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Hi. This is Andrea Fava coming at you for RheumNow here at ACR in Washington DC. And I wanted to talk about what I think is a fibroblast renaissance. In the last few years, this cell type that we kind of ignore for the last for the many years is coming in everywhere. We are discovering its role in multiple autoimmune diseases and also discovering new roles because we think that yes, it's a cell that makes collagen and drives fibrosis but there may be more than that.

And the first abstract I want to comment on is an abstract presented yesterday at plenary one by Angela Zhu from the Brigham and they did a fascinating study, in fact it was a plenary and studying the fibroblast cells in the synovium of rheumatoid arthritis. A couple of years ago, our group, as part of the Accelerated Medicines Partnership, found that there's a group of rheumatoid arthritis patients refractory to treatment that actually have fibroblasts that are inflammatory and then can drive disease. But now they try to understand more about this and what they found through a very elegant system is that if you have an inflammatory fibroblast that can be driven to become an invasive fibroblast that then can cause damage and affect the cartilage. And this is like fascinating because they were able to identify the transcription factors that drive this transition and perhaps that can drive the design of new treatments. The other abstract I want to highlight was presented today by Jasmine Sweater from NYU and that's about lupus.

And they have presented last year, and the paper is in preparation, a study focused on class two lupus nephritis, which is the underdog of lupus nephritis. Milder, sometimes we don't pay enough attention to it, but it's the very early stage of disease. And what they found by using single cell RNA sequencing of the kidney is that myofibroblasts actually are incredibly increased in these patients as compared to all other classes. And so now they studied the urine of these patients and they found that actually there is a strong signature of fibroblast activation in these patients confirming the signature in the kidney. Bringing our attention to the fact that these important cells is also implicated in lupus nephritis.

So with this renaissance of information hopefully we're going to have treatment that can treat the inflammation driven by fibroblast and perhaps even prevent fibrosis and with that chronic damage. And for more information you can go on RheumNow on the website. Thank you and bye bye. Hi, this is Andrea Fava from ACR in Washington DC coming to you for RheumNow and I'm going to talk to one of the topics that I care the most about and that is lupus nephritis and its diagnostic challenges. So lupus nephritis, bad manifestation of lupus, it can lead people to kidney failure needing dialysis and the problem is that we have to rely on protein in the urine for diagnosis because most patients are completely asymptomatic.

We screen for protein, we get kidney biopsies and then we treat based on it and then to figure out if a patient is responding to treatment we monitor proteinuria over time. But that comes with the problem. The proteinuria, so protein in the urine, does not reflect the inflammation in the kidney. And what do we do? We treat kidney inflammation with anti inflammatory and immunosuppressant and the data are telling us that if we follow protein we are going to be fooled because when you repeat a kidney biopsy you can see that patients with no protein in the urine can still have histological activity and patients with histological activity in the kidney can still have proteinuria above 500.

And so we are being fooled. And so for the last many years, we've been working on a better way and this better way, I believe, are non invasive biomarkers. And we focused on urine because urine collects the byproducts of kidney inflammation and you can collect it super non invasively. And the abstract presented this morning in the plenary too was about developing panel that was made out of 12 protein that could be clinically useful. We don't want a biomarker that can be just as good as proteinuria.

We have that. We want something that can tell us something more. And in this situation this biomarker was trained starting from 1,200 proteins to identify which patients, who are the patients who have an activity index in the kidney in terms of histological inflammation greater than two because that's clinically meaningful. And this biomarker outperformed expectation. We found that, with this 12 protein we could accurately predict who had active histological histologically active lupus nephritis with what we called an area under the curve of more than 90% which is about 90% accurate.

And this is fantastic because we could monitor that over time. We could see that a decline of the score telling us that the patient is having a resolution of inflammation in the kidney as early as three months predicted clinical response at one year. But even more exciting is that in patients who at one year of treatment still had persistent elevation of the score telling us that there was persistent inflammation in the kidney, these patients were more likely to develop kidney function loss in the next five, seven years which is what we care about. And this bit of information was adding to proteinuria by showing that it outperformed proteinuria by combining it which is telling us that is giving us a piece of information that we couldn't get through proteinuria and is clinically useful and that could be used to aid diagnosis non invasively. It could help us monitoring treatment response, change treatment and guide treatment and perhaps even become the new treatment outcome.

So in collaboration with commercial entity, Exagen, this biomarker is being developed into something that physicians can finally be able to order and so hopefully in the next couple of years this will be available to everybody. If you want to learn more about it, please go on roomnow.com. Thank you.

