EULAR Daily Podcasts Day 4 Save

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

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

Asymmetrical sacroiliitis, asymmetrical syndesmophytes. Half if you're lucky are B27 positive, a lot of cervical involvement. Of course they're the same disease, but they're two phenotypic expressions of the same disease and they'll both respond to therapy. They'll have different symptomatology and they'll have different imaging and genetic background. It's like leprosy.

Is it granulomatous? Is it lepromatous? It's still leprosy. It's still axial involvement and it's splitting hairs whether it's axial PSA or axSpA with a rash. Of the same disease just two different phenotypes.

Treatment implications are not going to be that different. You treat symptoms and you treat inflammation that you can see on imaging and I think we'll find that what are we going to do call PSA dactylitis different to Axbar dactylitis? Are we going to call PSA enthesitis different to Axbar enthesitis? So I think this will come down to splitting hairs that won't make a huge treatment difference. Thanks for your attention.

Hi everybody. Peter Nash reporting for RheumNow at EULA Vienna twenty twenty four. One of the sessions that was quite interesting in the AxSpA PSA space is initiative that's being driven both by EULA and by GRAPA to define difficult to treat PSA. It's been popular that difficult to treat RA, difficult to treat AS, and now they're trying to define difficult to treat PSA. So what are the three views about this particular subject?

The definition of difficult to treat PSA will depend on an SLR, it will depend on patient room surveys, but the bottom line is going to be that to be called difficult to treat you have to have failed one conventional synthetic DMARD, two biologics of different mechanism of action and have ongoing evidence of inflammation. Not laboratory markers, but imaging markers, MRI or ultrasound of active inflammation. So that's defining difficult to treat. Now they're separating that from the second issue, which they're calling complex to manage PSA. Now there are people who have no evidence of inflammation, have failed a number of drugs, often cycle endlessly through expensive biologics, but their pain is considered non musculoskeletal pain, chronic widespread pain, central sensitization pain.

And these people are just asymptomatic, but rather than cycling through biologics, you should think about non drug initiatives as well as things like pregabalin, tricyclics and treating them along neuropathic and noceoplastic lines. Just as valid but a different way of treating these particular patients and non drug methods may be very helpful. Even things like cannabis might be helpful, but that needs to be proven. Now, the third aspect of this whole discussion is what are the implications of diagnosing difficult to treat PSA in the first instance? Well, it's got to have therapeutic implications.

We have to start thinking of ways of defining them early and doing something more aggressive early to try and break that vicious cycle. It might be combinations from day one. It might be safe combinations like TNF plus IL-seventeen inhibition or TNF plus IL-twenty three inhibition, a study currently undergoing, worldwide, use right now. So how you get two biologics for your patient is very difficult. In our country for these very difficult patients, we have the RheumNow prescribe one biologic and our Durham College colleague prescribe the other.

It has to be a safe combination. I don't think JAK plus TNF will be safe because of, adverse effects, but some of the newer agents like seven eight and twenty three, there'll be no safety signal if you use them in combination, but that has to be proven. So this is an ongoing field of interest, to treat, complex to manage, then the implication of what you're going to do about it. Thanks for your attention.

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

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

The data came from formerly known as the Corona registry, the Coravitas registry of patients with psoriatic arthritis. So a very large N. And the question is, what drug will last longer? And then what will be some of the predictors? So when you're starting your first line advanced therapy, if you use a TNF inhibitor, there was more durability than using a PDE4 inhibitor.

And that's not surprising as we often think that the TNF inhibitor might be stronger, might give a deeper response. So they went on to look at predictors, including some of the patients were on both TNF and then adding IprimaLOS. They also looked at predictors, male versus female, disease duration and things that might be predictive. But I think for me, the take home message from this poster was the bottom line is it looks like TNF inhibitor might give a longer response or longer utilization than a Premalast. So the next question is the age old question.

If a patient has psoriatic arthritis and they've been on a TNF inhibitor with psoriatic arthritis, should you go to another TNF inhibitor or should you change the mechanism of action? And this study, poster two sixty six, looked at the second line therapy of advanced therapies in active psoriatic arthritis after a first TNF inhibitor, going to another TNF inhibitor, or to go to an IO-seventeen inhibitor. And the results were a little bit surprising to me. It looked like in general, was no difference whether you stayed within the class of drugs, TNF to TNF, on response and durability of the response or drug retention over time, versus if you switch to a new class, like an IL-seventeen. They also looked at predictors of who would do better.

And interestingly, it did look like men had less good retention. Sorry, it looked like by gender the retention could vary, but it varied by the drug. So men might've had a different retention than women, men being better on a TNF inhibitor. And some studies have shown that treatment response is attenuated in women on IL-23s, IL-twelve, IL-twenty three, and IL-17s, but not so much TNF inhibitor. So it is a study that you have to think about, but I think it allows us to have options.

