EULAR2025 Topic Podcast PsA 2 Save

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Hi, this is Eric Ruderman from Northwestern in Chicago. I'm coming to you from room from the ULA meeting in Barcelona for RheumNow. And I wanted to talk about some issues I've been seeing relative 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 their 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 a 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 trying to really define those two subgroups and it and it looks like roughly ten to maybe a little higher percentage of patients are difficult to treat in which they in in 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 Grappa 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.

And 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 a room now 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, 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 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 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 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 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 arthritis 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, you 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 ULUR meeting in Barcelona for RheumNow.

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 retrospective cohort analysis.

Overall, was a very large cohort, 9,000 patients, and then they included approximately 3,800 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 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 low socioeconomic 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 Siebert who decided to kindly join me for an interview today and we're going to discuss about PSA. So Professor Stefan Stibert is an expert in the field of PSA, is the co convener of the Difficult to Treat PSA Task Force. Thank you, Stefan, for joining us.

Great, Oily. It's great to talk, discuss this and speak to you.

Yeah, so discussing we 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 task force.

Yeah, no, great. I mean, as you know from our clinics that we share sometimes and that's, 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 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 and 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 to manage PSA. We can talk through some of those if you'd like.

Oh yeah, yeah, absolutely.

So

let's do a thirty second summary of the definition for So the

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. Know 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 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 and again as I say that the aim is that we can have a similar 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 will 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, 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 going to 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 there'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 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 treatment 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 patient's 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 demons 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 Serib. 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?

I think two answers just to say 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 have failed drugs they've had a good trial but they have still got active inflammation and that's 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 these 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 get 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 there 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 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 pool the data.

Absolutely, yeah. So that's definitely a space to watch. Probably next day, Agiola, we'll have much more to discuss. But, yeah, no, thank you so much, Stephane. 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, Stephanie. Thanks, everyone.

Hi, everyone. This is Jieha Lee 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 l b zero zero zero one 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 new oral medication that blocks the signaling protein tyrosine kinase two or TYK2. So this drug is 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 biologic naive. This was a large international randomized controlled trial involving 670 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, 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 ACR 50. 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 to cabozantinib 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. And initially, there were none significant, but after some more sophisticated analysis looking at the distribution and such, they found that actually people with ducaracitinib have less progression of joint damage compared to placebo. So this is promising, and we'll 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 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 of 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.

This coverage was brought to you by our EULAR sponsor, Johnson and Johnson. Check out their new data this week on the first and only IL-twenty three inhibitor proven to significantly inhibit progression of joint structural damage in active psoriatic arthritis by visiting RheumNow's virtual poster hall at roomnow.com.