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

Hi. This is Eric Ruderman from Northwestern in Chicago. I'm coming to you from room from the ULAR meeting in Barcelona for RheumNow. And I wanted to talk about, some issues I've been seeing relative to psoriatic arthritis at this meeting. One of the first is that there are a lot of, abstracts and discussion about difficult to treat psoriatic arthritis.

I think this mirrors a lot of what's being done in rheumatoid arthritis right now, as well as some work in, axial spondyloarthritis. And the issue has been that there are patients who just don't respond to therapy. And there's there are efforts going on to try to identify exactly who those people are, to try to clarify them so that they can be considered for specific clinical trials, and also to try to understand that issue so that it helps us make treatment decisions. In psoriatic arthritis, it's been very intriguing. The the issue is that there are patients who, have been difficult to treat and that they've had challenges responding to therapies.

Typically, the most common, delineator is failure of, two biologics or two targeted synthetic DMARDs. And there's data being presented at this meeting, or at least recommendations from EULAR. There's an also paper from GRAPA, but a number of discussions on this. And I think the really interesting feature, and one of the things that the psoriatic arthritis folks who are looking into this are doing is trying to differentiate between people who are difficult to treat because they have refractory disease. Their inflammatory disease is refractory.

And those who are difficult to treat because they have other management issues. Either they have central pain, they have some tolerability issues. There are other factors that go into the reason that they, are not doing well on their current therapy. One of the things that's coming up this meeting is trying to really define those two subgroups. It looks like roughly 10 to maybe a little higher percentage of patients are difficult to treat in which they in that they're not responding to a couple of different targeted therapies.

But of that group, it looks like about a third are are sort of complex to manage or difficult to manage. And and the interesting thing is that that terminology has been a big discussion that, within GRAPA, that's been called complex to manage. Within ULAR, they're calling it difficult to manage. And I think there's some effort afoot to try to harmonize those. But the issue there is there are patients who aren't responding and some of that is central pain or fibromyalgia, if you will, in some cases.

And so that switching their biologic DMARD isn't going to make them any better. And then there are patients who are just not responding to their biologics. And that's important because we have to find what the right drug is for that person. And there's some interest, from pharma companies and trying to look at that. There are no answers yet, but I think it's really been an interesting discussion and it's something that's coming up, and being talked about a lot at this meeting.

And as I said, it's being talked about not just in psoriatic arthritis, but in axial spondyloarthritis and in rheumatoid arthritis. And I think it's one of the next areas that, we're really looking at in rheumatology to try to identify those patients. We're always talking about sort of unmet needs, this may be an unmet need, and it may not be an unmet need for a new drug. It may be just trying to understand those patients better, so that we can use the drugs we have better, or decide when maybe it's not appropriate to switch drugs, but to think about other ways of managing pain besides another biologic. So, stay tuned.

I think there's a lot of work in this area and I think we'll see more, over the next few meetings. But it's going to be really important to help us understand how to manage those patients who are just a challenge for all of us as clinicians. Anyhow, I'm coming to you again from, ULAR here in Barcelona, this is Eric Ruderman for RheumNow. Hi there, this is Eric Ruderman, from Northwestern University in Chicago coming to you for RheumNow from the ULUR meeting, in Barcelona. I had a really interesting conversation, outside of one of the posters, at this meeting.

The poster number itself was poster number 0016. And it was, some really preclinical data. It wasn't clinical data, but it was a poster describing a modification of an antibody. And what they had was an antibody to IL 17 a and IL 17 f, basically like bimekizumab. But they'd modified it, by changing some of the amino acids in the Fc portion of the antibody, and by doing so, had extended the half life of the antibody quite significantly.

Again, nothing clinical, but in modeling that out, they suggested that perhaps in patients, if this actually proved to work, that the drug could be given maybe two or even three times a year, so every four or six months. And I had a conversation with a dermatologist who was presenting the paper. And, you know, in my mind, I don't think that's going to be that attractive for rheumatologists. I don't think we are really phased by injectables that have to be given, you know, once a week, once every two weeks, once a month. And in fact, I think in some cases, stretching it out longer than that may be problematic because patients may forget to take it until they start to get symptoms again.

