EULAR 2024 RA Daily Topic Podcasts Save

This is the UR 2024 podcast with daily reports on rheumatoid arthritis. Hope you enjoy this podcast.

Hi. It's David Lou 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, and 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 co stimulation in the form of a Batasept. 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 which 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's the AMPLIFIED study, which looked at early rheumatoid arthritis, rheumatoid factor ACPA positives, and gave abatacept versus adalimumab.

And the idea is that there's been some promise shown 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, and adalimumab did slightly better in the others.

But, 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 abatacept. And yes, maybe a really high ACRA positive titan might do that. Although that's not yet entirely proven. What we do know is that this study really did not show any difference between abatacept 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 Georg Chet 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 a Batacet. 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 the idea that that 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 nabatacept to follow idea, essentially giving two biologics that seemed 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.

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 POS three zero nine.

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 work 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 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. 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 RoomNow.

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.

And 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, everyone. This is Aurelie Naj reporting live from Vienna at Tular 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 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 that 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. They call one of them the indirect effect that is measured by surrogates of inflammation, 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 superdacitinib 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 at olimumab 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 that than adalimumab.

And so that is suggesting that there might be something in a jack step 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 what are the specific mechanisms for that. But that's definitely something to follow-up on. And that is leading us to the second abstract, which 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 a mix of everything receiving is also targeted to take the DID mods or is it 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 thirty fifty percent, or seventy percent 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 of people achieving an improvement of 50 or 70% with 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, I surely don't, although we do think about it as so we obviously in the absence of contraindications and so on, 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. It's now time for me to go 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, David Lu here from Vienna, EULA 2024. 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.

It's 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've 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. Roomnow.com.

Hi, it's Doctor. Janet Pope reporting at room now from ULAr 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 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. It's David Lu here reporting from Vienna, July 2024, here, obviously, in the Congress Hall, where a lot of good stuff has happened. I just wanna tell you a bit about a poster, which I'm a little bit late to, but I think gives a really important message. And I don't know why we're not talking about it a bit more. And this comes down to rheumatoid arthritis patients on abatacept and looking at their shin grips response.

Now, we know that co stimulation is potentially important in forming that immunogenicity against a vaccine. And what have we seen in this is we actually saw in amongst the trial, at Shingrix vaccination in patients treated with abadacept. The long and the short of it is that it's a bit disappointing, a bit scary. Because we saw that in terms of a humoral response, the antibody response, you had a modest increase in antibody titer. And, you know, at twelve weeks we did have sixty four percent of people respond despite being on abatacept.

But that faded away through to twenty one percent at sixty weeks. And the titers are really disappointing. And then probably more pertinently, the cellular response, which we know is so important when it comes to vaccinating it against herpes zoster, was really a swing and a miss. And we really did not see any cellular response at all, basically. So I don't know what this means for abatacept treated patients.

We probably need to come up with some better strategies on how we're going to manage this. Should we be withholding abatacept in the lead up to vaccination to try and optimise that response? Are we going about this the right way? I'm relying on smarter heads and this poster was from Kevin Winthrop and Jeff Curtis and many other smart minds. So I'm sure they're thinking about how to improve this for our Batiset patients so we don't leave them out in the cold when it comes to shingles.

For plenty more on rheumatoid arthritis and everything else for rheumatology at YourLive twenty twenty four, you know where to go. Rheumnow.com.

I'm Anthony Chen. I'm a consultant rheumatologist from Reading, United Kingdom, and I'm here in EULA 2024 in Vienna. And here at the conference, there's been a lot of new developments in the field of digital rheumatology, particularly looking at areas such as machine learning and artificial intelligence, and how we can leverage that into the whole field of rheumatology, from the diagnosis to the management and to the prognostication to help with our patient care. There was a session that ran here at July 2024 looking particular in this topic, and I'm very happy that I'm joined today by Professor Thomas Hugo from the University Hospital Lausanne in Switzerland. He did a very nice oral presentation, the number is OP0112, where he used a model of calcium pyrophosphate deposition on hand radiographs and how deep learning model could be used for an automated detection of patients with CPPD.

