EULAR2025 Topic Podcast RA2 Save

You're listening to a RheumNow podcast coming to you from Barcelona, Spain and EULAR twenty twenty five. Hope you enjoy it.

Hi. I'm David Liu reporting from busy Barcelona for EULAR twenty twenty five for RheumNow. It's been a great meeting. Lots of interesting stuff today. I want to tell you a little bit about JAK inhibitors and some of the stuff that's been going on, the latest from the Jackpot study as well.

So I was part of a great session with Andreas Kush, Bhauma and Kim Lauper going through a little bit about where JAK inhibitors are going. Andreas, who's been heavily involved in the two sets of points to consider on the use of JAK inhibitors that Yulah put out. Had a lot to talk about the new avenues that JAK inhibitors might be explored in certainly beyond the indications that we're used to and thinking about things like GCA, PMR, lupus, Sjogren's disease, even things like vexus. And he really went through the data beautifully. It was lovely to see actually that even though there were some fears, I think, that oral surveillance would lead to the end of the drug development pipeline and JAK inhibitors, that's been far from the case.

Kim really went through beautifully the oncology risk from JAK inhibitors, where some of the upsides potentially could be, some of the plausible mechanisms. It really was a masterclass. But I think all of that underlies the idea that maybe we've got over the shock of oral surveillance, we've started to know how to process this all a little bit better. Here in Europe it's been interesting to see how the response has been to rheumatoid arthritis prescribing for JAK inhibitors versus other therapies, and how that's gone in amongst new entrants to the market, as well as EMA warnings, as well as the release of the oral surveillance results. And so there's a really interesting poster from the Jackpot Collaborative on the floor, posted 150, which detailed a lot of those things.

The Jackpot Collaborative, of course, has multiple national rheumatoid arthritis registries which band together to look at the utilisation and outcomes from JAK inhibitors in rheumatoid arthritis. In this poster, they looked a little bit the overall utilisation in the markets that they serve, and to what extent we've been using more or less of different JAK inhibitors and how that's all played out. And some really interesting data, because it showed for starters that well and truly before the release of the oral surveillance results, use of tofacitinib was really levelling out and, if anything, declining here in Europe. I think that was largely supplanted by firstly baricitinib, then upadacitinib, which has continued to grow. Maybe it would have grown more sharply if it wasn't viral surveillance, but certainly the utilisation in absolute terms has continued to grow.

So, I think that gives us an idea that of course despite the EMA warning, despite the regulatory limits on how we might use JAK inhibitors, that we are using more of JAK inhibitors and that's probably appropriate. I can't say for certain off the base of those broad numbers, but it would be appropriate for the utilisation to increase. Clearly, there are a lot of patients out there in whom even with an EMA warning, the use of JAK inhibitors in rheumatoid arthritis would be appropriate. And it makes sense that we're not going too far one way or the other. We're not using them with reckless abandonment at the same time, we're not using them.

There's not a chilling effect on our use of JAK inhibitors, and we're not inappropriately withholding them from patients who would benefit from them. So I guess that's the balance of it all. It's always really interesting to see how this plays out in different parts of the world. We can see actually in The UK and in Australia, there's been more of a chilling effect the regulatory warning, or certainly at least a decrease in utilisation of the regulatory warning. And it would be very interesting to compare that to The United States.

So plenty more on rheumatoid arthritis, JAK inhibitors and everything rheumatology, you know what to do. Go down to rheumnow.com. Hi, it's David Lou here reporting from day three of EULA twenty twenty five. It's flown by. It's all been happening in the very warm Barcelona inside the conference centre.

It's also running hot. I just want to tell you a little bit about some data that was presented in one of the oral abstract sessions, which extends on. I went back and had a look at my EULA twenty twenty two tweets and I found the tweet about the ARIA study back then. And the ARIA study back then was six months of abadacept treatment in patients who were high risk clinically suspect arthralgias. So that is to say they were ACPA positive, they had MRI findings, and they had pain.

