EULAR 2024 PsA Daily Topic Podcasts Save

This is the UR twenty '24 podcast with daily reports on psoriatic arthritis. These psoriatic arthritis reports were sponsored by UCB. Enjoy.

Hi. This is, Eric Ruderman, from Northwestern University in Chicago coming to you live from the, EULAR twenty twenty four meeting in Vienna, Austria for RheumNow. I spent some time at this meeting looking at a number of abstracts and other information that we're seeing relative to spondyloarthritis. And several questions have come up to me this week. One in particular, which I have struggled with is whether we truly need more interleukin seventeen inhibitors and more JAK inhibitors for spondyloarthritis, either psoriatic arthritis or axial spondyloarthritis.

The number of trials that we're seeing, the interest from industry would suggest that after the success of the existing IL-seventeen inhibitors, there's a lot of interest in identifying new drugs going after this target. I'm not sure that the market is going to bear all these different drugs, but the number of papers and abstracts and the amount of information where they're seeing at this meeting is pretty impressive. These include newer antibodies directed against IL-seventeen, and in particular one that we've seen before, bimekizumab, which is a monoclonal antibody that targets both IL-17A and IL-17F, two versions of IL-seventeen, which is distinct from the existing approved monoclonal antibodies that target only IL-17A. We've seen data, and at this meeting, there's data on IL-seventeen nanobodies. These are smaller parenterally injected molecules, that don't have some of the limitations of full on antibodies.

In theory, they're being used in cancer, and in theory, they may have better tissue penetration. Not clear that that's really the case in our diseases, and, whether this translates into improved clinical benefit has yet to be seen. There are a few small molecule inhibitors, that can be given orally for IL-seventeen and IL-twenty three that are early in development, nothing here at this meeting particularly. But we're also seeing some additional data on oral JAK inhibitors at this meeting, including a new JAK1 inhibitor that's being studied at axSpA. And we're seeing data on TYK2 inhibitors, TYK2 being the fourth member of the JAK family.

The rationale for TYK2 inhibition is that interleukin 23, in particular, signals through TIC two, and interleukin 23 being an important cytokine in spondyloarthritis, it suggests that this might be a better pathway for JAK inhibition, or at least JAK family inhibition, for these diseases, potentially, and I say potentially, with a reduced, risk of adverse events. Some of the things we've seen at this meeting, abstract, OP-one 195, which is a phase two study of Sonalocumab, a new interleukin 17, nanobody that targets both IL 17 a and IL 17 f. And there's also an abstract for Ezocopep, a nanobody that targets IL 17 a that's being presented as a late breaking abstract number zero zero zero five. Also at this meeting, there's some data on vunekizumab, another IL-17A inhibitor, that's poster o eight zero three. And one that I thought was interesting is an abstract on TAK-two seventy nine.

That's a selective TIC two inhibitor. This is a phase two study, being presented as an oral presentation, abstract, OP 138. One of my favorite, things about this particular molecule, it has had a it has acquired a generic name, which is zosacitinib, which I think is one of the best generic names, for a small molecule that we've seen in a while. All of these, are showing great data in psoriatic arthritis or axial spondyloarthritis, and so there's no reason to suspect that they're not effective molecules. I think time will tell whether the TYK2 inhibitors are not only effective but potentially safer than the existing JAK inhibitors.

But I just don't know if we're gonna need this many agents targeting the same pathway, for these diseases. We'll see. And I think ultimately once these trials are run through into phase three, and hit the market, the market's gonna tell us what is necessary. So that's my thoughts on this coming to you from, EULAR twenty twenty four, for RheumNow. Stay tuned for more information from this meeting.

Hi. I'm at Janet Bourdeaux is my, ex name, Janet Pope. I'm reporting for AtRoomNow at ULAr twenty twenty four in Vienna. I wanna tell you about JAK inhibitors for new indications. So there's three newer indications that you might or might not be aware of.

