ACR24 - LUPUS Save

Hi, this is Andrea Fava coming at you for RheumNow here at ACR in Washington DC. And I wanted to talk about what I think is a fibroblast renaissance. In the last few years, this cell type that we kind of ignore for the many years is coming in everywhere. We are discovering its role in multiple autoimmune diseases and also discovering new roles because we think that yes it's a cell that makes collagen and drives fibrosis but there may be more than that. And the first abstract I want to comment on is an abstract presented yesterday at plenary one by Angela Zhu from the Brigham And they did a fascinating study, in fact it was a plenary, and studying the fibroblast cells in the synovium of rheumatoid arthritis.

A couple of years ago, our group as part of the Accelerated Medicines Partnership found that there's a group of rheumatoid arthritis patients that are refractory to treatment that actually have fibroblasts that are inflammatory and then can drive disease. But now they try to understand more about this and what they found through very elegant system is that if you have an inflammatory fibroblast that can be driven to become an invasive fibroblast that then can cause damage and affect the cartilage. And this is like fascinating because they were to identify the transcription factors that drive this transition and perhaps that can drive the design of new treatments. The other abstract I want to highlight was presented today by Jasmine Sweather from NYU and that's about lupus. And they have presented last year and the paper is in preparation a study focused on class two lupus nephritis which is the underdog of lupus nephritis.

Milder, sometimes we don't pay enough attention to it but it's the very early stage of disease. And what they found by using single cell RNA sequencing of the kidney is that myofibroblasts actually are incredibly increased in these patients as compared to all other classes. And so now they studied the urine of these patients and they found that actually there is a strong signature of fibroblast activation in these patients confirming the signature in the kidney. Bringing our attention to the fact that these important cells is also implicated in lupus nephritis. So with this renaissance of information, hopefully we're going to have treatment that can treat the inflammation driven by fibroblast and perhaps even prevent fibrosis and with that chronic damage.

And for information you can go on RheumNow on the website. Thank you. Bye bye.

Hi, everyone. Jack Cush. I'm on the floor of the ACR Exhibit Hall. It's ACR convergence twenty twenty four. We're in Washington DC.

This is day one, morning one. We're excited to be here. Looks like a lively meeting. Lots of folks, lots of buzz. The exhibit floor in our booth is really happening.

If you're here at the meeting, come by, visit us. We'd love to meet you. Say hello. Give you one of the new RheumNow pens. Hope you like that.

I want to talk to you about what I think you should be doing and what's new at this meeting. You know, the meeting is is really the same meeting. Right? It's face to face and that's what people want. Some things are new.

And we have the same old sessions, the great debate. This morning, they had the the year in review. We're gonna have knowledge bowl and other highlights including a wrap up at the end. But plenary sessions are have flipped. They're in the morning at 09:00, and the posters are beginning right about now at 10:30.

So that's something that's new. I think for you watching this video, how am I gonna learn the ACR? I'm gonna give you a few pointers that I think you should pay attention to. Number one, come to the meeting. See us at the booth.

Go to your favorite sessions. Number two, if you're at home, I'd recommend that you follow us on Twitter. On Twitter, you're gonna get this constant stream of information and what's happening really right to the minute. And it's almost like watching a ticker tape of what's going on at the meeting. I think that's kind of exciting, but maybe you're not a Twitter person.

And maybe you wanna get a feel for what happened at the meeting. I'm gonna give you three ways that you can do that. Number one, that is at the end of every day at 6PM eastern time. We're gonna live stream the daily recap where it's gonna be me and three or four of the faculty, and we're gonna review the happenings of that day and what was notable, exciting, and something you wanna take home. Number two, starting next week when you get home, you can view the video that's gonna be called the lupus topic panel or the RA topic panel or the PSA.

We have topic panels with me and four experts in lupus, RA, etcetera. And we're gonna do RA, PSA, SPA, lupus, JAK inhibitors, tick inhibitors, and IL seventeen drugs. And so that's like six different videos that you'll be able to look at. And the third way that makes the most amount of sense is this go to the RheumNow website and you might already subscribe and get a daily email or a weekly email. But if you're an RA person or a lupus person, we have an email list and you can sign up, check the box.

I want the topic email list that'll come out once a week. And if you check the box on whatever topic you like, you're gonna get an email after ACR and all the lupus stuff that we produce. So you'll have that in your inbox to review. By the way, everything I just said that's in video form will also be in podcast form. You can listen to the daily recap podcast.

