EULAR 2024 Daily Podcasts Day 3 Save

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 abatacept, 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 abatacept before 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 rheumnow.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 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 HPZUS 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 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 minimise the risk of activation. And certainly this depends on has been done in, other health care services. For example, in The UK, we can only administer, a single vaccination in a patient 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, and RheumNow for more coverage of the Congress content. Bye bye.

David Lu here from EULA twenty twenty four in sunny ish, Vienna. And here to talk a little bit about one of the most anticipated abstracts, the Select GCA study, which was presented as a late breaking abstract today, PBALBA0001. So the late breaking abstract was for the study that looked at upadacitinib versus placebo in giant cell arteritis. And we'd already heard that there was a positive result in a press release about two months ago. And so everyone was really interested to see what the actual results looked like.

So this study looked at two different doses of upadacitinib. Seven point five milligrams, that's half of our normal rheumatoid arthritis dose, and fifteen milligrams daily. And in fact, the seven point five milligrams daily just missed out on hitting the primary endpoint. So the p value was 0.057. So just missed out on that.

But fifteen milligram women truly hit the primary endpoint, which was the proportion of patients achieving sustained remission from week twelve through to week fifty two. And we saw that at forty six percent in the upadacitinib fifteen percent group versus twenty nine percent in the placebo group. So, I think that's quite a nice result. I mean, it's certainly of the magnitude that maybe we would have expected from tocilizumab as well. They did a whole lot of secondary endpoints, and you can see actually that the steroid spared is is about over the course of the fifty two weeks.

They gave upadacitinib a twenty six week taper versus a fifty two week taper and placebo, And that saved about one point two grams of of of prednisolone. And I think critically, what everyone was looking for was about the safety. Because all the And inevitably, there was a question about, well, given the regulatory safety warnings, should we be And thinking about the kind of disease that GCA is with relatively high median age, is this the kind of thing where we should be using it that, using a JAK inhibitor? So firstly to say, within this twelve month period of time, of all the types of things that you might be concerned about, actually, upadacitinib came out really well. So major adverse cardiovascular events were two in the study, both of which in the placebo arm.

Serious infections were actually lower in the upper groups versus placebo groups probably because of the steroid. And I think it's a good opportunity to remind ourselves steroid is what drives a lot of this in terms of a problem. And actually, wasn't really much of a zoster signal either. And malignancy, we didn't really see much, although it's too short of a period of time as well. Nevertheless, I think it makes a really interesting point and one actually that came up in my debate with Janet yesterday, which is really about trying to, in terms of when we're trying to assess JAK inhibitor safety, we've got to think about what disease we're looking at and what the comparator is.

And frankly, when the comparator is glucocorticoid, then that's a problem. And I think we've got to also think that maybe tocilizumab, which is the other currently approved alternative ipadasibnum for giant cell arteritis, that there's increasing questions about whether that's doing enough overall to truly suppress the disease, and especially at a vascular level, and whether it will actually truly wash out to prevent as many ischaemic complications and vascular remodeling issues as we might think it- might hope it would do otherwise. So really a lot of space there for OOPA. Some really exciting results there. Obviously, I'd like to see the full paper in due course, I'd like to see extension data, I'd like to see structural outcomes and long term safety.

But also, I think we're getting to the point that now if we're starting to see more agents, really love to see a head to head between upadasubmib, tocilizumab, maybe secukinumab if it washes out in g captain. Plenty plenty more to watch in this space. So plenty more on all of EULA twenty twenty four, roomnow.com.

Hi, everyone. This is Aurelie Najm. I am reporting for 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, 400 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, 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 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 display 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 not exclude that, but I think this is definitely something that we need to look into more.

Follow me on Twitter for more content, AureliRomo, and follow RheumNow, and don't miss our 6PM panel for a recap of the day. See you around. Hi everyone, this is Ohelin Mejj, live from Vienna Conference Center. After three days of conference right now, I can confidently say that I have learned a lot as always. Couple of abstracts I want to discuss with you and it comes down to the eternal question we ask ourselves in clinics which is in PSA after a first failure of a TNF inhibitor, what do you go for?