What's my question here though? What would be the data if we looked at maybe going to an IL-twenty three or an IL-seventeen, as IL-17s are quite often used after a TNF and sometimes even before? So we don't know that yet, we'll await the publication, but the N is large and some insights are coming from it. The final thing is, can I predict who might respond with psoriatic arthritis treatment when you use a TNF inhibitor? And wouldn't that be great to personalize medicine?

So this was poster nine ninety two. And what they looked at were a series of biomarkers, cytokines, other molecules that were signaling that might or might not be important to suggest a better response to a TNF inhibitor. At this point in time, we don't have like a blood glucometer of a response. We don't have a lot of tests that will help us figure out who will respond. The usual predictors of response are usually present.

You're younger, you have active disease, but not really active, obviously you haven't failed a lot of other treatments and it's your first advanced therapy, those patients will do better than older or failing a lot of therapies already. So it's not ready for prime time, but I think these sort of data are the start of precision medicine for looking at biomarkers of a response to treatment before we even start the treatment. So please follow us at RheumNow, and thanks for listening. Bye now.

Hi everyone, Peter Nashu reporting for RheumNow from EULA, Vienna 2024. One of the interesting elements that's discussed, number of papers presented are thinking about ways of preventing psoriasis turning into psoriatic arthritis. Now this has been looked at with therapeutic implications, it's been looked at from a biomarker point of view, an imaging point of view, different ways of trying to define the highest risk patient and we can define them. Bad family history, nail disease, a lot of skin rash, bad function requiring analgesia that is beyond the norm, those with arthralgia already and bad skin, scalp involvement, we can certainly define the patient is at the highest risk. And then it's a question of can we go into our PSO clinics, image them, biomarker them and see if we can define the patients who are going to either evolve into PSA and then the implication of what we're going to do about it.

So a number of studies presented one from a database of 200,000,000 people that had 1,000,000 patients with psoriasis, about a 100,000 already developed PSA and they looked at the use of various biologic agents in the PSO population and they're able to show when they compared 17 against TNF, when they compared 23 inhibition against TNF that those two were superior to TNFs in preventing the progression. The 23 seemed to be the best. The twelve twenty three and the twenty three inhibitors seem to be able to prevent the progression the best and it reduced that progression by about thirty seven percent. So an area of increasing interest, they're looking for the biomarkers to help us decide who's progressing. They're looking at imaging data, particularly ultrasound, power Doppler, painted emphyseal sites, patients with arthralgia, see if we can prevent that progression and the use of, active agents early on to try and prevent the progression.

So we'll have to watch this space. Thanks for your attention.

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

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

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

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

Follow me on Twitter for more content, or reallyromo, and follow RheumNow, and don't miss our 6PM panel for a recap of the day. See you around.

Hello. I'm Jonathan Kaye reporting from EULAR twenty twenty four in Vienna, Austria. I'm gonna talk about two posters that were presented at EULAR. These are posters number four fifty one and six zero seven, both of which come from the University Hospital Lausanne in Switzerland, the group of Thomas Hugel. During the COVID-nineteen pandemic, we faced the challenge of assessing patients with rheumatoid arthritis remotely.

We switched from in person visits to telehealth. And since rheumatoid arthritis is a disease that is largely assessed based on physical examination, we were challenged in ways to detect joint swelling as well as joint tenderness. Thomas Hugo and Marc Blanchard in his group and others have developed some digital applications for an iPhone, which allow patients to record their hands and give a sense of swelling or loss of motion. The first app is one called Detectra, which is one where the patient captures a real world image of the second through fourth proximal interphalangeal joints. And because with swelling, the folds over the finger joint expand and the ratio of the distance between these folds increases with swelling compared to no swelling, they're able to come up with a reasonably reliable way of detecting finger joint swelling, both worsening and improvement.

They trained this model using a convolutional neural network on photographs of seventeen eighty three proximal interphalangeal joints from patients with rheumatoid arthritis and an additional 151 proximal interphalangeal joints to come up with fingerfold number and proximal interphalangeal joint diameters. They calculated a fingerfold index as the ratio of the joint diameter to the mean pixel length of detected fingerfolds and came up with a reasonable correlation with the DAS28 CRP and swelling and pain on a single joint level. This may be a useful tool to use with remote patient monitoring or with telehealth visits when patients are unable to come into the office, either because of illness, pandemic, or distance. Another challenge is how does one detect function? And they came up with another digital application called Mephisto, which is looking at finger motion.

