details there. And you could not have any evidence of joint inflammation to get into our study. We picked the drug to intervene of hydroxychloroquine, also known as Plaquenil. The rationale behind that was rheumatologists were already using that drug in people who had low-grade autoimmunity, thinking, the drug is pretty safe, and we think it may be effective. So people were already doing it, but we had no data, so we said, let’s use that. Plus, it’s a pill that’s relatively safe. It does have some side effects. Long-term use can cause some eye toxicity. Every once in a while, there’s an allergic reaction, but it’s relatively safe. So we said, let’s take people who are at risk for rheumatoid arthritis and give them this drug that’s a pill, pretty easy to take, usually pretty well tolerated, that should have some immunomodulatory effect.Hopefully that’s going to be enough in this early stage of RA development to alter the course of disease. Turns out that, in our study where we enrolled about 142 people, randomized half of them to get hydroxychloroquine, half a placebo, gave them drug for a year, and then stopped the drug, and then followed them for 2 years after that, and I’ll get back to that point in just a second. Drug didn’t work at all to either make them feel better while they were taking it, so if they happen to have aches and pains, it didn’t help, and it didn’t delay the onset of rheumatoid arthritis at all.I’ll get back to that study design. We gave the drug for a year and followed up for 2 years after that, to that point I talked about earlier, it was a shoot-the-moon hypothesis. We thought if we can catch these people at this early stage of RA before they actually get joints inflammation, wouldn’t it be great if a short-term use of a drug could actually reset their immune system? Turns out it didn’t work in this study, and we can talk about this in the next few minutes. Other studies have also taken that approach for RA prevention. They also have not seen a complete reset of the immune system, but that was sort of the philosophy behind that, the whole, what we were calling the Stop-RA study.Robert Rogers: Right, so it’s a really powerful and beautifully done study, and it’s really informed so much data in this field, and like you said, you really were able to identify these patients who were at high risk. Your hypothesis that the criteria you used to identify patients that were at high risk of developing RA proved to be true, right? Because in both arms of this trial, many of these patients did go on, so that’s a very powerful finding, but the particular intervention that was tested, which is a relatively benign intervention, the medication is well-tolerated and widely used, didn’t really move the needle. So tell us a little bit more about maybe some of the other similar interventions that have been trialed in that particular window of opportunity, how those results may have been similar or different to what you found in the Stop-RA trial?Kevin Deane: Most of the studies that have been done for prevention of rheumatoid arthritis have used that anti-CCP test as the anchor risk marker. And as you said, what we did prove in the Stop-RA study is that that marker is associated with about 30-40% of people developing rheumatoid arthritis within 3 years, so it proved we can predict RA. The drug didn’t work. Other studies have used different drugs. The two studies that use the same drug that is most successful were called the ARIAA, and then the next one is called the APIPPRA study. The ARIAA study is done in Germany, APIPPRA study largely done in the United Kingdom. They use the drug Abatacept, which is a biologic or injectable therapy that targets B and T cell and interactions and T cell, and specifically T cell activation, which was thought to be a key player in the development of autoimmunity, especially at this early stage. It’s a drug that’s been commonly used if you have full-blown rheumatoid arthritis. We thought, let’s just move it earlier into this window of opportunity.So, same study designs in both of these studies, I won’t go into huge detail there. The drug was given for a period of time, either 6 or 12 months, depending on the study, and then stopped. People were followed afterwards. This drug worked extremely well while people were taking the drug in the study, the rates of development of rheumatoid arthritis were exceedingly low. Fantastic effect on drug. However, when they stopped drug, they accelerated, and the people who stopped the drug then started getting rheumatoid arthritis.They still made their primary endpoint, so at the end of the studies, less people had developed rheumatoid arthritis who had been on the study drug than were off of it, but they sort of lost effect after 3 to 4 years afterwards. So it wasn’t a complete reset, but it did demonstrate the right drug at the right time can really develop significant decreased rates of rheumatoid arthritis. That’s informing the field going forward. We may wind up, to prevent RA, just starting treatment earlier, before anybody ever gets their first swollen joint. And that would still be, as we talked about earlier, a victory, because if they never developed that first swollen joint, even though they’re taking drugs, that could still be beneficial.Robert Rogers: Wow, that’s really interesting. So, it sounds like, you know, there is this… this real hope, this real aspiration that you identify these patients who are at really high risk of developing rheumatoid arthritis, you know who they are, you can identify them, you intervene with these different immunomodulatory agents for a time-limited period of time, and then that will have lasting benefits, and the benefits will be durable, and that you might be able to achieve this reset. And that really, unfortunately, hasn’t yet panned out with our existing agents, but the hope still very much remains, based on the abatacept data and perhaps these other clues, that if you just start the treatment earlier and continue