ACR 2025 Daily Podcasts Day3b Save

This is an ACR twenty twenty five podcast coming to you from Chicago. Hope you enjoy it.

Hi. Welcome, everyone. It's doctor Janet Pope. I'm here tweeting at our lovely RheumNow booth. I'm at ACR twenty twenty five in Chicago.

I just attended a session that was on secrets and pearls in rheumatology, and I wanted to just tell you a few that I actually learned at this session. So the first one is if you're working up a patient, say she has inflammatory arthritis, she's RF and CCP negative. Obviously, we know to look at nails. We know to look at the scalp and at the back of the neck, the nape of the neck for psoriasis. But something I learned was that if you look basically at the IP of the toe, not m t not first MTP.

It's not crystal. IP of the toe commonly involved in early, axial Spall with peripheral arthritis or early PSA. So that's a good take home for me. And I think for trainees listening, always examine the feet and all our patients and in particular, seronegative patients. K.

The next thing is that patients with PSA often report SICA, dry eyes, dry mouth. I'm not sure why that is. I had noticed it in my practice, but I'd never really formalized it. So if they're reporting SICA, I'm not necessarily going to do an anti Roe or LAW antibody unless if I think they're an overlap. What's the next thing?

This was one that a tip that I didn't know about at all. Patients that present with POTS could be having autoimmune neuro neuropathy problems, but that could be a first presentation of Sjogren's disease. So when you're working up someone with POTS, as we are seeing them sometimes in rheumatology clinics, don't forget to do ANA. And if ANA is positive, think of ENA. And if ANA is negative, you can still think of doing the ROH antibody.

The next thing is IgA vasculitis. If you have an older person presenting with IgA vasculitis, don't just think about HSP, hemoxylamine purpura. It might be cancer associated. So I think the take home from this session is that if we really think about the history and the physical, then it really can help us in understanding what the patient might have, and these little secrets and pearls can give us clues to what's going on. Thank you, and please follow me at Janet Birdope.

Hi.

I'm Andrea Fava coming to you from ACR in Chicago. I wanna explore a third part of how to best address lupus nephritis and the themes that we are developing in the last few years. And I think that a key theme is time intended as how fast to get people into remission. And the answer is obvious, as fast as you can. In this meeting, there have been data showing that the time to complete remission, which is from the time you diagnose patient, from the time you diagnose to the time that you get patient in remission is critical.

The faster is this, the shorter is this time, the better are the outcomes, and the the lower is the risk of developing permanent loss of kidney function. So how do we do this? We do this by treating patient aggressively, but we really don't want to wait. If the patient is not going in the right direction, we need to keep escalating as fast as we can to get patient in remission as fast as we can because time is kidney. There were data presented as a plenary session by myself, on Monday morning that you can review online where we showed that a reduction of urinary biomarker that capture intrarenal inflammation as soon as three months can predict kidney function preservation at five years.

And we have data coming from Argentina from repeat biopsy studies that have shown that the majority of the scar tissue, so the permanent damage in the kidney, is accrued in the first six months. So the first six months is the window of opportunity to prevent lupus nephritis from becoming permanent damage. And so we need to get our patient into remission fast. And by doing so, we need to, diagnose early. We need to treat aggressively and get the patient in into remission as fast as we can.

If you learn if you want to learn more, please go on the room now.

Hi. I'm doctor Len Calabrese from the Cleveland Clinic. I'm here with a friend of mine. Cassandra Calabrese.

Also from the Cleveland Clinic.

And we are really flattered and excited to present a concurrent session on Monday at 04:00 entitled fake room. We have been thinking about this for a long time, and we're really gonna talk about diagnostic reasoning and the pitfalls in diagnostic reasoning that all rheumatologists confront with tough diagnoses. We are rheumatologists. We're considered master diagnosticians by many of our sub specialist colleagues. And we're going to talk about cognitive aspects of making a diagnosis, and we're going

to talk about gaps in knowledge, and we're going

to talk about point of care, AI, and beyond. And Cassie has put together an incredible number of real cases.

Real cases. We're going to work through and see the cognitive bias at play at intersection of rheumatology and infectious disease, a space where we work and see complex patients and often, cognitive biases are a great challenge. So come check it out Monday at 4PM.