Do you go for a different mechanism of action? Do you go for another TNF inhibitor? EULAR and GRAPA recommendations have not formally stated whether it should be one or the other, and so the first poster that tried to answer that question is poster two seventy eight and so what it does is that it looks at a cohort of four hundred plus PSA patients that were and it's interesting it's from The Netherlands and they have this historical cohort where there was only TNF inhibitors available that was before IL-seventeen, so obviously they had to kind of cycle yeah and then they have this was a cohort of about a few more patients that they did swap from TNF to AL17 and they look at the three years retention rate as a surrogate for efficacy as well as one year disease activity. So what they find, I found it quite interesting, is that when they do adjust for discontinuation reason, which I think is a very thing to adjust for and a lot of other cohorts haven't done that, They don't see any difference in retention which does make sense in some ways and also they don't see any difference in that CRP in the two swapping versus cycling groups at one year.

One thing they did see though is that when they separate groups between male and females, they saw that males actually that were cycling rather than swapping for a different mechanism of action did have a worse prognosis. In fact, they had an odd ratio of failure of the drug of 1.67, but this was not found in females, which in itself is also an interesting finding that requires further studies. And then the other poster was two sixty six and this one finds somehow different results. It was the BRAF cohort, three forty plus patients with PSA, a group that swapped, a group that cycled again, and then they did find a better outcome in people that were swapping, which is also interesting. But one thing to note there is that they did not adjust reason for discontinuation, and I don't think, I mean they don't describe having adjusted on a lot of data actually, so I would be a bit more wary about these data.

But I think what we need actually is probably a trial so that we know exactly what to do, and I'd be interested to hear what you do in your practice. But for now, I will go and thank you for this, your attention on this, and follow me on Twitter orlibromo and follow RheumNow.

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 looking at Shingrix vaccination vaccination in in patients patients treated treated with with abadacept. Abatacept. 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 humoural 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 Baticep 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 rheumatology at Euler twenty twenty four, know you where to go. Rheumnow.com.

I'm Anthony Chen. I'm a consultant rheumatologist from Reading, United Kingdom, and I'm here in EULA twenty twenty four 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 EULA twenty twenty four 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 and he did a very nice oral presentation. The number is OP0112 where he used the 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 in 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 would 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. On And 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 at specific sites. So we trained a model to recognize calcification on TFCC or MCP three or two on Hendrik radiographs and that's labeled by two independent radiologists by my colleague Fabio Bece from Lausanne.

And then we trained the model 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 a combined model detecting TFCC but also MCP2 or three classification is the best. We 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 area on the radiograph where the algorithm took its decision, 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 number. What was the area under the curve when you did the 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 with 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 up as well. Yeah. Yeah. So 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 that was also very interesting.

Yeah it seems to be in quite a lot of areas now where that certainly in my sort of and especially area of interest in this spondyloarthropolis 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 kind of share with us from this session in the whole field of AI and machine learning before we sort of close?

Imaging is number one. I think simple tasks such as detecting calcification will be automized or you will have it supported 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 Hugo, for your time today, and hope you enjoy the rest of the year, love.

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. K. And today, I am going to be talking about one of the posters that were presented at EULAR this year.

It's POS seven thirty, 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 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, 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 dealt 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 the 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 was done in the Brigham and Women's Rheumatoid Arthritis Sequential Study, the BRASS registry, and there were around fifteen hundred 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, found that compared to the non difficult to treat rheumatoid arthritis patients, more of them happen 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 abatacept 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 rheumnow.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 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, 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 this presentation, the abstract, number was OP0092. So in this study, a large number of patients were involved, were over 50,000 treatment, status, 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 the 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, had less disease duration compared to the TNF and other mode of action. And consequently, in terms of biologic naive, so there were more proportion in the TNF group compared to the CHK.

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 what has been done in, other health care services. For example, in The UK, we can only administer, machine gun 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 Kaye 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 fifty five percent 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. And 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 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 Kay, and I look forward to seeing you again soon.

Hello. My name is RheumNow Niday. 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 POS seven thirty, 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 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, 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 felt 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 the 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.

Hi. I'm doctor Janet Pope or at Janet Bourdeaux reporting at RheumNow at hashtag EULAR twenty twenty four in beautiful Vienna, Austria. I'd like to talk about glucocorticoids in SLE, and I wanna tell you about three things. So I'm going to tell you background, and then I'm going to talk about oral presentation OP-one hundred eighty. So rumor has it in past that when we withdraw glucocorticoids in people with SLE or lupus who are in clinical remission, that many of them flare.

