Daily Eular 2025 Recap Day 3 Save

You're listening to a RheumNow podcast coming to you from Barcelona, Spain, and you are '20 20 '5. Hope you enjoy it. Hello, everyone. Welcome to you are '20 20 '5. This is the day three recap.

I'm Jack Cush with RheumNow, and I'm joined by three friends and three of the faculty who have been dutifully color covering this meeting. They've been everywhere, tweeting, writing, and now doing a video. Today's session, the recap, we will discuss our favorite abstracts of today, day three here in Barcelona. As I said, I'm Jack Cush with RheumNow. I'll ask my my panelists to introduce themselves.

Oily?

Hi. Oily Nash. I'm from Glasgow.

Janet.

Janet Pope, London, Canada.

And Yus.

Hello, Yusuf from Leeds, United Kingdom.

Yes, and we're all here back in our rooms on Zoom recording this for you. We're going to each present two of our favorite presentations and abstracts from today. Let's begin with use.

Okay. So my one favorite abstract today is pertaining to the use of cirtalizumab in pregnant women with antiphospholipid syndrome. So the title is o p zero two seven three. So the rationale behind this was from the animal studies that showed TNF cause placenta dysfunction, and they did some work in animal model that if you give a TNF inhibitor, it improved the outcomes. So this is a study in human, which is a single arm, open label study.

Population was women with APS and also with lupus anticoagulant positive. When they did the trial, they needed 45 participants. And if there was only twenty percent adverse pregnancy outcomes, then the trial could be considered positive and potentially you can base that to power in a phase three trial. The adverse pregnancy outcomes that they define included fetal death during more than ten weeks gestation or if you have severe preeclampsia and also if placenta problems and causing delivery less than thirty four weeks. So what they found in the study, so they administered the cirtolizumab between weeks eight to twenty eight, and they found for the intention to treat population, there were actually exactly twenty percent adverse pregnancy outcomes.

And per protocol, it was eighteen percent. These studies showing that proof of concept that administering in the KNF inhibitors such as certolizumab during the pregnancy actually improve the adverse pregnancy outcome. And you know that these women are high risk. And just you know as well, apart from, the certolizumab, they also administered your usual standard of care, which is the lower molecular weight heparin and also low dose aspirin. So,

Yuz, how do we know that this was a significant result? There was no control population.

Yeah. So, basically, the control was based, on the previous studies, if, only, the standard of care, which is like lower molecular heparin and also LDA, you know, just aspirin. So the rate was forty percent. So basically, they powered it. If you improve, you know, by twenty percent, then that that that that will be a positive outcome.

Yeah.

So this was published last month in ARD and is available to everyone. It's called the impact study. I think this is great. Any other comments?

So I have just a brief one. I think the standard of care has really changed. I don't think it'll be that anyone will be willing to sign up for a trial. This study albeit some of it was run during COVID, but it took about ten years at multiple sites to enroll. And it's a very very important study but even without a control group my next patient who's triple positive APS with probably an outcome and past a miscarriage, a DVT, a stroke or something, I would give standard of care and I would offer this because we're not using certolizumab pegol indefinitely and we already know the safety in pregnancy and RA.

So I would find it very difficult to do a trial now even though obviously we'd love the gold standard.

Yeah, I think one of the big surprises here for me was kind of gets away from the old idea that recurrent fetal loss could be treated with steroids and an inflammation targeting drugs, and we kinda went away from that in this population going more towards anticoagulant based therapy. But this says there is a role maybe. So we'll see. Alright. Let's do the our next one's going to be, orally.

Yeah. So, today, I was I was quite interested with the treats earlier five year extension data of the of the trial. So, it was oral presentation all three to four. So treat earlier. It's a was a randomized controlled trial that was presented before.

Subclinical RA, ACPA positive, and ACPA negative. So two groups and they did methotrexate for one year after an I'm injection of glucocorticoids, and they had the placebo control. And so what they showed back then was that methotrexate was extremely great. The primary outcome was whether or not they could prevent RA and retard it, the clinical RA. And so yeah, I wasn't really convinced by it back then, but when they looked into different population, it seemed that the ACPA negative population would benefit more as opposed to the ACPA negative.