Baricitinib has been approved in some jurisdictions for alopecia areata, four milligrams a day, no cardiovascular or VTE signals. And the SALT score, which is the proportion of alopecia left behind, was quite a high level where patients did very well and obviously better than placebo. So there's hope for our patients with autoimmune alopecia. The next thing is upadacitinib has been approved for Crohn's disease. And Crohn's disease has an outcome called C.

Dye. So not our clinical disease activity score, but it's a Crohn's score. And the word on the street is that looking at the positive RCTs of upadacitinib at thirty or forty five milligrams a day for induction is that the scores were rapidly improved and far higher than some of the other comparisons that the Crohn's docs are used to. So keep an eye in that space. Then also hot off the press in June 2024, AbbVie announced that upadacitinib is now indicated for kids greater than or equal to two years with active polyarticular juvenile idiopathic arthritis, as well as psoriatic arthritis in children.

And so that's pretty interesting. Tofasidenib about a year ago in 2023 was also approved in polyarticular JIA. The newest thing is not an approval, but a positive study. So in April 2024, the phase three trial of GCA for upadacitinib usage, which was called SELECT trial, showed positive results in patients with giant cell arteritis. What else is happening in JAKs?

The JAK inhibitor upadacitinib and the TYK2 decravacitinib are moving into lupus trials. They're already in phase three. The trials are recruiting or maybe are even nearly recruited. So we'll have data in a year or so. Lots of new indications for JAK inhibitors.

Keep your eye on this space. Janet Pope reporting. I hope you'll continue to follow us at RheumNow. Thank you.

Hi, everyone. This is Aurelie Naj reporting from Vienna live at EULA twenty twenty four for RheumNow. I really am excited to be with you today and I wanted to share one of the abstracts that really did catch my attention. It's about psoriatic arthritis and it's about what we call the window of opportunity. And that's something that we know very well in rheumatoid arthritis, but haven't been studied so well in PSA.

And so it's OP0184 and it's the GOLMAY PSA trial. So this was a randomized controlled trial that was looking in very early psoriatic arthritis disease because people had duration of less than two years and they were naive completely of any drug including conventional synthetic DMARDs. And so there were two strategies there. One was methotrexate plus glucocorticoids and the glucocorticoids that were delivered the way we deliver them in The UK, which is not with tablets. It's usually intramuscular injection.

And this in this case, was one hundred and twenty milligram, which is quite a high dose. And that was this versus methotrexate plus glucocorticoids delivered the same ways and Skolimumab. So at TNF inhibitor. And so the primary outcome there was the difference in the PASDAS score at week 24, but the study went up to fifty two weeks and they looked into 84 patients in total divided in these two groups. And so I found the results quite interesting.

So, at week 24, the mean difference in the past as was 0.55, minus 0.55, which is not massive. And the P value is not significant, but it was 0.06, which is quite close to significance. Yeah, that's week 24. Now, when they looked at week 52, couldn't see any difference. ACR20 was really similar between two groups.

There's one thing though that would be different between the two groups it's the amount of steroid that the patients did receive through the study. And in fact, patients that were in the placebo arm rather than the galimumab arm did receive much more steroid and that's probably one of the reason why they've been doing so well. At the median dose actually was double in the placebo group, which means two forty milligram, which if you think about it over the course of a year is not a massive amount either. It's two intramuscular injections. There was no difference in the number of patients that needed other biologics later and there's also no major serious adverse events throughout the study.

But what is kind of interesting, I think there's a few things there. First of all, this is very tight control strategy through a trial. This is not usually what we see in real life. If you look into it, the number of people that needed biologic in both groups after one year was like three patients and five patients, which is a really low number. And so I wonder if it's just the tight control of, you know, seeing the patients very often and giving them steroids and so on.

But the other thing that it's telling us is that as opposed to rheumatoid arthritis, in which, you know, it's really clear that combination of biology very early can allow to reach remission faster and in a more sustained way. There is evidence for that, although we don't treat every patient like that because it's not necessarily justified. We don't seem to see that in PSA, which tells us something about mechanism of action of the drugs, but also importantly about maybe how the disease works and how different it is. The other thing we need to keep in mind is obviously PSA is a much more complex disease when it comes to this is activity assessment. And this cohort was a bit heterogeneous.

