EULAR 2024 SpA Daily Topic Podcasts Save

This is the ULAr twenty twenty four podcast with daily reports on spondyloarthritis. This podcast is sponsored by UCB. Enjoy.

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

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

In theory, they're being used in cancer, and in theory, they may have better tissue penetration. Not clear that that's really the case in our diseases, and whether this translates into improved clinical benefit has yet to be seen. There are a few small molecule inhibitors that can be given orally for IL-seventeen and IL-twenty three that are early in development, nothing here at this meeting particularly, but we're also seeing some additional data on oral JAK inhibitors at this meeting, including a new JAK1 inhibitor that's being studied at axSpA. And we're seeing data on TYK2 inhibitors, TYK2 being the fourth member of the JAK family. The rationale for TYK2 inhibition is that interleukin 23, in particular, signals through TIC two, and interleukin 23 being an important cytokine in spondyloarthritis, it suggests that this might be a better pathway for JAK inhibition, or at least JAK family inhibition, for these diseases, potentially, and I say potentially, with a reduced, risk of adverse events.

Some of the things we've seen at this meeting, abstract, OP-one 195, which is a, phase two study of Sonalocumab, a new interleukin 17, nanobody that targets both IL-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 zero zero zero five. Also at this meeting, there's some data on vunekizumab, another IL-17A inhibitor, that's poster o eight zero three. And one that I thought was interesting is an abstract on TAK-two seventy nine. That's a selective TYK two inhibitor.

This is a phase two study, being presented as an oral presentation, abstract, OP o one three eight. One of my favorite things about this particular molecule, it has had has acquired a generic name, which is zosacitinib, which I think is one of the best generic names, for a small molecule that we've seen in a while. All of these are showing great data in psoriatic arthritis or axial spondyloarthritis, and so there's no reason to suspect that they're not effective molecules. I think time will tell whether the TYK2 inhibitors are not only effective but potentially safer than the existing JAK inhibitors. But I just don't know if we're gonna need this many agents targeting the same pathway for these diseases.

We'll see. And I think ultimately once these trials are run through into phase three, and hit the market, the market's gonna tell us what is necessary. So that's my thoughts on this coming to you from, ULAAR twenty twenty four for RheumNow. Stay tuned for more information from this meeting. Hi.

This is Eric Ruderman from Northwestern University in Chicago coming to you live for RheumNow from the ULUR 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 Chen, 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, something we call Patient initiated follow-up or PIFU. 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 controlled 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 12 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 do 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 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's been a significant meaningful reduction in terms of the if cost by doing this type of tele monitoring and patient issues to follow-up. 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 control trial here on this, topic can help us to do that.

I'm Anthony Chen reporting, for RheumNow from EULA twenty twenty four.

Hello, everyone. This is Bella Mehta reporting from EULA 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 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 sacroiliitis 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 for synovium for instance. That's why we borrowed a methodology from our cousin, the 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 feature that are dependent from mean energy but also from the tissue histopathology. And this radiomic feature can be of course elaborated to provide you the DICOM as you know it, but they can also be analyzed as a raw continuous variable via 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 the radiomic feature extracted by bone marrow edema segmentation in the cell. What we did, we did is quite simple. We opened our diode on a software called Tradislicer. Tradislicer comes with tool that can allow for the semi automated segmentation of any lesion. It's incredibly easy to segment 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 features, built a very straightforward multivariate oxygen suggestion model to try to predict TNFI discontinuation in patients with the axiospondylar tract. We did, we add a long synthesis, this is a proof of concept study, but actually we found two independent predictors of TNFI the elongation and 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 affects. But we don't say the 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 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. So just using MRI features, extracting radiomic features, you know, and there's a lot of studies right now talking about diagnostic potential, but you 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 semiotomycin segmentation, we also employ dedicated radiologists, but I can swear that with the tool provided by the platform, the segmentation is quite easy to perform.