You can listen to the topic panels in a in a podcast. And you can also listen to podcast accumulated podcast reports from all our faculty who are here covering the meeting for you. Hope you enjoy this meeting. I'm going to. We'll talk more.

Hi, this is Andrea Fava from ACR in Washington DC coming to you for RheumNow and I'm gonna talk to one of the topics that I care the most about and that is lupus nephritis and its diagnostic challenges. So lupus nephritis, bad manifestation of lupus, it can lead people to kidney failure needing dialysis and the problem is that we have to rely on protein in urine for diagnosis because most patients are completely asymptomatic. We screen for protein, we get kidney biopsies and then we treat based on it and then to figure out if a patient is responding to treatment we monitor proteinuria over time. But that comes with the problem that proteinuria, so protein in the urine, does not reflect the inflammation in the kidney. And what do we do?

We treat kidney inflammation with anti inflammatory and immunosuppressant and the data are telling us that if we follow protein we are going to be fooled because when you repeat a kidney biopsy you can see that patients with no protein in the urine can still have histological activity and patients with zero histological activity in the kidney can still have proteinuria above 500. And so we are being fooled. And so for the last many years, we've been working on a better way and this better way, I believe, are in non invasive biomarkers and we focused on urine because urine collects the byproducts of kidney inflammation and you can collect it super non invasively. And the abstract presented this morning in the plenary too was about developing a biomarker panel that was made out of 12 protein that could be clinically useful. We don't want a biomarker that can be just as good as proteinuria.

We have that. We want something that can tell us something more. And in this situation this biomarker was trained starting from 1,200 proteins to identify which patients, who are the patients who have an activity index in the kidney in terms of histological inflammation greater than two because that's clinically meaningful and this biomarker outperformed expectation. We found that, with this 12 protein we could accurately predict who had active histological histologically active lupus nephritis with what we called an area under the curve of more than 90% which is about 90% accurate. And this is fantastic because we could monitor that over time.

We could see that a decline of the score telling us that the patient is having a resolution of inflammation in the kidney as early as three months predicted clinical response at one year. But even more exciting is that in patients who at one year of treatment still had the persistent elevation of the score telling us that there was persistent inflammation in the kidney, these patients were more likely to develop kidney function loss in the next five, seven years which is what we care about. And this bit of information was adding to proteinuria by showing that it outperformed proteinuria by combining it which is telling us that is giving us a piece of information that we couldn't get through proteinuria and is clinically useful and that could be used to aid diagnosis non invasively. It could help us monitoring treatment response, change treatment and guide treatment and perhaps even become the new treatment outcome. Outcome.

So in collaboration with a commercial entity, Exagen, this biomarker has been developed into something that physicians can finally be able to order and so hopefully in the next couple of years this will be available to everybody. If you wanna learn more about it, please go on rheumnow.com. Thank you.

Hi. It's Janet Pope here reporting at RheumNow, ACR twenty twenty four in Washington. I wanna tell you about a study that will actually change my practice. So I found a poster six twenty seven and it was a really important clinically question, clinically important question. We get patients all the time referred and they have a high positive ANA, we don't find an autoimmune disease or rheumatic disease and we go I don't know what it means.

So this, study was trying to address it. So they had about eight thousand five hundred patients with an ANA, didn't know what to do with it because there was no autoimmune disease associated. So they decided to look at high titer and low titer and about two thirds of three quarters were low titer, no surprise, but what did the high titer patients have? Very interestingly they had far more liver disease, not autoimmune, cirrhosis, fatty liver, other things like that. So what does that mean in my practice?

Well I think we always thought that in autoimmune liver disease we'd see an ANA and sometimes we'd see a false positive rheumatoid factor and say cirrhosis but they were probably in those days from hepatitis C because we couldn't measure it. What I think it means is if I get a patient with a high positive ANA and I don't know why and it could be variable patterns, there were all sorts of patterns with it, I'm going to consider looking at the liver, Maybe liver function, maybe transaminases, maybe even an ultrasound or FibroScan. So it will change what I do in clinic next week. Please follow me at JanetBirdoke. Thanks.

Good morning my name is Akhil Sood reporting for RheumNow here in Washington DC. Today I have the pleasure of speaking with Doctor. Chris Winkup from King's College London. Hi Chris how are you today?