Hello. My name is Runaal Nide. I am a rheumatology and internal medicine fellow working in London in The UK, and I'm delighted to be reporting for RheumNow from ACR twenty twenty five here in Chicago. I am delighted to be joined today by professor Marwan Bukhari who is a consultant rheumatologist at University Hospitals in Morecambe Bay in The UK and also a professor at Lancaster University. Thank you very much for joining me today, Doctor.

Bukhari.

No problem at all.

Thank you.

Thank you for asking me to comment about rheumatoid arthritis. I always like talking about it.

Yes, indeed. So, yeah, as you've just said, we are gonna be looking ahead to what you feel are the highlights from this year's congress in terms of rheumatoid arthritis. So what are you most looking forward to at the congress this year?

I'm looking forward to looking at some of the data really, looking at the influence of GLP-1s and the combination therapy with those and weight loss and whether that's going to create a difference in the outcomes of patients with rheumatoid arthritis. That's one thing. Although some of the TriNetX data are not really as robust as we would like them to be, but they're showing that we might have an answer there. Some of the other things that are really quite exciting are about the preclinical phases of RA and how you can predict people who will progress. And there's quite a lot of biomarkers that are being validated at this meeting, and we've seen a few of them today.

We'll see a few over the next few days. Although the really exciting thing for me is something really simple. How frequently do you monitor me to flexate?

Yes. There's

actually three papers about this, and it shows that we shouldn't be monitoring it as much as we should as we do now. And if we take it up to six months, we'll actually reduce the number of interventions in office visits which I think is a very good message to go. And the last bit in rheumatoid that we saw is again steroids. We're using far too much of them and we're underestimating how much steroids we're giving out to our patients And we keep on doing this, and every single year we hear the same story, but does practice change? Not sure if it does.

So if we can pick up on maybe a couple of those points. So just looking at the GLP one data. So I too was looking at the the TriNet data as well. And I think all of the abstracts here, unfortunately, are well, fortunately or unfortunately are coming from the same database. How do you think that area of research is gonna evolve to move forward?

I think it's it's a good dataset for things that are really rare.

Yeah.

So looking at looking at small events and very rare events,

Yeah.

Kind of

x data would be fantastic. But I think just looking at associations, you if we test enough times, we'll find an association. So an ingrowing toenail being linked with a flare and rheumatoid is not science. But you can actually prove that using TriNetX data. Yeah.

And that's not really what it's for. What it's for is for really rare events to have collect really large data and get some meaningful information to maybe inform clinical trials. Yes. But now what we're seeing is lots of hypothesis generating. And let's put it this way, you test a 100 things, you'll find five of them.

It'd significant.

Quite. On it. We need some real world data, really, but that's gonna take time, obviously, to come through. And then going to the methotrexate monitoring, there's also some really good abstracts on the final day, I think, on micro biome and using that to sort of detect who's gonna respond to methotrexate or not, which would be a good thing to do perhaps. So do you have any comments on that?

That's a really interesting abstract because what they're giving, they're actually giving my fiber. Yeah. And they're also giving methotrexate at the same time. And the idea is that your, you know, your mucosal surface is where it is. I mean, there's another one about mucosal surfaces which includes sputum CCP levels.

Yes. It's been

read on again. And again, they're very, very interesting in that we now understand that a lot of our immune systems all have a link with mucosal surfaces lining up your lung, lining up your gut.

Yes.

So I think we'll be lying more in bed with the gastroenterologists and with microbiomes a hell of a lot going forward.

Yes. And then just I think the final topic, if we look at pre RA. So, obviously, this has been a really hot topic for the past couple of congresses, what with all of the stuff coming out of London with a PIPRA now, Alto, and then yes. And then we've got the stop RA data of last year as well. So what are you most looking forward to specifically in the pre RA field?

I think the pre RA field, I think the important thing is to look at using AI to actually help you to see who's going to progress and use a combination of approaches to look at it. I'm sure we haven't seen Arthur and Diana at this meeting in the asthmatic ultrasound system. That might just give you something. We're not sure, but it's disappeared. It was a flashing advantage.