And so what they confirmed in this five years data set was that indeed those ACPA negative patients, they do seem to benefit even after five years from the methotrexate, which I found really interesting in particular if you put into context with the data that were presented by Endicope on the first day in the plenary, the three years extension of Alto, which was the Apipra one, which was Abatacept six months, and those who seem to benefit was those very active positive multiple IgG rheumatoid factors. So it's almost in my head now. There is this group of patients, very seropositive, very high risk, and it's almost methotrexate is not enough to prevent RA for them. Maybe they need some different mechanism of action. While those seronegative patients, maybe the tetraktate is enough for them to prevent.

So that's kind of how I see it. But I did not see the debate today. I didn't have the chance to do that. I don't know if any of you guys did, but I'd be interested to see what was said as well. But yeah,

that's kind of

how it pans out for me after this.

Yeah, there was a debate today. I missed it too. I was in another session about you should or should not treat clinically suspect arthralgia with the aggressive therapies. They were going to use this data like the TREAT earlier and the Apipra and the ARIA data to defend themselves or to argue against it. Janet, what do you think of this data?

Right. So first of all, I think it's kind of neat the concept prevention before your immune system has epitope spreading, say if you're aqua positive. The effect size is pretty small but the fact that the graphs still diverge on the as a for instance on the abatacept data, they only got six months of abatacept and there's still a change. So if it was my identical twin, if I had RA and the identical twin was ACPA positive or vice versa, I'd kind of say, you know, why don't you do six months of this and you won't get a chronic disease? But I think time will tell.

And I think we'd be all over it even more if it was a drug that we could easily get access to. The final thing is I'm not sure how many of these people ever will get RA because it looks like if you enrich for a population by five years, up to sixty or seventy percent will have RA so it's pretty enriched.

Absolutely. Jus, what do you think?

Yeah so yeah so I missed this abstract as well so can we just check was there any changes in ultrasound or like you know erosion damp or anything?

So the three earlier, the primary was either having clinical RA or there was a combo of physical function. I would have to check again for imaging outcome, but I don't think I saw any of it because they were already had subclinical inflammation, on imaging. That was as an entry criteria.

Yeah, that was one thing that was unique. That was an entry criteria. They didn't have to have, unlike the other prevention trials, you had to be seropositive to get in. This one you didn't. You had to have arthralgia and subclinical, arthritis or inflammation, mostly tenosynovitis.

One of the big questions that came up was, well, if they're seronegative, are those seronegatives really seronegative? It turns out a minority of them do have rheumatoid factor, so they all are seronegative for ACPA. Yeah. And ACPA seems to have a better influence in predicting future development of inflammatory arthritis. But other autoantibodies like carbamylated P and the other ones were either not there or just in very low frequency.

So yeah, I think this is gonna maybe change the way people think about this.

And I do think Aria, sorry to interrupt there, Apipia, one, the abatacept one that they presented, those who did get RA who were on had received previously Abitacept, they actually said their disease was more mild they had less erosions, but the erosions were just a very small amount. I think I remember that from the plenary.

Yeah. And a quick question as well. That just will build up the question whether how long do you need to treat them with methotrexate. I mean, there any answer there or did more longer follow-up will be needed if they tapered methotrexate?

Well, five years, those who were treated with methotrexate for one year, the ARPA negative ones, there will still allow a percentage of them progressing to RA. So that's a five years effect of a one year intervention.

Right. So in all these trials, it has been a partial treatment. The earliest one was Prairie where they got one infusion of one thousand milligrams of rituximab and had thirty months of benefit. The two abatastrous trial, apipra and ARIA, ARIA had six months of ABBA, and apipra had one year of ABBA, but they both show four and five years effects. So, and the question is, is that really what's good about this study is that the lines don't come together.

It looks like there's something different. All the other studies, their lines ultimately do come together. And I think it's good no matter what, because you have this long disease free interval and who knows as Janet's point was maybe come back as RA but it's kind of mild or whatever. Do you change the trajectory or the aggressiveness of disease by getting them at the sort of intercept point with one of our interventions? So we do need to, well, I think we like the old BEST study.

I think we're gonna see almost yearly reports on these cohorts and what happened to them. And I wanna see that myself. All right, did, Janet, you're next?