And it was a double blinded trial, you could either get abatacet for six months or placebo, and then you had a twelve month follow-up after that. I think the remarkable thing after that was twelve months later, there was still a gap between the lines and it's an upsizable one as that. Well, you know, to have twelve months legacy after that, after six months of a Batacet, maybe there's something of this. But we would like to see longer term data. Well, here we are three years later, another three year lives later here in Barcelona, we've got the follow on data from that median follow-up of just over five years.

There's been a little bit of drop out, so make of that what you will. But there's still a gap. The gap is narrowing at five years, no question. It was wider there for a while. But at this point in time, it does seem that six months of abatacept buys a forty week gap of rheumatoid arthritis free survival.

So, an extra forty weeks without rheumatoid arthritis. I don't know, is that worth it for the extra twenty six weeks? Obviously, this is not a homogenous thing and some people are doing a lot better, some people aren't getting that benefit. And I think that's what it comes down to. My takeaways from this, as well as the PIPRA as well, and I really applaud these studies, they're run by good people, really smart people, who think deeply about this and I think are on the right track.

But I think everyone would say, A) we would like to phenotype these patients better, more than just that, so we're getting the right people for that kind of intervention, if that's what we're going to do. And then b) we just need to find these patients better. Because it's really hard at the moment to try and find these patients. We know that both of these studies took a long time to recruit. And to finally act for positive patients before they develop full blown rheumatoid arthritis.

Some places in the world are clearly better than others. But if we're going to think about this type of preventative intervention, which think would help some people, then we've got to think about the infrastructure as well. I feel like this is a discussion that's been happening at Yula for at least the last ten years about how to operationalise early rheumatoid arthritis. But now that we're actually starting to get therapies that might do something in that space, now it's the time for us to think about implementation science and how we might go about figuring out who would benefit the most, and then actually figuring out how we would find those patients in practice and deliver them the therapies they need. For plenty more RA, you know where to go.

Rheumnow.com.

Hi, I'm Doctor. Janet Pope reporting at EULAR twenty twenty five in Barcelona for RheumNow. I wanna talk to you about how to properly use steroids in early RA, thinking about oral versus parenteral. And by parenteral, I mean I'm intramuscular or intra articular or both. So the first abstract is oral presentation three twenty seven.

So if you recall, this is a sub analysis of the randomized controlled trial of NORD STAR in early RA. And NORD STARR had various treatment groups which I will discuss. However this study wanted to look at tapering and stopping glucocorticoids and the risk of flare and therefore who can get away with it. So first of all they were going to look at a C. Defined flare rate and they wanted to look at what happens when you stop glucocorticoids and compare the three groups.

So they had three arms. The first was conventional or oral group Methotrexate plus oral glucocorticoids, just like the EULAR guidelines or recommendations that were updated today and didn't change. So at this part, they didn't change. So that meant methotrexate plus oral glucocorticoids. So they started at twenty milligrams a day of prednisone or prednisolone and tapered by five milligrams till week nine and then had to try to get off steroids by week thirty six in this trial.

The next group was conventional treatment. So instead of having oral prednisolone, they received triple therapy methotrexate, sulfasalazine hydroxychloroquine, and joint injections. Intra articular joint injections were mandatory for up to four joints at every visit until a certain time in the protocol, then it could be not mandated as much. Then the third group was the Biodemar group. So they got methotrexate and one of the biologicals, and there were a lot you could choose from or that they could be randomized to.

Sertralizumab pegol, Avataz after tocilizumab. Now all the groups could get intra articular glucocorticoids, but the one group with triple therapy was mandated if they had enough swollen joints and you could do up to four. So this was a pretty big trial, eight ten patients with active early rheumatoid arthritis. So what did they find? They found that the initial intra articular injection group had the same flare rate similar to the BD MARD group, despite most of the intra articular injections were early on in the RCT of that group that had triple plus intra articular steroid injections.

No surprise, the biggest flare when coming off of prednisone were those who were on oral glucocorticoids. I think that this begs the question that we should be reconsidering how we should be administering glucocorticoids to the majority of our early RA patients. We want to get them off them over time, and not everyone gets off if we have an intention for them to get off when they're on oral, but they're more apt to get off. And I'll tell you more about that if they're on parenteral, probably because we can control it as opposed to any physician or healthcare provider could give a prescription if they had the jurisdiction to give a prescription for oral glucocorticoids. And the patients would have a bottle and be able to use them on their own.

