Eular 2025 Day 1/2 Recap Save

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Hello, everyone. Welcome to the day one day two recap from UR twenty '25. We are all in Barcelona, Spain. We had a very busy two days. We're now back in our rooms, and we're bringing you some of the highlights of the first two days of the meeting.

I'm Jack Cush with RheumNow, and let my guests introduce themselves. Nelly.

Hello, Jack. I'm Nelly Zadde. I'm from Lebanon.

Anthony.

Hi. I'm Anthony Chen. I'm from The United Kingdom.

And Minnie.

Hi. I'm Minnie. I'm a rheumatology fellow from The UK as well.

Okay. So if you've heard these before, it's gonna be the same format. We're going to go around and hear from everyone what their favorite abstract was, in the first two days that they wanna share with you. And then we'll come back and we'll do it again, do a second round, a little bit shorter presentations. Let's, begin with Nelly.

Okay, so I start with a topic from a session about the clinical abstracts in PSA. So this was presented by Fabienne Proft. It's OP0175, establishing definitions for complex to manage or C2M and difficult to treat PSA. So this is the insights from the GRAPA initiative. Briefly, the methods, there was a literature review, there were surveys for the GRAPA members, for patients as well.

They did an initial draft, a Delphi round, a refinement, a second Delphi round, then a voting by the GRAPA members, and a final consensus definition. So they have five overarching principles. I will not go through them. So some of them are really classical about shared decision, about addressing different domains, about looking for other diagnosis if there's no response. The fourth one is actually the reason to inadequate treatment were classified into two entities.

The first one is C2M, or complex to manage. This is a broad and heterogeneous group that includes factors such as comorbidities, persistent symptoms, despite effective control of inflammation, and significant impact on the quality of life. And within this large group, there's a difficult to treat PSA or treatment refractory PSA. It's a smaller specific subgroup characterised by objective evidence of ongoing inflammation despite multiple attempted therapeutic strategies. And the fifth overarching principle is about having objective evidence of ongoing inflammation.

Now, for the definition, they define C2MPSA as a disease state characterised by persistent symptoms despite at least one adequate trial of a TS or BD MART recommended for PSA treatment as per the GRABAA recommendation. Treatment refractory or TR PSA, it's a state defined as a failure to respond to at least three previous treatment for PSA with different modes of actions, including at least one TS or BD marts, and persistent symptoms perceived as problematic by both the treating clinician and the patient, and the presence of objective evidence of ongoing inflammation. They classify this in an algorithm saying that this is a dynamic definition, which means that you can move from one definition to another. And finally, they presented it to the 184 Grata members and it was endorsed by 95% of them. And so now they plan to do the publication, to validate and real world data, and to disseminate and implement clinically.

So, I want to be clear, they have two definitions. And you start out by talking about difficult to treat PSA, but then you talked about treatment refractory. Those are the same, correct?

Yes, yes. So difficult to treat or treatment refractory. This is the same word and the broader term is complex to manage.

So complex to manage is not quite as bad as treatment refractory, that being work. Why did they feel the need to have these two levels? What's the advantage of that?

So I think that in the second level, they wanted to really have the people who have inflammatory persistent disease. So like in other abstracts, you can differentiate inflammatory and non inflammatory difficult to treat disease. And so in this more stringent definition, they wanted really to have the people who have high inflammation, high CRP, really resistant to different treatments. So not just the patient, maybe with additional fibromyalgia who is not reaching disease regression state.

So Anthony, you're a spa guy. What do you think of these definitions? Do we need both? Do you think that these will separate the non inflammatory from the inflammatory difficult to manage?

Yeah. Thanks, absolutely. I was at this session as well this morning and, following this, there was a whole series of presentations on inflammatory versus non inflammatory pain in PSA and also there was a group looking at the use of ultrasound to detect subclinical inflammation in these patients as well. So I think you know nutshell I think the D2T or treatment refractory is more objective, more inflammatory. The complex to manage is more comorbidity driven and non inflammatory.

So I think in terms of management we would not just focus on drug therapy but also non pharmacological treatment in the complex to manage group.

Of course the advantage of this is I think the hope is that this will be will mirror what happened in RA. Once EULAR came up with a definition of difficult to treat RA, what we saw was a plethora of papers on d two t RA patients describing the spectrum of disease, the and they separated them out into inflammatory, non inflammatories, the fibros or the inflammatory kind of people. And and that has really changed our understanding of these patients and the approach and their studies. And so it's helping quite a bit. And I guess the hope is it'll happen the same in in in PSA, especially.