Hi. This is Eric Dine live from ACR Convergence day two. One of the sessions from this morning that is available on demand for anyone that has missed it was a great session on ACR advocacy and I'm joined by two of the SARs from it. We have, doctor Christina Dellany and doctor Caitlin Britton, who are the the heads of the the governmental affairs committee and and the Rheumpack Committee. Tell me what's what's new.

There was obviously a big election. There was a lot of people that were interested in this talk. What where do we stand in terms of the government that's that's wrapping up and the government that's starting?

Yeah. I think there's a lot of anxiety about the changes that are coming trying to foresee and kinda read the tea leaves of of what's going to happen. And, while that is very important to anticipate the future, we still have to work in the congress that we have right now. So the lame duck session, is still in session and there are about twenty working days left for us to act on some of the priorities that have already been set and have bills that are moving in the house.

And what are the top priorities that ACR sees as what's affecting rheumatologists and what we can get done?

Absolutely. So number one is Medicare reimbursement. So as you're aware there have been cuts to the physician fee schedule every single year and 2024 was no different but there is a bipartisan bill that's in the house right now that we are hoping will go ahead and get through to the finish line and get on president Biden's desk so that he can sign it. And that one actually mitigates some of the cuts that we have seen. The second issue is telehealth.

So telehealth has become critical in the way we practice medicine, and it's on the chopping block. The expansion that was put in during the COVID era is coming to a close 12/31/2024 unless there is action. There is a bill that's moving. It has, both house and senate bills. Again, hoping to get it through the finish line and have president Biden sign that so that we can continue to reimburse for the services that telehealth provides, at least for the next two years.

And then obviously the long term goal on both telehealth and physician reimbursement is to get something in place where we're not having to kick the can down the road every single year and that we have some meaningful long term reform. But right now, are the priorities that actually have a very realistic chance of happening with the right amount of support from our members.

And it's good to know that there's the ACR committees and the staffers that are working on it. If you're a rheumatologist that's watching this, what can be done? What should a rheumatologist know about what they can do to help out?

So I would say go to rheumatology.org and click on the advocacy link and send letters to your legislators. They need to hear that this is important to us and it's already pre templated. It's an easy ask. All it takes is two minutes. And the other would be donating to the room pack.

The pack is the vehicle by which we get that face time to explain the importance of these to the lawmakers and having their understanding of the importance both to us and our patients really really helps advance that policy so we can get them across the finish line in the next twenty working days.

Perfect. So it's all on rheumatology.org?

Absolutely. Rheumatology.org will get you to the PAC website and it will also get you to the advocacy front page. And if you're interested in advocacy efforts and want to stay in touch throughout the sign up for the ACR at work newsletter. It comes to your in basket every two weeks. It has calls to action.

It'll keep you abreast of any legislation that's happening, anything in the regulatory space, and really helps you take good care your patients by knowing the best ways to navigate the system that we're stuck with.

Perfect. Thank you for your time and all the work on this. Stay tuned to RheumNow for more coverage.

Hi, everyone. My name is doctor Trish Harkins reporting for RheumNow from ACR twenty twenty four. Today, have the absolute pleasure of being joined by Professor Barry O'Shea, a consultant rheumatologist and professor at Trinity College Dublin, Ireland. Today we're going to discuss his abstract fourteen forty entitled Significant Factors Identified for Carotid Doppler Use, Ultrasound Use in Axial Spondyloarthritis Patients Without Conventional Cardiovascular Risk Factors. So firstly, thank you so much Professor Hsieh for joining us today.

To begin, I just want to know what the inspiration for your group study?

So thank you very much for giving us the chance. So this work is largely done by my colleague Doctor. Brona Denine. So it's a pleasure to present it on her behalf. So as you are probably well aware, EULAR have told us that we really need to screen for subclinical cardiovascular disease in various forms of inflammatory arthritis axial spondyloarthritis being no different.

So we were interested in trying to figure out exactly what is the role of carotid Dopplers in this. It's not really feasible to be doing carotid Dopplers on an entire cohort. So we felt if we could, examine this in a little bit more detail, we shed some light on it. So we went to our clinic in St. James's Hospital and we took out our axial SPA patients that had no history of cardiovascular disease are significant risks for it.

