EULAR 2024 Daily Podcasts Day1&2 Save

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 17 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 Tik two inhibition is that interleukin 23, in particular, signals through Tik 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 sonolocumab, a new interleukin 17, nanobody that targets both IL-17A and IL-17F. And there's also an abstract for Ezocopep, a nanobody that targets IL-17A that's being presented as a late breaking abstract number 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 TYK-two inhibitor. This is a phase two study, being presented as an oral presentation, abstract, OP-one 138. One of my favorite, things about this particular molecule, it has had 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 going to 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, everyone. This is Orelinav reporting for RheumNow for Vienna. I am super excited, super psyched to be here. I have, you know, selected all of my abstracts and I'm just delighted for all of this science to come. And 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 10 presented by 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-twelvetwenty three inhibitors, IL-twenty three inhibitors and IL-seventeen inhibitors.

And the results are quite striking to me really. So what they show is that if somebody is treated with an IL-twelvetwenty three or an IL-twenty three 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 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 risk developed PSA within 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 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 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. 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. Tofacitinib, 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 dekrevacitinib 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 OP zero one eight four and it's the Gull May PSA trial.

So these 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 they were delivered the way we deliver them in The UK, which is not with tablets. It's usually intramuscular injection. And in this case it 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 scolimumab, so TNF inhibitor. And so the primary outcome there was the difference in the past that score at week 24, but the study went up to fifty two weeks and they looked into eighty four patients in total divided in these two group. And so I found the results quite interesting. So at week 24, the main difference in the past as was point five five minus point five five, which is not massive. And the P value was 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. ACR 20 was really similar between two groups. There's one thing though that 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 some patients with endothelial 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. This is Eric Ruderman from Northwestern University in Chicago coming to you live for RheumNow from the EULAR twenty twenty four meeting in Vienna, Austria. I've been looking at some of the abstracts related to spondyloarthritis at this meeting, and thinking about the implications for clinical practice. One of the things that's been interesting is that there are several abstracts looking at whether therapies, particularly biologic therapies, inhibit structural change, either in the spine or the sacroiliac joint in axial spondyloarthritis. Two that were most notable was one looking at a post hoc analysis of a trial with ixekizumab.

This was OP0046. They looked at MRI imaging and looked at the impact of ixekizumab therapy on structural lesions in the sacroiliac joint. They found that treatment with ixekizumab reduced bone marrow edema, which we knew, it reduces inflammation, but they were also able to show that there was some backfill of existing erosions in the sacroiliac joint and additional fat deposition. The implication for this is that they were filling in erosions as a response to therapy. I happened to be at this, particular presentation, and I asked, the presenter about the clinical significance of this, and he honestly, couldn't help, you know, that the issue of filling in erosions is an interesting imaging finding.

But whether it translates into real clinical benefit and whether this is really healing of those erosions, healing of the bone, or this is just filling it in, with, tissue that, is structural but is not normal bone, I don't think we know. There's no histologic data to show what's happening here. There was another abstract presented at this meeting, POS o o five eight, a poster that essentially looked at the same thing, with bimekizumab, the newer IL seventeen inhibitor that inhibits both IL 17 a and IL 17 f. They showed the same thing. The authors were many of the same authors, also showed that treatment with this IL seventeen inhibitor, seemed to improve the structural changes of the sacroiliac joint, filling in some of these erosions.

But, again, is this is this truly backfill and repair, or is this just filling in with, some sort of nonfunctional structural tissue? We don't really know. Ultimately, I'm not sure how important these findings are gonna be. It gives us some insight into mechanism of these drugs, but it doesn't really tell us if this is gonna improve outcomes in patients because most of the symptoms in our axial spondyloarthritis patients are related to inflammation and not structural change or structural damage. So I think there'll be more to come on this, and I think that hopefully some of these groups will give us some information on the potential clinical relevance of what they're seeing on the MRIs, but we'll have to wait for that.

Stay tuned here on RheumNow for more information from EULAR twenty twenty four in Vienna. See you soon.

I'm Anthony Chan, consultant rheumatologist from Reading, United Kingdom, and I'm here in Vienna at EULAR twenty twenty four reporting for RheumNow. There have been some interesting abstracts and presentations on the field of spondyloarthritis here at EULA twenty twenty four. And I'd like to bring, to your attention one interesting, presentation, which is oral presentation 120 from Hermans et al, from The Netherlands. And in this group, they looked at the very important and interesting topic of can we see patients less frequently if we monitor them using tele monitoring and also patients having a say on when they would like to come back This is something that we have been doing ourselves in The United Kingdom. There's a big drive for us to identify patients who might be suitable for less frequent appointments but at the same time ensuring that it is safe for them to do that and that no harm comes to them.

In this oral presentation O120, it is actually a randomized controlled trial which is really important for us to have evidence that what we are doing here firstly safe and secondly it's effective. It was a pragmatic multi center randomized control trial which randomized patients into the first arm which is the patient initiated follow-up and tele monitoring arm and then in the other arm which is the usual care arm. They had 100 patients in each, arm of the study and they followed them up for just over two years and and to kind of see what their outcome were long term. They followed the patients up at six and twelve months to just check how they were doing. In the patient initiated follow-up and tele monitoring group, they had a follow-up visit at twelve months but at six months, they had a telephone call to see how they were doing and in the usual care group, they did not have any fixed appointments, they had the appointments were at the discretion of the treating physician.