It measures the angle of motion of flexion of the proximal interphalangeal and distal interphalangeal joints. And they ask patients to make a fist rapidly five times. And it captures, using an algorithm, the angle as well as the rate of motion. And patients who have increased pain and swelling will flex their finger joints more slowly, and those who improve can do it more rapidly. They found that the rate of swelling as well as the, I'm sorry, the rate of flexion as well as the maximal flexion of metacarpophalangeal and proximal interphalangeal joints correlated with the HAC DI as well as the DAS28 CRP.

So with these two applications, we're reasonably into being able to assess patients remotely using digital rheumatology. This will need to be borne out with further study and additional applications will need to be developed to assess function and other aspects of the physical examination. But this is both interesting and promising for the future of rheumatology. For more information about this and other presentations at EULAR twenty twenty four in Vienna, go to roomnow.com. I'm Jonathan Kay, and look forward to seeing you again soon.

Hello, everyone. My name is Youssef. I am a consultant rheumatologist from Leeds, United Kingdom. Today, I'm reporting for RheumNow, at the twenty twenty four EULA Congress in Vienna. This, conference, there have been, many stories about progression of CAR T cells therapy in SLE and also other autoimmune diseases.

However, watch out. There's one more interesting therapy that will coming at you very shortly. So this, is an abstract, OP093. So this compound is called, BiTE or blinatumomab. So BITE stands for bispecific T cell engagers.

So as we all know that B cells play a major role in the pathogenesis of rheumatoid arthritis, systemic lupus and also other autoimmune diseases. Therefore, targeting B cells have been mostly evaluated over the last fifteen years. What we know as well, that the degree of B cell depletion through anti CD20 monoclonal antibodies is associated with clinical response. So, in this study, is looking at a different strategy, to cause profound B cell depletion, both in the blood and in the tissue. So essentially, this mechanism, called bispecific T cell engagers, has been evaluated in haematological malignancies such as acute lymphoblastic leukemia.

So, this work was the first in human, in patients with rheumatic diseases, namely the rheumatoid arthritis. So, what this group did was they look into six patients with rheumatoid arthritis. So all of them, had severe refractory diseases, as defined by failure, two, three, either target synthetic or biological DMARDs. So what, the principle of, this, BiTE, was that, the molecules, can engage, two cells, One, on the CD19 on the B cells, and also one, on the CD3 T cells. So when this engagement occurs, the T cells, will then cause the B cell killing and cause apoptotic death of the cells.

So again, using T cells, as a killer here. So in terms of, the treatment, how is it given? So basically, this is monoclonal antibodies. So patient needed to stop their biological treatment at least three months before. So then after that, they need to be hospitalised for five days, especially because this was a first inhuman.

They infuse very slowly within five days. And after that they administer another one five days as well. So it's two infusion. And what, they found in terms of safety profile, there was a very mild, slight increased body temperature, but there's no other, signs of cytokine storm. And what they also found, that in terms of the safety perspective, there was slight increase in the CRP level for the first couple of days, then after that it normalized.

So in terms of efficacy, so all these patients responded in terms of reduction, significant reduction of DAS28 score from baseline and also all the changes of musculoskeletal ultrasound improved. And interestingly as well, they also did some synovial biopsy which confirm there's also tissue depletion here and also restoration of the aberrant B cells. So this is really an exciting therapeutic target And the findings have been published in the Nature Medicines two months ago, if you want to have a look in more detail, but certainly something that we will look forward to for those people with refractory diseases. So this applied to RA, but will likely knocking our door for other diseases such as systemic lupus, Sjogren's and myositis and etc. One thing that may be quite favourable is potentially due to the cost, because the cost is estimated around $76,000 to $100,000 whereas the CAR T cell therapy somewhere around the ballpark of $300,000 to $500,000 And so maybe it will be good as well to look head to head trial between these two treatments.

Okay, I hope you found my summary useful. Please follow me in the room now on various social media outlets, including Twitter and YouTube for more coverage of the Congress content. Bye bye.

I'm Anthony Chang, 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. There are now many drives globally to reduce 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 was an oral presentation OP0310 which is a study of patients referred with chronic back pain to the clinic and then subsequently diagnosed with Axis Bar 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, they had 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 look 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 mean age in this group of the older patients who referred 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 Bondyloarthritis 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 the disease 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 respectively. 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 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 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 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 Chen, 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 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 exospondyloarthritis 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 2024 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 followed 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 edema 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 how 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 very nice study.

This one looks at the MRI lesions in X bar patients and also compared this to healthy controls patients who were postpartum and also in runners. In total there are 172 subjects in this study and they use 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 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 LT 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 certainly 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 linkage between structural and inflammatory lesions are also important in order for us to fully understand the condition that these patients have. I'm Anthony Chan, reporting here for RheumNow at EULA twenty twenty four.