So Thomas, thank you for coming to join us here on RheumNow today. I wonder whether you could tell us, introduce us to the area of your presentation and then maybe in the second half we can kind of look into the future as well as to how this whole field will go forward.

Thank you Anthony, it's a pleasure. So you know the idea of this study was based on the new classification criteria for CPPD from last year 2023 the EULA ACR criteria for the classification of chondrocalcinosis or calcium parasite deposition disease. So you can diagnose CPPD also without proof of crystals in the joint fluid, so by clinical parameters and radiological findings for example or ultrasound findings. So on hand radiographs you can find quite a lot of signs obviously we know this from the clinic for CPPD like TFCC calcification but also MCP2 or three calcification or osteoarthritis specific sites. So we trained a model to recognize calcification from TFCC or MCP three or two on Hendrick radiographs and that's labeled by two independent radiologists by my colleague Fabio Bece from Lausanne.

And then we trained the model in almost 1,000 radiographs. Of those around 300 positive for TFCC. We trained a deep learning classical convolutional neural network to recognize either TFCC calcification, MCP2three calcification, or a combined model with all three of them. And the findings were clearly that the combined model detecting TFCC but also MCP two zero three classification is the best. Got an accuracy of 0.85 which corresponds to, let's say, a sensitivity of 77%, a specificity of 80% in a relatively small data set.

We also then looked at it as specific sites of the lesions and did the five fold cross validation to see how it is, but the best is actually a combined model followed by a TFCC model for the detection of CPPD. We also showed some heat maps. Heat maps are very interesting, I think, also for clinical implementation because they show you where, let's say, the region of interest for the algorithm. So the area on the radiograph where the algorithm took its decision, I think heat maps will come into clinical practice to help us to guide us the way to diagnosis,

if you wish. So Very promising results, obviously, as you say, still early days and small numbers. What was the area under the curve when you did calculation? Because increasingly, it's one of those areas where we kind of now have to look at sensitivity and specificity and also the

AUC. Yeah, it was 0.86 and we also calculated the area under the precision recall correct, yes, to be a bit more precise, because it was an imbalance data set, meaning more CPPD negative than positives, and so we used the AUPR which was 0.77 and again best for the combined model followed by the TFCC side and then much weaker versus MCP two and three. Mean that's what we also see in the clinic.

So for our listeners, these seem to be the new parameters now where we are increasingly being exposed to this whole area of evaluating the the sensitivity and also the specificity of this particular test and then looking at the area under the curve. Now, very promising results. Where do you think along the the patient pathway will we be using this? In the early stage of diagnosis or when the diagnosis becomes more challenging because it is can be quite a challenging diagnosis to make CPPD sometimes we are confused we maybe say a different type of rheumatic condition.

That's a good question. The other rationale to do this study was actually to have a tool to screen other larger databases. Okay. So we did already did this. It's notably interesting in RA.

So we used it to screen our national registry data set with around 12,000 RA patients, but we cannot just score those images for CPPD. So the algorithm is very helpful and we found that almost twenty five percent of our RA patients were actually CPVD positive. So in first line, we want to use it to screen it in other databases or clinical trials, whether CPVD is a confounder, for example, in RA. This is very interesting. And then in clinical practice, I think either way it's probably more a bit in the elderly patients where in patients over 80, almost fifty percent has somehow CPPD.

I think it will be maybe more on the later stage. I think we will combine CPPD detection also with RA detection and OA detection or PSA detection and I think notably in combination with other models for RA, PSA etc this model will be interesting as a diagnostic tool potentially.

And how do you see this, particularly in that patient group where they're a bit older, maybe more females as well? How did the model work, you know, do you, you know, project that the model will be able to differentiate between OA, which is probably very highly prevalent in that population with the CPPD?