And what they were trying to measure at the end of this was was there a difference in the number of visits in the both arms and they were hoping that at least they would achieve a 25% reduction in the patient initiated follow-up tele monitoring group as compared to the usual care group. And so as the study went on, they measured this outcome and at the end of the study, they found that in the patient initiated follow-up group, there was a mean of 1.9 appointments which is lower than the usual care group which was 2.6 appointments over this period of time of the study. This, meant that there was a less reduction of 0.7, fewer appointments in the patient initiated follow-up group and the tele monitoring group as compared to the usual care group. With regards to the number of telephone consultations they had or telephone contacts they had in the study, this was equal in both groups with a mean of 0.6 telephone consultations in both groups. So while the patients were not coming, the number of telephone contacts were similar in both groups.

So that was the primary outcome of the study. It met its target which is a reduction of greater than 25% difference in the tele monitoring group compared to the usual care group. With regards to secondary outcomes, they were looking at cost effectiveness and also they were looking at safety. In the area of safety, non inferiority was shown as then there was no worsening in the people who had the patient issued follow-up or the tele monitoring group and no adverse events were recorded in this harm compared to usual care. When they looked at the cost effectiveness, they used qualities or quality adjusted life years and in total there was a net benefit of €273 when comparing the two arms in the favor of the, the patient issued follow-up and tele monitoring group.

So in conclusion, this, the authors, have shown that there has been meaningful reduction in terms of the if uh-uh cost by doing this type of tele monitoring and patient issues to follow There was no significant harm posed to the patient or any harm in terms of the patient's safety but has demonstrated that it's possible to run a program like this in order firstly to improve capacity, in our clinics to reduce the number of people who are coming, but also to have, the patient involved in their care and also for them to have a say as to when they would like to be seen, but at the same time providing a safety net because these patients were being monitored using the tele monitoring service. So I think this, poster here would hopefully help us to shape some of the, practical aspects we try to implement such a program, in different parts of the world. And hopefully this, first randomized controlled trial here on this, topic can help us to do that. I'm Anthony Chan reporting, for RheumNow from EULA twenty twenty four. I'm Anthony Chan, a consultant rheumatologist from Reading, United Kingdom, and I'm here in EULA twenty twenty four in Vienna reporting for RheumNow.

One of the big areas of in terms of management of patients with inflammatory arthritis is the concept of treat to target and what we mean by that is that we would set a treatment target and this usually would be an outcome score and we try to achieve this target using the therapies that we have. While this is widely demonstrated in rheumatoid arthritis and also psoriatic arthritis, it has been less demonstrated in Axial Spondyloarthritis and there are reasons for that. Often there is a long delay to diagnosis and also the definition of early Axial Spondyloarthritis until recently has not been defined. More recently we've had some important publications. Firstly, the ASAS EULA guidelines 2022 for spondyloarthritis has been useful in terms of the management and sequencing of treatments in order to achieve a treatment target.

And secondly, the ASUS definition of early Axial Spondyloarthritis which is symptom duration of less than two years prior to diagnosis. When having this information allows us to then set up a framework with regards to how to achieve treatment to target. Here at Yula twenty twenty four, there is a very interesting abstract. It's oral presentation zero one five two and this is a study looking at the treatment to target approach and how this can be achieved in Axis Bundle Arthritis. We know that there's a diagnostic delay for up to eight years and also only more recently the definition of early access bar has been defined as being less than two two years.

So using a tight control treatment to target approach, the authors of this study looked at a fifty two week open label prospective trial where patients were recruited when they met inclusion criteria which is a symptom duration that is less than two years and these patients were then randomized to treatment within the type treatment to target approach. They used the Asas Eula guideline as the the guiding principle regards to management decisions. When patients were in the study, they were first given anti inflammatory medication, NSAIDs. They were given two NSAIDs for four weeks and the target was to achieve SDAS CRP which is the Excess Bundle Arthritis Disease Activity score with CRP of less than 1.3. Or they would want to have an improvement of more than 1.1 in terms of the change in the S test and achieving a low disease activity of less than 2.1.

So these were the targets as in the they were trying to achieve using the treatments first starting with NSAIDs. If patients did not achieve these targets after they had the anti inflammatory drugs then they were put onto fifty milligrams subcutaneous once a week and these patients were then followed up and the target this time after commencing was that the S test CRP would be less than one. Three on two occasions twelve weeks apart. If patients achieve this target of S test CRP of less than one. Three then the the treatment was stopped.

And then they were followed up to see how how how they were having achieved this target. They were 55 patients recruited into a study and the symptom duration was very short. So, they were symptoms the onset of their back pain to the time of diagnosis was less than one year. These were patients who with a mean age of 28 years of age. Just over half of them were males at a 58.

Six percent were male and eighty six percent were HLAB27 positive. The the mean Esther CRP was three. So these patients had active, axial spondyloarthritis and seventy six percent of them had active, sacroiliitis and so these patients had active disease and in order to achieve, an S test of less than 1.3, this would be a very big significant improvement in their condition. When they looked at the outcome, thirty four percent of them were able to achieve remission with an S test of 0.9 and this was a very good outcome and another twenty one point eight percent achieved low disease activity. So in total around sixty percent of patients in this study achieved a good outcome score based on the treatment to target approach.