I know they're doing the same thing in spa, and so that's gonna happen. Minnie, are they doing that in lupus that you know?

There is I I know I can't remember if it was ACR or ULA last year, but there's definitely interest in difficult to treat lupus. It's not an area I work in, but I do work in difficult to treat RA. So I I'm keeping an eye on it. It has been touted, but, of course, like, the characteristics and the the things that we focus on in each of these different diseases is gonna vary, which is one the of things I was interested in seeing with the SPA and the PSA compared to the RA. So, yeah.

Yeah. I mean, I'll just I'll just say that my bias on this is that when I lecture on difficult to treat RA, I spend very little time talking about new drugs to treat those patients. It's not about the next new sexy expensive drug that's going to, you know, fix our problems there. It's actually reconsidering those diagnoses and what entails them and how we can change our approach to them, whether it is structural disease, for instance, or functional or inflammatory and maybe different mechanisms. So I like the way this is going in multiple areas, I think.

Why don't we go to doctor Day and and her favorite?

Yes. So, my abstract is one that was presented in the, new new things in lupus earlier today, and this is a study that was conducted in Sweden on a cohort of lupus patients looking at the impact of social determinants of health and mortality and damage. So we know increasingly that social determinants of health are very sort of important to disease outcomes in people with lupus in particular, and there's plenty of evidence about sort of things like income, education, work status that can influence health outcomes. But particularly across Europe, there's quite a lot well, not a lot, but there's some data on this in The US, but not as much in Europe. So this was a population based study looking at the association between social determinants of health and long term outcomes, mainly organ damage and mortality.

So as I said, this was in a national Swedish cohort of patients newly diagnosed with SLE. This was using national health and administrative registers, and the study followed just over 2,400 patients aged 23 to 59, so quite a broad age range, diagnosed between 2,000 and five and twenty twenty one. And the researchers looked at several social factors at diagnosis, so such as income level, education attainment, marital status, employment, work disability, and whether the person was born in Sweden or not as well. Essentially, found that forty percent of participants experienced organ damage and about five percent died during follow-up. And the the key bit here is that the people with lower income and shorter education had a thirty to forty percent higher risk of developing organ damage, and actually marital status also matters.

So divorced or widowed individuals had a higher risk than those who were with a partner. And finally, a history of sick leave and disability was also more strongly linked with organ damage and mortality as well. So really, the findings underscore the importance of social determinants of health, particularly even in countries where there is equal access to healthcare. So a country such as Sweden or where I'm from in The UK. And these are critical really in determining health outcomes and obviously have probably impact for clinical care and policy as well.

So do you think that they adequately separated out the risk associated with these social determinants from the risk that's ethnically associated? Because there's a lot of overlap between those two, isn't there?

So absolutely. So I can't actually remember if someone might have been controlled for race and ethnicity. Usually, in these kind of studies, they would. But yeah. You're absolutely right.

I mean, the the the thing about whether someone was born in Sweden or whether they'd moved into Sweden, that that would be something to to look into further as well. There is some work on, for example, migrant data as well that's being presented at the congress, which would be important to look at in relation to that.

Does this have a correlate in the other diseases that we take care of? I'll ask that of, Anthony or Nelly.

Yeah. We we have seen across the two days the presentations in SPA and psoriatic arthritis with D2D and complex to manage and one thing that's come up very clearly is the level of education of these people and they tend to be more difficult to treat in when you have low education, lower sort of you know, below and some more in poverty and they tend to be the group that tended to be more difficult to treat or difficult to manage.

In axial SpA, I reviewed there were several studies yesterday about axial SpA and there were factors like important comorbidities like depression, fibromyalgia, unemployment. So these were also predictors of difficult to treat.

So I hate to be like the curmudgeon on this, but to me this sounds a little bit like, first off, I agree with it. I know it's there. It's a big problem. It's something you have to consider when you're taking care of people with lupus, especially. But isn't this a little bit like vitamin d?

Meaning, we're blaming, you know, social determinants on to be the evil culprit in a lot of different situations. But what's the evidence that if we correct it, that life gets better, that the outcomes are better and whatnot? The I I would assume that the Swedes have such great data that maybe they could answer that. Did they, doctor Day?