it, you could really reduce the, you know, the onset of actual clinically apparent disease and the severity of the symptoms. And so then I guess, it becomes somewhat of a, of a, of a risk-benefit trade-off of, you know, how many, patients are you going to be treating with these agents who perhaps may not have needed it, and not deriving the benefit from it, versus all those patients who… for whom you are greatly controlling their symptoms. Is that the right way to think about the trade-off?Kevin Deane: Yeah, it’s exactly right, and the field is doing exactly what you just said. We’re looking back at this trial data to find, of all the people that were in the trial, who is really most likely to get rheumatoid arthritis? Because those are the people, you’re exactly right, you feel better about the risk-benefit. These people really do need a drug because they’re really gonna progress to disease. That’s underway now. I think lots of diseases actually have that challenge, right? I think I just heard a talk on cardiology where, if I can use the term, the number needed to treat, i.e. the number of people you need to give some kind of intervention to, to prevent one person from developing that disease or that endpoint, I think it’s, like, around 40 to 60 for, like, using cholesterol-lowering medicines to prevent one heart attack. That’s a lot of people being treated to see one person benefit. We’re trying to get those same numbers together for rheumatoid arthritis.Some of the early calculations from the APIPPRA study showed the number needed to treat was 6 people to have one person have a delay of onset of rheumatoid arthritis by about 2 years. That needs to be validated, but that kind… those kinds of things are what the field is going to have to look at going forward.Robert Rogers: Right, and so then, of course, to just carry that idea a little bit further, the logic of prevention here is really dependent on a couple of things. One is how tolerable and what the side effect profile is of the drugs that you’re going to use, especially over a long period of time, but also how likely an individual patient is to have really severe disease. Like you said, a lot of patients, you know,they are well controlled on our first-line agents. And so, I just wanted to take one step back. We talked about this ability to predict, based on sensitive blood tests, which patients will have onset of RA, or onset of other autoimmune diseases, to any extent. But if a patient comes to you for the first time, where is the current state of research in defining who’s gonna have a more severe course going forward, and who’s gonna have a less severe course going forward? How good are we at sort of being able to define that risk right now?Kevin Deane: Yeah, that’s a good question. We’re fairly good at a lot of autoimmune diseases when somebody comes in the door and has full-blown disease, engaging how bad that’s gonna be. In rheumatoid arthritis, combinations of things, number of joints involved, levels of autoantibodies, so it… actually, the levels do matter, like, the higher your CCP, the more likely you are to have persistent and severe disease.Other markers of inflammation, such as just general blood inflammatory markers, something we call the C-reactive protein or erythrocyte sedimentation rate. All those things can be factored in to say, you not only have disease, this is going to be a bad form of disease, and so we should be likely more aggressive going forward. Those are factoring in.Fortunately, those same kind of things are actually also predictive of who’s going to get rheumatoid arthritis in the future if you catch them in the asymptomatic or before the onset of disease. The models, though, that we’re working on are trying to make that really actionable. Because right now, it’s hard in medicine across the board when you start testing multiple blood tests to have all that come down to one easy answer for a person who’s at risk for disease or has a disease themselves to say. You have all these tests, and they tell me that you’re 50% likely to have bad disease, or get disease. So I think the near future is trying to use AI and other approaches to be able to let us use a lot of different blood tests and other factors to give really accurate prediction and prevention for specific individuals.Robert Rogers: How do patients react to learning that they have positive blood tests or autoantibodies that place them at high risk of developing RA if they’re not currently symptomatic? I’m curious what you observe to be the different spectrum of reactions there.Kevin Deane: There’s a lot of variability, and we’re… it’s not my area of expertise, but having talked to a lot of people who are at risk for rheumatoid arthritis, we get to see this a lot, ranging from they’re not worried at all, versus very scared and very worried. Some of it is dependent on their prior knowledge of rheumatoid arthritis. You can envision, if you’re a young female whose mom had severe rheumatoid arthritis, and you saw her be disabled from that disease, and you find out you have that blood marker for rheumatoid arthritis yourself, that’s very different than a person on the street who’s never known anybody with rheumatoid arthritis, and that their blood test is elevated. So it’s a wide range. I think the field is also trying to now understand that, how we incorporate a person’s personal perception of their risk, and their perception about what they would want to do with that risk, and how much they want to know into the whole approach. Again, not my area of expertise, but we think about this a lot. Lots of people now know that they’re gonna get their cholesterol checked at a routine doctor’s visit that’s part of their cardiovascular disease risk prevention, and are sort of aware of that. Less people know about autoimmune diseases, and the autoimmune disease testing can be a little bit more esoteric. And so trying to incorporate what people have learned in other diseases like cardiovascular disease