There was in patients with disease and patients with more swollen joints, less swollen joints and that's something that might have contributed to that result. In any case, I will catch up with you later to report more data. Follow me on Twitter AureliRheumNow. Follow RheumNow for more content and don't miss our daily live panel at 6PM every day. See you later.

Hi, everyone. This is Oeyelinav reporting for RheumNow for Vienna. I am super excited, super psyched to be here. I have selected all of my abstracts, I'm just delighted for all of this science to come. One abstract particularly caught my attention, as I know and you probably know as well that transition from psoriasis to psoriatic arthritis is quite trendy right now and there's a lot of discussion as per whether or not we can prevent it.

Obviously, we know what are the risk factors in people living with psoriasis telling us that they are likely to develop psoriatic arthritis. However, we have not been able to my knowledge so far to find strategies that could help us reduce that transition and that risk. And that's how this abstract which was OP zero zero ten presented by Hobany Benez and Al really I found exciting. So they looked and this massive database yeah. It was over 200 millions of charts, medical charts that they looked at.

And by doing so, they were able to see what was the percentage of conversion, a transition from psoriasis to psoriatic arthritis, and looked into whether or not there were differences according to what drug these people would receive to treat their psoriasis. So they did adjust to quite a few different risk factors for psoriatic arthritis. And then they looked into TNF inhibitors, IL-twelve, twenty three inhibitors, IL-twenty three inhibitors and IL IL17 inhibitors. And the results are quite striking to me really. So what they show is that if somebody is treated with an IL1223 or an IL23 inhibitor, the risk of developing psoriatic arthritis over the follow-up, over the three and five years time points was lowered by thirty seven and thirty nine percent, which is a lot, it's less, it's more than one third less patients that develop psoriatic arthritis compared to TNF inhibitors.

And that was to those patients that were treated with these drugs in first line. Those people that were treated with the IL-twenty three inhibitors or IL-twelve twenty three inhibitors in second line, their risk of developing PSA was also lowered for about thirty percent compared to TNF. And they also compared the risk in people treated with IL-twenty three inhibitors and IL-seventeen inhibitors. And what they saw is that the rest of PSA was in three and five years was lowered from roughly fifty percent, one out of two in people treated with IL-twenty three. So what does it tell us?

First of all, it's, you know, there's always a risk of channeling bias, you know, in this type of studies and that's something we need to acknowledge. But that's not what I want to emphasize. What I want to emphasize is that there's a question there and it's telling us something about pathogenesis and and understanding. And the first one is we know that IL twenty three inhibition does work slightly better in the skin. And so is it just because we control psoriasis better than we prevent people to develop psoriatic arthritis?

Or is there some specific mechanism of action by blocking IL-twenty three that does reduce the risk of joint disease? So that's definitely something I think that was following up and investigating because if that is a thing, then you know it would support the fact that people with high risk of developing PSA would be treated preferentially with this mechanism of action. So that's that was it for me today. That's what I wanted to share with you. Follow me on Twitter, Aureli Romo and follow RheumNow for more content throughout the conference.

Hi everyone, this is Aureli Najm. I am reporting for RheumNow live from Vienna Conference Centre. It's day three and there's been so much great science so far. I want to draw your attention on one poster that I saw this morning that reminded me that maybe I need to do a bit more for my patients in my current practice when it comes to mental health. This is a poster, poster nine forty six, that looked across diseases in both rheumatoid arthritis and psoriatic arthritis.

There were two cohorts, four hundred plus patients with RA from the T RIGS cohort, five hundred plus patients with PSA from the DPR cohort, and what they looked into was whether or not people had anxiety, depressive symptoms, and so on. And so they looked at baseline, and then they looked how that would affect the outcome at two years. And so, first of all, big numbers. At baseline, one patient out of five had depressive symptoms. One patient out of three had anxiety disorder.