That's a good question. Here this model I presented was purely on calcification. We have published another model to detect DRP osteoarthritis, so that's the next step actually. We want to combine the calcification model with an OA detection model, so we know exactly what is calcification, what is OA and then potentially also with clinical data to give predictions.

So you're training a model but then the eventual application may be beyond CPPD. It's in other areas where it can also be refined and Clinically sharpen ups as well. Yeah. Yeah. Here at the EULA, there were a lot of other interesting presentations, certainly in your session, which we all enjoyed attending.

I wonder whether you wanted to share with with us some of your highlights from maybe that session that you were presenting at.

Yeah, so a lot was imaging and I mean that reflects a bit the over 800 FDA approved AI algorithms. Most of them are in imaging and that was also the case in this session. There were different types, for example predicting progression of knee osteoarthritis by MRI or actually in arthralgia the use of MRI findings to predict the development of arthritis. That was interesting. One highlight was actually a technical issue that one speaker showed first relatively good results and then he pointed out a technical problem how to interpret the results of the algorithm and showed that it was actually not that good.

So they had to retrain it and so that gave me some methodological insight. There was one paper on large language model for patients receiving joint replacement, actually also a methodological paper to design questionnaires, then to assess patient satisfaction. I think those were the ones and another one on bone remodeling markers and then to predict actually inflammatory arthritis. Found that was also very interesting.

Yeah it seems to be in quite a lot of areas now where that certainly in my sort of own special area of interest in this spondyloarthropathy today. There was a lot of good poster presentations, but particularly looking to some of these areas as well. So from early diagnosis to prognostication of patients response to the treatment by using, machine learning algorithms to work on that. So any other things you'd like to share with us from this session in the whole field of AI and machine learning before we start closing?

Imaging is number one. I think simple tasks such as detecting calcification will be automized or you will have support by AI models. Clinical predictions are more difficult. We have seen this. I think that the AI models could help maybe in the shared decision process.

They're too complicated just to rely on, especially when it comes to treatment decision which type of drug you should take. So I have nothing seen that tells me which type of drug we should use. So we're waiting for this kind of study, but it's promising. A lot will be integrated in the electronic medical health record. I think that's important to have those algorithms support us and save time, not create more time by opening a browser or something.

They should be accessible and then I think AI will be very helpful.

Thanks that we are on this journey now. Certainly from EULA twenty twenty four, it seems like the community is taking this on. We're not there yet, but I certainly can see the direction of travel being there, that will get better in terms of stratifying our patients to hopefully achieve one day, which is our great aim of personalized medicine. So thank you very much, professor Ugil, for your time today, and hope you enjoy the rest of the EULA. Thank you very much.

Thank you.

Hello. My name is Rinalini Day. I am a rheumatology fellow from King's College London in The UK. And today, I am going to be talking about one of the posters that were presented at EULAR this year. It's POS0730, and the title of this abstract is self reported cognitive function in among older adults with systemic lupus erythematosus compared to other rheumatic and musculoskeletal conditions.

Now, this one caught my eye because I think it's fair to say as clinicians, I think we're pretty poor in our lupus patients that are asking about cognitive symptoms, by which I mean, for example, forgetfulness, brain fog, as well as wider neuropsychiatric symptoms as well. And I think we sort of neglect these symptoms in general when speaking to all of our patients with RMDs. So, the aim of this particular study was to look at self reported cognitive function among an older cohort of individuals with SLE, as compared to conditions such as rheumatoid arthritis, osteoarthritis and fibromyalgia of similar ages. So, this data actually comes from the large forward registry, which is based in The United States, and the cognitive symptoms were assessed using validated measures. And then the symptoms were compared between people with SLE and the people with the other diseases that I mentioned.

And actually, the authors concluded that cognitive symptoms were far worse among older individuals with SLE compared to individuals of a similar age with the other rheumatic diseases. And furthermore to that, the worst perceived cognitive function was then associated with worse self reported disease status. So, clearly, this is having a much broader impact than simply a number on a page. The perceptions of cognitive function from the patient were also associated with less satisfaction with their health, for example, even after the disease was thought to be controlled. So, the reason this was quite a fascinating poster for me was that I definitely will be making sure that I try and ask about these symptoms much more in future.