And then we put them through a carotid Doppler, specifically looking for their carotid intima media thickness to see as pointer towards carotid artery disease. It was a small sort of proof of concept idea. There was only 30 in the entire cohort that we did this, but these were asymptomatic patients with no risks. So they all went off and had their carotid Dopplers and a little over a third. So eleven of the cohort had abnormal carotid intimal media thickness.

So 11 abnormal, 19 normal. So then we examine these in a little bit more detail, looking to see if we could get particular any predictors for, you know, what might guide us towards, identifying these patients earlier. So some were maybe obvious, but it was reassuring that those patients that had higher blood pressure in the cohort that were abnormal versus normal, more abnormal cholesterol and lipid profile were ones that pointed out. And also another useful clinical indication in our clinic is the waist hip ratio. So patients that we would think would be a pointer towards cardiovascular disease and they were the ones that turned out to have normal carotid ultrasound.

We had a couple like anything research, there was a couple of maybe or more unusual findings that we need to examine a little bit further. We thought or we presumed and maybe you shouldn't ever do that. We presumed that the cohort that would turn out to have abnormal carotid Dopplers would have maybe a strong family history, of cardiovascular disease. In fact, was the other way around. It was the normal cohort, that's, where that was identified.

So we need to, examine that. The other bit of a red herring was we presumed maybe would be the cohort with the longer disease duration. But again, that was the other way around. It was the patients with the normal carotid Doppler's that had the longer disease duration. So it was interesting.

Like any good research, think it's shown up, given us some good information, thrown up some more questions that we need to work on.

And did you look at any laboratory parameters like look at inflammation, CRP, ESO, or any kind of VASDI scores or anything like that?

Yeah, so we had CRP on the entire court and again maybe thinking there might be a difference between those with a high inflammatory burden, so high CRP, again there was no difference. We had the various indices that are frequently used to assess these patients, their BasDi questionnaire and probably a better marker of disease activity, the ASDAS. But again, there was no difference. So it doesn't seem to be a feature of disease activity. The other features we looked at obviously frequently we assess a BASFI, so functional index and a metrology index, a BASMI, again maybe thinking that it might reflect longer disease duration, more impaired function.

But there was actually interesting no difference between the BASMI and the BASFI scores in the patients that had normal and abnormal, crawdits on their ultrasound.

And I suppose moving on from that, do you guys have a plan to expand to a larger cohort or what's the future plans for the research?

Yeah, so this was done in our own unit on a sort of a pilot group so to give us a feeling of where we should go with this. We have a national registry in Ireland with a number of different centers that are still actively recruiting. There certainly will be the opportunity to roll it out to bigger cohorts because it'd be nice to bulk up this numbers and see if it's reproducible. Other things we'd like to look at was obviously other indicators or markers for cardiovascular disease. Coronary CTs would be interesting, very interesting effect that can be difficult to get in some institutions.

We may have to come up with some kind of research question and see if we can get some funding for that because it'd be really nice to take this in another modality, not just crawdits, but seeing what their coronary arteries are like.

Absolutely. Well, thank you so much for talking to us today. So guys, that was abstract fourteen forty. And follow us all on RheumNow for further coverage of ACR twenty twenty four.

Hi, I'm Queeland Connolly reporting for RheumNow at ACR. I'm joined today by Julie Pack, who is an associate professor at Johns Hopkins and also director of clinical trials at Johns Hopkins. We're going to discuss her abstract three twenty two evaluating the role of cardiac MRI in myositis. So Julie thank you so much for your time today. Do want to tell us a bit about why you asked this research question?

Yes so thank you so much for having me here. I was really excited to look at this population because patients with myositis we don't really think about the heart and the heart is a muscle and we always want to determine if there is heart inflammation we want to be able to treat it appropriately because it can have severe outcomes like heart failure, arrhythmias and that's something that's a little bit beyond the scope of the skeletal muscle but extremely important in terms of their long term health outcomes.

Great so clearly a very important question so how did you ask that question?

Yes so we got some funding to do

a pilot

prospective study to really screen for myocarditis which is you know heart inflammation in the heart inflammation and we did that by screening with troponin, proBNP so biomarkers that we could test in the blood and then also cardiac MRI and what we found was out of the twenty six patients that we did as a small pilot study we found almost close to thirty percent had myocarditis even if they didn't even have any symptoms which was really surprising to us and really taught us that we cannot forget about the heart because that could truly lead to poor outcomes.

Great so were there any particular patients who seem to be at higher risk or a higher prevalence of myocarditis?