So not in this study, but, the the thing with social determinants of health is that obviously some are modifiable and some are not. So I'm trying not to tout my own work, but yesterday, I presented an abstract in the in the public health session exactly on this. So what is modifiable and what isn't? And so I was looking at health literacy. And so that also associates with persistently active rheumatoid arthritis.

And so what we need to do is we need to tease out the modifiable social factors because we do know that if we can modify them, that does have an impact. So it comes back to Nelly's abstract maybe on, you know, when we have these difficult to treat patients. It's not just as you were saying, a case of escalating treatment. There are other things we we can definitely do.

Yeah. I I love to see more research on that because, you know, we can get better at what we do when we start addressing these kind of things. But most people who are busy in practice don't know how much and when and what the impact is going to be. So, again, this is really important stuff.

But since the data is cross sectional, excuse me, so it's it's very difficult to know what is a chicken and what is the egg sometimes.

Yeah. Absolutely. In which case sometimes you have to do all that you can, shotgun it, you know, manage everything that is modifiable. Theoretically, should be doing this. I mean, you it's it is about treatment of the whole patient when we're managing them.

So alright. Doctor Chan, what do you got?

I've got the abstract number is OP0091 and this is a biomarker study where they looked at the IL-17F gene expression after a patient who had failed the TNF. Very interesting study and this comes from the reanalysis of the B optimal study. They called this study the examine PSA study. What they found is that the people who failed TNF they responded equally well to the IL-17A and F you know whether they're naive or experienced and we're trying to understand why is this the case and they found that people who had TNF inhibitors and subsequent analysis found that there was an increase IL-seventeen gene expression in these patients who had TNF treatment and also there was increase in the Th17, T4, CD4 cells as well. Perhaps explaining why they may respond after the TNF failure Because in traditional ways we always think that if you've had TNF your response to the IL-seventeen will be less than if you were naive but in this study they perhaps tried to explain.

The caveat it was they did not reach statistical significance. This was more a study a trend now and future studies will help us to kind of understand this a bit more. So I thought that was quite an interesting in terms of a mechanism as to why we see some of these changes in trials.

So is it possible then that upregulation of IL-seventeen or overexpression of IL-seventeen might be a biomarker for people who won't respond?

I think that is what they are proposing here. That perhaps inhibiting you know and through the experience of having IL-seventeen, sorry TNF exposure there might actually be an up regulation of IL-seventeen in this group and then coming in with the second treatment might be more beneficial. So it helps us to maybe rethink about cycling and switching in some of these patients.

Nelly, do you think of this data?

Well, I think it's interesting to explore, but as always, we understand better when we do clinical data because sometimes we find something else.

Yeah. It's we were all raised in a learn at the bench and apply it to the bedside when but history has taught us that bedside to bench is more satisfying research and usually a lot more insightful. I I I'd look at that, and I wonder, is that a rebound effect? Like, if you, you know, if you give a TNF inhibitor, you're gonna get ANA positivity for a lot of different reasons. And one might be that you, have a rebound in IL 10, which stimulates B cells and also in alpha interferon.

And these are things that drive autoantibody production as a result of it. So again, if you inhibit TNF, are you driving the expression of IL-seventeen in some people? Or is it constituently elevated in some people? Think that more research is needed but how big was the study?

We were trying to find out the number of patients in the study. I don't think they came through but it was part of the, the original study in, in the IL-17A. So it is a reanalysis or subgroup of that.

So it was a part of a clinical trial. It's gonna be a good number, right?

Yeah.

That's impressive. Alright. My abstract is call was called the PALABA study, not palabra, the Spanish word. Palaba, no r. And you'll understand why it's called the Palava study.

It's o p o one zero five. It is a trial that was done in Spain, a multicenter trial done in patients with palindromic rheumatism. A group that's sort of A, hard to understand, B, hard to really know what to do as far as treatment. You know, we do know that there's a subset of those people that go on to be, develop RA and little more likely when they're seropositive. But other than that, there's a lot of unknowns, but this is a strange little subset.

And I think we commented on this at ACR with another study that made me consider palindromic neurotism as another variant of preclinical RA. So in this study in Spain, seventy patients with palindrome rheumatism meeting criteria, and also to get in, they had to be seropositive with rheumatoid factor or with, ACPA antibodies, and they were randomized to either receive abatacep subcutaneously or daily hydroxychloroquine, all in standard doses. This was, a one year trial, And I'm sorry, this is a two year trial. And the endpoint of the study is how many of those people, roughly thirty five per group, went on to develop rheumatoid arthritis. And in the end, there was a clear cut advantage for those who got abatacit over those who received hydroxychloroquine.