And it just shows how much further we need to go in not only trying to pick these symptoms up in clinic, but also the research gap that's there to see what we can do to try and reduce this huge cognitive burden in our patients with lupus. If you'd like to know more about that particular abstract, you can check out the abstract in the EULA repository or look at the poster. And do go to roomnow.com to find out the latest news coming from Vienna and EULAR twenty twenty four. Thank you. Hello.

My name is Rinalini Day, and I am a clinical fellow at King's College London in The UK. I am in Vienna for ULAAR twenty twenty four. And today I'm delighted to share with you one of the abstracts which I actually saw yesterday. This is OP 156, which was part of the difficult to treat rheumatoid arthritis session. So the title of this abstract was difficult to treat rheumatoid arthritis in a large patient registry validation and prevalence.

So if I just step back a little bit, taking this session as a whole, this was looking at difficult to treat rheumatoid arthritis. So there were several abstracts looking at various parts of this definition, which was brought out by EULAR several years ago now. And as I was saying in the discussion for the live recap, if any of you caught that, this is actually a bit of a double edged sword, because it's really great that we now have a definition within rheumatoid arthritis for difficult to treat disease. And this encompasses treatment failure, characterization of active disease, and clinical perception of the difficult to treat condition. But at the same time, this is actually one of the first studies to validate the definition in a large patient cohort.

So, this done in the Brigham and Women's Rheumatoid Arthritis Sequential Study, the BRASS registry, and there were around 1,500 patients within this study. And they observed a prevalence of around fourteen per one hundred persons of difficult to treat rheumatoid arthritis. And they were basically applying that definition within their cohort. And actually, the definition was able to successfully identify the subset of rheumatoid arthritis patients who have not achieved low disease activity, despite having multiple biologics and targeted synthetic DMARDs. And actually, they found that compared to the non difficult to treat rheumatoid arthritis patients, more of them happened to have a younger age, higher BMI, greater proportion of female gender, lower education levels, and more comorbidities.

So, all of the things maybe we may or may not expect, and actually a lot of those factors came out in many of the other studies, which shows some consistency across cohorts as well. But one of the key conclusions of this study was that we really need to be, first of all, doing more validation studies in different cohorts, not just in these limited cohorts, but so that we can then apply and make sure that we are able to apply this particular definition in our observational studies going

forward.

The difficult to treat rheumatoid arthritis definition, as I started this presentation by saying, is a double edged sword because it's really great that we have it, and it brings attention to difficult to treat disease. But also, it's a very strict definition. You have to have the three different criteria in order to meet difficult to treat RA. So, this was a really fascinating abstract for that reason, and it will be really interesting to see what it shows when it's applied across various different cohorts. If you would like to hear more about this abstract or anything else at ULAW twenty twenty four, do make sure you check out roomnow.com.

Thank you.

Hello. I'm Jonathan Kaye reporting from EULAR twenty twenty four in Vienna. Yesterday, Kevin Winthrop from Oregon Health Sciences University presented two very interesting papers, both about immunization with herpes zoster vaccine in patients treated with various biologics or targeted synthetic DMARDs. He presented one paper about patients who were on upadacitinib in the SELECT COMPARE study who were immunized with a dose of recombinant herpes zoster vaccine at baseline and another at eight weeks after that first dose. The patients who continued to take both upadacitinib and methotrexate developed both humoral immunity and cell mediated immunity to herpes zoster virus.

In contrast, patients in another study that he has been conducting who were taking abetacept either intravenously or subcutaneously were immunized with a similar schedule to receive either the recombinant herpes zoster vaccine or placebo at baseline and then eight weeks later. And in contrast to the patients continuing upadacitinib, there was humoral immunity in about two thirds of the patients receiving abatacep, but no cell mediated immunity. This study is ongoing, but suggests that abatacept should be stopped perhaps two weeks or even four weeks before vaccination. However, the exact timeframe with which to stop abatacit before herpes zoster vaccination has not been established. On the other hand, patients receiving upadacitinib and probably other targeted synthetic DMARDs, JAK inhibitors, can continue taking the JAK inhibitor and methotrexate without stopping and still develop immunity to herpes zoster vaccination.