And we've all had patients where they're on four or six milligrams of prednisone, and as we go down, they feel worse, or they actually clinically flare and they go back up to the dose that they were on that we're trying to get them off of. This study was to look at if patients were in clinical and serological remission, so a SLETE I score of zero, so that's no active lupus by complements or double stranded DNA, and no clinical lupus, and they're on low dose prednisone, less than or equal to five milligrams a day, and stable immune suppression. And what they did was they looked at people retrospectively, not randomized, but those who got off glucocorticoids and those who really couldn't get down. And they looked at the rate of flares, and a flare was saying that their lupus disease activity index went up above zero. So it could have been inflammatory arthritis or a low compliment double stranded DNA.

And in this study, they had three sixty patients who were able to get off their low dose prednisone, and about a quarter or one hundred and twenty four who couldn't. And they looked at the flares and the time to flares. And basically the annual flare rate, if you got off prednisone was one point six five per 100 patient years, and it was eight point five per 100 patient years who stayed on prednisone. So the conclusion was, number one, if you get off prednisone, you don't have more flares, but number two, this study is biased because the people who didn't get off prednisone probably knew that they had to keep it on board or they would flare, and if you tried to insist and you got them changed up a little bit, but not off prednisone, they flared. So the patients probably knew and maybe the physicians knew.

And number three, there is a PASS randomized controlled trial of low dose prednisone in lupus, and if you're randomized to a very slow taper versus keeping them fixed at say five milligrams a day, there is a higher flare rate. So this study is contrary and opposite to the RCT. And I think the take home message is if you're trying to taper and the people flare, just put them back on the previous dose. If you're trying to taper and they're not flaring, try to get them off prednisone altogether. So three items that will help you when you're treating your patients on low dose prednisone who are in full remission from their lupus.

Please follow us at RheumNow and enjoy your day. Thank you.

Hi everyone, I'm Andrea Fava. I'm a physician scientist from Johns Hopkins, connecting here from Mueller in beautiful Vienna. And I wanted to give my thoughts about tapering of immunosuppression in lupus. There's been a lot of research going on in the last few years, new clinical trials, always trying to use less treatment or at least less steroids. And this year, this has been reflected in many sessions.

In particular, there was one focused on how to taper or withdraw treatment in rheumatic diseases. And I wanted to focus on the talks that focused on lupus. The first one was from Marie Horowitz from Canada, and they wanted to tackle the idea on how to taper that last five milligrams of prednisone in patients with lupus who are in remission. And this started from a previous experience from a Toronto cohort, the cortical loop trial, in which patients who were on remission but were still on fivopranisone basically had the prednisone withdrawn and the experience was not good because after one year, twenty seven percent of the patient had a flare as compared to seven percent of the patient who remained on prednisone. And so they took a different approach and they elaborated this taper regimen by which patients had to taper prednisone by on average one milligram every seven weeks.

And they had more than 100 patients per group, they were randomized and propensity matched. And it was quite interesting to see the results because the surprise was that the patients at one ear who flared more were the patients who remained on prednisone five, and so they were like twenty nine percent of flares in the patient who remained on prednisone versus 17, and at twenty four months it was pretty much the same with just a higher number. What was interesting to see is that the damage accrual as expected was much higher in the group that remained on prednisone with a seventeen percent of total damage accrual versus six point nine patient that increased their damage. And the damage accrual was both from prednisone and also non steroid independent. The reason for this higher FLAIR, it's unclear, but it's definitely an interesting one.

The second session I wanted to comment on is about the tapering of immunosuppression in patients with lupus nephritis. And this was presented by Doctor. Panagiotopoulos, and they enrolled one hundred and thirty seven patients that were induced for lupus nephritis and they were mostly on mycophenolate maintenance, and after a median of about three years, they decided to taper, actually withdrawn mycophenolate, and they looked over time at people who flared and looked for predictors of flares, and what they found is that being non responders in terms of lupus nephritis at one year was associated with a higher risk of flares, and instead having an early response was protective for not having a flare upon removal of mycophenolate. Having higher prednisone use at twelve months was associated with more flares, whereas being on hydroxychloroquine was protective by cutting in half the risk of having flares. Having classified lupus nephritis had less risk of flares, but I think that the striking finding here is that sure, we want to taper immunosuppression, we want to sometimes take this little risk, but this risk comes at a price because in fact, the patients who flared had a significant increase in the risk of losing GFR permanently with a GFR drop of more than thirty percent all the way to end stage kidney disease and death, with a rate that was quite high.