Only nine percent on abatacit developed RA, whereas twenty eight percent on hydroxychloroquine developed, RA. And by the way, for those of you who follow the clinically suspect arthralgia at risk RA, preclinical RA, we do know that those people, arthralgias, but no synovitis with seropositivity. Seropositivity brings a constituent of thirty percent risk of developing RA. That's the result you saw in the hydroxychloroquine group. Sounds to me like hydroxychloroquine didn't do nothing, and that is supported by what we reported last year on the stop RA study.

Right? That was patients who had just arthralgias and seropositivity, I believe. And then they were given hydroxychloroquine placebo with no effect. The ABBA group behaved as ABBA has behaved in other preclinical or CSA clinically suspect arthralgia studies, a very low level of developing RA. You can never say it prevented disease.

You can say it looks like it might have delayed the onset. Also supporting these findings was that the people on ABBA had less attacks of p of palindromic rheumatism. So one endpoint was developing RA. Another endpoint was ongoing attacks that were short lived, and they were more common, fifty six percent with hydroxychloroquine, less common with abatacep at twenty three percent, both those both being significant. Again, I think this data supports the idea that palindromic rheumatism really is a subset of of of preclinical RA and trying to figure out what to do.

What I like about that is I don't know that any of us can agree on, you know, your favorite RA patient, you know, granddaughter showing up, and she has arthralgia and is ACPA positive but doesn't have any synovitis. I don't know what to do with her. But with palindromic rheumatism, they're seeing you because they keep having these attacks. I am compelled to do something with them. The question is what am I going to do?

This data might help me. Minnie, what do you think?

When I see this kind of data, the first question that comes to my mind is how long? So for example, you have a palindromic rheumatism and you treat them with abatacept and they are okay, everything is fine. And then what do you do? You continue two, three, four years? How long?

So this is like a little bit of concern because as you said, it seems like it's just delaying but not preventing the disease.

Yeah, and I think that that's a really, very important point. And all the studies have been done that have tried to prevent RA have given a limited course of therapy, usually six months or like one shot of rituximab or one year of of of abatastib, and then they see how long the effect is. And that's being covered here at this meeting with long term extension studies for the ARIA study and the APIPRA study. But, you know, my answer to that is as long as you need to. And you might say, well, they didn't prevent it, it already came back.

And I might come back to that as, well, did something unique here. And maybe what it did is it changes the trajectory of disease. You know, to have a sudden rapid onset that's persistent can't be a good thing if one's going to have chronic inflammatory arthritis. But to have it stalled and delayed, or to know that you can stall and delay it, might be a long term good thing, but we're gonna need long term data to know what to do with that. Minnie, what do you think?

Yeah. No. I agree with the, the the duration question, but also, as you were speaking, I was thinking about the Apipora and the Alto results that are being presented here. My I think the other thing to think about, which I think we discussed at a previous meeting as well when similar data was presented was it's not just preventing or delaying the RA, you're delaying the comorbidities and the burden that comes with that as well. We know that people have two or more comorbidities when they're diagnosed with RA.

So you're kind of preventing the the bubble around the RA as well. My main concern would be that, you know, a lot of these studies, you know, they're using abatacept, for example. In The UK, anyway, it'd be, you know, cost is like a big red flag above Abatacept, I guess. So it'll be interesting to see maybe if other drugs can show similar effects. I know that, you know, obviously many trials have been done now, but Abatacept seems to be coming out.

Yeah. There's an advantage for them, but, you know, rituximab had a little bit of a, you know, positive methotrexate and treat earlier, seems to work in high risk seronegative patients, oddly. So, but I like that each of these studies gives us a little rule that maybe you can apply to clinic. Anthony, you get last say on this.

Yeah, think supported again by the Alto study presented at Plannery on day one, where if you if you intercept at one year you can still see an effect at year three with a better set in terms of preventing the rheumatoid. I think the palindromic group they are probably more acceptable to therapy. They are getting symptoms whereas the non you know people who just act positive with very little joint symptoms they may not necessarily want to go on to some drugs.