When they looked at the predictors as to what were the patient factors that allowed these patients to achieve clinical remission. The multivariate analysis showed that male patients were more likely to achieve a clinical remission, a low baseline best eye entry and also not smoking. So these were important characteristics of patients who were more likely to achieve the clinical remission in a treatment to target approach. When they also look at other outcomes, in terms of flare ups, so these patients who were followed up, and if they had treatment and then the treatment was stopped, upon achieving the treat to target that was set up. Eighty four percent of these patients had a flare in the trial but looking as time to flare from stopping the treatment in the NCA group this was a mean of sixty one days in the group, this was one hundred and fifty five days.

So, there was twice and more longer time to flare if you're in the group compared to the group. So, this is a very important study because it adds to our body of knowledge with regards to treatment to target in particular in excess spondyloarthritis where there has not been conclusively shown but I think this is a very important study to kind of help us to understand. And secondly also helps us to think about how we should be diagnosing and detecting these patients a bit earlier so that they can have this type of approach where sixty percent of them can achieve clinical remission or low disease activity state. So I think this is a very interesting and important study that hopefully will help influence and also shape our thinking regards to treating to target in axial spondyloarthritis. I'm Antony Chen reporting for RheumNow here at EULAAR twenty twenty four.

Hello everyone, this is Bella Mehta reporting from EULAAR twenty twenty four and I have a friend with me Vincenzo Vinitero from Italy and wanted to, I came across this interesting abstract with him looking at MRIs in axial SpA. Can you tell us more about your study?

Absolutely and thank you Bella for the invitation, it's a pleasure to be on now. Yes, we use radiomics to try to investigate the information contained into bone marrow edema of active sacroleitis in patients with axial spondyloarthritis. Actually we do not have any minimal invasive procedure to assess histopathology information of bone marrow edema as we do synovium for instance. That's why we borrowed a methodology from our cousin, oncologist, Radiomics.

So what is radiomics for like an average rheumatologist? It sounds fancy, but I want to know what does it do?

Absolutely. You have to imagine that any imaging test is a result of the interaction of a physical phenomenon, magnetic field, unising radiation, ultrasound with a tissue. So this interaction in physics provides a plethora of physical parameter, the so called radiomic features that are dependent from mononin energy but also from the tissue histopathology. This radiomic feature can be course elaborated to provide you the DICOM as you know it, but they can also be analyzed as a raw continuous variable by statistical modeling or machine learning to predict any outcome in oncology.

So the DICOM images are like MRI images. Yes. And you do statistical modeling with machine learning to do this.

Yes, on radiomic feature extracted by bone marrow edema segmentation in cell. What we did, it's quite simple. We opened our diagram on a software called Translicer. Translicer comes with a tool that can allow for the semi automated segmentation of any lesion. It's incredibly easy to segment the bone marrow edema on serous segments because of the difference in intensity, then we extracted via some Python API so called radiomic fissure.

There are 120 radiomic fissure that we extracted, we normalized that, we checked for autocorrelation, and then we retained 39 of them. With that 39 radiomic fissure, we built a very straightforward multivariate oxygenation model to try to predict TNFI discontinuation in patients with access spondylarthract. So we did, we add a low sample size this is a proof of concept study but actually we found two independent predictors of TNFI the discontinuation the elongation and the sphericity. Sphericity is the roundness of bone marrow edema and elongation is the ratio between the two principal components. So let's think to ratio between horizontal axis and vertical axis.

Actually we found that our model had a goodness of fit for short term prediction. With the mid term to long term prediction it fails. But we demonstrated potential of radiomic fissure for predicting treatment outcome. For me the most fascinating aspect of radiomics is that MRI together with radiomic analysis measures not only as a diagnostic exam but also as a prognostic procedure.

And the prognosis was within three months or six months?

Actually our our mean follow-up time was about thirty months.

Okay, so it's a very good time. Yeah. So just using MRI features, extracting radiomic features, you know, and there's a lot of studies right now talking about diagnostic potential, but he also sort of, it caught my eye because it's also showing prognostic saying, will this patient be on a TNF inhibitor or not in the next few months? Is that

right? Absolutely, absolutely. It's right. And actually the added value of the whole radiomic analysis is time saving because this is an incredible fast to do. The whole process for a single patient takes only one minute and three or five seconds.

Time saving and people who are not radiologically trained can also use this? Yes, actually for semi automatic segmentation we also employ a dedicated radiologist but I can swear that with the tool provided by the platform, the segmentation is quite easy to perform.

That's great. So again, you know, we've loved your work, Oren, and more to come. Any one last line that you would

tell viewers to look out for the future? I think that we need to validate this data on external court before an option, have to compare that with Spark. So it's important to compare with the gold standard from bone marrow edema quantification. And after that, who knows, probably this could help us rheumatologists.

Yeah, well, let's get these into mainstream and with that signing off here from EULAR, Bella Mehta.

Thank you.

And thank you so much for coming.

Thank you.