I'm very good thank you very much it's nice to be here with

you. Absolutely. Yeah so today I want to talk to you about CAR T in lupus. So just for the general audience tell us a little about CAR T for the non basic scientists from a clinical side.

Great so I think CAR T cell is an area of Rheumatology that was just getting to terms with. We're learning a lot from our colleagues in hematology with regards to this treatment when I try to describe it to people I say that this is a drug but it's almost a living drug what we're doing with CAR T cell therapy is we're asking patients to typically donate their own blood particularly their T cells which we all know rheumatologists are important in the immune response of many of the autoimmune conditions we treat and these T cells are then taken to a lab and genetically reprogrammed to target something else in many case CD19 or BCMA which we see on B cells. So it's a very very extensive and precise way of B cell depleting. These new genetically modified cells are then reinfused to the patient where they don't just stay dormant they expand they grow and they find their target so for example B cells and they deplete and kill those b cells leading to a very profound b cell depletion and what we're seeing in many of the studies and bear in mind these are very small numbers and open label studies is significant clinical response following that treatment so it's a hugely exciting area we're learning a lot from our colleagues in hematology but one of the things that I'm talking about here an awful lot is how can we change this treatment?

How can we look at using this treatment en masse for autoimmune conditions? So it's a really exciting time to be in this field and doing this type of

Absolutely yeah thank you for sharing that and my one question for you is you know which in specific specifically in lupus which patients would you be would you want to consider CAR T therapy for and which ones would you want to be cautious for?

Yeah so I think obviously with many of the typical trials that we do in lupus we're looking for patients who tend to have more severe and refractory disease and certainly that's where some of the data lies already. I think there's good reason for that you don't know the long term efficacy and safety of this treatment yet so those patients who have exhausted many options who have quite severe disease that if left untreated will lead to long term consequences tend to be the patients going into the study. That said I think we're very good in the lupus community of saying what low disease activity or maybe remission looks like but we perhaps don't quite have the terminology for someone who is hugely active in terms of their disease and so there's a lot of debate in the field as to exactly what level of disease activity should we be using for CAR T cell therapy. I think one of the interesting things is if we show that this is a safe and effective treatment that gets people into treatment free remission, you may find that that level lowers in future studies and perhaps more moderately active disease is considered.

But for the time being it's really focusing on those with severe and active disease refractory to at least few lines of therapy.

I see and so I guess one question to follow-up on that is that in the armamentarium of therapies that we're having coming up for lupus where do you see CAR T maybe now or even in near future as a line of therapy? So I think

this is one of the really exciting things about being here in Washington. So my first ever ACR conference was in Washington eight years ago where we were seeing a lot of data for a few biologics starting to come through and that was all we were really talking about. And now here we are talking about CAR T cell therapy but a number of other targeted agents for the treatment of lupus. So I think this is really exciting time to be looking after patients with lupus to have so many promising agents coming through. I think in terms of the question of where this is going to fall in terms of treatment of patients with lupus will be predominantly decided by the long term and safety of this treatment.

If we see a period of efficacy that lasts for a number of years then I think that really does suddenly say we need to use this in quite a lot of patients. If we find alternative agents that are very good at giving similar results that may be easier to deliver, it might be that this therapy is used for those really sick last line evidence type of patients that need the most severe and profound immunosuppression. So I think we don't really know where this currently falls at the moment. There are some other interesting agents that are available not just CAR T cell therapy but other cellular type therapies such as T cell engagers. But this is a really exciting time to be here to to be here talking about a number of treatments that are really causing very profound responses.

It's a long way we've come in the last eight years since I was last in Washington. So I do think that we will probably know an awful lot more in the next eight years time and there's a lot

of reasons to be very optimistic here. Absolutely and do you envision CAR T leading us to a steroid free era in the near future?

Yes, I think even if we take CAR T cell therapy out of this I think we all need to be looking at steroid free treatment at least in the long term I think steroids will always have their place in the short when patients are very sick. If we look at rheumatoid arthritis and a lot of my job is looking down the corridors almost enviously at my colleagues who deal with rheumatoid arthritis, seeing they have many agents available to treat their disease. And it's very rare you'd find a patient with rheumatoid arthritis who is on long term low dose steroids. Now we've not yet moved there with lupus but as we see a number of agents of which CAR T cell shows promise but we know that other biologic agents are coming through that we may have more options that mean that we don't need to leave patients on long term steroids and I do hope that we will get there fairly soon with the newer therapies that in particular are in later stage development that we do hope will come through in the next few years.