So there were fifty three percent of patients who had one of these adverse outcomes among those who flared, who taper mycophenolate versus sixteen. So quite high. So we really need to find a strategy on how to best decide who are the patients in whom we could safely taper immunosuppression and not just hanging it because it comes at a permanent risk for patients. And of course there are studies that have been described in this meeting, such as the ReBioLoop studies led by Ioannis Porodis and Fred Ducio in which they are looking at the value of per protocol repeat biopsies after one year of treatment to decide eventually how, and understand how we could use this information to taper. And of course there are big proponents of doing repeat biopsies to do so.

And of course, I'm biased, but I think that the answer will come from non invasive biomarkers, which will help us eventually to decide who we can taper. And the very last comment I wanna make is again on prednisone use, not so much about tapering, but it's a comment, it was a study was highlighted in the plenary on the first day by Lauren Arnaud, and there was a plenary on what's on the horizon for lupus. And he highlighted a study from Ali Duarte's group at Mayo in which they did a meta regression on several lupus nephritis studies and looked at the effect of IV steroid pulses on the rate of response in lupus nephritis, and what they found that patients who received IV pulses had higher rates of response without significantly increased toxicity. So this is giving us a sense that perhaps hitting hard at the beginning, it's a better strategy that will allow us to use less prednisone later on and therefore avoiding damage, which resonates on the approach that we often have in some of these bad flares. Anyway, very interesting studies, very interesting comments heard here at Hewler, and for more information, you can go on RheumNow on the website.

Thank you. Hi everyone, my name is Andrea Fava, I'm a rheumatologist at Johns Hopkins, and I'm coming at you from, beautiful Vienna here at Hewler, where I've just listened this morning to a very fascinating session, that was titled, Auto inflammation at the Crossroad of actually, or the Crossroad of Auto Inflammation and Autoimmunity, Auto What? So, auto inflammation has been, very dear to my heart. I am a lupus specialist and yes, we think of lupus as a quintessential autoimmune disease, but, when we treat patients, there are many manifestations that truly are borrowed from, the manifestation that we see in auto inflammatory conditions. We see all of this interferon.

And then if you, several years ago, we discovered this interferonopathies, which is a group of diseases that are driven usually by a monogenic defect that lead to an excessive expression of interferon with features that partially overlap with lupus, but many that are unique. And so lupus to me, it's really this kind of mixed, group of molecularly diverse and clinically diverse diseases. And sometimes I see my clinic features that match with what we think is autoimmunity, others, other manifestations that are more autoinflammatory. But this concept is expanding, to all other rheumatic autoimmune condition that we treat in our clinic called rheumatic inflammatory condition. And so this morning, this was this session in which they try to break it down, to focus on what are the features that we know about auto inflammatory conditions and

what are

the features that we know that are more typical of, autoimmune conditions. And then how about the mixed type in the middle? So let me just give you a couple of definitions. Auto inflammations are diseases in which there is an excessive activation of the innate immune system, whereas autoimmune diseases are those where there is an excessive or an abnormal activation of the adaptive immune system. And by adaptive, we mean the immune system where there is memory.

So for example, you get a virus and then you get antibodies and you get T and B cells against this virus, so we don't get the virus again. And so you can think about that, for example, when we have autoimmunity, such as autoimmune thyroid disease, there are antibodies that are targeting one organ that can be directly pathogenic. Whereas autoinflammation, think about familiar Mediterranean fever where there are like bouts of fevers that are abrupt, and at the molecular level, they're not triggered by a given antigen necessarily, but they're just in excessive response to non specific stimuli. Gout is in that category. Mean, we know that it's coming as a response to uric acid, but this uric acid just triggers the macrophage and the neutrophil and immune system just to react to something bad and they release a lot of interleukin-one and they cause a lot of this bad inflammation.