These studies are important because patients on JAK inhibitors are at increased risk of developing herpes zoster. And it's very important to immunize these patients ideally before beginning a JAK inhibitor. But certainly, if they're started on the JAK inhibitor, herpes zoster vaccination should be performed as soon as possible. For more about this and other studies from EULAR twenty twenty four in Vienna, go to roomnow.com. I'm Jonathan Kaye, and I look forward to seeing you again soon.

Hello, everyone. My name is Youssef. I'm a consultant rheumatologist from Leeds, United Kingdom. I'm reporting for RheumNow Live, from Vienna to cover the EULA twenty twenty four Congress. Today, I would like, to talk about, JAK inhibitor.

As, we all are aware, JAK inhibition treatment has revolutionized therapy for various, autoimmune rheumatic diseases, including rheumatoid arthritis. However, this strategy has become under scrutiny, over the last couple of couple of years, since the publication of the oral surveillance, clinical trial data. In this, oral surveillance data, they found, that, there was increased risk of malignancy and also major cardiovascular events, in patients treated with tofacitinib compared to TNF inhibitors. Therefore, the regulatory, have issued a warning to be careful in using a JAK inhibitor, particularly in those above 50 years old of age and also with multiple comorbidities. One other aspect as well is pertaining to infection.

The data from the randomised controlled trials as well as the long term, extension studies, did show some increased risk of, opportunistic, infection, as well as herpes zoster. So does this, data reflect in the observational study? So, Jackpot, is, one of the largest, collaboration of registries which involve 14 registries in the Europe, and also Canada. So in this study, the main aim is, the main aim was to compare the infection risk, and also Herpes Zoster risk, between patients treated on JAK inhibitors, versus TNF inhibitors and also versus other mode of action. So other mode of actions include including rituximab, tocilizumab, abatacep, and etcetera.

And the this presentation, the abstract number was OP0092. So in this study, a large number of patients were involved, were over 50,000 treatment, starters that were analysed. And looking at the key results, there was no, increased risk of, any infection or, severe infection between patients treated with JAK inhibitor versus TNF. The anti serious infection rate was quoted as nine out of one hundred patient years, whereas TNF is seven out of one hundred patient years. To me, this sounds still a little bit low for a real world, and this is sometimes what you might expect with observational registry data because there potentially could be some reporting bias as well that's not been captured.

In terms of other comparison, those treated with other mode of action had a higher rate of any infection and serious infection compared to the TNF inhibitors. Also, it's important to let you know there were some baseline, characteristic differences, not a lot, but, there were two that I could detect. One were, due to the disease duration. So the TNF inhibitors group, had much less, less disease duration compared to the TNF and other mode of action. And consequently, in terms of biologic naive, so they were more proportion in the TNF group compared to the JAK.

So this could potentially also influence the infection outcome. And another important key here was regarding to the Hirschspritz zoster rate. And in this real world data, it showed that the incidence ratio were two times more likely in the JAK inhibitor groups compared to the TNF, whereas there was no difference between the other mode of action versus TNF. So what this data showed that in the real world there was no difference in terms of, risk of infection. However, there was increased, risk in terms of herpes zoster, and how this may impact our clinical practice.

So I think, we need to think of some measures, to reduce infection risk, not just in JAK inhibitors, treatment, but also in other biological treatment. We can counsel patients, to help with other modifiable risk factors such as, to stop smoking, and to live an active life and some exercises, but also can, also try to help manage their comorbidities better such as diabetes and hypertension, for example. And importantly, with regards to the zoster risk for the JAK inhibition group, we also want to advocate vaccination, shingles vaccination in order to minimize the risk of activation. And certainly this depends on what has been done in, other health care services. For example, in The UK, we can only administer, a single vaccination in, patients with, autoimmune diseases, who are 50 years old or older.

