RheumNow EULAR 2026 Rheumatology Round Up Save

You're listening to a RheumNow podcast coming to you from London in EULAR twenty '26. Enjoy. Welcome to EULAR Roundup. This is the 2026 edition of the roundup we do after each meeting. This one is from UR, which used to stand for the European League Against Rheumatism, and now we know it's the European Alliance of Associations of Rheumatology held in London last week.

I'm Jack Cush from Dallas, Texas.

Arti Kavanaugh from San Diego.

In this session, we're going to be discussing abstracts and presentations of interest from the meeting that we thought, were of high quality and high impact on practice and rheumatology. There were many live sessions that were attended, a lot of, in person paper posters, and that was a big hit. There's a lot to cover. Artie, why don't you start us off?

Alright. Well, thanks and welcome to our audience. Some of you may be thinking, well, boy, Artie's dressed pretty casually today but what I'm doing is kind of advertising. Those of you in the know recognize this as a memento of Room Now Live 2026. So you'll hear a lot of what we're going to discuss now and a lot more at Room Now Live twenty twenty seven and maybe even get a sweet T shirt like this.

So, anyway, the I love going to the meetings and I think I I like when I really learned a bunch of stuff and one of the abstracts, I think that prompted that was OP one twenty and this is mosaic loss of the Y chromosome may differentiate giant cell arthritis from poly mal to Rheumatica across the GCA PMR spectrum. There's a bunch of stuff that was in here. Actually, the abstract itself was sort of promissory. They had done some work in the past, which is interesting, and I think it's a very interesting future. The idea is that we've learned a lot in recent years about somatic mutations.

Now, are genetic mutations that don't occur in the germline. So, you're not born with them. They occur during the course of our lives. Generally happen in older persons. Men seem to be more susceptible than women and we've learned about a number of these conditions, vexus, where there's a genetic defect in UBA1, IDH1 and two, even the whole category called CHIP or clonal hematopoiesis of indetermined potential.

What these have in common is they're somatic mutations in a line of cells, generally myeloid cells, and they come to rheumatology and hematology because they have a number of musculoskeletal type issues, and also they have myeloid issues like the deficiencies in various cell lines. Think of Vexis. So this actually, I did not realize this. The most common defect in men is the loss of the Y chromosome and up to forty percent of men who are 70 lose the Y chromosome in certain cell lines. And think of the disease population we're talking about.

We're talking about older persons with inflammatory arthritis and inflammatory systemic conditions. So, you think of those conditions like Palm Mayo's Rheumatica and Giant Cell Arthritis. In this analysis, they looked in their center and looked at people who only had PMR and only had GCA, and what they found is that the number of people who had the mosaic loss or Y was ignorable in the PMR population, but definitely present in a subset of the GCA population. Previously, they had looked at the relapse of GCA and found similar over representation of mosaic loss of Y among those persons who had relapsing disease. So I think it throws open an entire new consideration of these somatic mutations that we see in various cell lines.

In some cases, we have specific treatments that can address them, But I think it's super interesting scientifically and something that we need to watch for clinically.

So again, these CHIP studies, the clonal hematopoiesis studies have shown up before. They're often positive with aging, right? It's a part of immunosenescence. But it has disease associations, as you say, in rheumatology, hematology, it's got a lot of associations in vasculitis. And what's really intriguing about this study is it showed this nice distinction between PMR, the disease we prefer, and GCA had all this somatic mutation activity.

And could that be a factor where you could tell people maybe at risk? It may have a clinical utility. This is going to need to be, I think, redone with larger populations. There was a really good sized population for GCA, a smaller population for PMR. But I think this is really intriguing and its utility for the future.

When I look at these, clonal hematopoiesis studies, and we've covered them in the past, I often think this is really cool, but I don't know what to do with it. This might be what we do with it.

Yeah, and if there was a star at this year's ULAR, PMR would be in the running. A lot of material in lupus, a lot of material in PSA, but PMR was really a star. Think of many ACRs and ULARs in the past, nothing about vasculitis, nothing about polymyosomatica. Now there's a lot of great stuff on that, and this highlights it. And it's a fascinating question.

They are overlapping. We know that the symptoms and signs can overlap, but they're also distinct. And that we're seeing that with therapeutic approach as well. So fascinating abstract, I thought.

Yeah, and I agree with you that it was a little bit of a fire hose on PMR and GCA at this meeting. There were guidelines put out by EULAR about the management and assessment of patients with PMR, GCA, and they threw in Takayasu's for some reason, and it was an odd sort of grouping, but I think the audience will appreciate the new guidelines in PMR and GCA, and that's been covered on RheumNow. But I'm going to present a PMR study. It was called REPLENISH. It was presented at the meeting, and it was also at the same time published in New England Journal.