I mean, obviously, we want to compare that with the general population, and it didn't do that, but you know, it still looks like it's a lot. That was for RA, and then in PSA, was roughly twenty percent of one patient out of five for each depression and anxiety, which again is a lot. And so one thing that was really interesting as well is that those people that do display depressive symptoms and anxiety disorder were less likely to achieve remission in two years whether they've got RA or PSI, and the odd ratio are pretty impressive, especially in PSA. The odd ratio to not achieve remission at two years when you've got depression is like six. So it really does matter.

Mean, obviously there's a lot of confounding factor there potentially, but also does it really matter whether or not people have confounding factors? Maybe this is just something we need to address and treat appropriately, which I don't think a lot of us do on a regular basis. Now the other thing that I found really interesting, they look at one year and those people that display depressive symptoms at baseline also had higher ESR at one year and these are RA patients and those PSA patients with depression at baseline had a higher number of swollen joint count as well as CRP, which as well is not only how do they feel, but they do display higher signs of inflammation as well. So once again, this could be related to confounding factors, and we need to not exclude that, but I think this is definitely something that we need to look into more. Follow me on Twitter for more content, or reallyromo, and follow RheumNow, and don't miss our 6PM panel for a recap of the day.

See you around. Hi everyone, this is Orelin Mejj, live from Vienna Conference Center. After three days of conference right now, I can confidently say that I have learned a lot as always. A couple of abstracts I want to discuss with you and it comes down to the eternal question we ask ourselves in clinics which is in PSA after a first failure of a TNF inhibitor, what do you go for? Do you go for a different mechanism of action?

Do you go for another TNF inhibitor? EULAR and GRAPA recommendations have not formally stated whether it should be one or the other and so the first poster that tried to answer that question is poster two seventy eight and so what it does is that it looks at a cohort of four hundred plus PSA patients that were and it's interesting it's from The Netherlands and they have this historical cohort where there was only TNF inhibitors available that was before IL-seventeen so obviously they had to kind of cycle yeah and then they have this was a cohort of about a few more patients that they did swap from TNF to AL17 and they look at the three years retention rate as a surrogate for efficacy as well as one year disease activity. So what they find, I found it quite interesting, is that when they do adjust for discontinuation reason, which I think is a very thing to adjust for and a lot of other cohorts haven't done that, they don't see any difference in retention, which does make sense in some ways and also they don't see any difference in that CRP in the two swapping versus cycling groups at one year.

One thing they did see though is that when they separate groups between male and females, they saw that males actually that were cycling rather than swapping for a different mechanism of action did have a worse prognosis. In fact, they had an odd ratio of failure of the drug of 1.67, but this was not found in females, which in itself is also an interesting finding that requires further studies. And then the other poster was two sixty six and this one finds somehow different results. It was the BRAF cohort, three forty plus patients with PSA, a group that swapped, a group that cycled again, and then they did find a better outcome in people that were swapping, which is also interesting. But one thing to note there is that they did not adjust for reason for discontinuation, and I don't think, I mean they don't describe having adjusted on a lot of data actually, so I would be a bit more wary about these data.

But I think what we need actually is probably a trial so that we know exactly what to do and I'd be interested to hear what you do in your practice. But for now I will go and thank you for this, your attention on this, and follow me on Twitter at orilyromo and follow RheumNow.

Peter Nash reporting from EULA, Vienna 2024 for RheumNow. One of the topics of interest, it's a big debate. GRAPP has had a huge project in it. The AXIS study is trying to define whether axial involvement in PSA is different to axial SpA with a psoriatic rash. They're putting a huge amount of effort into trying to differentiate the two.

From my point of view, there are two aspects of the same disease. I call it NASH type one and NASH type two. If you're sitting in a clinic that is a back pain AS clinic, you see the first phenotype, bilateral sacroiliitis, high percentage B27 positive, symmetrical, typical AS and nine percent of those people have a psoriasis rash. So you'll think it's just AxSpa with a rash. If you sit in the peripheral arthritis clinic like I do, you see a very different phenotype so called phenotype type two asymmetrical sacroiliitis asymmetrical syndesmophytes half if you're lucky are B27 positive, a lot of cervical involvement.