Hi, everyone. This is Aurelie Naj reporting live from Vienna at EULAR twenty twenty four for RheumNow. There is a super trendy topic at the minute, which is pain. It is unfortunately has been an issue for a lot of people living with arthritis experiencing pain, and sometimes it's very difficult to treat specifically as there are many different mechanisms for pain and some can be related to inflammation and some aren't and and we don't have really good drugs for that and so there have been discussions as per whether some biologics or targeted synthetic DMARDs could be better than others in addressing pain and pain in its different mechanisms, whether it's nociceptive, and so on. And so there's a couple of abstracts in the aspect that looked into that more specifically.

The first one is OP 72 and that study was the SELECT COMPARE study. So it was a randomized controlled trial looking at upadacitinib versus placebo versus adalimumab. And so what they did in this study, I think was really smart, is that they separated specifically different type of the effect of the drug on pain, and they call one of them the indirect effect that is measured by surrogates of inflammation, which would be swollen joint, ESR, CRP, but also what they call the direct effect, which is more related to either pain specifically in the patient global or the number of tender joints. And by doing that, they looked at twenty six weeks and they compared upadacitinib, placebo and adalimumab. And what I found really interesting there is that first of all, we see that both upadacitinib and adalimumab do reduce pain as early as two weeks, which is great.

That's mainly through indirect effects and inflammation control. And in terms of control of inflammation, both treatments atolimumab and upadacitinib were similar in how they improved pain. However, when they looked at the direct effect on pain, looking specifically into the tender joint count, they were able to show that upadacitinib showed an improvement of that aspect twice more, two times greater at weeks twelve and twenty six than atalimumab. And so that is suggesting that there might be something in a jack stop pathway that is related specifically to pain and it could be through the nervous system. It could be there are people studying that at the moment and looking into why the specific mechanisms for that.

But that's definitely something to follow-up on. And that is leading us to the second abstract, is OP 86, which was a study called BRAEAL study. And that study looked at, it was an observational study based on perspective for three years, looking at people with RA treated with baricitinib or any other biologic and targeted synthetic DMARDs. And so what they looked specifically at there was the association of pain in the context of remission or low disease activity at three months after starting a new treatment. And they compared the baricitinib cohort, the TNF inhibitor cohort, and then the third cohort, there was a bit of mix of everything receiving is also targeted to TIDMO, it's also mechanism of actions.

And so what they looked is that the improvement of pain. And so they were looking at those people that improved their pain by 30, 50%, 70% basically. And so what they show is that those people that were treated with baricitinib, while there was no difference in the achievement of a 30% pain improvement amongst group, there was a difference in percentage of people achieving an improvement of 50 or 70% was sixty seven and forty six percent in the Bari group, while it was fifty seven and forty one percent in the other mechanism of action group. And so what it's showing, it's a different way to look into, you know, achieving pain improvement although it's not looking specifically at the different types of pain. It's also telling us that there is some form of difference in how JAK in this context, Barry improves pain, but I think it's a general JAK inhibitor effect rather than a specific compound.

And that's kind of encouraging and you know, it makes me wonder and I don't know if something that you do already in your practice, surely don't, although we do think about it as so we obviously in the absence of contraindications or prioritize JAK inhibitors in these people that have very, very strong pain compound component in their rheumatoid arthritis. So that's definitely something to keep in mind and maybe to look further into. And it's now time for me to get back to the conference and I will make sure I report anything else I found exciting for you guys later. Follow me on Twitter orilleryroom or follow RheumNow, and I'll see you around.

Hi, it's Doctor. Janet Pope reporting at RheumNow from EULAR 2024 in lovely Vienna. I'd like to give you the top three messages about JAK inhibitor safety. So I was part of a debate, and the debate was today on a topic of our regulatory bodies too harsh in the recommendations on JAK inhibitors with respect to safety and restricting prescribing. And the bottom line that came out of this debate, as well as the data that both David Liu and I reviewed, are avoid JAK inhibitors in high risk patients.

And there's risk and then there's high risk. So the risk is all kind of relative, so to speak. So the higher risk patients from oral surveillance that was looking at safety was age over 65, ever or heavy or current smoking, high cardiovascular risks such as already having myocardial events, and high malignancy risks such as smoking, older age and more in men. So the audience voted slightly more than half that the regulations are too harsh. So what would I say?

Top three things. Do a shared decision with the use of JAK inhibitors and use them in caution when appropriate and high risk patients or even medium high risk patients with cardiovascular malignancy risk. Do stratify the risk as some risks are far more relevant. Past MI or revascularization is a lot higher chance of having another MI than borderline high cholesterol or mild hypertension. And smoking is a big risk.

So my call to action is identify who's smoking and try to help the patient stop smoking. That should reduce their cardiovascular risk, and it also decreases over time the risk of cancer. Please follow us with lots of reports at RheumNow. Thank you. Hi.

I'm doctor Janet Pope. I x or tweet at Janet Berdeau, and I'm reporting today for hashtag ULAR twenty twenty four with the At RheumNow group, and, hopefully, you'll be following us for up to date reporting. I want to tell you why ULAR twenty twenty four was worth the euros. So there's three reasons why, and it's all about in this update on AtRoomNow giant cell arteritis and polymyalgia rheumatica. So giant cell arteritis, the late breaking abstract one, which hasn't been presented yet, is on the positive RCT of upadacitinib and giant cell arteritis being steroid sparing.