This is a phase three double blind randomized controlled trial of three eighty one PMR patients with relapsing disease. And I think that's something to note from the start when you look at PMR studies, are they brand new onset patients, which is a different can of worms than is the relapsing patients? And, you know, more than fifty percent of patients are going to relapse when you start taking away their steroids. And, again, the important prelude to this is a few years ago, secukinumab was studied in GCA in a phase two trial, the TITAN study, and looked really good. And then they did a phase three trial, and it didn't meet its primary endpoint.

And now even though, you know, IL-seventeen and TH17 cells are thought to be involved in PMR and GCA, you know, what happened? Why did that not happen? Well, here comes the REPLENISHED study showing that secukinumab, the IL-17A inhibitor, does work in relapsing PMR. So again, it was patients with relapsing disease. They either got, one of two doses of secukinumab or placebo, and they had data out to, I guess it was a year.

The primary endpoint was at week twenty four. Both doses of secukinumab were superior with over forty percent, what was it, response rates compared to placebo, it's about twenty percent. And the primary endpoint was sustained remission. It's a very stringent endpoint. It's what was used in the Sapphire trial, was also in New England Journal on the other JAK inhibitor, which one, Arty?

Blanking on it. Sapphire study was?

Cirilimab.

Yeah, Cirilimab, sorry, not JAK inhibitor, Cirilimab. And they use the same endpoints and had the same kind of results here. But again, sustained remission is being in remission from weeks twelve to fifty two. So there's no room for error there. You needed to respond by week twelve and stay in response and be in remission.

That was achieved in twice the number on drug compared to those on placebo. It also turned out using the IL-seventeen inhibitor, not an IL-six inhibitor, that you actually use less steroids, five hundred to one thousand milligrams less than the placebo population. And because these people were of the relapsing variety of PMR, it was not uncommon that they would relapse later on in the study, except the relapses were much more in the placebo population than they were on IL-seventeen treated population. So this is exciting data. I think this paves the way for possibly an indication in the future.

Yeah, super exciting data. Well, super exciting to have data in GCA and PMR in recent years. This is very exciting and one exciting aspect is the potential safety. And this has been talked about. The IL-six inhibitors have been great and could certainly well tolerated medicines in general, but you always think about bowel perforations.

We don't know exactly why there's a bowel perforation issue with IL-six inhibition, but there was another abstract that showed that it appeared that it was GCA more than PMR, making you think that it's a combined impact of steroids. But having something like an IL-seventeen inhibitor would be great. It'd be great to have another option. And we have, I think, a good understanding of the safety profiles of the IL-seventeen inhibitors. In this study, as you said, interesting, there was no dose benefit.

The three hundred was not better, at least by appearances, than the one hundred fifty. So you wonder, what about a seventy five milligram dose, which has been looked at in other diseases with, for example, in some of the AS studies with secukinumab. So might you be able to get away with even a lesser dose? But as you said, Jack, these studies are, they're tough because in GCA and PMR, steroids are the treatment of choice. So you have to treat with steroids.

And then you wonder how much did you use? How fast did you taper it? And that's one of the first things we look at when we look at study design is, let's look at that. And that maybe study design issues were some of the reason why it failed in GCA.

Yeah, there was another one that the Jack Spear study of baricitinib in new onset PMR, and that was very successful. That was a late breaking five. And it's different though. They gave the JAK inhibitor right quick, and with a rapid eleven week or eight week steroid taper, and they showed really significant results. So again, we want to get away from steroids.

We can't get away from steroids in these two disorders. But if we have effective therapies that are really steroids bearing, we can now start to think about where we're going to put them.

Yeah, boy, it's exciting. You have a brand new area with so much new data to pore over. So my next one, I think we always like positive studies like the REPLENISH that you just talked about. Super exciting. But sometimes you learn and we have to address negative studies.

And one big negative study I think is POS 63. And this is from Johan Oskling's group in Sweden and it looks at time trends of lymphoma risk in rheumatoid arthritis. So, this is an old story. Back to the initial times when TNF Hembers were new, one of the things that we saw is that there were side effects among the people with TNF inhibitors, including infections, but including also the risk of lymphoma, particularly diffuse large B cell lymphoma. Looking at the patients who were treated, it kind of made sense because we've known even before the TNF inhibitors that the association between rheumatoid arthritis lymphoma was driven very much by those with the most severe, the most active disease.

At the onset, that's who got TNF inhibitors. So it's a real confounding or by indication kind of a bias that you're treating those people who are meant to have those side effects. So, we we thought, well, you know, you're treating people who are at greater risk. You're going to see this but really, we always had in the back of our minds that eventually, if we do better with treatment of rheumatoid arthritis, that risk should go down. And we've seen that with other aspects of disease.

You see that with we're doing better in RA, we need fewer joint replacements. Overall, we see fewer extra articular manifestations. These days, if I see a patient in the clinic with rheumatoid nodules, I go get to medical students and show them because we don't see rheumatoid nodules and all those manifestations quite as much. So the idea was that eventually the incidence of lymphoma would go down. So this study, and we walked up and talked to Johan asking, that this is kind of depressing?