Absolutely. Yeah, thank you so much for sharing this and this is really helpful and very insightful, information regarding CAR T in lupus therapy and really exciting in the present and in the future. Thank you so much for sharing the insights into CAR T and this is actually reporting from now. Thank you.

Hi everyone it's Mike Putman reporting to you from ACR24 in Washington DC. Today I want to tell you about Abstract six seventy, which is a very interesting randomized controlled trial of mycophenolate versus cyclophosphamide and tacrolimus. Now this is a very interesting study to me because we all have a rough sense that for patients with lupus nephritis, mycophenolate and cyclophosphamide are roughly equivalent. That was what was shown by the ALMS trial. Because of the safety profile, most of us favor mycophenolate, although in some cases I'm still using cyclophosphamide.

Now these investigators performed an open label, so everyone knew which group they were getting into, randomized trial of mycophenolate, cytotoxin, or tacrolimus, which I think is really exciting because I would be curious to know if there were another option in this disease. Ultimately it was a relatively small trial. Each group had about 30 patients, but what they found was surprising. Patients in the tacrolimus group, mid-sixty percent response. The primary endpoint was assessed at week twenty four, complete or partial renal response.

So the tacrolimus group, sixty some percent. Same as mycophenolate group, didn't look any different. The cyclophosphamide group did a little bit worse, but I think that's probably because this was a smaller trial. I suspect if they scaled up, you wouldn't see that. But the nice thing here is that we do see that tacrolimus might be an option for induction therapy of lupus nephritis.

I would not have expected that. I have to say that I don't think this is going to change my practice immediately. The truth is that this is a very serious disease and I think I'm going to want to lead with the standard of care therapies. But if there was a situation where I was trying to find something else, this was quite encouraging and something I would at least think of as maybe an add on. So interesting study, would not necessarily start doing this right away, but it merits further investigation and given the known utility of calcineurin inhibitors in lupus nephritis, I think there's certainly some biological plausibility that this could be an option.

Thanks so much for tuning in to all the coverage from RheumNow and have a great day.

Hi. This is Bella Mehta reporting for RheumNow from the ACR twenty four convention. I'm originally from New York, and there are a few very interesting abstracts that I'm seeing at ACR this year. One very interesting one that I wanna talk about right now is the late breaking abstract number 11. It is reading ANAs under immunofluorescence in an automated approach.

So as we all know, rheumatologists are almost associated with ANA. A lot of nonrheumatologists say that's all we do, but, obviously, we don't. But as we know, it's a very important laboratory parameter. And, especially, it's not just the positive or the negative, but the titer and what kind of pattern or immunofluorescence does it exhibit. So what the researchers did is they took thousands of images, around 13,600 images of ANA, immunofluorescence pattern, which were already read by a technician who has been doing this for thirty years.

So with a lot of experience reading these. And what they did is use machine learning as well as complex neural networks, so CNN models to automate and see if the machines can learn by itself how or what these patterns are, and not only the pattern, but also the tighter quantification. They tried a bunch of models because, you know, not each ML model would be as good. So they tried around eight machine learning models and four convolutional neural networks. And what they found is at least one of the machine learning models did very well, and they had a 96 to 97 AUC, which is sort of the prediction probability of detecting the right pattern as well as tighter.

And, you know, it pretty much correlated very well with somebody who had thirty years of experience doing this. What it tells me is that some of these tasks, which can be easily visualized might be more so outsourced to the AI models as long as they can they can work well. And again, the more data we pull in, the better these models will get. And, again, these days finding technicians who are so experienced with these things is difficult, so getting some help from AI might not be a bad thing. And, again, there's a lot of coverage at ACR about AI, machine learning, convolutional neural networks, and I'll be covering a lot of those.

So follow me more on Twitter at Bella underscore Mehta as well as on RheumNow live. Thank you.

Hello. My name is Rinalini Day. I'm a clinical fellow from London in The UK, and I'm here with RheumNow reporting from ACR twenty twenty four in Washington DC. Thank you for joining us for this video. I'm delighted to be joined by Doctor Chris Wincup who is a consultant rheumatologist and academic clinician working at King's College Hospital in London in The UK and today we are going to be talking about neuropsychiatric lupus.