So two IL-6s are going to work in GCA and now we have a JAK inhibitor. There's other things happening in GCA. There's insights into residual inflammation after treatment of GCA with tocilizumab or an IO6 inhibitor. So on repeat biopsies in OP0233, one third of the biopsies that were repeated at six months on a protocol still had active GCA despite in general having suppressed inflammatory markers. Now, most people don't consent to repeat biopsies, so I don't know if there was something different about these patients.

The next thing is what about when you stop drugs? What happens? This is stopping tocilizumab and polymyalgia rheumatica after six months because then you could have a rapid taper of glucocorticoids. Well, the good news is after six months following for up to a year, one quarter didn't relapse. The bad news is three quarters did relapse, and that's oral presentation six twenty one.

One last thing, a thought on PMR, and I chose this abstract because it's clinically relevant to me. This abstract said looking at the data from a study of patients that were collected, they said leflunomide twenty milligrams a day was better than methotrexate, albeit at a lower dose of about ten to fifteen milligrams once a week. Leflunomide was more effective for both prednisone sparing and preventing relapses. I haven't thought about using leflunomide too much. I think methotrexate was under dosed, but leflunomide might be an option for our patients, especially if you can't get access or it's not indicated for some of the biologicals that are being looked at in PMR.

That was poster two eighty. So I think you have three reasons why in GCA and PMR why EULAR $20.24 was worth the euros. Please continue to follow us. Thank you.

Hello. Hi, everyone. My name is Youssef. I'm from Leeds. I'm reporting for RheumNow at EULAAR twenty twenty four Congress in Vienna, and I'm reporting live today.

This is day one of the congress, and we have had so many fantastic presentation today. But one abstract that caught my eye in the field of systemic lupus erythematos is an abstract OP zero zero seven seven. So this is an abstract pertaining to longitudinal assessment of biomarkers from the obinutuzumab, which is a type two c d 20 monoclonal antibodies in phase two randomized controlled trials called nobility. So I'm privileged today to be accompanied by the main presenter, doctor Edward Vital. Hi, Ed.

Hi. Hi. Nice to see you. Thank you for joining us today. And would you like to tell us about the background of the studies?

Yes. So B cell depletion has been around for a long time. We've used we've using it for about twenty years for lupus in the form of rituximab with variable efficacy, sometimes good. And what was shown a long time ago when I did my PhD was that it was the depth of depletion achieved that determined whether rituximab was going be clinically effective or other. And what that led to is attempts to make other therapies that would deplete B cells more efficiently.

And one of those is abinutuzumab. It depletes B cells better than rituximab does by a variety of mechanisms. And that's been shown to be effective in a phase two trial in lupus nephritis. Nobility, as you say, the purpose of this abstract was to show do differences in depletion and other biomarkers explain those responses.

And can you just describe a bit how do you measure the depletion in this study?

So, yeah, B cell the best way to measure B cell depletion is with something called highly sensitive flow cytometry that we've used for some time, which is a more advanced flow cytometry protocol. You have to look at subsets naive memory, plasmablast, particularly the plasmablast subset that have to be measured. And that was applied not on every patient in the study, but a substantial number of patients in the study got highly sensitive flow cytometry at several time points up to two years.

Okay. And what was the main findings? So the

main thing was that so basal depletion was profound with abinutuzumab. Abinutuzumab was dosed at baseline at six months, and then no more abinutuzumab was given, but the patients were followed up for a total of two years. And what you see is that obviously while abinutuzumab is being given, there's profound depletion, but after you stop giving it, the depletion remains for quite a long time until they eventually repopulate similar to the placebo arm at two years. But when you look at the B cell subsets, you see a different story, which is it's naive B cells that come back by two years. The memory bases and the plasmablasts remain suppressed even two years.

So eighteen months after the last dose of abinutuzumab, the memory bases and the plasma blasts remain low. And that is the pattern that we previously showed is predictive of best response to rituximab. So with rituximab, you see it on certain patients. They get that really good repopulation pattern, good long term outcome. In here, it's being seen at a group level because of the more profound depletion.

Oh, that's fantastic. So, again, this validate the importance of achieving deep depletion, you know, to obtain sustained and good clinical response. So just in term of implication of clinical practice, I know that we're all waiting for the result of phase three trial in lupus nephritis that will make about soon. In the meantime, what is your view in terms of context of, you know, how can we achieve best using the, you know, B cell depletion?

There's several interesting things here because one is, as you say, should this drug be in the clinic, phase three trial reporting quite soon, it's fully enrolled. So if that comes expecting to get it as a licensed drug for lupus. It also tells you something about what you need to do with B cell depletion in general, whatever drug you're doing with a condition like nephritis, it might not be just keep depleting forever and ever. It might be more like it's part of the induction phase of therapy. And that forms part of a more wider idea about lupus nephritis in particular, which is this kind of inverse pyramid strategy where patients might start on a number of drugs.

I think it's no longer correct that a single immunosuppressant like mycophenolate is correct. I mean, all patients have combinations. So you might have mycophenolate, steroids, and then a combination drug. We've already got bulimumab, lactoseporin, lysis maybe a bit two and hydroxychloroquine, and then you start tapering things down as time goes on. So I I think that's the the future of arthritis therapy.