Yep, so I'm gonna talk about an old drug, but some perhaps novel insights. So the first one is poster nine eighty seven. And this was a large group of patients from Taiwan who were on hydroxy chloroquine for rheumatic indications. So lupus was common, but also RA, MCTD, SSC, other CTDs. So that's in and of itself a little bit interesting because often people are talking about drug levels and lupus.

So what they wanted to look at was the varying by dose, but with respect to the toxic or sub therapeutic or therapeutic drug levels by GFR. And so they had four different ways of looking at dosing and they had four different GFR. So it was GFR greater than 90, so normal, less than 90, but better than 60, less than 60, better than 30 and less than 30. So, you know, bad, a low GFR in that last group. And at four hundred milligrams per day, the numbers are small because you start subsetting, but just to know every patient low end had with the lowest GFR had a toxic drug level, everyone, four hundred milligrams, even if they're a big person like higher than, you know, where you're dosing your five milligram per kilogram, all of them had a toxic level at the lowest GFR.

And even two hundred milligrams per day at that lowest GFR, one in four had a toxic range. Now low numbers, because we're subsetting all over the place in this study, but in general, so six milligram per kilogram per day, all the low GFR people were super therapeutic. And even the next two levels of like 60 to 90 and even the 30 to 60, even in those levels, one third had super therapeutic levels. And that's if even if you look at lower dosing, so if you went about four milligram per kilogram, none of them had toxic levels in general of normal renal function, none at all. So I think the take home is we have to really dose adjust for GFR.

This isn't something new to us, but it's not always discussed. And we did a study way back when. So one of the, well, two trainees were in the study with me, both of whom one's a rheumatologist, one's going into room. So shout out to them, but we published an ACR open rheumatology in 2023. We looked at lupus itself adjusting for everything seemed to be a higher risk of having a retinal toxicity possibly because we really want them to be adherent.

We talk about it more possibly because of GFR, but I think we do have to be very careful that if their GFR is low, but not that low, maybe you try to get a drug level. So I think the take home is small and more data will come, but it's important to think of GFR when you're dosing.

That, you know, there was a session yesterday on hydroxychloroquine levels, and very well done, good overview, confirmed a lot of data from Michelle, therapeutic levels being seven fifty to eleven fifty, I think was the number.

Yeah.

They talked about the population of people who had, renal insufficiency also in there. And that's the great thing about monitoring. You're gonna get the level and you dose adjust according to that. So this kinda tells us what you're talking about a priority before you start knowing what their GFR is, you're gonna dose adjust. But then ultimately, if you're gonna, you should be doing levels, we all should be doing levels, believe.

Then you'll really know where to be and how to keep the patient safe. Amongst the four of us, who's doing hydroxychloroquine levels in their patients?

Access, can't get them.

Well, you can get them now in The US with a commercial lab. So, yeah, we're all in different countries. Glasgow, Leeds, Canada, and I'm in Dallas. I so I can get it. I have the the the worst excuse except I'm working in a charity clinic.

I tried to get my university to do it before I left, and they had all kinds of I think that they are going to get it or they're just about to get it now. But it's, I think that we're at a by not doing it. And I think that should ask around about where you can get it and ask about your commercial lab. I I think Labcorp is capable of doing that right now. I don't know about Quest in The United States, but anyway, any other comments on this?

User, what do you think? Yeah.

Just to back up. Yeah. So the so the abstract yesterday was a o P0199. Yeah. Think that the abstract highlighted the importance of monitoring particularly people with CKD stage three at least.

Yeah. So I think the the four and five is okay but I think for CKD stage three and above, tend to, you know, can get more increased risk of retinal and cardio toxicity. So I think it's quite important to monitor them. Just quite out of interest because we don't, you know, there's only a few sites in The UK that can do hydroxychloroquine monitoring. And if we want to do it, we have to send to London.

But there's some feedback also mentioning that, you know, the turnover was quite long, you know, take well, so I'm just wondering, like, in in your areas, Jack, as you know, how long turnover is before you get the in the script results?

Okay. Again, I think we gotta make a pitch to get this available to us. It it really improves monitoring. I remember Madrid, you are many years ago, Michelle first presented this. I said, is this for anything more than, you know, compliance?