And he said, Yeah, this is depressing. Because what they found in their Swedish database comparing the rheumatoid arthritis patients over time to the general the rheumatoid arthritis patients retain their increased risk of developing lymphoma, even though the population use of biologic agents has gone way, way up over the time period. They look from 2005 through about 2025. They don't find a difference. So what else is going on?

It raises some interesting questions, and in our discussions people said, What about methotrexate? What about maybe the TNF inhibitors? They're lowering the inflammation, but they're contributing. We don't know. We don't know.

But so it still could be that longer periods of time we keep doing better with RA. If we look at people by remission, and this is a population study, so you can't look at disease activity. But instead, I think we were all rooting for this to be positive and it wasn't.

Yeah, another interesting conversation I had on this was, first of it was very deflating. I thought for sure, if you control inflammation, you'd lower risk, and that's not the case, and they show this very well. Those of you who are just listening, imagine a population risk of lymphoma, just the general population running along the baseline and varying year to year. And then the RA risk line is above it, like fifty, sixty percent higher. It was like ten per, what was it, one hundred thousand or was the rate, I can't remember, was ten versus six, and it stayed that way over time, even though they got more aggressive therapies.

But I think a nice argument that I heard might be risk of lymphoma is not driven by, let's say, the CRP and sed rate inflammation. It may be driven by the chronic dysregulation of immune response, that years of a dysregulated T cell, B cell activity now sets you up for this. If you're doing that RA for two or three or four years, that's what gets you into a lymphoma risk category that you can't quite get out of. And that's my new hypothesis that someone else is gonna have to shoot down. But what I do like about this is the data proves the point that the drugs that have the lymphoma risk in the warning section of the package insert, these drugs don't cause lymphoma.

This study, while it showed that inflammation didn't get better and the risk didn't get better, it also showed increased use of these drugs didn't drive up the risk of lymphoma. And it's okay though that you warn your patients about a lymphoma risk because it goes with RA. You want to blame it on the drug, fine. I think that's a mistake, but that's up to you to decide. The good news is you have a lot of other choices.

So if you don't want to use any, like a TNF inhibitor, for instance, you have many other choices. But I think they're also at the same risk of lymphoma by having chronic RA.

So if it is immune dysregulation early in the disease, what about something like CAR T in rheumatoid arthritis, Jack?

Yeah, well, that's a good tee up for, the next one. This was an important presentation. Let's see if I can find the number. It's OP0008, presented in Plenary Hall. CD19 CAR T cell therapy in aqua positive active refractory rheumatoid arthritis.

This was the compare study, and they've developed a CAR T cell preparation. It was an early phase one, phase two. They reported on six patients. They have 12 others in trials. They've developed something called MIV cell autologous fully human anti CD9 CAR T cell therapy.

Patients were very refractory having failed four to seven biologics and targeted synthetics going in. Very active in that they were all strongly seropositive with mean dash 28 scores of greater than six, ranging from four to 7.1. And they all were pretreated with lymphodepletion by fludarabine and cyclophosphamide, and then received one infusion of CAR T cell therapy. They stopped their DMARDs, they're on no other background therapies, and when you looked at the graphs, you saw a lot of the things you want to see. CD19 or B cells going boom, just down and gone.

And it stayed down for a while, although there was some, repletion after time that most of these people became neutropenic. Most of them became hypogammaglobionemic. Rheumatoid factor and CCP dropped, although not completely, and some, you know, a very steep decline, others kind of slow and waffling. And then from the podium, the author said, and the good news is that they all went into remission. And if he had stopped there, that would have been the headline in the press.

CAR T cell therapy puts everybody in remission in RA. Not so fast, Bubba, in that when you look at the ACR twenty, fifty, 70 scores at different time points, week 12, week 24, it wasn't so good. I mean, it wasn't as great as you think. Meaning the ACR 20 response rate at week 12 was only fifty percent. That greater response rates approaching eighty percent were seen when you went out to week thirty six and fifty or 48 and things like that.

So there was a good response, not fabulous. We were kind of hoping that in RA, cellular depletion therapy, especially CAR T cell targeted therapy might do what it did for rheumatoid arthritis as reported by Gaylord Shet, but I don't think it's as magical as that. I think there might be some role for it, and maybe this says something about the pathogenesis of RA, that B cell activity is an important part of what's going on there. We certainly have autoantibodies that are distinctive for the disease and may be involved in the pathogenesis, but it's not quite as clear as it is in lupus where double stranded DNA, SM, what's going on in the kidney, you can really connect the dots much better, and maybe that's why we've seen better responses. So there's a lot of excitement about this, it got a lot of press.

I think it's positive, but it's not in my opinion a magic bullet, not yet.