Thank you, Ed, for the wonderful insight and and also explaining about your work. I'd like to thank everyone for listening and tune in to RheumNow. You can follow me and also to follow RheumNow reporters and key leaders through social medias, and we'll catch up with more news from from us. Okay. Bye bye, everyone.

Bye.

Hi. I'm doctor Janet Pope. I'm reporting at RheumNow here in beautiful Vienna 2024 Uilar. I wanna tell you three things that I think might be the cool hot topics in lupus at this meeting. So there's three areas.

One is biomarkers. One is, is prednisone poison or not? And the third one is really looking at under treatment of membranous lupus nephritis. Let's talk about membranous lupus nephritis first. That's poster seven thirty two.

That's the Toronto cohort. And what they're finding is that when they've looked back over the years, that membranous also has a poor prognosis, not as poor as GN, but not as good as we might have thought. And maybe that's food for thought that we should be giving more immune suppression to that group. The next thing is what about biomarkers? So there was one biomarker study looking at IL-sixteen in the urine of patients with GCA.

And it has been found in last year and in other years that it's an important biomarker in urine and lupus patients. But there was a soluble biomarker study this year, OP0255. And it really is not ready for prime time in my opinion because it's hard to know is this validated, but it did find big differences. But you know, some of these cytokines can change over time. We'll see.

The final thing is, prednisone. Is it good, bad, or ugly? Certainly in all the guidelines, including EULAR guidelines, the least amount of prednisone is the best. So Monash and his group looked at the Pacific Australia lupus patients who are a really large cohort now. And what they found was that if they looked at patients in low lupus disease activity of seven point five milligrams a day or less of prednisone, or they looked at a group of five milligrams a day or less of prednisone, the bottom line is they found that damage was no different between the two.

There's a caveat though. Of the thousands of patients visits, one hundred and four of the patients only were between five and seven point five milligrams of prednisone. So everybody else is included twice. The less than five or the less than seven point five. So I don't think we have the answer out.

And for now what I would say is prednisone the least amount that keeps your patient in a good disease state is the best. Great. Thanks. Follow me. I'm at Janet Bourdeaux.

Thanks.

Hi, I'm Jack Cush reporting to you from Vienna and you are twenty twenty five. It's the first day of the meeting, a lot of interesting things. I heard a message several times today and the message being our thinking on steroids and lupus is changing. One such abstract where that's portrayed is this abstract, OP0059. It was an oral presentation, in a lupus session presented by, Doctor.

Askenazi with other authors being Ken Colounian and Maria Dallara, talking about how we treat lupus nephritis patients. This is a re analysis of data already presented. One study being the ALM study, and two other studies, were the AURA LV study and the AURORA-one. In this study, they did a propensity matching, and they compared the OMS study to one hundred and seventy nine patients to one hundred and seventy nine in the AURA LV plus AURORA one study. And they wanted to look at outcomes, renal outcomes, which is the primary endpoint, but also side effects and whatnot.

The main differences were A, in the immunosuppression. The OMS study received either up to three grams per day of mycophenolate or IV cyclophosphamide and a higher dose of steroids starting out at sixty milligrams per day, lowering every two weeks until they got to ten per day, but with, not a lot of success and a lot more overall steroid exposure in the ALM study. That was compared to the ORA LV and the AURORA one, where the patients received, two grams of mycophenolate plus voclosporin, the lower daily dose, plus steroids starting at twenty five milligrams per day, and then decreasing down over sixteen weeks to two point five milligrams a day. That second group, oral LV or oral one had less steroid exposure, but also had the addition of the voclosporin. They call that triple therapy.

I don't know if I agree with that. Mycophenolate and voclosporin, that's double therapy. Adding steroids to that, I don't think that we're using enough steroids to consider for this to be truly immunosuppressive, but they call it triple, with the third big drug in there being steroids. The end result of this was that, you know, there were more side effects AEs, in the ALM study than in the other two. SAEs were the same, serious adverse events were the same.

But the AURORA LV and the AURORA one, had urinary renal endpoints and that being a 50% reduction in UPCR and whatnot, and overall had less steroid toxicity. So yeah, it makes sense to use combination immunosuppressors and lupus nephritis. But I think that you're going to hear at this meeting as you get from this particular trial, that limiting steroid use is going to be important in the overall success. And success is not just measured by getting to that renal endpoint, but also how much toxicity you're going to incur along the way. Anyway, that was an interesting one from UMULAR twenty twenty five.

Tune in for more at RheumNow.

Hello, my name is Rinalini Day. I am a Clinical Research Fellow and Fellow in Training in Rheumatology and General Internal Medicine in King's College London in The UK. I am in Vienna for EULA twenty twenty four, and today is day one. And actually today, I'm delighted to share a piece of work which I will be presenting later in the conference on Friday, during a poster tour. And this is POS0309.

And this abstract is looking at understanding the psychosocial determinants of health in people with rheumatoid arthritis. And this is actually a qualitative study. So, why did we feel that this work is needed and why it's important? So, there is increasing evidence that social determinants of health have a great impact on the outcomes of people with various chronic diseases, including rheumatoid arthritis. And much of this work has been done in important observational studies, as well as smaller qualitative studies.