So for those of you who may have reviewed the program here at ACR, this is actually a relatively less spoken about set of symptoms and so I'm really interested to hear Chris's thoughts on neuropsychiatric lupus in general, but also what we can do to raise awareness of, this particular manifestation of, lupus, which is, of course, a very complex condition. So thank you for joining me, Chris. So first of all, can you just tell the audience briefly about what is neuropsychiatric lupus?

Sure. So neuropsychiatric lupus, we can define relatively easily because the ACR has already done that. And it basically reports a number of symptoms the patients with may suffer from involving the central nervous system and the peripheral nervous system and it's a fairly exhausted list of symptoms but sometimes we consider that there may be symptoms beyond this that are not included within that criteria. We know that we've got good definitions, they're very broad, but we know that patients can present a number of different ways and it's often difficult as a clinician to delineate between what is neuropsychiatric lupus due to active lupus within the nervous system versus the side effects of medicine versus damage versus something else entirely and I think that really does play some of the challenges that we see when treating patients with these symptoms but perhaps more importantly identifying those symptoms.

Okay so just picking up on that last point so identification of symptoms a lot of our audience are going to be practicing clinicians. How can we better identify, these symptoms? And I know there's been a large body of work done in The UK recently about this.

So, if if you want a one word answer is how do we better identify these symptoms, that is ask, and I think asking about these symptoms is important and I look at my own practice over recent years and, I've noticed the importance of asking about these symptoms so I think sometimes as clinicians, particularly rheumatologists looking after people with lupus, that you think that you would identify the rate of symptoms that the patients are experiencing because we expect them to be fairly profound. So if a patient has a seizure, you would imagine that you would at least if you don't see that patient have a fit you would see it on their medical records the patient may tell you they've had a hospital attendance with this but from the research we've done, we note that patients are often under identified even with fairly profound and obvious symptoms such as that. Now imagine you're looking at other symptoms, for example, hallucinations, mood disturbance, cognitive dysfunction, which are a lot more subtle, then you really do need to inquire about these. And some of the work that we've done in the past has shown that many rheumatologists underappreciate how many of their patients with lupus experience these symptoms.

And when I first saw the data, I I thought, this can't be true that many patients are reporting these symptoms. So I did a test myself, and in clinic, I started asking patients questions I hadn't asked before for example have you suffered a hallucination, have you had, auditory hallucinations or visual or tactile hallucinations, how is your mood and I think as rheumatologists we often think that we encompass many of those in the questions that we do ask. I'm surprised by the number of patients who do have these subtle symptoms that do very well at masking them because we're not asking about them and I think some of that is a degree of it is challenging for patients to talk about these very distressing symptoms and so we must make an environment for patients to feel feel comfortable and that they'll be heard to talk about this but I think as rheumatologists we also have to take a look at ourselves and say I find it very difficult to talk about these symptoms with patients because if they do say I have got one of these symptoms we're often under trained and under prepared to know what to do with this and so close working relationships with psychiatry can also help so to identify the symptoms I'd say inquire but you will inquire more easily and more confidently if you had good relationships with psychiatry and neurology to understand what to do when you identify these symptoms.

Yes. Yeah. I know from my own clinical practice it is very difficult and as you say we don't get trained. So particularly so I'm a fellow at the moment, and we don't get trained about these symptoms. But I think actually reading about the work that's been done recently, I have tried harder to ask about these symptoms.

And actually, think patients really appreciate it. So what can we do from a research standpoint to try and increase awareness in the research world? Because clearly there's an unmet need both in terms of how we treat these patients, identify these patients. Yeah what can we do from the research side of things?

So I think clinically let's imagine you've got someone with severe neuropsychiatric lupus that is fitting or psychotic or has a lymphocytic meningitis. Sometimes it's relatively easy clinically to say that's active neuropsychiatric lupus but it can be challenging because some patients will have possible other comorbidities could there be an infection in particular in the setting of meningitis. So I think I answer your question about research first and foremost saying clinically it's often very very difficult even with the most marked symptoms to quantify them. And we can see depending on which study you look at and which research has been done the prevalence of these symptoms are vast when you compare different papers. So we know that we have these very good definitions from the ACR of what neuropsychiatric lupus is classified as but we should be very very accurate in terms of our research but we're not and I think that even if we're looking at these severe symptoms quantify.

