EULAR 2025 - Day 5 podcast Save

You're listening to a RheumNow podcast coming to you from Barcelona, Spain, and you are '20 25. Hope you enjoy it.

Hi, everyone. This is Adela Castro reporting from ULUR twenty twenty five here in Barcelona. I wanted to share with you an abstract that I find very interesting. This is the poster number 1276, and it was about biologic switching in psoriatic arthritis. It was a cohort analysis.

Overall, it was a very large cohort over 9,000 patients, and then they included approximately three thousand eight hundred patients that were starting on biologic therapies, and they found that the initial therapy was most likely to be TNF inhibitors, but then when the patients to switch therapies, the second therapy that they were most likely to switch from a TNF was actually a second TNF, and then followed by these was IL-seventeen inhibitors, and then subsequent switches were either back to TNF or IL-twenty three or JAK inhibitors. It was very interesting to see that switchers were most likely to be female. They were obese, they were smokers, and they were from loss of economic status. Something that I didn't see on this ASTRA was kind of like the disease activity, which I was kind of hoping to see there was a reason for the patients to kind of like switch the mechanism of action or the medication. So for more information, follow us on RheumNow.

Hi everyone, this is Orelinage from Glasgow reporting live from RheumNow. I'm no longer in Barcelona, but on my way back to Glasgow, I had a very interesting conversation with Stefan Seebeth who decided to kindly join me for an interview today and we're gonna discuss about PSA. So, professor Stefan Seebeth is an expert in the field of PSA. He's the co convener of the Difficult to Treat PSA Task Force. Thank you, Stefan, for joining us.

Great, Tori, it's great to talk, discuss this and speak to you.

Yeah, so we were were discussing obviously the criteria for difficult to treat PSA and I was wondering if you wanted to maybe talk us through what the process was for you to get there and develop this with the task force.

Yeah, no, great. Mean, as you know from our clinics that we share sometimes and that's you know, we're really lucky in PSA that we've got a lot of choice now and what it's showing us is that actually we aren't missing number of drugs because we've got lots of different agents, different classes but there's still a group of patients who just don't do well even though we've tried a number of these drugs and that's sort of the concept of difficult to treat. Rheumatoid has been out there for longer and the EULA guidance has been there but actually what's very clear as well is that PSA and axSpA as well are very different to rheumatoid. You know there's lots of other domains involved, the underlying disease is different and we shouldn't assume that the patient who's difficult to treat or fails to respond to a lot of the agents and the one disease is going to be the same as the other one. And as part of this, so we proposed this EULAD task force and one of the things that was very obvious was that a lot of people are interested in this difficult to treat.

We've all got these patients and we all want to help them and but actually when you look at the literature and as part of our task force we did a systematic literature review. There's people are writing lots of papers which is great but everyone's using a different definition and it's very hard to compare and put them together and do bigger meta analysis. In fact we could hardly do any meta analysis because of that that you just couldn't compare the same cohorts. So we all have this concept but we're not speaking the same language and I think it's important that we do and I think that's important both when we speak to each other as clinicians but much more importantly if we want to do robust research and that's all the way from epidemiology to trials we need to have a definition that we agree on and so we can compare between studies and then we can actually start moving the field forward and saying actually this is what we're talking about, these are interventions we could test because that's how rheumatology and medicine works. We want to test something and the answer is A or B and then at least we learn something we move forward.

At the moment there's lots of interest, of noise but actually little progress. And so we had the EULA task force and it was followed the usual EULA SOPs with them. We had patient partners joining us and a lot of clinicians across Europe with really interesting and invaluable experience and we had a number of meetings and we were privileged to that Helena Mazza Otega who's the co convener was able to present those points to consider for the definition of difficult manage PSA and we can talk through some of those if you'd like.