So I hope, you found this summary useful, for your clinical practice, and follow me in RheumNow for more coverage of the, Congress content. Bye bye.

Hello, I'm Jonathan Kay reporting from EULAR twenty twenty four in Vienna. Interstitial lung disease and rheumatoid arthritis has been a hot topic at both EULAR and the American College of Rheumatology annual meetings for the past several years. The incidence of rheumatoid arthritis interstitial lung disease is about seven percent. This year at ULAR, there were several posters about rheumatoid arthritis associated interstitial lung disease. The first was a poster from Hong Kong where they looked at how they might be able to screen for interstitial lung disease in patients with rheumatoid arthritis at high risk for this.

Individuals who were seropositive, who had active disease. And they looked at patients and they performed high resolution CT scanning as their gold standard. And then they performed lung ultrasound where they looked for what are called B lines. And they found that the presence of five or more B lines on ultrasound yielded a sensitivity of about 55% and a specificity of eighty seven percent for the detection of subclinical interstitial lung disease. And they proposed that using ultrasound is something that can be done at the bedside and doesn't require radiation exposure.

So, is an interesting approach to looking to screening for interstitial lung disease in patients with rheumatoid arthritis. Another poster was presented from the collaboration in the Nordic countries. This came out of Sweden, but looked at patients from Denmark, Finland, Iceland, Norway and Sweden. And they looked at patients in the rheumatology registers from these countries who were initiating a first biologic or targeted synthetic DMARD patients with rheumatoid arthritis. They looked for incident cases of interstitial lung disease, And they found that there were a significant number of patients in the rheumatoid arthritis population who they could study and also in the general population as comparators.

And what they found was that the mortality from interstitial lung disease in patients with rheumatoid arthritis was similar to that for individuals with interstitial lung disease in the general population without rheumatoid arthritis. However, the presence of both rheumatoid arthritis and interstitial lung disease conferred an increased risk of mortality compared to patients with rheumatoid arthritis who did not have interstitial lung disease. So it's very important to screen for and identify interstitial lung disease and probably to treat interstitial lung disease among these patients with rheumatoid arthritis. So what is the cause of death among these patients with rheumatoid arthritis and interstitial lung disease? There was another poster from Spain that looked at a multicenter prospective cohort of patients with rheumatoid arthritis associated interstitial lung disease who were followed for a decade between 2013 and 2023.

And they found that there was a high risk of serious infection among patients with interstitial lung disease. Most of these were pulmonary infections, And of the individuals with pulmonary infections, there was a significant mortality. So, it's important, first of all, to screen for interstitial lung disease. And this might be done at the bedside with ultrasound if the study from Hong Kong can be generalized. And then once these patients are identified, they should be followed closely.

And if they develop an infection, the infection should be identified promptly and treated so as to avoid the increased mortality that one sees in individuals with the combination of interstitial lung disease and rheumatoid arthritis. For information about this and other studies from EULAR twenty twenty four in Vienna, go to roomnow.com. I'm Jonathan Kaye, and I look forward to seeing you again

reporting for RheumNow everyone, 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 look into was whether or not people had anxiety, depressive symptoms, and so on.

And so they looked at baseline, and then they looked how 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, 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. So, 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 and 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 exclude that, but I think this is definitely something that we need to look into more. Follow me on Twitter for more content, or really, 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 Hugler. 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 endophalangeal 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 rheumnow.com. I'm Jonathan Kaye, 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 OP 193. 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 NTCD20 monoclonal antibodies is associated with clinical response. So, in this study, it's looking at a different strategy to cause a 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 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? Basically, this is a monoclonal antibodies. So patient needed to stop their biological treatment at least three months before. So then after that, they need to be hospitalized 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, 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 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 is 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 including Twitter and YouTube for more coverage of the Congress content. Bye bye.