Yeah so we looked at all different types of, myositis patients but it seemed like the patients who had anti coo antibody had a higher risk of more severe outcomes like severe arrhythmias requiring defibrillator placement and heart failure.

And how should this change clinical practice do you think?

I think I think greater awareness is very important because I think in the community we don't think about the heart when we're thinking about someone's skeletal muscle inflammation they're so weak and their CK is really high but you're like oh I got to treat that you're not thinking about the heart I think this first step and the most important thing is to actually make sure we think about it and actually order a blood test to see if there's any heart inflammation and then if that's positive not everybody can get a cardiac MRI but if that's positive then we definitely want to do the next step and more rigorously for heart involvement.

Fantastic and in patients who do have cardiac involvement does that impact your management strategy?

Yeah I think it absolutely does because we were surprised that some patients respond to you know immunosuppression IVIG for their myositis, but then the heart inflammation didn't respond sometimes, in which case we needed to expand and further add other immunosuppressants. So I think it could definitely change management how we approach it.

Fantastic. Well, really important study and congratulations on all your fantastic work. And, really, really enjoyed your, presentations and and talks during this program. So thanks very much, Julie. And if you want any further information, you can go to RheumNow.

Hi. This is Arti Kavanaugh coming to you from the American College of Rheumatology Convergence twenty twenty four in Washington DC for RoomNow. So lots of subjects being covered about lots of diseases, Big interest in psoriatic arthritis, and a very recent interest in psoriatic arthritis has the impact of sex on the disease characteristics and, of course, the response to therapy. There have been a couple of abstracts on that, seventeen oh nine, fourteen seventy one, and there was also a seminar where Leahy Ader, who's the senior author on those other abstracts, was talking about the response to therapy, and Laura Coates was talking about just differences in disease characteristics in psoriatic arthritis patients based on sex. It's an interesting topic.

Among the rheumatic diseases, psoriatic arthritis is one that's about equal in men and women, about fiftyfifty, unlike rheumatoid arthritis, where it's 80 women for 20 men, or ankylosing spondylitis where it's reversed. So I guess for a while we didn't really consider the impact of sex as we do for something like systemic lupus, but it does have a lot of relevance, and it's been a topic that hasn't had a lot of attention paid to it, but it's certainly changing now. If you take baseline characteristics of patients with psoriatic arthritis, for example, in clinical research studies, there are differences that you see in a lot of studies. Women tend to have more pain and assess their global activity and function worse. Men tend to have a little bit more inflammation measured by the CRP, and more skin disease relatively.

Over the course of treatment, in general, across quite a number of therapies, it seems like the response or the effect size for women with PSA may be less than that of men. The intriguing thing is we really don't know why. Some people have suggested that maybe it's a pain, their perception of pain, and that certainly can be different between the sexes, but there are also distinct immunologic differences, and the subtypes of different immune active cells like macrophages, we don't know how that relates to the clinical differences nor to the response to therapy. Of course, that too is a very complex topic as the hormonal milieu for men and women absolutely changes over time. And how does that change impact the clinical manifestation?

So a lot that we don't know, but I think we all recognize now that there can be important differences. So we're at least paying more attention to clinical trials to know that the data need to be assessed according to the sex of the patient, among the other important baseline characteristics. So kind of a stay tuned. I think this is an area that's a hot topic. I think it's one, hopefully, we'll have really more concrete answers for in the future, which will help us take care of our patients with psoriatic arthritis.

From the American College of Rheumatology Convergence Washington DC, this is Arti Kavanaugh for RoomNow.

Hi, my name is Akhil Sood reporting for RoomNow here in Washington DC. Suppose you have a new patient with newly diagnosed lupus. They have the positive ANA, the low complements, and the classic rash. You start them on prednisone and hydroxychloroquine. Should you add anything else?

Abstract six sixty four found that when patients with newly diagnosed lupus were started on belimumab, a biologic, early in their disease course, they were much less likely to receive lower doses of prednisone over the long term. And this is a big deal since steroids carry a wide range of side effects. Similarly, APRIC six sixty seven found that after introducing biologics including belimumab, rituximab, or anifrolumab, within the first three months of diagnosis patients were able to achieve lower doses of prednisone and lower their risk of relapse. And this highlights that early intervention with biologics is key for better control of lupus. But here's the catch, despite these advances abstract 2421 shows that over the last five decades the use of steroids in lupus hasn't changed that much.