That's great. So again, we've loved your work, and more to come. Any one last line that you tell viewers to look out for the future?

I think that we need to validate this data on external court before adoption. We have to compare that with Spark. So it's important to compare with the standard, 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.

I'm Anthony Chan, 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 2024, 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 excess spondyloarthritis. We know that there's a diagnostic delay for up to eight years and also only more recently the 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 SDAC CRP which is the Excess Bundle Arthritis Disease Activity score UCRP 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 two. One. 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 it is Esther CRP would be less than one.

Three on two occasions twelve weeks apart. If patients achieve this target of Esther's 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. There 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 and a fifty eight. 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 on entry and also not smoking. So these were important characteristics of patients who are more likely to achieve the clinical remission in a treatment to target, treat 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 from stopping the treatment in the NCA group this was a mean of sixty one days and in the Golimumab 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 with regards to treating to target in axial spondyloarthritis. I'm Anthony Chan, reporting for RheumNow here at EULA twenty twenty four. I'm Anthony Chan, consultant rheumatologist from The United Kingdom and I'm here in EULA twenty twenty four in Vienna reporting for RheumNow. One of the challenges that we have in Axospondyloarthritis remains the delay to diagnosis. And there are now many drives globally to reduce the time from symptom onset to diagnosis.

And also this gives us an opportunity to study the clinical features of patients who have early disease and this was presented here at EULA twenty twenty four. It's an was an oral presentation OP0310 which is a study of patients referred with chronic back pain to the clinic and then subsequently diagnosed with Axispa and this came from the space cohort and these patients who were referred with chronic back pain they look for the features of clinical features of spondyloarthritis They measured the acute phase markers, the HLA B27, the radiograph and also the MRI and they followed them up over a period of time and they were looking for patients who had the diagnosis from the time of symptom onset of less than two years and then they divided them into patients with XBA and non XBA and looked for the characteristics that would help predict the diagnosis of XBA in these patients with early symptoms. In total they had five forty eight patients who were referred with chronic back pain. They asked the clinicians to rate their level of confidence from zero to 10 in terms of how confident they were of the diagnosis. They looked at also the symptom duration and the overall the the mean age in this group of the all the patients who referred with was 31 years and the mean time from symptom onset was thirteen months, about a third of them were male and about forty one percent of them, had HLA B27.

From the five forty eight patients that were referred with chronic back pain, two fifteen of them, had a diagnosis of, Excess Bondular Arthritis of less than two years. The mean time to diagnosis was thirty five months. And so what they were looking was to see how what were the clinical features in this group and whether they these could help predict the diagnosis in this early group. And they found that the clinical features of XPAR clearly were higher in the patients who had the condition, but HLA B27 positivity and sacroiliitis both on x rays and also MRI were the strongest features, at the start of the symptoms and also this when followed up at two years were the best predictors of current and also the diagnosis remaining stable at the two year mark. And this gave the HLA B27 and the sacroiliitis increased the likelihood by four point two and three point five When they look at other clinical features, peripheral arthritis, uveitis and also psoriasis raised the likelihood by two times in terms of the current and future diagnosis of Axis bar being stable.

Other clinical features included the the response to NSAIDs, the male sex and also of a younger age. On the converse, there were also features that were not strongly predictive of the diagnosis including the the first presentation of inflammatory back pain were not a strong determining factor of regards to the current or future diagnosis of Axial Spondyloarthritis. So as we are increasingly trying to drive the time to diagnosis down, it appears that strong objective findings, mainly HLA B27 positivity and also the presence of sacroiliitis both on x rays and MRIs, weighted strongly with regards to the diagnosis in this early cohort. These were then followed by some of the other clinical features as highlighted here in this abstract. So we can learn from studies such as this as we try to see patients much earlier in regards to their symptom onset and how we could be using some of these, both, radiographic features as well as, clinical features to help us to make histiocytosis.