Yeah. For the audience the ALTO study, ALTO is the long term follow-up of the Epiphora was presented on day one of the plenary session by Andy Cope. Good presentation. Look for that on RheumNow. Our next round is gonna be our short round, a quick hit.

Let's start again with Nelly.

So I'm going back to difficult to treat PSA. From the same session, OP0177 presented by Doctor. Louise Madromowin and Niehlung. It's exploring definitions and prevalence of difficult to treat PSA. I like this study because first, it's about more than 13,000 patients from five Nordic registries.

This

is

the first reason I like the study. The second reason is they did a lot of simulations. They tested different definitions. What would be the percentage or the prevalence of people with difficult to treat PSA? They did increasingly strict definition on the prevalence.

This is observational cohort studies. They regrouped the Nordic biologic registries from Denmark to Danube, Sweden, SR UK, Finland, Norway, and Iceland, and with at least two years of follow-up after treatment start. Then they studied the prevalence of G2T in three different categories, so treatment failure of at least two, this is group one, at least three, or at least four biologic or TSGMAD during follow-up in the registry. And then after having these three groups, they tested additional parameters. So first parameter is that you have a lost effect or adverse event in the most recent BE or TSG MARD.

Second, the failure of more than two different mode of action. The third, this is something that we did not see yet in other definitions, failures occurred within three years from baseline, because this has been a lot of comments about this, so when we fail within three months or within five years, this is not the same thing. Another parameter failure, sorry moderate or high disease activity, and finally patient perception of a problem. Thirteen thousand eight and seventy two patients with at least two years of follow-up were included, fifty two females and mean age 48 years. This is duration five point six years.

If you use the first definition, the less stringent one, thirty seven percent are considered as difficult to treat. This is more than at least two failures. If you fail at least three, so it's nineteen percent. If you fail at least four, it's ten percent. And then when you add more, the other parameters that I said, you drop to 106%.

So according to the definition that you choose, you can have a prevalence of G2T of thirty seven percent or of six percent. Finally, they explored the factors associated with more failure, so it was again females, opioid use, and a higher patient global score.

What about obesity?

It did not come up in the table. So this is the these three were the things that were statistically significant. It's not even on the table, so I'm not sure if they study it or not.

Yeah. I mean, again, in the there are things that are gonna I think gonna be similar between RA and PSA in difficult to treat disease, and, I always look for the surrogates that tell me it's more of this non inflammatory phenotype, the the ones that have underlying fibromyalgia, depression, anxiety. Obesity tends to be in that group of noninflammatory, but it'll be interesting to see. That number is pretty high for the complex to manage.

Yeah. Thirty seven percent. Yeah, it's high.

It's a

failure of at least two treatments.

Yeah. You know, there's a problem. I think there's a problem in psoriatic disease, both in psoriasis and psoriatic arthritis and durability of drug. And the question is, are they different biologically, these folks? That they, you know, many of the studies that look at how long they stay on drug show at two years, only about thirty or forty percent are still on the drug that they started, even when it's a brand new one.

And that's not as good as what you get in RA. And the question is why, is it because there's so many options in PSA? Or is it maybe that they're constitutively different? And maybe this kind of research will tell us why.

Well, they did study the time from the first treatment until the failure of the other one, it's three to four years.

Well, that's that's kind of encouraging. I mean, you know, you certainly don't wanna see it at one or two. Right? Anthony, what do you think of this data?

I think it's, know, very interesting data. I was sending a poster to us this morning and many posters on D2T in Expo which is the other area and the Greek study showed that the females being female was not a risk factor for D2T. So I think there's going to be some population in the specificity regards to these type of data and how how you know, how how this can also play into the definition.

Yeah. I I almost wanna see this this kind of research speed up and catch up to RA because when you get to this point, you're now starting to see better understanding and also that translating to some treatment options. Still still don't know what to do with these folks with difficult to treat treatment refractory PSA. You know? And and the rheumatologist default on this, and I know this because I asked rheumatologists in formal ways, the default is to choose the next drug that they haven't used.

You know? And, usually, it's the more the newer ones, the more expensive ones, and that isn't always the answer is my my come back to that. But then again, I don't know if I know the right answer. Right? Many any of this gonna change your approach to difficult to treat patients with psoriatic disease?