Yeah. You had, you know, biomarkers like fourteen thirty three F and the Vectra chip. They they wax and wane Yes. Over time. So we're just we're not sure that we've got the right biomarker.

It tells you who who's going to progress from clinically suspect arthralgia

Yeah.

Into developing rheumatoid. And that's really the important thing that we need to know. But lots of hypotheses, but still some answers to be had in RA.

Perfect. Right. Well, thank you very much for sharing your insights. We have done a whistle stop tour on what you can look out for in the rheumatoid arthritis world here at the congress, so we hope that you manage to catch some of those sessions. If you'd like to know more about what's going on here at ACR twenty twenty five, do keep watching the RoomNow coverage, and I'll see you again on the next video.

Thank you. Thank you.

Hi, this is Doctor. Al Kim again from Washington University School of Medicine reporting for RheumNow. I'm the faculty head for the CAR T and T cell engagement group here that's been very busy reporting on numerous abstracts at the ACR Convergence twenty twenty five conference. I'm gonna be presenting data actually from four different abstracts that have finally given us high resolution molecular data to justify why deep depletion that CAR T cells have been able to demonstrate to date may be the reason why we have the extraordinary durable clinical responses that we are in lupus patients treated with CD19 CAR T cells. So as a little bit of a background about B cells and why they're dysfunctional in lupus, remember when B cells grow up in the bone marrow, they develop there, they come out as naive B cells.

Now in uninfected people or people that don't have any recent vaccination, these B cells stay as naive B cells. If you're vaccinated or you get an infection, these B cells move to what's called the B cell follicle in lymph nodes where then they initiate germinal center responses. Here, the B cells differentiate so that they are able to create high quality, high affinity antibodies which can be then be protective once you get re exposed to that particular pathogen. In lupus, this is completely hijacked. In the case of lupus, the B cells emerge out of these naive B cells but they are never brought into the lymph node B cell follicle.

Instead, they are activated in what's called the extrafollicular pathway. And what this does is that it creates a unique population called double negative two B cells that are strongly associated with lupus pathogenicity. In fact, these B cells harbor almost all of the auto reactive B cell clones that you see in lupus patients. So as a result, the clones that in terms of if you wanted to graph out all your B cell clones in a pie graph, these would occupy maybe 80 or 90% of them. And then when they eventually then grow up into antibody secreting cells such as plasmablast, they are making most of the autoantibodies in lupus patients.

So in these four separate abstracts, what we are seeing in the pre CAR T state is the, very low naive B cell counts but very high double negative B cell and plasma blast populations consistent with what we see in lupus patients that are flaring. Early on within weeks after getting CAR T cells up to six months, we see numerous changes in the B cell compartments. First, there's a strong reemergence of naive B cells with a substantial reduction in plasmablast and these double negative B cells. So that's great. On top of that though, the B cell repertoires in terms of the B cell receptor, they're not auto reactive.

They tend to homage, become very heterogenic and are equally represented amongst all the different B cells. Again, suggesting almost a pre disease state. Looking further out to twelve months, the Erlogen group here has shown that this remains durable. There is a population of these double negative B cells that do come back, but they're not the pathogenic ones. They're called DN1 cells.

They're not DN2 cells. And, also there's evidence that these B cells are activated through the germinal center and not through the exofilicular pathway. So I think when we sum all of this complicated B cell biology up, basically what we're seeing is complete reconstitution of the B cell compartment after CAR T cell therapy. In this case, all CD19. Some people have been calling this immune reset.

I'm not exactly sure how we're going to define that specific term, but I think this is extraordinarily encouraging, something we've never really seen before in autoimmune diseases and it's something that we're going to be looking at long term, years down the line for lupus patients, but also for other autoimmune diseases being treated by CD 19 CAR T cells.