On the other hand, the dermatologist, and I think this seems to be the general consensus in the dermatology community, is less frequent dosing is more desirable. And that's what patients really want. So we'll see where this plays out. This company that's developed this antibody is also looking at some other antibodies. Again, looking at extending the half life to the point at which they may be able to be injected once a year even.

And I think we'll see where that gets taken up in the community. I don't know that for rheumatologists, that's going to really move the needle very much and really persuade us to use these drugs if they're not particularly more effective just because they're given less frequently but it seems that for dermatologists, that may be a selling point. We see that already. Interestingly enough, with Bimekizumab that was recently approved for psoriatic arthritis and axSpA. It's been around for psoriasis for about a year now.

And the dosing for psoriasis is once every two months. The dosing for rheumatoid for psoriatic arthritis for rheumatologists is once a month. The total dose is the same. They just give a double dose every two months in derm. And I think the idea there is to sort of compete with other drugs because dermatologists like to give them less frequently, and they believe their patients want that.

I don't know that that's going to be as important for rheumatologists, but we'll see. And I think, know, in a world where there are a lot of biologics coming along, a lot of biologics available, it'll be interesting to see whether this is a particular issue, that may change people's minds or may drive, people to think about one drug over another. Any case, something to think about. Again, Eric Ruderman coming to you from the EULAR meeting in Barcelona for RheumNow.

Hello, everyone. I'm Nelly Zadeh, Associate Professor of Rheumatology from Beirut, Lebanon, reporting for RheumNow from the EULAR Congress in Barcelona. I had the pleasure to interview earlier today Doctor. Fabian Proft. He's a division head of rheumatology at the Charite University in Berlin.

He's a GRAPA Steering Committee member, young GRAPA PAS chair and young ASAS chair. Doctor. Proft presented on Thursday a talk OP0175 on establishing definitions for complex to manage and difficult to treat psoriatic arthritis, the insight from the group for research and assessment of psoriasis and psoriatic arthritis, GRABA initiative. So, as you know, many patients with psoriatic arthritis experience treatment and efficacies and persistent burden of disease. Less than fifty percent will reach the state of remission.

So, the idea of GRAPA was to develop consensus based definition to address the reasons for this treatment failure in PSA. So, the methodology started with a literature review, then surveys with Derma, RheumNow, and the patient research partners included. They did an initial draft, which was reviewed by the steering committee members, Delphi Round one, Delphi Round two, and then voted by GRAPA members, and finally, the final consensus. So, I will take you directly to the definition. So, the definition of the complex to manage psoriatic arthritis, it's a disease state characterized by persistent symptoms despite at least one adequate trial of a TS or biologic DMARD recommended for PSA treatment as per GRAPA recommendation.

And this definition received 89% agreement. It's meant to be a broad definition to include not only persistent inflammation, but also other status like comorbidities, overlapping condition, and some treatment related challenges. So when I asked Doctor. Proft about the choice of the complex to manage PSA, he said that it was mainly the choice of the patients because as you know, in RA and in AS, we have the difficult to treat and the difficult to manage. Actually, the patient had their voice at this GRAPA consensus definition, and they felt that the term difficult is like a bad connotation for them and bad label.

And they insisted on having complex to manage psoriatic arthritis. The second definition is a smaller group of patients who are more difficult or more complex, and they label them difficult to treat psoriatic arthritis or treatment refractory psoriatic arthritis. So this is a state defined as a failure to respond to at least three previous treatment for PSA with different modes of action, including at least two TS or biological DMARDs and persistent symptoms perceived as problematic by both the physician and the patient, and the presence of objective evidence of inflammation. This has received an agreement of 100%. The whole project received an endorsement by 95% of the GRAPA members.

Also, I asked Doctor. Praft, why are you choosing two definitions for this difficult or more difficult group of patients. So difficult to treat and treatment refractory. And the idea was that they wanted to be in line with the psoriatic arthritis definition and with the axial SpA definition. So the psoriatic, me, the rheumatoid arthritis definition and the axSpA.

So rheumatoid arthritis is D2T, difficult to treat, and the axSpA is treatment refractory. So for now, they kept both of them to indicate this particularly challenging group of patients. So this is the first consensus based definition for treatment failure in PSA. We hope that it will start a new research project and will help to better understand the reasons behind this treatment failure. Thank you for listening, and please follow along now for more coverage from EULAR twenty twenty five in Barcelona.