Of course they're the same disease but they're two phenotypic expressions of the same disease and they'll both respond to therapy. They'll have different symptomatology and they'll have different imaging and genetic background. It's like leprosy. Is it granulomatous? Is it lepromatous?

It's still leprosy. It's still axial involvement and it's splitting hairs whether it's axial PSA or axSpA with a rash. Two of the same disease just two different phenotypes. Treatment implications are not going to be that different. You treat symptoms and you treat inflammation that you can see on imaging and I think we'll find that what are we going to do call PSA dactylitis different to axbar dactylitis?

Are we going to call PSA enthesitis different to axbar enthesitis? So I think this will come down to splitting hairs that won't make a huge treatment difference. Thanks for your attention. Hi, everybody. Peter Nash reporting for RheumNow at EULA Vienna twenty twenty four.

One of the sessions that was quite interesting in the AxSpA PSA space is initiative that's being driven both by EULA and by GRAPA to define difficult to treat PSA. It's been popular to have difficult to treat RA, difficult to treat AS, and now they're trying to define difficult to treat PSA. So what are the three views about this particular subject? The definition of difficult to treat PSA will depend on an SLR, it will depend on patient room surveys, but the bottom line is going to be that to be called difficult to treat you have to fail one conventional synthetic DMARD, two biologics of different mechanism of action and have ongoing evidence of inflammation, not laboratory markers, but imaging markers, MRI or ultrasound of active inflammation. So that's defining difficult to treat.

Now they're separating that from the second issue which they're calling complex to manage PSA. Now they're people who have no evidence of inflammation have failed a number of drugs often cycle endlessly through expensive biologics, but their pain is considered non musculoskeletal pain, chronic widespread pain, central sensitization pain. And these people are just asymptomatic, but rather than cycling through biologics, you should think about non drug initiatives as well as things like pregabalin, tricyclics and treating them along neuropathic and nociplastic lines. Just as valid, but a different way of treating these particular patients and non drug methods may be very helpful. Even things like cannabis might be helpful, but that needs to be proven.

Now, third aspect of this whole discussion is what are the implications of diagnosing difficult to treat PSA in the first instance? Well, it's got to have therapeutic implications. We have to start thinking of ways of defining them early and doing something more aggressive early to try and break that vicious cycle. It might be combinations from day one. It might be safe combinations like TNF plus IL seventeen inhibition or TNF plus IL-twenty three inhibition, a study currently undergoing, worldwide, use right now.

So how you get two biologics for your patient is very difficult. In our country for these very difficult patients, we have the RheumNow prescribe one biologic and our Durham College colleague prescribe the other. It has to be a safe combination. I don't think JAK plus TNF will be safe because of, adverse effects, but some of the newer agents like seven x and twenty three, there'll be no safety signal at the Usulin combination, but that has to be proven. So this is an ongoing field of interest, difficult to treat, complex to manage, then the implication of what you're going to do about it.

Thanks for your attention.

Hi, I'm Doctor. Janet Pope. I'm reporting from AtRoomNow. I'm here at EULAR 2024 in Vienna, Austria. My Twitter or X handle is janitburdope.

I'm going to report a few things on the meeting today, and these are posters that I thought were interesting, And I'll tell you shortly why I chose them. So I'm titling this thematically, Predictors of Treatment Response in Psoriatic Arthritis. So the first poster was poster nine ninety. This was looking at psoriatic arthritis and looking at a durability of response of treatment in psoriatic arthritis patients who were active, who were treated with TNF inhibitors or a PDE4 inhibitor, which is a Premalast. The data came from formerly known as the Corona registry, the Coravitas registry of patients with psoriatic arthritis.

So a very large N. And the question is, what drug will last longer? And then what will be some of the predictors? So when you're starting your first line advanced therapy, if you use a TNF inhibitor, there was more durability than using a PDE4 inhibitor. And that's not surprising, as we often think that the TNF inhibitor might be stronger, might give a deeper response.