No, it was surprising because those of us with gray hair remember using cytotoxin, cyclophosphamide in RA where it works actually really well, but of course it's very toxic. Also, Flunarabine, 2CDA, another chemotherapy that is effective in rheumatoid arthritis. Given those as conditioning, you thought, boy, you really think that you would have had a good response even besides the CAR T. So I think you hit it right on the head though, Jack. I think what this tells us is that all RA is not driven by B cells, and it's not a question of if only we could eliminate more B cells, which I'm not sure that's the case in lupus, but it's certainly much more the case than it is in rheumatoid arthritis.

And that fits in. We did a study years ago called Arise, and we looked at synovial biopsies and it turned out that the clinical response was not predicted by anything you saw in terms of changes of B cells in the synovium. So it's not the whole story in RA. And given the other issues with CAR T, especially the cost, the potential for side effects. So they didn't get into it much.

And these these CAR T studies always make me chuckle a little bit. And this one, there were six patients and 35 authors. So, I mean, I think is that something that the you know, practicing rheumatologist is going to go for? I don't think they're going to go for it in RA. Now, maybe as you're seeing in lupus, these other, the offshoots, the bispecific and trispecific T cell engaging sort of therapies, which may not need the conditioning, maybe simpler and cheaper.

Maybe they will have a place but boy, I I thought the data were really, really quite disappointing.

Yeah, I agree.

So, lot in PSA, I'm going to, there's a couple that usually our listeners know Jack and I try to find the the the real pearls among the abstracts but there are couple of PSA posters that were so impactful. We think most people are probably aware of them, but I think everybody needs to be aware of them because the patients are certainly going to be aware of them. This one is OPO 69 and it's called Together PSA and it's actually been published. And what it is, is a study of a combination of IL-seventeen inhibitor ixekizumab with GLP-one family of medication, that is tirzepatide, for obese or overweight patients with PSA. Talking about this in in for years now.

The importance of obesity as a comorbid condition in PSA. Obese persons don't do as well. They have more refractory disease, it's bad, bad, bad, bad. Those of us in practice know, we talk to nine out of ten patients who come through your door, you're talking about weight loss. And we've not had a great way to have people lose weight, but now we do.

So what impact is that gonna have? This was randomized study. Average BMI was thirty eight. So big group of patients. Lot of them were biologic DMARD experienced.

The primary endpoint and you could say, well, well, jeez, they kinda, you know, biased it a little bit. It's a ACR 50 and that's appropriate for a head to head study of two active therapies plus 10% or more weight loss at week thirty six. Most of the patients finished the the study. Adverse events were what you would have thought of. GI stuff with the GLP.

Not really much with the IL seventeen. And they blew it away. The primary endpoint was thirty five percent or so with a combination treatment and almost zero with a placebo. The weight loss, of course, gigantic in favor of the tirzepatide. But it's interesting, the ACR fifty alone was significantly better with the combination therapy.

The CRP was perhaps the most dramatic difference in the active treatment versus the placebo. It kind of was stable, increased a little bit in the placebo group, went down in the combination therapy. So this, the combination of a GLP-one and IL-seventeen inhibitor were great. Weight loss improvements in across the domains of psoriatic arthritis. I think if the patients haven't come to you about this, they're gonna.

So I think, you know, because of access issues, I think we've sort of not done as much with the GLP-1s, but I think that's gonna be coming. It's gonna be part of something we're gonna be able or really take on responsibility for prescribing.

So, my first question to you is, how can you, in that, I think the most interesting bit of data is the ACR 50 alone, not the combined endpoint. And it was really, if you look at the bars, it's like high for the combination and very little for, execizumab by itself. How do you know that the, great ACR50 response was something due to an added immune or anti inflammatory effect of IL-seven, of the GLP-one versus just the weight lowering effect?

Well, yeah, and I don't know that you can. And you know, it's funny in PSA, we've been studying it for twenty, almost thirty years, and we always worried that there was unmasking. So if your skin psoriasis is better, you know you're not on the placebo. In this study, the difference in ten percent or more weight loss was like eighty five percent with the active treatment, I mean, with the combo treatment and five percent, less than five percent with the IL-seventeen alone. So the patients knew if they're losing weight, they know.

And the ACR fifty is a great outcome measure, but it's driven in some part by patient reported outcomes. So does that bias it in a way? I think that's always possible, but you know what? We don't care. I mean, your patient loses weight, they feel better.

That's great. Don't care why. I tell people that all the time. It's like, you know, your first dose of whatever medicine you think you're cured, it's in your head, but you know what? That's fine.

You go ahead and believe that. And that's why I think the CRP data is really compelling. Can't placebo your placebo response your way to a lower CRP.

So in the last year or two, I've had conversations with some leading rheumatologists who have weight loss clinics operating inside of their rheumatology practices, saying, Oh, you've got to do that. You've to get data on it. You've got to, you know, it's getting to the point now that this is low hanging fruit for rheumatologists. You should have a weight loss arm of what it is that you deliver. It could be run by APPs and very protocolized.

This whole thing, this is combination therapy. Who's going to pay for the GLP-one and the IL-seventeen? Well, that's like other combination therapies. One specialist writes for one, the other specialist writes for the other. So maybe your patients do have to see an endocrinologist, weight loss specialist to get the GLP-one, you know, old generation, new generation preparations because they're going to get better and better.