I'm Anthony Chen, reporting here from Vienna at EULA twenty twenty four. I'm Anthony Chan, Consultant Rheumatologist from The United Kingdom here at EULA twenty twenty four, in Vienna and there have been some important presentations, in the field of axial spondyloarthritis and I would like to highlight, two oral presentations and abstracts and looking at the area of imaging in axial spondyloarthritis. We know that imaging both radiographs and also MRIs have a big role to play in the diagnosis of Axial Spondyloarthritis and there are now criteria with regards to the number of lesions that should be seen on MRI to help classify patients with Axospondyloarthritis. The MRI findings of Axospondyloarthritis include fat lesions, erosions and also sclerosis. One of the challenges that we have is as we increasingly use more imaging such as MRI, there is also the possibility of false positives.

These are patients who may have changes that seem or look like Axospondyloarthritis but do not have the condition. And there are groups of patients we know who may have this from healthy controls to women after pregnancy in the postpartum phase and also from mechanical stress in, people such as runners. And this has now been looked at here at EULA twenty twenty four and first is the OP222 which is the abstract number and this was looking at the presence of bone marrow edema in postpartum women and they follow these patients up for five years and the aim was to see whether there was any evolution or involvement of the bone marrow edema over a period of time. And they studied 35 patients. Now when they looked at the clinical features of these patients they did not really fit the criteria in terms of a clinical diagnosis of XBA.

They did not have there was no true association from of the bone marrow edema that was found on the MRI with the inflammatory back pain symptoms. So firstly they do not really fit the clinical picture but yet they had the MRI changes suggestive of XBA which was bone marrow edema. Interestingly when they followed them up, over five years there was no change, there was no progression structurally, from this bone marrow edema. In fact in some of these patients while they remain there was also an improvement in some of them over this period of time but certainly no worsening or no changes that were typical of axial spondyloarthritis in the bone marrow oedema lesions over this period of time. So this is quite a stable appearance over this time and hopefully this could also help us if we were to follow-up our patients who may have these changes at baseline but don't really have clinical features that these there should not be any real progression in these lesions.

The next is the abstract OP303. Again a very nice study. This one looks at the MRI lesions in X bar patients and also compared this to healthy controls. Patients who are postpartum and also in runners. In total that one hundred and seventy two subjects in this study and they used the spark criteria to measure and define the the lesions on the the MRI and the mean findings were that in the in terms of structural lesions, these were very more prevalent in the, X bar group.

Seventy nine percent of them had structural lesions, but very low in the, the non X bar group. So they took these healthy controls postpartum and also runners who didn't have expo. Thirteen percent of non expo patients had this patients with chronic back pain but also it was found in people who were not symptomatic. So eight percent of runners and six percent of healthy people in the study also did have some structural change but much less than the X bar group. When they looked at more stringent criteria so the criteria of greater than three three or more erosions and or five or more fatty lesions and when they raised the standard of the the classification for the changes on the MRI then about forty three to forty five percent of the X bar patients had these lesions but much much much lower in the healthy and also in the postpartum group when they were analyzed.

So not only was there a reduction in some of these structural lesions that we would have seen in XBA in the healthy and also postpartum groups but also there was less of a concordance so there was a discordance between structural lesions and inflammatory lesions in the healthy and postpartum group compared to the X bar group where there was more relationship between the presence of inflammatory lesions and structural lesions which was not seen in the the other groups. So I think this both these abstracts here help us because one of the issues that we also have is over diagnosis using the MRI solely and then making a diagnosis which isn't how it wasn't how the the study showing that we should be doing this because there will be a small number of patients who on MRI surgery would have these changes but not clinically and also having more stringent criteria also help us to understand whether these patients fit the criteria on MRI for the condition. And finally the the the linkage between structural and inflammatory lesions are also important in order for us to fully understand the the the condition that these patients have. I'm Anthony Chan, reporting here for RheumNow at EULA twenty twenty four.