So what supports this further? So poster six forty four is from our CATCH cohort. So that's our Canadian early arthritis cohort. And it was led, this analysis, by Doctor. Andrew Fernandez Codina, who is a rheumatologist in both Canada and here in Barcelona.

So what happened in this study? There were two thousand two hundred and twenty two patients with early rheumatoid arthritis. This is an incident cohort across Canada. As you would suspect, mean age 55 years, mean disease duration at onset of enrolling five and a half months, seventy five percent nearly were females and eighty six percent Caucasian. And basically most of these patients are on methotrexate with a mean dose of twenty milligrams ranging really from a bit less than that up to twenty five milligrams oral or sub q weekly.

So the C. Dye scores were looked at at baseline in twelve months as well as six months. And basically the majority in this study received no glucocorticoids at all. In fact, seventy five percent, very much not like the practice style of the EULAR guidelines. The oral only glucocorticoids were nineteen percent of patients, parenteral only just five percent, and both oral and parenteral was one percent.

So about twenty percent were on chronic oral and five percent or so on parenteral only IA or I'm So the group with the no glucocorticoid started off with lower disease activity. And at the end of a year, they were all in about the same disease activity. But the C. Dye was about the same at the end, but the no glucocorticoids were less apt to progress on to an advanced therapy. Really only about eight percent of them were on glucocorticoids at a year at most, and about eight percent had gone on to consideration.

So not surprisingly glucocorticoids at twelve months were approximately eight percent in the group that started with no glucocorticoids and the group that was on oral glucocorticoids almost half, forty seven percent were still on oral glucocorticoids. For the I'm IA, about half that were still on glucocorticoids, which still could have been I'm regularly or IA regularly or even oral. So about twenty six percent in that group. And if they were on both oral and intra articular or oral and intramuscular, sixty three percent were still on glucocorticoids. I think there's a dose response that the more steroids you got, the more likely you had higher disease activity and a marker of being difficult to treat.

The other interesting thing was that if you didn't have any glucocorticoids, again they were milder, about seven percent moved on to an advanced therapy at the end of a year, whereas it was higher if they were on glucocorticoids. More went on to an advanced therapy. So a couple conclusions of this study. The initial use of glucocorticoids is low despite EULAR recommendations, so they're not followed the same way in Canada. Perhaps we follow closer to The U.

S. Recommendations or a hybrid of the two as we often start in combination therapy with CSD MADS. But the no glucocorticoids had milder disease and were less apt to have to move on to an advanced therapy and were certainly far less apt to be on chronic oral steroids at the end of a year. If you were an I'm or IA as a patient getting that, group of patients, twenty six percent were still on steroids at a year. However, if you were on oral from the beginning, half those patients were still on steroids.

And if you were on both oral and parenteral, two thirds are still on steroids. So again the take home of these two abstracts I think is better to give a jab than to give a pill. So in other words, you should control the glucocorticoids intra articular or intramuscular, and you'll get more people off glucocorticoids and less needing to go on to an advanced therapy. Please follow us at room now. It's JanetBurdope reporting.

Thank you.

Hello. I'm Jonathan Kaye from UMass Chan Medical School in Worcester, Massachusetts, reporting for RheumNow from EULAR twenty twenty five in Barcelona, Spain. Today, there was a clinical abstract session on prevention and early treatment of rheumatoid arthritis. Rheumatoid arthritis represents a heterogeneous group of diseases. There are patients who are seropositive with either rheumatoid factor, antisitralinated protein antibodies, or both.

Then there are those who are seronegative. But these are not necessarily the only subgroups of rheumatoid arthritis. There's a need to identify distinct subgroups that might have different disease trajectories or respond differently to various therapies. There were two very interesting oral presentations at this session, both given by Ciardo Marvecin from Leiden in The Netherlands, working with Rachel Knievel at that group, about subgroups of rheumatoid arthritis. They used unbiased machine learning cluster analysis of the Leiden early arthritis cohort and identified four distinct patterns of joint inflammation: inflammation predominantly involving the feet, inflammation predominantly involving the hand, oligoarticular inflammation involving only a few joints, and then polyarthritis involving multiple joints.