I'm Jonathan Kaye reporting from ACR Convergence twenty twenty five in Chicago. Large language models have been used in studies of rheumatological diseases such as rheumatoid arthritis and are increasingly being incorporated into electronic health record systems to abstract data from medical records and patient notes to do studies from real world populations. Abstract 02/1960 from the Mayo Clinic used a large language model trained on medical records from two thousand eight hundred patients with rheumatoid arthritis and patients without rheumatoid arthritis, looking at six point six million notes from patients without rheumatoid arthritis, 1,200,000 notes from patients with rheumatoid arthritis, not just from rheumatologists, but also nursing notes and other notes. And they were able to find evidence of rheumatoid arthritis antedating the diagnosis of rheumatoid arthritis. They were able to find various aspects in the notes with a precision of 0.8, one year before the diagnosis of rheumatoid arthritis, that predicted the onset of rheumatoid arthritis, and with lower precision, as far back as ten years antidating the diagnosis of rheumatoid arthritis.

This use of large language models to abstract data from electronic health records not only can help with epidemiological and clinical research, but also might be used as a biomarker to predict who is at risk for developing rheumatoid arthritis without the requirement for a serum sample or a digital biomarker measuring physical function, for example. Going forward, it will be very interesting to see what happens with the use of large language model models to abstract medical records, to teach us more about rheumatoid arthritis and other diseases. For this and more from ACR Convergence twenty twenty five, go to roomnow.com. I'm Jonathan Kaye.

David Lu here from Melbourne, Australia and here in Chicago, as ACI twenty five starts to slowly wind up the last poster hall today. And I want to share with you one abstract that I saw in the vasculitis section. I think really gets us to a question about in these vasculitis trials, in the AAV, PMR, GCA, and therapeutic trials, what seems to drive infection? So this was a systematic review, they scattered out, they extracted out the average steroid sparing capacity of all the different therapies that were being considered in these trials and then the infection rates. And what's very clear, except for one outlier, basically, the better the steroid sparing capacity, the lower the infection risk.

So really, what can you conclude from this? The infection risk in these trials is not coming from tocilizumab or sorrelimab or Baticept or anything else. The risk is coming from the steroids. And the key bit if we really want to avoid infection in these patients is to reduce down the steroids. For all the vasculitis coverage and everything else, you know where to go.

Roomnow.com.

Hello, I'm Doctor. Jeffrey Curtis from the University of Alabama at Birmingham. I wanna talk to you about two abstracts related to use of GLP one drugs like tirzepatide. GLP one drugs have taken the world by storm as the implications of obesity and its cardiometabolic complications continue to plague the developed world. In an abstract our group at UAB presented using data from their ACR's RISE registry, more than sixty thousand rheumatology patients in that registry either are or were treated with GLP one drugs.

We know that these drugs help people lose weight. People lose generally about 10 to 20%. But what else do they do? In the two abstracts I want to cover, in a cohort of eight hundred and eighty five patients with lupus and diabetes, patients were either treated with GLP-one drugs or SGLT2 inhibitors. They found that both MACE events and lupus nephritis was lower in the GLP-one exposed patients by about fifty percent and mortality was decreased by about twenty six percent.

A second and complementary abstract by a different research group but the same data source of electronic health record data studied patients with lupus nephritis and they found that progression to either diagnosed chronic kidney disease or MACE events was also significantly lower. Both of these are interesting and tell us about the cardiometabolic benefits including mortality of GLP-one drugs, but what I find important and perhaps controversial is what is the extent to which these benefits are mediated by weight loss? Are they treating only excess weight or is there some inflammatory component that's also being treated by GLP-one drugs? Assuming that these initial observations hold up with replication and ideally in a prospective study, we need to understand what mediates the benefit of GLP-one drugs. Also, there's no off ramp to these drugs.

What happens if people stop? They gain weight back. Does that mean they lose all the protective benefits that I just mentioned? Whether any of these observations, both good when you're on them and perhaps bad if you stop, we just don't know, is going to influence how rheumatologists think about them and whether rheumatologists are willing to prescribe them as a field remains yet to be seen. But there's no question that this is gonna be an expanding field as time progresses.

Hi, everyone. This is Orelinage from Glasgow, Scotland. We are day three of ACR twenty five in Chicago. As yesterday and the day before, very exciting, lots of science. And I have a very fresh poster from the late breaking abstracts poster tour.