What we aim to do was gather in-depth patient perspectives on psychological and social factors that drive specifically persistently active disease in rheumatoid arthritis to help us to try and understand the factors that may be contributing to this and try and optimize patient care. So we worked together with patient research partners in order to develop a semi structured interview, in order to gain these perspectives from patients. And then following some pilot interviews, we conducted the final interviews and focus groups with 45 patients in total. And what we were able to find, first of all, we were very lucky and privileged to have a very diverse group of patients take part. And particularly, for those of you who are able to read the abstract and join me on Friday, we have a very ethnically diverse population, approximately 50% Caucasian and then other ethnic minorities as well, making up the rest of the cohort.

We specifically found that forty seven percent of patients self reported that their RA symptoms were not under control at the time of doing the interview. But ninety six percent of patients had attended their rheumatology clinic less than six months prior to participating in our study. So what did we find? Well, through doing these in-depth interviews and running thematic analysis, we were able to extract six main themes on psychosocial factors that may impact RA management and drive persistently active disease. And these were identified from various barriers and facilitators that we were able to identify from talking to these patients.

And so the main themes that we managed to find included aspects such as health literacy, patient education, impacts on work, and there were various other ones which you can see if you come along and look at the poster on Friday. Why does this all matter? Well, we're first of all going to take all of these results and use them to inform a large survey based study, which we'll then use for a larger epidemiological analysis later in the year. So watch this space for results of that. And also, all of this work can help to guide aspects of care, such as social care policies, resource allocation, and just trying to understand what it is that we can do for these patients with refractory and persistently active disease in order to try and give them a more holistic care and management alongside their pharmacological therapy.

So as I said, if you'd like to know more, do come and join me on the poster tour at 11:00 on Friday. And for up to date information from across the conference, do make sure you keep up to date with RheumNow at roomnow.com. Thank you.

Hi, it's David Lu from Melbourne, Australia, and I'm back reporting from Vienna for July 2024. And the meeting's kicked off. I had our first abstract session, and I want to talk to you a little bit about rheumatoid arthritis therapeutic strategies and converting what's a biologically plausible promise into actual results. So especially in seropositive rheumatoid arthritis, there's an idea that I guess we've got a better idea as to what's going on, and that plausibly we can interrupt what we think is the likely process behind that, especially when we know what we know about the shared epitope. We know what we know about co stimulation and the role it has in the beta cell T cell interaction.

And we know that we have an agent that can interrupt the co stimulation in the form of a Batacept. So it's a promising idea that we can try and hit with the right sequence of therapies to try and turn off RA and really induce a tolerogenic state. Unfortunately, sometimes things seem good in theory, but aren't always perfect in practice. And so we saw two studies in the abstract session, tried to take advantage of what I've just told you, but unfortunately didn't really show the results we would have liked. The first one is the amplified study, which looked at early rheumatoid arthritis, rheumatoid factor ACPA positive, and gave abatacept versus adalimumab.

And the idea is that there's been some promise change from abatacept in this type of population. Could it outperform adalimumab? You can already tell by the way I'm setting this up that, in fact, that's not what happened. In fact, what we saw was that abatacept and adalimumab performed exactly the same over the overall cohort. And now abatacept did slightly better in the high ACPA positive patients.

Adalimumab did slightly better in the others. But, you know, the shared epitope didn't seem to stratify this. And it's really disappointing that we thought we might have some form of biomarker, the form of ACPA positivity or the shared epitope that might help predict who would respond to a Bataseptan. And yes, maybe a really high ACPA positive titer might do that. Although that's that's not yet entirely proven.

What we do know is that this study was really did not show any difference between the abatacitinib and adalimumab, and that's a bit disappointing. Another study along these lines, much smaller study, but from the Erlang group, so the Department of Gaolchette in Germany, looked at the idea that maybe you could give, you could try and induce autogenic reset by giving rituximab and inhibiting B cells, and then after that hitting the patients with abatacept. So they looked also at ACCA positive rheumatoid arthritis and tried to do the B cell T cell one two combination. And they looked at 20 patients and they compared that one two combination with just straight rituximab, small numbers where they really didn't see any difference in disease activity either. Even though it seems like kind of the idea that that kind of might work, unfortunately, it was a bit of a swing and a miss.

These studies are still useful. We know that maybe that kind of approach might work in other diseases, and we saw the safety of rituximab and the abatacept to follow idea, essentially giving two biologics that seem to work quite well, to be quite safe from that point of view, that certainly didn't lead to advantage of rheumatoid arthritis. Nevertheless, you've got to applaud this and it's back to the drawing board. So we try more to try and find something that's better than our current therapies in rheumatoid arthritis. For plenty more on RA and everything else at this meeting, you know where head on down to roomnow.com.

Hi. It's Doctor Janet Pope reporting RheumNow from ULAr twenty twenty four in lovely Vienna. I'd like to give you the top three messages about JAK inhibitor safety. So I was part of a debate and the debate was today on a topic of our regulatory bodies too harsh in the recommendations on JAK inhibitors with respect to safety and restricting prescribing. And the bottom line that came out of this debate, as well as the data that both David Liu and I reviewed, are avoid JAK inhibitors in high risk patients.