Anyway, so these are the features of both inflammatory diseases, with rapid onset, fever. There are many, many of those, like they have interferonopathies, those associated with inflammasome, those associated with NF kappa B, but of the diseases that we see in our practice, there are some surprises. And so for example, we think of Still's disease or in children, we call it a systemic JIA, and we think of those to be auto inflammatory condition, but it's interesting to see that actually the strongest genetic correlate is HLA. And so wait a minute, we have an inflammatory disease that is associated with HLA that mechanistically speak to antigen presentation and memory. And so there is some mix there and probably we need to understand this better.

Doctor. McGonagall showed that Takayasu is probably a CD8 driven auto inflammatory disease, is a vasculitis. There is a link to inflammatory bowel disease, neutrophilic dermatosis. There's a lot of features suggesting this, inflammation, coming from CD8 with the release of interferon gamma and interleukin 12, but, it's somewhere in the crossroad. He also showed some interesting data about MDA-five dermatomyositis.

What dermatomyositis is an auto inflammatory condition? Well, dermatomyositis, especially MDA-five is a pattern recognition, is a molecule that recognizes pattern in particular, double stranded RNA, which is something that senses when we are infected with viruses and react with interfering response and an inflammatory response that we need to fight off infections. But what they noted in Yorkshire, which is in the center of The UK, they found the peak. They're not used to see these patients and they found the peak, a few years ago of a lot of patients with MDA-five like dermatomyositis without the rapidly progressive ILD that we tend to see. And they figured out that there was a very nice overlap with exposure to not so much COVID, but the COVID vaccine, with the idea that perhaps the exposure to certain nucleic acid can trigger MDA-five in some one, making it immunogenic, and they started to see this excess response and interferon with the syndrome.

Something I, it was not on my radar, but something that I learned today. But I think that looking at the crossroad, which was the presentation that came from Doctor. Shekhanachuk, that he was looking at what the diseases have a little bit of inflammation, little bit of autoimmunity, and he made a few examples. So I'll just list them for you. One is that seropositive rheumatoid arthritis with ACPA, so citrullinated antigens, well, found these antibodies in atherosclerosis with the idea that, well, you have an antigen specific response with autoantibodies against a specific target found in the plaque and they lead to excessive interleukin production, which seems to drive eventually cardiovascular disease.

So a nice interaction. Spondyloarthritis. Yes, there is evidence of autoimmunity in spondyloarthritis with 20 of patients with specific antibodies mostly used in research, but there's also very strong inflammasome activation saying, okay, we have both. We have a bit of autoimmunity and a little bit of, auto inflammation. And so he showed more and more example in calling this term of MH-one apathy.

Now I know that the clinicians, when we start talking about too many molecules, this can become a little bit boring, but MH-one, HLA, is a molecule that it's important to present antigens. And in this umbrella of people who, diseases that have an association with this important molecule, there is psoriasis, spondyloarthritis, Behcet's, Still's disease. And so, it seems that these diseases tend to share a lot of the pathogenic, features. And so sometimes we get trapped in this, you know, nature is complex, medicine is complex, our body is complex, our brain is simple, our mind is simple. So we simplify diseases so we can put them into boxes and so we can put a label and follow a treatment algorithm.

Well, perhaps we are oversimplifying things here and these newer discoveries are helping us understanding where is the blend and perhaps we should reconsider how we understand disease. And so the last presentation was from Ian McGinnis, beautiful presentation about, immune memory and other things. I just wanted to, quote one of his, metaphors. He brought up the concept that diseases such as lupus that we think are autoimmune and they are very heterogeneous, perhaps are kinetically diverse. What he means by that is that the disease starts at different points and then we just capture them as a snapshot.

Think of seeing a marathon and just everyone starts at the same point, but then you look at where people are after twenty minutes, they are all spread out and you cannot tell from the twenty minute picture where people started at the beginning. And so this is what we see in practice. We see disease that perhaps are very heterogeneous, but there is this different capturing time. And so we try to simplify things about understanding which cytokine comes first and explain the other so we can decide which treatment to pick. But this may be more chaotic than we think, it may be more complex.