They observed in this cohort of patients with rheumatoid arthritis of less than one year duration that those with the joint involvement pattern involving predominantly the hand, those patients responded best to methotrexate, and those with polyarticular disease responded least well. Those with hand involvement were most likely to achieve C. Dye remission, and those with polyarticular involvement, as expected, would be least likely to achieve C. Dye remission. In this presentation, or in this study, they performed independent data meta analysis of data from the NORD STAR and BEST strategy studies.

The NORD STAR cohort included eight twelve patients with DMARD naive early rheumatoid arthritis, and the BEST study, a similar group of patients, five zero eight individuals who were randomized to four different strategies in each of these trials. They found that these joint involvement pattern subgroups were reproducible in each of these cohorts. Of these subgroups, the pattern involving predominantly the hand tended to be older individuals, and the pattern which was polyarticular tended to have higher disease activity both by Cdai and DAS28 CRP. C. Di improvement over one year was greatest in the hand predominant group and lowest in the polyarticular predominant group, with C.

Di improvement over time being worse in females, but independent of age, sex, serology, and symptom duration. C. Remission at one year was achieved most by individuals in the hand group and least by those with a joint involvement pattern being polyarticular. When they looked at the subgroup of patients in each of these studies who were treated with biologic agents in NORD STAR with cerdulizumab pegol, abatacept or tocilizumab, and in the BEST study with infliximab, they found that biologic therapies were similarly effective or ineffective for all joint involvement pattern subgroups. In the next presentation, Doctor.

Marcevin went on to address the question, how do these joint involvement pattern subgroups correspond to synovial histology? What is the biologic basis for the distinct subgroups? To do this, he collaborated with Stefano Alvarini in Rome, who has a Syngem cohort of two sixty two DMARD naive rheumatoid arthritis patients who underwent synovial biopsy of the knee. Now, in the hand predominant group or the foot predominant group, the knee is not necessarily the most involved joint, but the knee is most accessible for synovial biopsy. So, they looked at synovial biopsies from the knees in patients, and they found that the same joint involvement pattern subgroups could be identified in this Syngem cohort.

They then looked at three characteristics of the synovial biopsies and found that the hand and polyarticular involvement group were relatively similar with most severe lining layer hyperplasia, stromal density, and inflammatory infiltrate. These characteristics were least severe in the oligoarticular group and intermediate in the foot predominant group. So, in this second study, they found that these joint involvement pattern subgroups appear to be distinct biologic entities. Now, the next step in proceeding toward personalized medicine will be to identify biomarkers that characterize each subgroup and might serve as predictors of disease trajectory. These two studies taken together help to characterize more homogeneous subgroups of patients with rheumatoid arthritis who might perhaps respond better to specific therapies and might be studied individually in clinical trials of novel therapies and also of existing therapies for rheumatoid arthritis.

I look forward to seeing more coming from this group about this topic. I'm Jonathan Kaye, reporting for RheumNow at EULAR twenty twenty five in Barcelona, Spain. For more about this and other topics, go to roomnow.com. See you later.

Hi. It's David Lu here reporting from Barcelona for EULAR twenty twenty five. And right now I want to tell you a little bit about one of the really interesting RAILD abstracts. Now, I don't always present on RAILD, partially because often we've got people on the team who are far more have far more expertise in ILD than I do. But I was really excited by this abstract and I think it is the kind of thing that might excite you too, even if you're not a specific IOD aficionado.

And that's because I think the fundamental issue that I have with RA IOD, that when a patient comes into my room, sometimes they are the one that really just accelerates and blows out their RAILD when they have it. And they go from zero to 100 really quickly. And then sometimes it just sits there and doesn't really do anything, and it just stays static. And it's really hard for me to know which one is going be which, and there are some broad measures and I think we've seen a lot of progress in that space. But nothing really that's been able to bring them all together in a predictive tool.