Hello, everyone. I'm Nelly Zadeh, Associate Professor of Rheumatology from Beirut, Lebanon, reporting for RheumNow from the EULAR Congress in Barcelona. Now I will talk to you about emerging therapies in axial spondyloarthritis. I want to tackle three treatments that were discussed at the Congress. First one is exelezumab, an anti interleukin-seventeen A inhibitor.

The second one is Ivarmacitinib JAK1 inhibitor. And the third one is not an old one. It's not a new one. It's an old one, but with a new delivery mechanism, it's colchicine. So let's start with the new one, with the first one.

It's always difficult to pronounce the name. This is OP0102. It's gazeliezecumab in radiographic axial spondyloarthritis, efficacy and safety. This is a phase three trial. So this is a fully human monoclonal antibody that selectively neutralizes interleukin 17A.

This was a forty eight week phase three multicenter study conducted in China comprising a sixteen week core treatment period, then a sixteen week maintenance period and a sixteen week follow-up period. The eligible patients were randomly assigned to receive GZALI-one hundred, GZALI-two hundred or placebo. At week sixteen, the patients receiving placebo were then re randomized to receive either GZALI-one hundred or GZALI-two hundred. What was the primary endpoint? It was a proportion of patients achieving an ASAS-twenty response at week sixteen.

So they included four sixty five patients. At week sixteen, there was a significant higher proportion of patients in the treated group, two hundred and one hundred, achieving SS20 remission compared to placebo. So, four percent in the two hundred milligram, sixty five percent in the one hundred milligram, and thirty six percent in the placebo group. The efficacy was sustained through week forty eight in the Exeli treatment group. They also saw a significant reduction in disease activity as measured by Asthdas, ESR and CRP.

Also, improvement in physical function and spinal mobility with two hundred doses showing slightly better benefits. Concerning adverse events, there were no really surprises. One point six percent of SAEs, no unexpected safety concerns. So we hope that this is again a new option for treating our patients with axial spondyloarthritis. The second poster is POS0757.

It's about evarmicitinib in patients with active ankylosing spondylitis. This is a post hoc analysis that stratifies the initial results by baseline of a two phase two phase three trial. So, what is evarvacitinib? It is a selective GYANOSKINAS1 inhibitor and has shown already efficacy in patients with active AS. And this time they are trying to see if it stays active significantly efficient in patients across different categories.

So one hundred and eighty six received placebo, one hundred and eighty seven received ivamacitinib, and they showed a significant improvement in ASAS 20 in all subgroups. So, what did they study? Age, less 40, male or females, BMI below twenty four and more than 24, people with a disease duration less than five years or more than five years with and without history of biologic or JAK inhibitor with a vast score of back pain less than 60 and more than 60. So across all categories, the treatment was effective, but mostly in patients who were young, so less than forty, with a lower BMI, with asset duration of less than five years, and without a history of biological or JAK inhibitors treatment. So no real surprises.

Again, another option for our patients. And the last treatment, as I said, it's not a new treatment, it's an old treatment. It's called SHISINE, our old friend. It's POS 13. And what they did is they did intra articular slow release treatment with microspheres containing colchicine in an inflammatory arthritis rat model.

So this is a novel intra articular combination sustained released colchicine and ropivacaine anesthetic in a RAC model of acute inflammatory arthritis. So they encapsulated colchicine with microspheres of biodegradable PLGA polymer to enable sustained release. They combined it with the anesthetic ropivacaline. They adapted a model of intra articular carrageenan induced arthritis in knees or ankles in the mice. They induced the arthritis and in the following one minute, injected either the colchicine or other also parallel groups, including dexamethasone, for example.

So after injection of the car, all animals developed an inflammation. And they found, for example, that dexamethasone exerted a significant effect on pain, inflammation, and joint destruction, but also colchicine was effective for all these three parameters. So pain relief, inflammation, or destruction. And as a concentration in blood over seventy two hours after injection remained at very low levels and significantly below toxic thresholds. So what hope does this study give us?