Even with newer biologics many patients still aren't receiving them early in their disease course. So what does this tell us? While early introduction of biologics is key and this can help lower the use of steroids, not all patients are getting these therapies and we need to explore these barriers whether it's physician hesitancy, patient concerns, or larger issues at the healthcare system level including accessibility and affordability. These are the conversations we need to have to ensure every patient with lupus is getting the best possible care because at the end of the day reducing steroid use isn't about the numbers, it's about improving the quality of care for our patients. Thank you.

Hi, my

name is Jeff Sparks. Welcome to ACR twenty four and I am really glad to be joined by Doctor Scott Mattson from the University of Kansas, a pulmonologist here who gave an invited talk on abstract 17 S 14. This was about treatment considerations for RA ILD. This was an incredible talk. It was standing room only and actually the overflow room was also completely filled.

So a lot of interest in this topic. So first I wanted to see what are the most recent advances in the treatment for RA ILD?

Yeah, thanks Jeff. It's a great question. You know what our group's been focused on is how we can best understand the kind of individual patient factors for patients who have RA in terms of what about their ILD can help us understand how they may respond to available treatments. And I think there's been a paradigm in the pulmonary field certainly where we think about these patients as either having a fibrosis predominant ILD or a more inflammatory patterned ILD. And so what we presented today was from data from our group where we've looked at treatment outcomes for patients with RA ILD who were started on immunosuppression and we looked at a few different things about those patients.

So we looked first of all at the overall outcomes and what we see is that these patients generally do worse before they get this directed ILD, immunotherapy and then at the time of immunomodulation initiation for these patients they have stabilization of lung function. And what we talked about today was some secondary analyses from that outcome where we looked at patients who had RA that had a UIP pattern, the more fibrotic pattern ILD compared to those without. And what was interesting in this data set is that these patients with UIP who had the more fibrotic patterned ILD actually had a numerically greater improvement in their FVC trajectory when compared to the non UIP group. We followed that up with some quantitative CT analysis of the same cohort and what we see in that analysis too is that the degree of fibrosis and the degree of ground glass, even though the paradigm is sort of that it's only those patients with more ground glass and less fibrosis that we think we should potentially only treat those patients with immunomodulation, in our analysis, it's essentially all negative data. And so I think what this means is that there's a lot of questions still about which patients with RA ILD will respond to immune suppression best.

But at least as of now, seems like radiographic pattern and the way we define fibrosis on the CT scans is probably not the full story there and those patients may still have a positive response to immune suppression.

So you had given some data that many different immune suppressants seem to stabilize the disease course. Could you tell us about what if patients continue to progress and when would you consider getting anti fibrotic in the mix?

Dr. Yeah, it's a good question. So the data that we looked at was a real world observational outcomes of patients who had been on Rituximab, Azathioprine or Mycophenolate and that was immunotherapy that was started to target the ILD. I think in the real world what we see is that a lot of times even when you start that kind of therapy patients continue to progress. And I think what we know from the trail one investigators and anti fibroidics and RA ILD is that it's safe safe to add anti fibrotic to these patients and that it does have meaningful improvements in FVC change when compared to placebo.

So I really don't hesitate in the real world to trial patients who are progressing who have fibrosis on anti fibrotic because you can continue to alter immune suppression in the background and if a patient can tolerate it, it does seem to probably have meaningful outcomes especially if you imagine that carried forward beyond one year.

So you're a pulmonologist here at a group of, many rheumatologists. I'm curious from your perspective, do you have any advice about practicing rheumatologists? When they find RAID, how would they best co manage the patient with a pulmonologist?

Yeah, it's a great question. I think that bringing together these two fields of expertise in terms of how frequently we should monitor it, in what ways we assess disease progression, and then I think it's just really about this kind of collaborative care. A lot of times there's so many variables we have to adjust that if you can be on the same team and time some of those adjustments so that if you're adding an anti fibrotic it's not at the same time as you're altering immune suppression. In those scenarios you can maybe better tease out in that individual patient which patient's responding and which patient's not.

And I'd say in closing, it's incredible how little data we know. There's only been one dedicated RAILD trial and in fact there's probably less than 300 patients who've ever participated in a randomized trial for RAILD. So there's really a lot of opportunity despite it being our most common disease. And there's already been other abstract sessions. There's another session about lung disease, tomorrow.

So this is definitely a topic that, there's a lot a lot more room for growth. So thank you very much for your interest in our field, and I look forward to continue collaborating. So thank you again for your attention, and we'll look forward to our next videos at RheumNow. Thank you.