It's l b zero zero eight presented by Philip Meese, and it's about isocubep. So I don't know if you remember, but last year, our ACR, we saw the phase two results of this molecule. It's a small molecule, an affibody, which is targeting IL 17 a, so specific of IL 17 a. And the phase two in psoriatic arthritis was actually quite impressive. It showed in particular a very good results on anxiety scores, which according to the company that has it, because of the size of the AFI body, it would be able to go more into the the tissues.

Well, that's not been demonstrated yet, but that was the idea behind it. And certainly, the phase three was long awaited, and so the results of the fifty two weeks were presented this time. And so there were three arms. There was a placebo arm. It was 350 patients roughly.

Placebo arm. The drug hundred and sixty milligram weekly and then every other week in two separate groups. And the primary outcome was the ACR fifty at sixteen weeks. And then after sixteen weeks, patients would cross over and those who got the placebo then got the active compound up to fifty two weeks. So the results are really good.

Sixty percent sorry, fifty percent of patients with ACR fifty response at fifty two weeks, minimal disactivity fifty percent, ACR 70 between thirty five and forty percent depending on the group, and then PASI 100 again, fifty five to sixty five percent. So very good. When it comes to anxieties though, because I was particularly curious about that. So they had sixty percent of their baseline population with anxieties, but the LIDS anxiety scores were actually quite low. It was about two.

And so they weren't really able to show the same signal. I spoke to the to the authors, and they were there seemed to be saying that in those people with the highest endositis scores, they seem to had a really high efficiency, but it's not something that was presented. And I guess we'll have to wait for the manuscript to be published to look specifically into that. I would also be super keen to see if there are specific granularity in terms of phenotypes that seem to be responding better. But, again, for that, we'll have to to wait for the manuscript safety profile.

Very similar to as a selective I seventeen a. So low we we, you know, we don't find specifically the candidosis issues in this in this population with this inhibitor. A no new safety signal overall. So definitely something to look forward to. Look into the manuscript and then see also obviously how that will compare in terms of efficacy to also IL seventeen inhibitor.

Stay tuned on RheumNow for more content and follow me on Twitter at AureliRomo. See you later.

Hi, everyone. Professor Peter Nash reporting for RheumNow from ACR Convergence in Chicago. And this time I think we'll discuss the T cell engagers. Are you really engaged? We talked about CAR T, we talked about fantastic efficacy, manageable safety, but given cost, given hospitalization, given lymphodepletion, given the requirement for heme onc and the access to fill gastrin and tocilizumab, it's not very feasible.

So what might be feasible for the rheumatologist? So the T cell engagers are bispecific antibodies and one of the, heads binds to c d binds to t cells, c d three or c d 47. And the other one binds to the exact targets that we want so we can take out the b cell. These are b cell eliminators, b cell depleters. So you take out c d twenty like Ritux does, but that doesn't get the plasma blast and the plasma blast is the cell that makes all the pathogenic antibodies we're interested in.

JO-one, SSA, double stranded DNA and half of SCL 70 of scleroderma. So CD 19 does take out the plasma blast. That would be ideal as the second head of the bispecific monoclonal antibody. And indeed, they're the ones that are under development as well. And that leaves the plasma cell alone.

So you don't run into trouble with infections from COVID, issues with candida, tetanus, pneumococcus, all the things that we need to keep our immunity to because the long lived plasma cells aren't touched. And lastly, in oncology, where you want to get rid of all the malignant B cells, BCMA, which does take out the plasma cell and therefore long term, you're going to run into issues of loss of immunity for those things we've just talked about. So, oncology has seven approved molecules that are these T cell engagers and there are 10 more under late stage development. In Rheumatology, there's two that were presented at this meeting that we're going to briefly discuss and four more under development. So as a target, they're bispecific monoclonals that take out CD20, CD19 or BCMA and they are combined with a T cell engager like CD3 or CD47.

The two that they presented here, one is called blinatumomab and this is being studied in a number of immune diseases like rheumatoid. Interestingly, the hypothesis is take out the ACPA and then do you put rheumatoid into remission as well as, systemic sclerosis and lupus where you want to take out SGL-seventy in double stranded DNA. The advantages of these and the second one, that blurtubomab is a monoclonal that takes out, CD three and CD nineteen, whereas teclistamab, the other one presented at this meeting, takes that CD three and BCMA. As we've said, that might have some issues. Now, blinatumomab is given as an intravenous infusion, to Clistamab as a subcutaneous injection.