So we know that colchicine is a very effective drug. However, several times you are limited by the dose that we can deliver because of the toxicity. So this could be a very good option for treating acute inflammatory arthritis to limit all the toxicity of oral colchicine. And with that, I would like to thank you for listening and to follow RheumNow for more coverage from EULAAR twenty twenty five in Barcelona.

I'm Anthony Chan reporting here at EULAAR twenty twenty five for RheumNow. And today there was an interesting presentation on chronic pain in XBA, the whole concept of fibromyalgia and also central sensitization. This is from poster O213 which was presented here at EULA twenty twenty five. Chronic pain as you know is common in XBA even if effective, anti inflammatory treatment. Historically, chronic widespread pain is often labeled as fibromyalgia, but this sometimes doesn't capture the full picture.

And so this study explored the role of central sensitization as an important contributor to chronic pain in XBA. Why do I think this is important? We know that forty percent of patients have XBA can continue to experience chronic pain despite treatment. And chronic pain we know in XBA is complex. It is a combination of nociceptive pain which is inflammation driven and nocciplastic pain which is central sensitization.

And ICD 11 recognizes that chronic secondary musculoskeletal pain is being distinct from fibromyalgia. So accurately characterizing these patients are essential for better targeted treatment. In this study which came from the Gila LES cohort, the Groningen Lewanden XBA cohort, they had one hundred and ninety nine patients of XBA fulfilling ASAS criteria and they were assessed for a few things. Firstly, they were assessed for fibromyalgia based on ACR criteria, then they were assessed for central sensitization inventory CSI and quantitative sensory testing QST and then they were also assessed for the Estes, Besti and CRP. They stratified the groups into three groups.

Firstly, the fibromyalgia group that made up about twelve percent, the non fibromyalgia group these were people with either high CSI which is a score of above 40 and low CSI which is a score of below 40. The high CSI made up about thirty percent and the low CSI fifty eight percent. What were the results of this study? This study essentially said that fibromyalgia underestimated central sensitization which I thought was quite interesting. So only twelve percent of these patients met fibromyalgia criteria.

Over thirty percent of the remaining showed evidence of central sensitization so a CSI score greater than 40 and this suggests that central sensitization is much commoner than fibromyalgia and XBA. And also patients if a CSI of more than 40 had significantly worse disease activity, pain and also QST abnormalities compared to those with less than, CSI 40. Regards to the traditional outcomes that we measure such as STAS and Basti, the patients were divided into those with fibromyalgia. The mean disease activity STAS was three and those who had high CSI was 2.4. In contrast, those with low central sensitization the S test was lower at 1.8 and the same similar result was seen for best time fibromyalgia and, people with CSI greater than 40 had higher best eye, whereas those with a lower CSI less than 40 had a lower best eye.

These were quite interesting, the CRP did not differ between the group suggesting that non inflammatory pain mechanisms were probably driving this and also we found that, the people with a high CSI and also fibromyalgia group also had more confirmed pain facilitation scores as well. So I thought this was quite interesting, chronic pain in XBA is a spectrum, it is not just inflammation, and not just fibromyalgia. Many patients experience central sensitization without fulfilling fibromyalgia criteria and these, composite measures that we have at the moment such as S test and best eye may be influenced by these non inflammatory pain mechanisms, possibly leading to overtreatment if not recognized. So pain management needs to be individualized. We have to think of it beyond our traditional methods of assessing patients and I think combining anti inflammatory therapies with strategies such as to manage central sensitization such as exercise, cognitive behavioral therapy or neuromodulators might be important.

So chronic pain it's, remains a major unmet need in XBA. I thought this study today, was quite helpful in terms of trying to determine whether patients have more fibromyalgia phenotype or made in more central sensitization type phenotype and we have tools such as CSI and QST to assess these patients and we should probably use these to evaluate the pain phenotypes so that we can optimize management for our patients. So I'm Anthony Chen, reporting here for RheumNow in Barcelona, at EULA twenty twenty five. I'm Anthony Chen reporting here for RheumNow in Barcelona at EULA twenty twenty five and there were interesting presentations on novel therapies in axial spondyloarthritis here at EULA twenty twenty five and I wanted to share with you some highlights of emerging treatments in the field of XBA and there were three key developments. One, a new IL-17A inhibitor, Venekizumab, JAK inhibitor, Evamacitinib and then a highly individualized exercise intervention study.