Oh yeah, yeah, absolutely. So what is the let's do a thirty second summary of the definition for the

So I think that's it's difficult is what I would say and there was lots of voting and agreements and again our patient partners were really invaluable and what's different to rheumatoid is again the number of drugs but similar to AxSpa interestingly, the group came to the idea that there's this bigger group of difficult to manage and again this is terminology we tested with our patient partners and they were really helpful and encouraging. We wanted to make sure that this didn't feel like it was putting blame on the patient. This is something a descriptive term but it doesn't imply any fault of anyone and so we've got this bigger group of difficult to manage patients and that's really driven by failure of a number of therapies. So you've done the test, you've tried at least in this case two biologic therapies of different classes and the patients failed to respond and as you know there's lots of reasons for that they go from safety side effects to no response to comorbidities and so there's this bigger group but we also wanted inside that we've got a smaller group of people who are treatment refractory and so they are people who have failed to respond to these but we believe that you know that the drugs had a good trial and they've still got active inflammatory disease.

So that because you can already imagine the interventions you might test in those would be quite different. But also built into that there's a lot of flexibility because there's lots of domains you know skin comes into extra musculoskeletal manifestations. We wanted to have a target the patient should achieve the target because we know they have better outcomes but also there's this flexibility like the rheumatoid ones where if both the patients and the physician think it's not well controlled they can still be put into this again as I say that the aim is that we can have a simple definition and start comparing and speaking the same languages and I would declare at this stage that actually at the same time GRAPA have developed this independently and so they presented those initially and so we are going to have two lots of definitions and I think on some levels maybe people say that's troublesome but I think they're both generated from bottom up and actually it'll be quite a good test if we being able to compare those because it would allow a bit of comparison almost the control arm if you like in between the two and we and I think these definitions will be refined over time.

So I think it's a good place people are really interested in this and we'll start being able to do some robust research but it's really based on failure of number therapies, different arms, you've tried a different class of action. And then if you're in the treatment refractory, the one where we think there's really an inflammatory disease that you need evidence of that, some objective evidence.

Yeah, no thank you, thank you Stefan, I think it's very nice to hear from you and what the process was and I think what's also really interesting obviously is that we do have knowledge and experience from the difficult to treat RA and and and I know I think what's what's kind of becoming pretty obvious is that we have very different patients obviously within that group and as you said probably you know as far as the definitions from before even about the the the Pira and the Nira and the so the non inflammatory, the inflammatory and I think so obviously for PSA did you did you find the same type of stratification but also do you think it's necessary to add an extra layer of stratification according to domains, which is something we don't have in RA, and how is that gonna influence potential trials in the future and all that? What are your thoughts on that?

Yes, think that you're completely right. I think two comments one, I think in PSA it's a lot harder to be sure of inflammation because it's less systemic inflammation rheumatoid. So I think those that stratification is a little bit easier in rheumatoid than it is in PSA. You can't be as sure even with ultrasound even with imaging and the same in axSpA and I think the comorbidities play a bigger role here you know differentiating degenerative diseases is quite hard in the spine for example and so I think that's that definition isn't quite as clean as in rheumatoid but I do think that we discussed whether it's a domain or not but each patient has their own priorities and so actually you know that comes into the shared decision making but we felt that actually we've got drugs that work in all domains of PSA now and actually if a patient hasn't responded well it doesn't really matter which one it is but you're quite right if you are testing an intervention you might want to say these are your treatment refractory patients and then you might want to say these are the ones where skin is the dominant problem and where the joints are and you can see we could design some really nice stratification trials and actually saying already taking a group of patients with disease that's meeting these criteria but then doing different interventions for them and actually starting some platform trials and some really interesting tests and hopefully test a number of interventions and start getting some answers where we can put that back in and say if we had known upfront we could have stratified you and used this treatments and gotten it right the first time.

So I think in a way the difficult to manage and the difficult to treat feeds back and actually will make for every patients better because we'll one hopefully be able to stop preventing patients getting to that stage, getting the right treatment upfront and you know, and so I think that this will feed into a nice precision medicine stratification development in the field which is what we all really looking for.

Absolutely. And talking about intervention, there was this oral presentation, I think it was 90, was presented on the first day, I believe. And it was this case series about patients receiving combination of two biologic or biologic and and targeted synthetic demods. And this is something I'm always you know when it comes to clinics and you know we have had this conversation in the clinics as well. You know, it's it's something that I we really don't take lightly, right?