Because in lymphoma and multiple myeloma, they get a lot of CRS because you're killing a very large volume of lymphocytes. They're worried about CRS, so they started with a very low dose in the French cohort that was presented here and increased the dose in the German cohort, better efficacy and still no because the absolute load that you're killing of B cells is quite small. So, they've done some nice studies, blinatumomab, IV infusion, you have to be in hospital for five to ten days, so this is one of the early generations, but very nice B cell depletion, very nice tissue depletion, not as complete as CAR T, but pretty good. You get rid of the autoantibodies you want to get rid of and you show nice responses in these diseases. Problem, there's a recurrence of B cells within three months.

There's a recurrence of, disease down the line quickly and it's a question of how safe it is to keep infusing this stuff and are you going to induce immunogenicity, anti drug antibodies, etc. With the Teclistamab, where you take out BCMA, it's been studied in systemic sclerosis, Sjogren's, Rheumatoid, immune muscle disease. You can stop your, immunosuppression. Both drugs need a pre med. You get very nice b cell depletion.

You get very nice reduction in the Rodman scores, improvement in DLCO and FVC. The autoantibodies are reduced to zero. Again, you need pre med. Again, there's a recurrence over time. So maybe these two treatments will make great induction treatments, and then you follow it up with another thing that we'll discuss.

But because it took out BCMA, they started having problems with hypogammaglobulinemia and with infections and these people started to need gamma globulin injections to help them recover. But very nice efficacy. The blinatumomab studies, they induced B cell depletion and then got good response and continued abatacept with the patient. And in the blinatumomab, in the teclistamab, they, followed some of these patients up with cyclosporine and with belimumab to keep them under good control. So perhaps induction of remission and then maintenance with medications that we've already got freely available.

So I think these are just the first cabs off the rank. Clearly IV in hospital for ten days is not going to fly. I think the best target is CD19 not BCMA. Sub cut given weekly for a while, induced remission, and then think about keeping people in that remission. Again, another watch this space.

Thanks very much for your attention.

Hi. I'm Jack Cush at ACR twenty twenty five Chicago. Today, a presentation, a great poster, abstract l b late breaking 15. The title of this had something to do with fiber and methotrexate. Did you take your fiber today?

This is an interesting story. The idea, behind fiber is that it's good for you and maybe one of the ways it's good for you is it could change your microbiome. And maybe you follow the microbiome literature, maybe you don't, but there's some literature in there about the microbiome changing disease sometimes by changing how drugs work. Either the metabolism of the drugs or their absorption or their effectiveness, and this applies to a lot of chemotherapies. It's been linked to methotrexate.

So in this, small pilot, multinational study of forty nine patients with mild to moderate rheumatoid arthritis, they looked at what happens when you give fiber to RA patients. Who are these forty nine RA patients? Mild disease. Generally about five to seven tender joints, about two swollen joints. CRP, a medium was seven milligrams per liter.

So again, to moderate disease. It's a one month study. Half the group got twelve grams of inulin, which is a source of complex dietary fiber or a sugar pill, and they looked at the outcomes one month later. It turns out that at thirty days, the ones who got fiber had, and again, had mild disease to begin with, had greater achievement of EULAR good status, fifty seven percent versus the placebo, twenty two percent. They had a reduction in both t h 17 cells in the periphery as measured by flow cytometry and the ratio of Th 17 to Treg cells, and this was significant.

And then lastly, for those who are on methotrexate, they had a significant drop in DAS score minus one versus those that were on placebo where the DAS didn't change very very much. It was minus 0.38. Now and again, the numbers here are too small to be significant. But the eye but when you look at the the graphics on this, it looks like dietary fiber can augment methotrexate responses. They had a a a small control group of patients, but there are only six that were on other DMARDs, and it didn't look like fiber did anything for them.

But they need to repeat this. It's a good pilot study. Dietary fiber could make methotrexate more effective. More from ACR.