So they went on to look at predictors, including some of the patients were on both TNF and then adding a premilost. They also looked at predictors, male versus female, disease duration and things that might be predictive. But I think for me, the take home message from this poster was the bottom line is it looks like TNF inhibitor might give a longer response or longer utilization than a premilast. So the next question is the age old question. If a patient has psoriatic arthritis and they've been on a TNF inhibitor with psoriatic arthritis, should you go to another TNF inhibitor or should you change the mechanism of action?

And this study, poster two sixty six, looked at the second line therapy of advanced therapies in active psoriatic arthritis after a first TNF inhibitor, going to another TNF inhibitor, or to go to an IL-seventeen inhibitor. And the results were a little bit surprising to me. It looked like in general, was no difference whether you stayed within the class of drugs, TNF to TNF, on response and durability of the response, or drug retention over time, versus if you switch to a new class, like an IL-seventeen. They also looked at predictors of who would do better, and interestingly, it did look like men had less good retention. Sorry, it looked like by gender, the retention could vary, but it varied by the drug.

So men might've had a different retention than women, men being better on a TNF inhibitor. And some studies have shown that treatment response is attenuated in women on IL-23s, IL-twelve, IL-twenty three, and IL-17s, but not so much TNF inhibitor. So it is a study that you have to think about, but I think it allows us to have options. What's my question here though? What would be the data if we looked at maybe going to an IL-twenty three or an IL-seventeen, as IL-17s are quite often used after a TNF and sometimes even before.

So we don't know that yet, we'll await the publication, but the N is large and some insights are coming from it. The final thing is, can I predict who might respond with psoriatic arthritis treatment when you use a TNF inhibitor? And wouldn't that be great to personalize medicine? So this was poster nine ninety two, and what they looked at were a series of biomarkers, cytokines, other molecules that we're signaling that might or might not be important to suggest a better response to a TNF inhibitor. At this point in time, we don't have like a blood glucometer of a response.

We don't have a lot of tests that will help us figure out who will respond. The usual predictors of response are usually present. You're younger, you have active disease, but not really active. Obviously you haven't failed a lot of other treatments and it's your first advanced therapy. Those patients will do better than older or failing a lot of therapies already.

So it's not ready for prime time, but I think these sort of data are the start of precision medicine for looking at biomarkers of a response to treatment before we even start the treatment. So please follow us at RheumNow, and thanks for listening. Bye now.

Hi, everyone. Peter Nashua reporting for RheumNow from EULA Vienna twenty twenty four. One of the interesting elements that's discussed, the number of papers presented are thinking about ways of preventing psoriasis turning into psoriatic arthritis. Now this has been looked at with therapeutic implications. It's been looked at from a biomarker point of view, an imaging point of view, different ways of trying to define the highest risk patient and we can define them.

Bad family history, nail disease, a lot of skin rash, bad function requiring analgesia that is beyond the norm, those with arthralgia already and bad skin, scalp involvement, we can certainly define the patient who's at the highest risk. And then it's a question of can we go into our PSO clinics, image them, biomarker them and see if we can define the patients who are going to either evolve into PSA and then the implication of what we're going to do about it. So a number of studies presented one from a database of 200,000,000 people that had one million patients with psoriasis about a 100,000 already developed PSA and they looked at the use of various biologic agents in the PSO population and they're able to show when they compared 17 against TNF and when they compared 23 inhibition against TNF that those two were superior to TNFs in preventing the progression. The 23 seem to be the best. The twelve twenty three and the twenty three inhibitors seem to be able to prevent the progression the best and it reduced that progression by about thirty seven percent.

So an area of increasing interest, they're looking for the biomarkers to help us decide who's progressing. They're looking at imaging data, particularly ultrasound, power Doppler, painted emphyseal sites, patients with arthralgia, see if we can prevent that progression and the use of, active agents early on to try and prevent the progression. So we'll have to watch this space. Thanks for your attention.