prevention, putting that into autoimmune disease, I think is going to be critical. And having people who really think about how we message risk for autoimmune disease, it’s gonna be important.Robert Rogers: Yeah, one of my major theses in this whole project of Foresight Medicine focused on the future of preventive and proactive care is that population-level guidance is really a little bit less useful, I think, nowadays than a really individualized risk-benefit assessment, and a big part of that goes into an individualized assessment of what a patient’s desire for proactivity is, and like you said, all these important background factors about their own personal experience and knowledge really have to be taken into account.So I’m curious, you know, you have thought about this fascinating field of prevention, interception of autoimmune diseases very deeply for a while. If there was going to be one major development in any of the areas that touch on this domain, could be diagnostics, could be therapeutics, could be kind of systems-level changes of how we take care of patients, what do you think would most move the ball down the field towards this goal of having really effective RA prevention?Kevin Deane: Gosh, limited to one thing. I…Robert Rogers: No, you don’t have to be limited to one thing. You can give a list in each category.Kevin Deane: Yeah, good, part of the challenge, there’s a chicken and the egg problem. To study an autoimmune disease, or any disease, to identify who’s at risk for getting it in the future, you have to test a lot of people, follow them, and see what happens to them, without knowing yet what to do to prevent disease. And so then that puts you in a pickle where you know somebody’s at risk for disease, you can’t give them anything that’s approved by FDA or some other regulatory agency to prevent it, then you just have to follow them. So what I would like to say is we would love to see a breakthrough soon in rheumatoid arthritis, where there’s going to be a prevention that actually works, that we can give in a sustainable way. So we have a goal, then. Aha, here’s a drug that actually works, then we can continue to study that and try and do even better in the future. So we need an agent or an intervention that works, and we’ve proven it to be so, and have regulatory bodies approve that.The other side of that, we also need broad population testing for people who are actually at risk, because those people are going to be able to, if I can use the term, feed the studies that are going to actually get us the answers to finding that drug, or whatever intervention that may be that works. I’ll use an example, type 1 diabetes. They sort of had to do this chicken and the egg thing for years. They had to test a lot of kids with autoantibodies to understand exactly how type 1 diabetes develops, and then had to do, I want to say, more than 10 trials before they finally found a drug that actually worked. And that whole pipeline had to get moving to the point where they now have an approved drug. So to get better soundbites for that, we need an intervention that works, and then we need to have broad population testing to find people at risk. In between that, if we can do the broad population testing that is refined enough that we minimize false positives and really identify those people truly at risk for going on disease, that’s the third thing that we need. I would say right now, even the anti-CCP test is pretty good, because anybody who’s positive for that test. Let me rephrase that. Of people who are positive, 30 to 50% will go on to get rheumatoid arthritis within 3 to 5 years. That’s a very strong predictive marker, and maybe enough to drive certain studies, but if we can even improve that better, I think that would be… that would be more… more beneficial to the field.Robert Rogers: Absolutely. Is there anyone for whom, as we sit here today, in May of 2026, you would recommend getting a screening blood test for RA or other autoimmune diseases, if they currently have no symptoms?Kevin Deane: So, you added a good point at the end there, currently no symptoms. So, this is, again, at the research stage, so this is not yet a public health approved approach. I would say if you have a family member with rheumatoid arthritis, those are the people who should consider having a risk assessment about their personal risk. And that can include testing for the anti-CCP antibody. If that’s negative and it looks like you may not be at high risk, that can be comforting, so I think that can be reassuring to that person. Still not perfect, we don’t have the data to support this. We don’t quite know, like, if you’re negative once at the age of 30, say, for these markers for RA, does that mean your lifetime risk then goes down to zero? We don’t know that. But I think people who have a family member of disease, those are the ones that are the highest risk for disease.Certainly, though, other people who are starting to develop signs and symptoms of autoimmune disease and rheumatoid arthritis, I’ll speak to that, that would be symptoms of aches and pains in their joints, I think they should have a conversation with their primary care provider about that, what their risk may be. There’s a lot of other things that can cause those symptoms, so that has to be done carefully, but if you’re starting to have symptoms, at the very least, if we catch you early, that’s where we have benefit. We’ll have to stay tuned for more public health-based approaches where we can actually start screening people.Robert Rogers: So would it be fair to say that if you fall into that bucket of, you know, having a family member, a close to first-degree relative who has RA, you could consider getting this blood test if you’re asymptomatic. If you’re having things that kind of are a little bit suspicious for the disease, then, you know, go ahead and get tested. But if you’re just the average person out there who falls into neither of these two categories, having kind of