No. I agree that, I think we need the it's good that the definitions are coming out and that people are thinking about this now. I think one thing which I really rely on in my clinical practice is that liaising with the dermatologists, particularly with the difficult to treat PSAs, because I think the skin really needs to come into this as well. I know it's not part of the definition or the, you know, the the research has been well, the definition that we have at the minute, but, like, it does play into a lot of the problems particularly. So that's that's where I go with with with this.

Okay. Minnie, what's your quick quick hit?

So it's another population based study. This one is coming from the Mayo Clinic. So it's the REP from Minnesota. This was examining the risk of VTE in patients with RA. It's o p zero zero seven zero, and it was fourteen hundred patients with rheumatoid arthritis, compared to matched individuals.

And this was a long term study done from nineteen eighty to twenty nineteen. And so, essentially, people with RA were found to have a significantly higher risk of DVTs and PEs. And when I say significantly, I mean sort of over double the risk for DVTs and 1.6 times hazard ratio for PEs. And the risk varied by decade. And what actually particularly struck me was that it increased after the millennium.

Now there could be several reasons for that, which I can come back to in a minute. But the risk factors which particularly were there for PE were seropositive RA and older age, obesity, comorbidities, rheumatoid nodules, and extra articular manifestations. And they were all associated with higher VTE risk, as well as smoking and lack of lack of remission for PE risk, on its own. So it shows that while we've got better treatments for RA, the VTE risk has not declined over time. Now in terms of why you've got that increase, which was also seen in the general population as well, are we getting better at detecting it?

Are we asking you know, are we imaging these people more for various reasons? Yeah. So it it was but I think for my clinical practice, it will make me a bit more aware than perhaps I previously was of the VTE risk in our RA patients.

So what wasn't a risk factor in this was an exclusion to be in this, which was a prior history of v VTE or PE or or DVT. That was an exclusion. And another non factor here is oral surveillance in JAKs. This went up to 2019 and that oral surveillance was only just getting started around that time. And so that's not tainting any of this data.

Anybody else have a take on this data?

It certainly increased awareness of VTE post oral surveillance. And I think we are perhaps screening more patients or thinking about it more when we are choosing therapies or managing the condition. But I think controlling the underlying inflammation, controlling underlying disease is probably still going to be the key thing here.

That theoretically is a modifiable risk factor, another modifiable risk factor for this, right? That if you control inflammation, you'll you'll also lower risk. Nelly?

Did they find any difference with the different treatments they were taking, like steroids or something else?

Oh, doctor Day is frozen by cameras, and we're all waiting for her great answer. I don't think that they kinda that they didn't find something there. So Okay. Let's see if she comes back and she can answer that. But in until then, I'm going to do my last quick hit.

Mine was about rheumatoid factor in patients with EGPA. Know, eosinophil granulomatous and polyangiitis, you know, is a unique often ANCA associated vasculopathy. And we have some great new treatments for this. It is a scary subset that's certainly different than GPA and MPA. And in this study, the authors had noted that a few patients who were rheumatoid factor had seemed to have worse disease.

So that led them to go back and look at their cohort, which I believe was over 200 patients with EGPA, and they only selected out the ones in whom rheumatoid factor had been drawn. Many of those rheumatoid factors were drawn in the early diagnostic phase when patients were being worked up for an unknown disorder. So they got the full, you know, 81,000 battery of tests. And, and so when a rheumatoid factor was drawn, so this is somewhat of a selected population. Overall, their population included eighty three patients, with EGPA, and retrospectively, when they looked at those, forty six percent were rheumatoid factor positive.

And while being rheumatoid factor positive didn't conform to a particular phenotype or manifestation of EGPA, it did portend a more aggressive disease. So, if you were, rheumatoid factor positive, you had a higher relapse rate as measured by the Birmingham Vasculitis Activity Score, BVAS, with thirty nine percent relapses if you're factor positive versus two percent if you're factor negative. You also were more likely to have higher CRP levels, 49 milligrams per liter versus 11 milligrams per liter in the factor. And lastly, the factor positive patients had more mononeuritis multiplex than factor negatives, fifty three percent versus thirteen percent. So, and when they looked at the predictors of relapse, you know, who or who was not gonna do well with EGPA, rheumatoid factor stood out big, way more than inflammation and CRP, way more than any other factor, looked at many different factors.

So when I talk to the EGPA mavens, the vasculitis mavens, they're all like, what's going on here? I never saw this, you know? And and the by the way, they didn't have any other data about or or present any other data about other autoantibodies like ANA or ACPA or anything like that. It's just rheumatoid factor. So I think it's important.