So I think this is all very interesting and to reconsider how we think our disease is and eventually how we treat. But for now is, perhaps a little bit too early to think about this in terms of precision medicine, but probably this is how we need to think of these diseases, reconsider them, deconstruct them, reconstruct them, and hopefully we will get to procedure medicines through this pathway. Thank you very much. And to hear more about this, you can go on the RheumNow website. Thank you.

My name is Jusuf. I'm a consultant rheumatologist from Leeds, United Kingdom. I am reporting for RheumNow live from Vienna, Austria. Today is day two of EULA conference. There have been many abstracts presented.

So one abstract that I would like to discuss is about the progress of CAR T cells. So in this conference, there have been so many advance, pertaining to CAR T cells. And if we don't talk about CAR T cell, it probably means that you've not attended this Congress. And so just to summarise quickly in terms of CAR T cells, so these treatments have been thoroughly evaluated in the context of haematological malignancy. But from the perspective of autoimmune diseases, these treatments were introduced about two years ago by Professor George Shetz's team for which they demonstrated successful outcomes of PIE-five patients with refractory SLE, who responded brilliantly and with good clinical, outcomes, as well as, drug free remission.

So we're rolling forward two years now to 2024. There have been many interests by pharmaceutical companies in producing the CAR T cells. So just to, recap in terms of the process, so CAR T cells, stand for chimeric antigen receptor. So the principle, is, to induce profound B cell depletion and hopefully will then reset the aberrant immunological abnormality. So what they do is initially infuse patients with strong chemotherapies to induce profound depletion.

And after that, the blood samples from the patients were taken, for which the T cells were extracted in process called apheresis. Then these T cells were then re engineered in the lab to produce a protein on the surface, which then respond to specific receptor. And the most common receptor will be the CD19 so that when these then, reinfuse to the patients, they can attack the cells, the pathogenic B cells. So at this EULAB Congress, there is now a novel approach in terms of attacking two receptors, so not just CD19. So this is, what we call it compound CAR T cells.

So using a double approach, of attacking two, receptors, one is CD19 and one also, BCMA. And the logic to attack the BCMA is because, BCMA, were expressed on, the specific, B cells, particularly the plasmablasts and also long lived plasma cells. And this will result in, pathogenic, autoantibodies elimination. Okay, so basically, regarding to this, abstract, so this, was a phase one open label trial in China. So the presenters presented data of, 12 patients, all, had severe refractory lupus nephritis.

All of them had a prior renal biopsy, which showed a range of classes from class three to class five. And all these patients underwent the treatment and the result was outstanding in that the majority of patients had profound clinical response in terms of reduction in proteinuria. Majority of them reached the complete renal response rate, which is proteinuria level at less than 0.5 gram a day, and the patient were drug free remission as well. And the data were presented for follow-up just over two years. So people were asking as well, what happened to the infection risk?

So because of the depletion of the plasma blast and also long lived plasma cells, people are concerned of this, but the data, the initial short term data showed minimal infections apart from mild COVID. There was one mild urinary tract infection observed. So, this novel compound approach appears to be showing early efficacy and safety, and is planned to be developed in later stage of the trials. So in terms of, how this is relevant to clinical practice. So, in this Congress, there have been, quite a few other, CAR T cells, data which were investigated in phase one open label trial.

I think the key thing is about, selection of patients, because, what do people mean by severe refractory lupus? How refractory is refractory? Does it depends on how many biologics that you've been undergoing? Or potentially maybe when you've tried B cell deep living therapies such as rituximab and people did not reach complete depth of depletion, so maybe these patients could be considered refractory. So, yeah, so this is still in the debate.

But also, other, important factors including safety, because, this C compound have only just over twelve months period of follow-up. And even, in Professor George Shat's cohort initially, the follow-up was up to two to three years. So we needed more longer term data because we don't know what happened after the B cell have returned. So potentially later down the years then it may bring a disease relapse and what happened then? I mean, we going to give another CAR T cells therapy which potentially significant side effect and etc?

So these are all questions that's still up in the air. But certainly, you know, there has been a lot of interest in terms of CAR T cells therapies, not just in SLE, but also in other across ANA associated autoimmune diseases. I hope, you found my summary interesting. And please follow me, and also RheumNow, on social media outlets, for more coverage of EULA twenty twenty four in Vienna. Thank you.