And she said, oh, yes. There's only Michelle Petrie Wood. Alright. My, first is the ARIA study, which is o p zero three two five presented today. Nice follow-up to the ARIA presentation that was, presented two years ago.

In this study, it's an RA prevention trial. Patients who are ACPA positive also, having, evidence of subclinical synovitis, by either MR or ultrasound. Ninety eight of them are enrolled and randomized to either receive standard dose of abatacep or placebo, for six months, and then they go off of the abba, and they're followed for another twelve months with an eighteen month endpoint. At six months, there was obviously significant protection, in those on abatacem, only eight percent developing RA versus thirty five percent who were on placebo. Even in that time period, those who were taking abetacep were afforded about a fifteen week RA disease free sort of zone just in that first six months.

When the patients were followed out to eighteen months, there was still protection, thirty five percent on ABBA and fifty seven percent on placebo went on to develop RA. And in this study that they're doing, presenting here, they they follow patients out. They're following them out for nine years. They're reporting at this point a median of five point nine years, where even at this point, there still is benefit with about ten months of being RA free when you compare the two cohorts over time. What I liked about this study, a little bit like the TREAT earlier study that we just talked about, is it gives us some instruction as to who might be the best candidates to receive this treatment.

And in their study with the way they looked at it was what were the clinical parameters that they saw in patients who developed RA during the trial, the period of observation. And then after eighteen months developed RA after eighteen months because many did and the ones that never developed RA. And what they showed that was significant was that markers of systemic inflammation, CRP being best sed rate, were really good along with pain, pain VAS, tender joint counts, HACS score, rheumatoid factor, those are the main ones that basically said when things were looking really and those are baseline numbers predicted those who would progress and those who wouldn't. So the ones who had tender joint counts or tender joints or painful joints of two or less were less likely in fact to progress, whereas the ones that had five or six. So the idea is the worse that you are on those systemic and pain and rheumatoid factor.

Interesting thing to get into the trial, you had to have subclinical synovitis. But throughout the trial, they did serial MRIs on people, and the MRIs were not predictive as time went on. Either osteitis, synovitis, or tenosynovitis, which we know from the work of many, including the leads group, tenosynovitis is highly predictive of who's going to go on and develop further inflammatory arthritis, what looks like RA. So, again, I think it's instructive. I think it's a good well done study, and that's why it was an oral presentation.

Any comments? Orly, what do you think of this data? You were in the same session as I?

Yeah, I think, I mean, you know, the body of evidence is kind of accumulating that some interventions seem to work in some patient in some way, but I think what we need to be better at now that we have all this evidence is to maybe stratify people really well and try to understand. It might be, I was kind of saying earlier, that there might be some subgroups of patients that would benefit from one intervention and some group, know, like the metrics and then the ACPA maybe those highly positive these these patients are at higher risk anyway to have severe RA if they develop RA. So that might be something else to take into account. And I think this is exactly what you you just described was the results of a barrier.

So there's a recent UR ACR risk stratification paper for CSA patient and clinically suspect arthralgia telling you who's at risk to develop RA. This is what you're talking about, Orly, who's at risk that they probably need treatment that you can predict who needs to get it. And we know it's ACPA, and we know it's subclinical synovitis. And that's why it's not just thirty percent who get RA, but when you start adding on these other things, it goes as high as sixty, seventy percent. But some of these papers like yours with seronegative and this ARIA one telling us that rheumatoid factor and HAC scores are also helpful.

I think it helps. A few more comments and we need to move on.

Oh, I agree. I think it's more will come in this space, like you said earlier. It's exciting still.

Okay. Let's, go on. This our our next round is gonna be a quick round. I'm gonna ask short presentations, very short comments even though what we're presenting gets us all excited and we wanna talk too much, and I'm talking to myself here mainly. So, again, who wants to go first?

Orly, why don't you start?

Yeah. Sure. So okay. Quick, one in the gout space. I I got excited because I've not seen many RCTs in the gout space in a in a long time and so there was a oral presentation all three zero two phase three RCT.

So it's a new class but it's not the only dragon of that class. There was other stuff presented before, in particular ACR, but it's called RUZINURAD and it comes together with another one, which has a pretty similar name. They are URATE-one inhibitors. So what they do basically when patient takes them is that the patient it increase excretion of urate through the kidney. So immediately when you think about is side effects potentially nephrolithiasis and it's been reported but in this trial what they did is they had the allopurinol group.