But that's what we've seen today from the South Koreans working with RheumNow's own Jeff Sparks on a predictive tool that's Abstract 0P0329 at today's meeting. And so in essence they took 138 RA IOD patients, saw how they progressed, tried to pick the ones that over the next two and a half years progressive disease, progressively fibrosing disease. And then they took some of those clinical features that we might actually have access to in clinic UIP pattern, ILD extent, DLCO, ACPA, as well as the specific KL6, which is a biomarker specific to ILD. But knowing that's not always available, they did a model without it and with it. And even in the model without it, actually the performance was pretty good.

The AUC was 0.75. So this is actually not bad. I'm sure that with bigger numbers these predictive tools will get better. They put the algorithm up on screen, it's one that it's got face validity, it's logical, it makes sense. So this would be really exciting if this washes out well in the external validation.

Because what I'd really like to be able to do with RAILD patients is know whether this is a high risk for progression, a medium risk for progression, a low risk for regression. And those high risk ones I'm going to be doing things a lot more intensely, both in terms of monitoring and potentially in terms of therapies, than I would do for the low risk ones. If we can start to stratify that knowing what we know already about individual risk factors, combining them into a predictive tool. And if that's something that we can use in the clinic room, then I mean I really think it's the kind of thing where we can hopefully treat the right RAILD with the right types of therapy, take the serious stuff seriously, and the stuff that won't progress we can relax a little bit. For plenty more w about

RA, and I mean plenty more, you know where to go.

Broomnow.com Hi, it's David Lou here, covering all the great rheumatoid arthritis material from July 2025 for RheumNow. This morning we had the second recommendation session. I always find these really fascinating because, especially when it comes to the recommendations, it reflects a little bit about how our thinking changes and really the standards of what we do, how they've changed over the course of time. It's been really interesting because this morning we saw Professor Joseph Smolin present the latest update on the rheumatoid arthritis treatment recommendations. These have had to be updated every couple of years as things have progressively changed, especially over the last fifteen to twenty years, as new possibilities and threats come on the horizon, we've had to gradually just iteratively change the advice.

So it's come to be that there's a new update for 2025 that's updated the 2022 guidance. I just want to run you through a few interesting points from there that are worth talking about. Firstly, I want to say upfront, Justice Mullen was very clear in talking about the evidence behind starting with methotrexate and glucocorticoids, rather than starting upfront with a biologic, And showing that there's really no substantive advantage in starting with a biologic. Having said that, there was a bit of an iterative change. Because previously, it had been about there'd been a bit of a question as to what to do after if you had an inadequate response to the first CSD mod, really methotrexate.

And previously it had been, depending on your prognostic factors, you might go to a second CSD model, or might be suggested to go straight to add on a biologic. That's really kind of shifted away now towards going straight through to adding a biologic here in Europe. Really, I think that reflects a lot of different things, including and this was a name checked in the session the fact that biosimilars have really changed the emphasis of the way things work here. Affordability of biologics is constantly changing when biosimilars work in the way they should, which is what happens here in Europe. So I think that's really pleasing.

Talking about the other end of that, there's a little bit less of an emphasis in the recommendations about trying to completely taper off and find drug free remission without any guidance, which I think has always been something which has seemed a little bit elusive for a lot of patients. So it's really more about continuing potentially spacing rather than completely stopping. That's been emphasised now in the recommendations as well. Once again, reflecting the way people are practising here in Europe. And then the final thing is that, as always, the JAK inhibitors have been flagged in terms of being a secondary option really when it comes to selection, especially after the first agent.

And there's still these questions about when we'll get some further determination on safety. Professor Smolden is certainly waiting eagerly to know the results of the baricitinib post marketing requirement safety study, the oral surveillance equivalent. It's due to report by FDA timelines next year. So I think we're all waiting with bated breath to see what that means in terms of extrapolation of oral surveillance results in terms of cardiovascular cancer risk for a high cardiovascular risk population, whether the results that we saw for tofacitinib really do apply across all JAK inhibitors. So, as much as it sometimes feels that we've got all the solutions for rheumatoid arthritis, A, we're far from that.

But B, even the way that we practise with the existing tools that we do have does seem to constantly iterate as time goes on. For plenty more of that, you know where to go. Head on down to roomnow.com.