So let's, go through these and explore their clinical implications. The first one is post two fifty four which is a vunakizumab. It's a novel IL-17A monoclonal antibody which was studied for, its use in ankylosing spondylitis. In the post op analysis four forty patients both TNF naive and TNF experience were treated. At sixteen weeks the ASUS 20 response in the TNF experience was 67% versus 45% in the placebo and the TNF naive was 65% versus 41% in the placebo.

So fairly similar in both, TNF experience and TNF naive and the ASUS 40 responses were also significantly improved. Importantly the response rates were similar as, in both the, TNF exposed and TNF naive groups suggesting quite broad utility of this treatment and, in terms of safety there were mild to moderate adverse events but no serious infections or malignancy seen. This study suggests that possibly Vunacizumab could offer additional IL-seventy in, A option for those, even those who were exposed to TNF, inhibitor therapy. The second poster was, poster O262 which is, evamacitinib. We are obviously now moving towards a JAK inhibition.

Evamacitinib is a selective JAK1 inhibitor. In phase twothree trials in three seventy three patients, they studied this and after twelve weeks the total back pain, visual analog scale, dropped by twenty five point six percent versus seventeen percent and this was significant. The night pain, visual analog scale also dropped by 25% versus 14.3% in the placebo and morning stiffness also dropped by 24.5% versus 15.8% in placebo all meeting, statistical significance. The, patient global assessment and ASCO also improved, significant. These are the quality of life measures.

So even, patients who switch from placebo to the active drug after twelve weeks caught up and showed a rapid improvement. So again, I think this supports, the what our current experience and JAK1 inhibition is a highly effective target for XBA offering rapid symptomatic relief, across multiple domains. So, another, one to add to our list of drugs that we could use to treat XBAW. Moving away from this drug therapy, there was an interesting presentation, post February and this is about individualized exercise program, beyond medications. I think structured, exercise is crucial.

This was an eight week study so quite a short study. They looked at cardiopulmonary exercise, training and also they looked at, trunk strength and mobility exercises using a specialist devices. And the results were the strength were improved by about fourteen percent in mobility, improved by fifteen percent in people who underwent this, this, treatment and the improvements were in, things such as ventilatory efficiency, the anaerobic threshold and also chest expansion. The best time also decreased from 3.5 to 2.9. So supervised individual exercise program, can significantly improve function, mobility and overall patient well-being, in XBA and this is again shown I think important that we don't just focus on the drug therapies but also the exercise as well.

So what did I take away from these, three, presentations today? Firstly, the treatment landscape for XBA continues to evolve. We have another IL-seventeen inhibitor option, Venacizumab, another JAK1 option, Evamacitinib, it was a rapid response and also comprehensive. The L17, drug here responded both, in both TNF naive and TNF experience and finally, support and adjunctive therapy individualized exercise, remains important and I think these developments underscore and tell us the importance of multimodal personalized treatment approach to our patients. So thank you for joining me for this update on, the latest, developments in XBA and I'm Anthony Chan reporting here at Barcelona at EULA twenty twenty.

Hi, I'm David Liu reporting from busy Barcelona for EULA 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, Bomer 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 you all have put out, had a lot to talk about 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 actually about 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, our 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 for oral 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. That's probably appropriate That 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 rare class 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 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 from 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. For 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. And 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 abatacept 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 they could either 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 that twelve months later, there was still a gap between lines and it's an upsizable one of that. Well, you know, to have twelve months legacy after that, after six months of abalacept, maybe there's something of this. But we would like to see longer term data.

Well, here we are three years later, another three yule hours 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 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 find the ACPA 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 I 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 Your Life 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 is the time for us to think about the 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 want to 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 and early RA. And NORD STAR 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, 26 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 RheumNow.

It's JanetBurdope reporting. Thank you.

Hello, I'm Jonathan Kaye from UMass Chan Medical School in Worcester, Massachusetts, reporting for RheumNow from ULAR 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, anti citrullinated protein antibodies, or both. And 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 a 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 STARR and BEST strategy studies.

The NORD STARR 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. Cdai improvement over one year was greatest in the hand predominant group and lowest in the polyarticular predominant group, with C. Diff 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, 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 rheumnow.com. See you later.