They had the group and basically the was doing better in reducing the levels of urine and the target of three sixty micromole per liter in their population. They had quite a few patients in there and the safety profile was actually not not bad. They had a few upper tract infections. They had a few you know liver enzyme elevation which is the case with allopurinol anyways. So the the the the tolerance look pretty pretty good the profile in my opinion.

So that was a Chinese trial. There was another presentation just before that OP or three hundred was another of this drug looking into to face gout and chronic gouty arthritis as well and seems to be working as well in in combination with allopurinol in these severe patients. So, think this is a space to watch but I thought that was quite exciting.

Yeah, you're at inhibitors. We've been waiting for them for years. They seem to have promise. I think it's not too far in the future that we'll be using those. Let's go on to using your next quick hit.

Yep. So my, abstract title is a poster tour, so POS zero three two five. So this work was done by my group for which I'm the senior author. So essentially, there's so many presentation at this EULA about CAR T therapies, and the main aim is to induce deeper depletion and also hopefully be immunosuppression free. But you can also get a super response with rituximab.

So we look into our cohort, we have 148 patients treated with rituximab, but we excluded a few, so we only included one hundred and fourteen because some of them we excluded because they were retreated on a clinical relapse, so you couldn't access the duration of rituximab on it. So what we found of those one hundred and fourteen patients, there were twenty percent of patients who had really long response to one single cycle of rituximab, so lasted for more than three years. And of this as under twenty percent, so seven patients are equivalent to so eight patients, so equivalent to seven percent actually were immunosuppression free after twelve months the first twelve months rituximab, and they they seem to be doing really well. So we were really interested to part to characterize this patient who are we considered as super responder. And what we found that the factors predicting this super responder included those who had a severe prognostic marker, such as the non European ancestry, you're black and Southeast Asian, and people with concomitant APS, and also if you used rituximab earlier, so shorter disease duration.

So this really put all things together that if you, you know, calls for if you start using rituximab earlier in these poor prognostic patients, so, they will have a better outcome and also long response as well. So that's the thing. And it serves as a pilot that currently trying to prepare. So we're doing a multi center trial in The UK to use Rituximab as first line biologic in early diagnosed moderate to severe lupus. So, I think that's probably watch your space in the next few years.

Yeah.

Janet, what do you think?

I think this is really cool. Interesting because I don't use it very much. We had access issues in lupus, but in RA, I've seen super long responders, but interestingly used, I've only seen them at about two or three years out of rituximab, a gram times two, if they're not in remission, another gram times two in six months, this is an RA. And then we, in Canada, we got access by treating them when they flared. And I've had people that maybe got three courses and now I have one or two of them six years out and I forget what they're on because they're not on anything.

They're just on hydroxychloroquine and the trainees say, you know, how come they're only on that? And I go, well, I think they're still on rituximab. So we had some people in RCTs and RA reflux and dancer that were possibly permanently CD19 or twenty B cell depleted, but getting no infections. We haven't had to redose them in ages. And so I think we sometimes forget this can be a pretty cool drug for some patients.

Like you, Janet, I've used a ton of rituximab because I did all the trials and a big believer, but I'm not a big believer in lupus. Many rheumatologists, in my opinion, are, and that reflects frustration. So use I like that you're gonna do a trial, but how you where is it gonna go when it's not currently a therapy that's being marketed for that? And we have coming up very soon, approval of the other anti c d twenty obinutuzumab. But so why do the trial when there's gonna be a better drug coming up?

Yeah. So I think what we're trying to say here is not all just about, for example, like, in the CAR T. So there are other mediums of you know, if you've got better depletion, you should get a better response. So I think that's the key, you know, finding from our study. So the reason why we use rituximab is it's a pragmatic trial and rituximab, for example, The UK is so cheap.

Now, biosimilar, it costs less than £400 per cost. So that is so cheap, whereas Erbinetizumab, we still have to wait a little bit longer. And if you do want to do another trials using Erbinetizumab, then it will just incur the cost even more for the funders. So I think that's the reason because UK and quite a few other areas that you can actually use rituximab, I think I believe I agree. I spoke to one of the colleagues now from Canada.