But we need to really invest in this, I think, going forward because, we're gonna see a lot more of these studies. And unlike CAR T, which is teasing us endlessly with, you know, fabulous responses, but no control data, we're gonna start seeing control data that's gonna end up in new indications, especially for our patients. Remember, the data is very strong for GLP-1s in OA, RA, gout, what else am I forgetting? PSA, PSO, I mean, and we haven't even begun to scratch the tremendous benefit on cardiovascular risk and death, which is a no brainer.

OA and gout are very exciting. The OA patients, we don't really have anything specific to offer. But if they're overweight, that is something very important that could be offered. And gout, I mean, I remember quite a number of patients over the years who lost five or 10% body surfing. Were still overweight, but the gout did so much better.

And now we have something to be able to offer them to help assist with that. So it's very exciting.

It is. So there are a lot of, again, as Arti says, we like to find these really cool, and I have a bunch of really cool abstracts and posters I want to present, but there are several that were big time that we got to talk about. And one was Be Bold. B BOLD was a late breaker presented on the last day by Joe Marola from UT Southwestern LB001. It's a head to head trial of bimekizumab versus rizenkizumab, the dual IL-17A and F inhibitor versus the IL-twenty three inhibitor, in adults with active arthritis, 53.

The primary endpoint was an ACR fifty at week sixteen. This was, as you know, covered by RheumNow as a press release and then as a pre EULAR release, and now they presented not only the week 16 data, but the week 24 data, and it still holds up. And what's interesting is that the primary endpoint ACR 50 was significantly different, forty nine percent for bimekizumab versus thirty eight percent for rizenkizumab. And then when they carried that out to week 24, it's still significant, 11 difference, 55% versus forty four percent. And then this is where things get interesting.

There are a lot of secondary endpoints, and whether it was at week 16 or week 24, they were numerically better with the, seventeen inhibitor, but they weren't significantly better. And so that included the MDA, Middle Disease Activity, DAPSA, and PASI 100. So that was all good. There were no unexpected safety signals as expected with IL-seventeen. There were more non serious candida infections.

And again, this was a positive trial. My biggest question, since I can't ask this to Doctor. Marola because he's not here, I'll ask you, Arti, why did this head to head work in PSA while all other head to heads or comparisons don't seem to matter?

Well, we love the head to head studies. We hate comparing effect size from one study to a completely different study done in different people and maybe even a different time period. So, we love the idea of the head to head. There's not that many of them. There's actually a ton in skin psoriasis and Bumikizumab has been really, honestly, it's kind of mopping up in the psoriasis studies and has been proven to be more effective than a couple of the other comparators including the TNFs, other IL-seventeen to twelve twenty three.

So in that way, it's not necessarily unexpected. I guess the the question if you polled RheumI Rheumatologists, I think the bias, not based on data, but bias before this would have been that the 17s are probably better for the joints than the 23s based on nothing, based on, you know, no data for that. But that's kind of the bias. This, I think, almost feeds into it. As you said, the skin manifestations, these are both great ways to treat skin psoriasis, and they get approximate to each other the longer you go out.

The joint manifestations stay different and maybe both can be good. Of course, the twenty three inhibitors have been proven effective for musculoskeletal manifestation of the PSA. Maybe there is a difference in the IL-seventeen inhibition at least with the AF inhibitor. Maybe that is superior in the musculoskeletal manifestations. It's super interesting data.

And the question is, which is better? And I don't know how to judge that. I mean, this study says, well, in this instance, this design, it's better. Another way of looking at it is what's better in, as you said, in psoriasis, skin only disease, again, bimekizumab looks good. And the IL-23s also look very good.

Which is better according to who's spending more in direct to consumer advertising on TV? Well, all these companies, including the IL-twenty three makers and the IL-seventeen makers are spending a lot of money on television. Which is better as far as sales? Turns out that rizenkizumab is doing, I think the best in psoriatic arthritis right now as of June 2026. But again, these are subject to advertising, market research, etcetera.

So, I like the competition. I like that this area is going to get hot here. I think patients will benefit.

Yeah, I think if it was based on who had the better jingle, Rizenkizumab would have won. But you know, that's not something we're supposed to consider in our scientific discussions.

I agree. A

poster that, well, two posters, one I want to cover and one very close to it deals with something that it used to sound like a fringe thing, but I think it's going to be more and more important. That's high resolution peripheral quantitative CAT scan. So we know we've talked before and in past meetings, why do we still do X rays? The amount of change that you see on plain X-ray films is so small. And if you think in RA, it's very small and PSA, it's incredibly small.

And you have sharp score changes of one minus point three and it's statistically significant. Woo hoo. But doesn't tell us enough, I don't think. So, there is a a technology, high resolution, peripheral, quantitative CT. It's not a ton of radiation.