So, the the data looked quite reassuring in that series. Obviously, it's a case series. So, what are your thoughts about that? Is it something you use a lot? Should we use it more?

How can we progress?

So I think two answers just to say that that part of the reason we've got the two definitions is, you know, so if someone's got difficult to manage PSA because of comorbidities or because something like that you don't want to be trying combination therapies. Their interventions fibromyalgia, osteoarthritis, their interventions may be very different and so we can do nice trials there as well that look different and then again so hopefully if we do combination therapies we'd be doing them in the true treatment refractory. So these are people who failed drugs, they've had a good trial but they have still got active inflammation and that's so one you've enriched for inflammation so you can really test but I think that the nice thing is rather than case series and we've all got this case series and we know the bias that comes with case series reporting bias and I agree with you I think so to date the safety profile is really reassuring but really we want to know you know what is the best combination. We all think we know but until you do it and so I think we can start doing those trials both you know really robustly with control arms whether that's a placebo without and I think that's rather than having lots of case series where we got lots of N is one experiments we actually start doing big ones and again we all got some of these patients but we haven't got thousands of them.

So the nice thing is if we start collecting it and doing the trial robustly we can start pooling data and getting statistical power and start answering these questions actually this combination is better than that one or actually they're equal and it depends on the patient but we can start answering that and I think you know I think that there's a lot of interest in combination therapies and particularly PSA where we have divergent responses in the joints and the skin and often we think we understand the biology and we get something completely unexpected and so I think we can really back to your stratification, we can start stratifying but also using combination therapies in people you know because there are risks to that, we think they are you know these are immunomodulatory therapies and we don't want to give it to the bigger difficult to manage group but the true treatment refractory inflammatory group we can do give it and again what you find when you look at the literature for combination therapies everyone's defined it a bit differently, everyone's used a different outcome and you just can't pull the data and I think that's what we owe our patients to do this, you know, even if it's observational, do it robustly and speak the same language and pull the data.

Absolutely, yeah. So that's definitely a space to watch. Probably next year, Joula, we'll have much more to discuss. But yeah, no, thank you so much, Stefan. I think it was very helpful.

And I invite you all to follow RheumNow for more content, and follow me on Twitter RheumNow. Bye, everyone.

Thanks, Thanks, everyone.

Hi, everyone. This is Cusha Li reporting for RheumNow at EULAR twenty twenty five. I have an exciting update on a potential new treatment for psoriatic arthritis that may soon change how we care for our patients. This is a late breaking abstract, number LB0001, by Professor Desiree van der Heide from Leiden, Netherlands. The abstract presents a week 16 data from what they call poetic PSA one trial.

It is the first phase three study to evaluate the drug ducruvastatin, a neuro oral medication that blocks the signaling protein tyrosine kinase two or TYK 2. So this drug has actually improved in many countries for skin psoriasis, but this is the study that explores whether it also works for patients with active psoriatic arthritis, especially those who are biologically naive. This was a large international randomized controlled trial involving six seventy people with active joint and skin disease. All participants had clinical inflammation and evidence also of joint damage on X-ray, meaning they were at risk for further progression and in need of treatment. So the patients received either dupilacitinib once daily six milligrams or placebo, and they were followed for sixteen weeks.

The main outcome of interest was to see whether the drug improved joint symptoms according to ACR 50. And the other secondary outcome was to look at skin improvement, physical function, fatigue, and whether the drug could also slow down radiographic progression. Now by week sixteen, over half of those on decravacitinib showed meaningful improvement in their joint symptoms according to ACR50. That's in comparison to just one third of those on placebo. And the benefits didn't just stop with symptomatic improvement.

The people who are taking decravacitinib also had better outcomes in skin clearance, daily functioning, overall well-being, and resolution of symptoms like staphylitis. One of the more nuanced findings came from imaging data. Now keep in mind, sixteen weeks is a short amount of time to really look at potentially meaningful radiographic changes. Initially, there were none statistically significant, but after some more sophisticated analysis looking at the distribution and such, they found that actually people with dupercitinib had less progression of joint damage compared to placebo. So this is promising and will be on the lookout for more long term data.