I think they said that rituximab is really expensive in Canada to use for that setting.

Okay, let's move on, Janet.

Okay, two really quick ones because they're on my hydroxychloroquine.

Very quick, they're my lupus.

Don't worry, two sentences. So RCT of herpes zoster vaccination in lupus, because they can get quite a high response to the vaccine. They already proved it was safe and effective. This just showed in the RCT poster 1005 that at one year there's still good humoral and cellular immunity and they didn't have many patients flaring, etc. So pretty cool.

Number two, real quick, poster nine eighty three, how does hydroxychloroquine work? So I always taught the trainees and I learned it stabilizes lysosomal membranes, whatever that means, right? So this was kind of cool, mild lupus patients only hydroxychloroquine monotherapy. Some had been sicker in past, one had had lupus nephritis in past, followed about every three to six months. They had low sleep eyes coming in.

They did single cell seq and they're giving the average of the small n of patients. But what they found was the cytokine signals can change even when, so some background noise and not everyone has the same signals, but drum roll, interferon type one is reduced in hydroxychloroquine and some type two as well. So maybe that's why it's a really good background drug when that cytokine can be quite important in some of our patients.

Janet, was there any specific cell subtypes where the signature was reduced to?

Right, so they looked, so to me it's a small n. Single cell seq doesn't need a big n, they looked in people that had skin, people that had prior lupus nephritis not active at the time, and there could be differences, but there's also some background cells that are very different in some of the different organs. I think it's an orchestra and interference is part of the orchestra.

Yeah, so just to add about that vaccination earlier as well, I think one of the analysis that they did was they looked into the titer of the humoral response and cellular response, but it seems like it's both of them were declining slowly over time. So I think it would be interesting to see what happened after that one year. And then it's supposed to question, like, you know, how frequent do you need to vaccinate, you know, with this adjuvant Shingrix for herpes zoster prevention. So that's interesting, and we can compare that with lupus and also other rheumatic diseases.

And would MMF and things make a difference too because that seems to attenuate a lot of vaccines like COVID.

Mhmm. Oh, yeah. Alright. So our last one is going to be, poster number one zero five one presented by, Marie Therese Holzer in Germany. The title was an eye catcher as I walked by.

It's myositis in the ICU. And it's their collective experience of twenty three patients with idiopathic inflammatory myopathy of different types that were admitted to the ICU. This cohort on average was admitted for thirty two days. The bad news is there were five deaths. What?

There were fourteen patients who needed mechanical ventilation. The deaths were either from bleeds or infection. So these people were generally admitted, to the ICU for myositis infection, surgery, other reasons, but the real reasons were mostly myopathy and lung reasons. And myopathy presented as not just weakness, but like dysphasia and myocarditis and whatnot. Complications of lung disease, was the other thing.

The types of patients were a third of them was the biggest subset of dermatomyositis. Seventeen percent, had overlapped. Seventeen percent were MCTDs. Ten percent were polymyositis, and I think was nine percent that had necrotizing myositis. Again, the, the other interesting factor here was at baseline, at in at entry, majority of them were on myositis treatment, eighty seven percent were on steroids.

These people tend to be on high steroids. They're a mess, you know, and they get more steroid related complications. They get more serious infectious events and hospitalizations and deaths, and we need to be, cognizant of that. That's why I like this particular abstract.

Right. MDA five, did they say how prevalent it was, Jack?

Not looked at in their population. They didn't get in they didn't get into these serologic subsets. This was a cohort analysis from 2014 to 2022. So maybe before people were doing MDA five, NXP two, TIF one gamma subsetting. I must say, until those three came along, I almost never got myositis specific antibodies.

What was it gonna do for me? It really was. But actually now, it's so easy to get these, autoantibodies, and and and these do have significant prognostic, capabilities that I do tend to order them now. Okay. Alright, folks.

I wanna thank our panel for a great discussion and being here doing the extra overtime after a really busy day at ULA. For you out there, you can see or hear the final day recap, day four tomorrow, same time, same channel, and follow us on RheumNow. We have a lot of good content coming to you from Barcelona and EULAR twenty twenty five. Thanks, folks.