They're small devices, kind of tabletop that you put your hands in and get quantitative CAT scan of peripheral joints. I think it may be coming because I think it's maybe it's a better technology and actually gives us more information. There are a couple abstracts. One is poster twelve sixty seven. The other is poster twelve sixty three.

The twelve sixty seven was very interesting to me personally. We have great radiologists here at my university. Very interested in in musculoskeletal disease. They find lots of erosions that you a typical radiologist might not find. But not all erosions are pathologic.

And that was the goal of this. They looked at two forty seven RA patients with a seventy eight age and sex match controls. They found a lot of small erosions in both populations. Mostly, they didn't progress. Bigger erosions over five millimeters or five cubic millimeters compared to less the small would be less than one cubic millimeter.

Large would be greater than five, and the rest were intermediate. The large ones were only seen in RA, really not in the normals, and they could progress. Not all of them did, but they could progress. The small ones never did. The other abstract, which was using the same technology, is twelve sixty three.

And at first when you read it, say, you know, so what? What they found was that erosions measured by the high resolution peripheral quantitative CT correlate with functional status. And you say, well, yeah, X-ray change correlate with functional status. But in plain films, it's only joint space narrowing that drives almost all of that correlation with functional status. Here, and it makes sense.

The more disease you have, the more like you are to have a pair articular erosions that correlates with functional says. I think it's the real deal. Have to see cost wise and availability wise, but I think plain x rays are gonna be a thing in the past. I think you won't even get clogged to read them anymore. It'll be like, hey, what are doing this for?

Go to high res PQCT. But I think it's a thing to keep an eye out for.

You know, I'm not popular with a bunch of my friends who like imaging because I've always said imaging is important at diagnosis to know whether they're erosive or not. But repeat imaging, what are you doing that for? You know, MRI is the drop of the hat. What are you doing that for? I'll do MR, you know, in an RA or PSA patient when I'm asking a hard question and let MR, which means I do two or three a year.

But my main gripe on imaging is it's going to be read by someone who's not an expert musculoskeletal radiologist, no fracture present, hello. And then if you read it and you're good as a rheumatologist, you're not going to have the old ones and you don't know how to score them. And all this to say, I'm changing my mind because now we were a number of presentations at the meeting about the use of AI machine learning to read, you know, MRIs or SI joints and pelvis, you know, to read peripheral joints, to read CT scans and whatnot. And their accuracy is, you know, really, really, really high, such that now all the new machines that are coming out, they're coming in with AI software, and that's how they're gonna be read. And now you as a rheumatologist can get a report that is both qualitative and quantitative and shows serial change.

Now I think that becomes a useful tool in practice, especially if we use something like, you know, high res QCT that can be done maybe a little more easily, and reproducibly, again, the patient's going to win.

Yeah, I think you're right spot on.

All right, so another big one, and I'm going to get to some posters after this, is the RA, RA Bridge study. This was a post regulatory commitment, where the FDA, requested that, the makers of baricitinib do a long term safety study on baricitinib and its risk of venous thromboembolic events, VTEs, meaning DVTs and pulmonary emboli. And again, this study was designed, to be enriched for people who would get these events. So the inclusion criteria were RA patients who had either one or more prior VTE events, or were obese or over age 60, or another one was a combination of things. There were four criteria, and they were going to accrue patients, who were treated either with one of two doses of baricitinib, two milligrams or four milligrams a day, versus a TNF inhibitor.

Most of those, I guess, were ritanercept or adalimumab, and keep the study going until they got to a certain number of VTE events. They halted study prematurely because they had enough data to make the point that they needed to make, which is, yes, the use of baricitinib at either two or four milligrams a day significantly increases the risk of venous thromboembolic events. And again, it was over three thousand five hundred patients. The study, most patients were more than three or four years. It has a lot of parallels to the oral surveillance.

You know, there are risk factors going in to enrich for the event of interest. There's not that much difference between oral surveillance and this, oral surveillance being over 55, cardiovascular event, disease activity, what am I leaving out? Those were enough. Here, they didn't have disease activity, but they had the age, they had obesity as a risk factor. But the interesting thing about this, it certainly nailed down this issue of whether JAK inhibitors cause VTEs.

Now what's the story about JAK inhibitors and MAC events and malignancy? That was not shown in this study. There was no significantly higher risk of major adverse cardiovascular events or malignancy in this trial. Also not increased were arterial thrombosis and opportunistic infections. The only thing that was significant and was not non inferior, saying there were more events with baricitinib for VTEs and also serious infections, just barely.

So I think it's a good follow-up to oral surveillance. I think it muddies up or murkies up the considerations about cardiovascular risk with JAK inhibitors and malignancy risk with JAK inhibitors, but it's in the label. You got to discuss it anyway. You got to fail a TNF inhibitor to get on a JAK inhibitor anyway, at least in North America. But Arti, how do you think this study is gonna change the way people, will it change the way people think or will it confuse them?