a widespread screening program like we do for, say, certain cancers is premature at this point, and it’s not something you would advise, but it’s something that we’re… you and others are studying really hard, so that maybe one day we’ll get there. Is that fair...?Kevin Deane: Yes, that’s exactly right. To get us to the point where we actually understand how to implement in public health care, there’s ongoing research projects, at least around rheumatoid arthritis and other autoimmune diseases that are also doing this as well. But I’m most familiar with the rheumatoid arthritis aspects. So we have at the University of Colorado Center we call the Autoimmune Disease Prevention Center. Within that, we have something that we call Stop-RA National. Stop-RA was the name of our prevention study that we did before, now we added National onto that. This is now a project where you can come and sign up under research now. Get your own blood tested for the anti-CCP, and we explain all that to you, what that means for your health. It’s not just through general healthcare, it’s through research, but people can participate if they’re interested in assessing their own risk of rheumatoid arthritis, and we can… we can walk somebody through that whole process. So, Autoimmune Disease Prevention Center at the University of Colorado, underneath that is the Stop-RA National Study. And that you can participate in understanding your personal risk for rheumatoid arthritis.Robert Rogers: Great, that’s really… that is a great use of this podcast to promote the wonderful research that’s being done at the forefront of preventive care, and I really hope that people, if they find this content and use that as a springboard to engaging with your research center, that would be great.Maybe one last question here. We’ve sort of mentioned this notion a few times, but maybe I would just like to develop it a little bit more, this idea of resetting the immune system. And so, I think that this notion has perhaps gained more credibility in the last few years, but generally, I think, in the context of very severe autoimmune disease that’s very well established. And the reason I say that is because there’s, you know, been patients who have, for example, I think the most well-known example is the systemic autoimmune disease lupus. Really, really bad cases of lupus. They have gone through all of the normal immunomodulatory therapies, and their disease is still raging out of control. And then there was this really brilliant idea to use these very advanced technologies, specifically cellular therapies, to basically wipe out all of their B cells, the arm of the immune system that produces antibodies and is responsible for a lot of autoimmune diseases, and lupus in particular, and this… that technology of wiping out our B cells with with what’s called CAR T-cells, really comes from the world of oncology, where a lot of the hematologic malignancies are of the B cell lineage, and so it was a great breakthrough 10 or 15 years ago when we figured out that you could treat those leukemias and lymphomas with this therapy, and the same idea has been applied now to a much smaller number of patients, but with very promising reports in some cases to patients with autoimmune diseases.And then it’s quite remarkable that, you know, in some of these cases, the patients have been able to come off of their other immunomodulatory drugs, and of course, we don’t have years and years of data here, but at least for several months or years, it looks like when they start to bring back their B cells or reconstitute their immune system, they are not producing those things that attack their organs in the same way, and so their immune system has truly been reset. And so, I guess, I’d love to hear your comments on that, but in the context of prevention, in the context of bringing advanced therapies forward earlier and earlier in the course of disease, do you think that we’re going to have to have very different modalities from that to be able to use at the interception and prevention stage? Is that just too extreme in terms of its expense and side effects profile, that you could bring it into the, into the early disease setting, or not?Kevin Deane: Great, I’m glad you brought that up. This has been groundbreaking for the field of autoimmunity, and as you mentioned, especially in severe disease, where we can basically reset the immune system with these very powerful therapies. I think this has given us great insights that you actually can, in some cases, reset the immune system, even long into disease, with very severe disease. We are looking carefully at now how you might carefully use that earlier and earlier in the period. Currently, the risks of some of these therapies are probably too great to implement in someone who feels well, even if they may have a high risk for developing an autoimmune disease in the future, but the concepts are there. I think as we get better at these cellular therapies and these reset interventions, I think we’re going to really look hard at giving this to people earlier in their disease process.We’ve actually had some people who are at risk for future rheumatoid arthritis actually come to us and say, hey, is this something I could do? Because it’s very appealing to have a one-and-done, shoot-the-moon approach where you could reset the immune system. And if this is how we do it, and we do this safely, I think this is the way of the future. I just look forward to working further and making sure this is refined. We know exactly the right people to do this in and can do this in the safest possible way.Robert Rogers: Dr. Kevin Deane, thank you so much for your time today on Foresight Medicine. We have learned a lot, and I’m really excited to follow the future developments in the field of prevention of autoimmune disease that you’ll be leading.Kevin Deane: Very good, thanks for, having me on. Thank you. Get full access to Foresight Medicine at foresightmedicine.substack.com/subscribe