I think I'm forever going to be ordering rheumatoid factor. I'm probably gonna be order ordering ACPA as well to see if I see anything there. But I think this was very interesting.

Do we do we know why they tested for rheumatoid factor in in this study? Was it as part of the screen or were they particularly checking it as part of the protocol?

There was it was it was random, and and just by their numbers, I'll say it was like two hundred, two hundred twenty patients with EGPA. They only had rheumatoid factor been drawn in less than a third or more a third, about forty percent. So, and then the question is why? Said that, again, a lot of them were done not even by the division that's managing them. It was often done by the internist or the family practitioners who were working the patient up, and they would order batteries of tests, not knowing what was going on and what looked like a multisystem disorder.

But many of the rheumatoid factors were drawn by the rheumatologists, and I can only assume that maybe they were more likely to have arthritis or arthralgia manifestations. But the author said that rheumatoid factor did not associate with any particular phenotype, including arthritis.

Could this reflect like a B surrogate marker for high B lymphocyte activity?

That's a great point. One that's certainly translatable to other disorders, autoimmune disorders, see multiple autoantibodies, for instance, ACPA and CCP showing up in immunologic lung disease or ACPA showing up in lupus lupus nephritis and what it means. Usually it doesn't mean, it's not a good thing, but we don't know if it really reflects, like you say, heightened humoral activity and just B cells being turned on, and that's got a clinical consequence. I'm hesitant to say that always more autoantibodies is a bad thing, because I think that can be somewhat misleading. But it is something I'd want to consider.

I think it's a very good question. Alright. Minnie, when we left, you were asked a question. Did you have an answer? Was the was the analysis any different as far as VTE risks by drug?

Yeah. Sorry about that. So yeah, I don't think they actually looked at the effects of drugs, but it would be something certainly to consider. I think that the thing about fluoro surveillance is actually very important as you say, it's not been taken into account as part of the study.

All right. So Doctor. Day, you're gonna end with our last presentation. Let's make it a quick one.

I think it's mine, I think.

Oh, Anthony, go ahead, yes.

Unless Minnie has got another one. Anyway, I shall new therapies in a sporadic arthritis. I've been following the Sonokilimab study, the nanobody IL17AF from last year. This was twenty four week data from the Argo trial, two zero seven patients recruited into the study and essentially the effect efficacy participated at twenty four weeks, sixty one percent achieved MDA, sixty three percent had a pass of 100 and these were active psoriasis, they were people with bad prognostic factors, they were large, almost half of them were more than one hundred kilograms. So, think it's you know, quite a promising results from this study and adds to our treatment options.

Do you think now, so this being a dual AF inhibitor like mexizumab, dual AF inhibitor, is there a plus side to dual inhibition that you can see at this point?

I think it increases the treatment options and we want to know how the nanobody is going to be different from the conventional antibody, the mechanism of action and also the kind of effects on the patient.

Nelly, what do you think?

Yes, usually nanotechnology is aimed at increasing efficacy and reducing side effects. So theoretically, it should be like a small upgrade.

One of the problems of dual inhibition is more candida. In the psoriasis trials, you know, we always worried about candida with IL-seventeen inhibition, but honestly, it almost never showed up. You know, it's never I I haven't yet a person who's had, systemic candidiasis or serious bad candidiasis. But at least in the psoriasis world, you're getting double digit reports, meaning ten, twelve, fifteen percent candidiasis. The good news is that it looks like it's all mucocutaneous and not systemic.

Well, did they talk about that at all, Anthony, in the report?

Yeah, they didn't have any increased new safety signals in candidiasis. They were all manageable. None of the patients needed to withdraw therapy. So very, you know, quite reassuring data.

Okay. Very exciting. I want to thank all of you for contributing to a lovely discussion of the first two days at Uilar twenty twenty five. I wanna remind the audience we're gonna do these daily recaps tomorrow, day three. It's gonna be on Friday, same time.

Day four is gonna be on Saturday, same time. I think that's 12:00 Eastern Time. You can get these live via Zoom or watch the livestream on YouTube x, also known as Twitter, Facebook, and LinkedIn, and also be available as a podcast or as a recorded video for you to take in the content as we go forward. Folks, have a good meeting. We'll be back.

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 rheumnow.com.