Well, it's tricky. As you said, the studies are so complicated, almost by design. What they want to show is that they were non inferior to the standard, the TNF inhibitors. They were not non inferior, which is what the heck does that mean? It's like, I'm not wet, but I'm not not wet.

It's not something easy to wrap your hands around. And especially since when you dive into the weeds of it, say, just say you're not inferior, you want to be within a certain margin, but that margin is relatively arbitrary. In this case, it was 1.8. So the upper limit of the 95% conference interval had to be smaller than 1.8 to be non inferior. And that came that was from the agency and that came from diabetes studies and kind of makes sense.

But I think, as you said, Jack, when you look at the graph, you say, you know what, the doses didn't seem to be different for the Barry, but the time to the first VTE was, you know, there's a separation, but only only after quite a number of years. The thing to me is, you know, in the clinic, I'm probably thinking somebody had a VTE, but here there were not there were so few of those who entered the study with that as a risk. It wasn't possible to separate that amount. But you asked what clinic impact it was going to be. I think that's it.

Somebody said, I had the VTE and it was unprovoked. What medicine should I start? I'd probably put the JAK inhibitors down the rung a little bit based on these data.

Yeah, I think worth considering and reviewing the data, and especially when it comes out in print form, which will definitely need to be done.

Yeah, and it's something, you know, we're gonna have to be aware of as rheumatologists because this is gonna be out there in the press, you know, and patients are gonna get access to this and say, Hey, doc, what the heck? Sort of thing. Something else to be aware of, a couple of abstracts on this. So there was a oral presentation 01/1966 and a poster February, and that's Brepocitinib. Brepocitinib is another JAK inhibitor with specificity for TYK2 and JAK1, and this was in dermatomyositis, and very interesting, meaning boy, we sure need therapies for Gnabdomyositis.

Tough disease to study. It's a heterogeneous disease. People can have no skin or a lot of skin. Of course, they have muscle involvement and that, how do you measure that? But there are outcomes that have been developed, like the total improvement score or TIS.

And this is a positive study. So brepicitinib was effective in improving skin manifestations and improving overall composite aspects of disease and allowing steroids to be tapered. This is another one of those diseases where steroids are part and parcel of how we treat them. So complex study design because you have to figure in tapering the steroids, and this was effective. So it seems like we're seeing more people with dermatomyositis or I don't know, maybe it's just now we're paying attention to them more, and we treat them on mostly on anecdotes.

There's good studies with IVIG, not really good studies with almost any of the other things we're doing. Some people still use high dose methotrexate. I like the calcineurin inhibitors. People like mycophenolate.

Leflunomide. I love leflunomide. Leflunomide. Leflunomide. Leflunomide.

Leflunomide. Leflunomide. Yeah, it's gonna take my, I once started to write a blog called The Anecdotal Rheumatologist because I was kind of writing about myself.

That's all of us.

Yeah, know, true. Sometimes you gotta go with what you know best, but I love to be disproven by good data and good trials. Again, everyone knows that preplacitinib was a New England Journal article, and I believe that's in queue to be a newly approved drug sometime in 2026 for dermatomyositis. So I think that's exciting. My next one is going to be a poster POS0788, the efficacy of colchicine and its withdrawal in patients with palindromic rheumatism.

This comes from Umesh and colleagues in India. It was a retrospective study from a tertiary rheumatology care center where where they had over seven hundred patients with palindromic rheumatism. And they had to, you know, use criteria as to who they were going to study, and it got down to one hundred and fourteen in patients who were treated with colchicine with or without hydroxychloroquine, and I don't know that number, but I think it was a minority, who were in remission and who they then withdrew therapy and had six month follow-up data. So, it turns out that, I think, something like forty percent were seropositive and sixty percent were seronegative of the palindromic rheumatism, and it didn't matter as far as the outcomes here. As we've talked about at ACR, when our last roundup that we did, I think we talked about palindromic rheumatism being another version of preclinical RA or CSA, and it should be considered as such and treated as such.

But in this study, again, one hundred and fourteen patients, and by protocol at that center, if you achieve remission for six months, then you withdraw therapy. And when they did that, the number was forty seven percent relapsed within six months, meaning with six months follow-up, fifty three percent stayed in remission. Turns out the people who stayed in remission were tended to be younger and they tended to have an elevated higher sed rates in CRPs at the time the therapy was initiated. The other good news to this was, so one, you can withdraw chronic colchicine therapy in these folks, but that if they do flare, the other half that does flare, restarting colchicine at the previous scheduled dose would recapture remission control in seventy five percent of patients. And there's just still a minority then of people who couldn't be controlled, and for those they just said they escalated therapy with other DMARDs, probably like they would in RA.

And again, lastly, it did not matter whether these people were seropositive or seronegative as far as the success of colchicine withdrawal.

It's interesting timing because we were in clinic yesterday and one of the residents rotating through asked me if colchicine works in rheumatoid arthritis. I said, I know that it's been looked at because in rheumatology we try everything for everything. And but that dates back to the really anecdotal days of rheumatology. You know, as when you see one, it's in my experience and you see two, it's case after case. When you see three, it's all of my patients, you know.