What about safety? That result was also reassuring. The most common side effect, as you would expect with any kind of biologic therapy, was the increased risk of upper respiratory infection, like mild cold. But serious side effects were actually rare. There were no new concerns about cardiovascular disease, blood clots, cancer, or serious infection.

Again, keep in mind, this is preliminaries first phase sixteen week data, and we might see other safety signals, but at least at this stage, it's very reassuring. So what does this mean for our clinical practice? So this is the first time, as I mentioned, that a TYK2 inhibitor has been studied in psoriatic arthritis at this scale, and it's delivering some promising results. The benefit of dupervastatin, it's a once daily oral medication. And so for patients who really don't want to take on injectable medication, this provides another option that can potentially target both joint and skin disease.

Now this aligns with what was discussed at the plenary session for psoriatic arthritis by doctor Laura Quotes from, Oxford University. The highlight message up there was that with psoriatic arthritis, there's an expanding landscape of potentially available treatment. And the idea and goal here is to match the domains of the disease to specific medications so that patient preference is taken into account and they have better outcomes. I wrote an article about this, and I encourage you to read that on RheumNow to learn more. This was Cheeha Li reporting for RheumNow at EULAR twenty twenty five.

Stay tuned for more updates for psoriatic arthritis, and thank you for listening.

Hi. David Li reporting from day four of EULAR twenty twenty five, the final day. And I was wondering the poster floor today, and I came across poster twelve thirty two, the subject of which was everyone's favourite new class of medicines, the GLP-one receptor agonists. And I think we started to see more and more data about how these drugs might affect our patients, knowing as well that we might not necessarily be the ones prescribing them right now, but actually our patients, because they live in the world and because they hear about these drugs, are getting them possibly for diabetes, possibly for weight loss, possibly just in general. So, what about for axSpA patients?

Well, colleagues from Philadelphia in this study looked at TriNetX data, so big insurance data that looked specifically at ankylosing spondylitis because that's how it was coded. And so there 5,000 patients in this analysis, adjusted for relevant factors and what washed out knowing as well that there's always a risk of residual confounding. But actually, they saw that for ankylosing spondylitis patients, the patients on GLP-one receptor agonists did better than the ones that did not as far as major adverse cardiovascular events are concerned, specifically stroke, and then also with chronic kidney disease as well. Now, there's certainly reasons why that might make sense. We do know that our axial spondyloarthritis patients do have a base risk of cardiovascular disease.

So it's not entirely surprising, but I think there's a lot that comes into the interaction here. It's hard to know whether a rheumatic disease does represent an extra factor that might be a reason why patients should consider GLP-one receptor agonists. Consider that kind of approach for diabetes or weight loss, or for other indications potentially. And it still seems like a bit of a moving phase because it is being used off label so much as well. Nevertheless, we will see in our patient populations what this does.

I think the real question though is more than the comorbidities, as important as they are, and certainly as important as cardiovascular events are, we're really interested in seeing what with disease activity, and really look forward to seeing how that plays out across the spectrum of our rheumatic diseases, especially the ones which are linked to the metabolic syndrome. Seeing how that plays out over the next few years, we will definitely get data to play with. So, for plenty more, for all things spa, and really all things rheumatology, you know where to go. Rheumnow.com. Hi, it's David Lu here reporting from Barcelona for ULI twenty twenty five.

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 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 RAIOD, 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, it just stays static.

And it's really hard for me to know which one is going to 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. So, in essence, they took 138 RA IOD patients, saw how they progressed, tried to pick 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, DLCO, ACPA, as well as the specific KL6, which is a biomarker specific to ILD.

But knowing that it'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 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 really think it's the kind of thing where we can hopefully treat the right RA ILD 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 about RA, and I mean plenty more, you know where to go. Roomnow.com. Hi, it's David Lu here, covering all the great rheumatoid arthritis material from July 2025 for 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 what 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, you 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, 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.

And 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 Smallman 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 tirvastatinib 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 practice 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 rheumnow.com.