And there's risk and then there's high risk. So the risk is all kind of relative, so to speak. So the higher risk patients from oral surveillance that was looking at safety was age over 65, ever or heavy or current smoking, high cardiovascular risks, such as already having myocardial events and high malignancy risks, such as smoking, older age and more in men. So the audience voted slightly more than half that the regulations are too harsh. So what would I say?

Top three things. Do a shared decision with the use of JAK inhibitors and use

them

in caution when appropriate and high risk patients or even medium high risk patients Do stratify the risk as some risks are far more relevant. Past MI or revascularization is a lot higher chance of having another MI than borderline high cholesterol or mild hypertension. And smoking is a big risk, so my call to action is identify who's smoking and try to help the patient stop smoking. That should reduce their cardiovascular risk and it also decreases over time the risk of cancer. Please follow us with lots of reports at RheumNow.

Thank you.

Hello, I'm Rinalini Day. I am a rheumatology fellow based at King's College London, and I am in Vienna for ULA twenty twenty four reporting for RheumNow. Today, I would like to highlight a really great abstract that I had presented in the clinical abstract session for RA this morning in Vienna, and this is abstract two zero two. It's part of the oral abstracts, and this is looking at ILD in rheumatoid arthritis. So, as somebody who is quite interested in the topic of comorbidities and extra articular features in RA, I was really excited to see this piece of work, because this is looking at clustering phenotypes in RA ILD.

So, as we know, RA ILD is not just a single disease. We know from HLCT patterns, for example, that actually there's quite a lot of heterogeneity. But are there any biomarkers, for example, or other ways in which we can actually form clusters of disease to try and delineate it a little bit further? So, this was actually results of an international collaborative study, actually included patients from 22, centers across 13 countries. So, really good sampling and, a good, spread of patients.

And there was a total of sixteen ninety six, so just under 2,000 patients who were included in this cluster analysis. And essentially, this study found that there was two clusters, which were found, and the team did this by collecting a total of about 37 variables, but then 20 of these were used to construct the clusters. So, just to give you an idea of what was in each cluster. So, in cluster one, they found that these people were more frequently male, older when they were diagnosed with RA, and when they were diagnosed with ILD, and more frequently of European ethnicity. So, I guess that's where this kind of study really has its strengths, because it was done across so many countries.

We can even delineate it according to ethnicity and country of origin as well. They also found that there was certain variants of the MUC5B genotype, which was found more frequently in cluster one as well. So, why is this important? Why does this matter? Well, as I said at the beginning, RAILD is a really heterogeneous disease.

We are still trying to grapple with not only treating it, but also whether we can, for example, predict prognosis better in this group of patients. And to do that, it would be really helpful to be able to delineate subsets of patients as well. And so, this is not only great for getting one step closer to being able to prognosticate for people with RA ILD, but also try and tailor their management strategies a little bit more closely. And also, when we diagnose people with RA, or we see that they are developing signs of ILD, It also helps us if we are able to group these patients into clusters, and therefore, we have a better idea and understanding of prognosis and potential therapeutic strategies. So, if you'd like to know more about that particular study, as I said at the beginning, is 0P0202.

And if you'd like to know more about anything else that's going on at ULA twenty twenty four, then do head to roomnow.com. Thank you for listening.

Hi, David Lu here from Vienna EULA twenty twenty four. Some of the highlights from rheumatoid arthritis today. Really interesting abstract from Leeds, from the powerhouse that is Leeds. And they looked at palindromic rheumatism, which is something that I think doesn't get talked about very much. But we do know that these patients certainly make a way in the door.

Often hard to know exactly how to follow-up on them. Should we be seeing them frequently just in case they develop inflammatory arthritis? Should we just send them back to their primary care physician and just hope that all goes okay? Where do we sit in between? And it seems hard to be able to pick who is going to be able to be sent back to their primary care physician and who we have to watch closely.

So in Leeds, they've been looking at this for fifteen years. And they've got fifteen years of data that they've been able to compile into a statistically into a point scoring system to help deal with this for you. So what they've done is they've in amongst that fifteen years of data, they figured out relative weightings. I'll give you the point scoring system now. So female sex, two points.

Age over 40, one point. Smoking, ever, one point. Typical interval between attacks less than one month, one point. Anti CCP positive, up to three times the upper limit of normal, two points. Greater than three times the upper limit normal, five points.

And then rheumatoid factor, positive, one point. So that just breaks it out into strata, less than two, between two to eight and greater than eight. And based on that, you can actually predict who's going to do what over time in their cohort. Obviously, it needs validation. But in that two or less, those people never develop inflammatory arthritis according to this cohort.

And then if you look at the moderate versus the high risk, that stratifies out quite nicely. If you look at it at one year, it stratifies out to be about ninety percent versus seventy percent in terms of developing not developing inflammatory arthritis. So that's, sorry, ten percent develop inflammatory arthritis versus thirty percent. And then if you go out to five years, we're looking at about a quarter developing inflammatory arthritis in the moderate risk group versus over half in the high risk group. So that really gives us an idea of if we can stratify at the beginning, then we can really direct care.

And really that's the kind of thing that we would like to see more of. Like to see it validated as well, but this is a really great start. For plenty more about rheumatoid arthritis and everything else at July 2024, you know where to go. Rheumnow.com.