And so it's interesting. I said, I don't. My my gut is that it wasn't that effective in RA, but it wasn't. It's just anecdotal that because I know people had used it when we were young, way, way, way back when it was old. So we did not great studies of that, but a very interesting topic.

Doctor. You know, think I had the same resident rotating through my clinic. I got the same question about six months ago, which then took me into too long a dive to find information on it. And you're right, there's almost nothing about its efficacy and a lot of anecdotes. And what was found, like it was reports from the 50s that suggested it, but who knew if they had the right diagnosis back then?

This was before you know, sensitized sheep cell agglutination tests and Rosewaller. So they may not have had the right diagnosis. All right.

So I got one less than a minute I'll cover just kind of as a public service announcement, if that's okay. OP221. I know what you people are thinking out there. You know what we really need in rheumatology is a new measure of lupus. Because the slam and the slick and the sled eye and the bileag and the Doris and the LLDAS.

And I'm not making these up. These are real measures of disease activity in lupus. Well, there's a new one that you may be hearing about. It's this is is it the poster is OP two twenty one. It's called the treatment response measure for lupus or TRM SLE.

Six different domains and measures disease activity, and they kind of came up with this, I call them sort of bog set recommendations, a bunch of guys sitting around a table. They seem to make sense, but then again, so do all the other outcome measures in lupus. You know, I get to love the real lupus aficionados. They're like Siamese fighting fish. Don't leave two of them alone in a room together because only one's coming out of the room.

So, this, you may hear about this or may not, TRMSLE.

You know, just remember back already to a meeting we went to in Lisbon twenty five years ago when Ted Pinkus got up amongst all the KOLs who were doing research and said there's something really, really wrong when the measures we use in clinical trials have nothing to do with what's done in practice. So, you know, I applaud people for working on outcome measures, but you got to, you know, that's why I've always thought CDAI, RAPID3, you know, those can be done in clinical trials, those can be done in practice, you know, but it is a step forward nonetheless. My last one's going to be, it's one of those things where you're walking in the poster hall, which is just a delight, and you get stopped, you take pictures, you have fun, but then you see faces and you know someone and you think, I know that guy, should I stop? Anyway, I couldn't help but go to this poster because our good friend Atul Diadar is waving me over and I can't avoid him even though I'm trying to get to somewhere. And he presents to me POS1350, the withdrawal of upadacitinib in patients with axSpA, who had achieved remission.

This was an extension study of a previously reported, phase three SELECT AXIS-two study, which I think involved, almost 800 patients who were treated with upadacitinib or not for axSpA and proved that it worked, and that's why it's got that indication. So the seven thirty four patients in the study, one hundred and ninety four were in remission at week one hundred four. And in those people, upadacitinib was withdrawn, and then they followed them over time. And they showed that seventy eight percent, not surprisingly, seventy eight percent flared, and it took a meantime to flare was three months, meaning that you really didn't need to be on that drug. And then that eighty percent were able to regain control by restarting upadacitinib.

And that's all good, well, and fine, and not too exciting. But what was exciting, I thought, was the converse story here, That when those people were withdrawn, and these followed these people for almost a year, twenty two percent stayed in remission. So think about it, an axSpA AS patient does great on a new therapy, and then they go into remission and they're happy, and then they stop therapy. And I said to, you know, I was standing there with two other rheumatologists and Doctor. Deidar, and my experience is I spent years yelling at young men saying, Dude, you gotta take this magic bullet for your ankylosing spondylitis.

And they resisted and resisted, and they wanted to keep taking Telectin or some non steroidal. And then finally they did it and they come back and they said, I can't believe you didn't give this to me sooner, you know, and I wanted to scream. And they stayed on whatever magic bullet it was, and then I don't know when, but two, three years later, they stopped the drug on their own and they're still doing good. Is Can going you do a reset in these patients? Should I get all militant on these folks when they stop their medicine?

My answer is no.

The maybe Atul is waving you over because this is exactly what you'd expect. I mean, this has been shown in RA, in PSA, and the and in AS also with other agents. The problem is we don't know how to identify those twenty two percent of patients. Exactly. A priori.

The only way to do it is to stop and find out. And the problem with that, and I tell the patients all the time, is that as soon as you feel an inkling of disease come back, you get on therapy because you may not get the response quick or you may not get it as full as you had had it before. That's the difficulty with all these tapering issues. But yeah, lots of people try it. I don't discourage them because you can't.

They're going do what they want to do anyway. And it's nice to have data to say you get a one in five chance and I can't predict for you if it's going to work for you.

All right folks that's it for you are 2026 roundup. It was a great meeting in lending. It was a great review of the content with Artie. We look forward to seeing you at room now live. Last weekend in January in Dallas or at home.

We're live streaming and we're live on stage. Hope you'll be there. Take care.

Bye bye.