You go to the slightly more subtle ones such as cognitive dysfunction, mood disturbance, even hallucinations. I think that what we need to do is find a way of better quantifying this. So number one comes back to what I said before. You need to ask and do the studies where you try and accurately quantify but number two I think as a rheumatologist we need something that we know that we can treat and make better. So for example if you have someone who's got proteinuria, you say they've got lupus nephritis and I will initiate treatment and if the proteinuria improves I know I'm treating that patient effectively.

With neuropsychiatric lupus many patients have very normal labs, normal investigations even their CSF and MRI scans can be normal on very simple terms. So I think we need to have better biomarkers and imaging to fully quantify that this is due to an inflammatory component and therefore you quantify it better and importantly you empower clinicians to treat that better because you see something that's abnormal that you can make better. So I think research needs to focus on biomarkers when we have actually quantified these symptoms properly and I think new imaging techniques that can pick up some subtle neuroinflammation and there's of very interesting work in MRI PET with different ligands going on at the moment that may make clinicians feel more confident and asking about these symptoms and when identifying them get the patient treated. So I think those are the areas we really need to focus on.

Great. We could talk about this all day and we have spent time talking about this before. But I think just to wrap up, can you maybe direct our audience to resources or particular landmark papers in this area that you feel that they should read if they wanna know more?

Sure. So I I I mean, I don't like to self promote but I think one of one of the papers that I was fortunate to work on was it was a piece of work published in rheumatology a couple of years ago with Melanie Sloane as the first author in which we asked patients how frequently symptoms are and then we also asked rheumatologists neurologists and psychiatrists how frequently do you think your patients with lupus have these symptoms and just look at the figures I would just say look at those figures to start up to see how often we are wrong in terms of where our prediction of the prevalence of these symptoms are compared with the prevalence actually reported by patients. So I think that's very helpful. I think resources is really important and I think resources can take a number of forms but particularly patient support organizations. So Lupus UK back home in England and the rest of The United Kingdom, but also Lupus Europe are doing a lot of work to try and help patients when they experience these symptoms.

And I think as clinicians, just need to talk about this more and make this more of an agenda of what we're doing particularly in the treatment of patients with lupus.

Perfect. Yeah. No. I am I definitely also as as the reader, I wasn't involved in the work, but when I read that particular paper that Chris has referred to, I was very struck by those graphs. So I would I would recommend, listeners to go and, take a look at that particular paper.

Well, thank you for, chatting with me today, Chris. If you'd like to know more about RheumNow's coverage at ACR twenty twenty four, do go over to the RheumNow website or you can follow me at doctor mini day on x. Thank you for listening.

Hi. I'm doctor Sheila Reyes from The Philippines, and I'm reporting live for RheumNow here at Washington DC for ACR convergence twenty twenty four. Earlier today, there was a session that was highly attended and I think it was really looked forward looked forward to. It was about the session on the latest updates of the 2024 ACR lupus nephritis treatment guidelines. And what I wanted to do this morning is to give some of my take home points from this session.

So the guidelines so they came out with recommendations, about 28 graded recommendations where it included strong recommendations and, it included conditional recommendations. I think one of the most important strong recommendations that still does exist in the current management of lupus nephritis is the strong recommendation to screen all patients without a history of lupus nephritis or newly diagnosed patients with lupus to screen them for lupus nephritis. And a strong recommendation continues with the use of hydroxy chloroquine for all the patients as well as the use of RAAS drugs in the management of proteinuria. Of note, for suspected lupus nephritis, doing a kidney biopsy was a conditional recommendation and they did recommend to do the biopsy promptly or to do a repeat biopsy in case that a new flare of the lupus nephritis would occur. Now, the guidelines also are they also showed that conditional recommendations came for the use of glucocorticoids and that for patients with newly diagnosed lupus nephritis, high dose corticosteroids, high dose false corticosteroids were still conditionally recommended and to taper it slowly and eventually in the next six months and if if probable would be to taper it as low as less than five mg per day.

We all know that steroids have a lot of side effects, have a lot of complications, and so keeping our patients down to the bare minimum or the least effective dose would really help our patients to avoid side effects as well and long term complications. And so the treatment overview for lupus nephritis included recommendations for class three and four with five or the purely class five alone. And what's new with this guideline is the use of triple therapy over dual therapy. So when we talk about triple therapies, this would include or triple continuous therapy. So this would include false steroids or oral steroids to taper plus mycophenolate mofetil and a choice between belimumab or AC and I.

So alternatives for triple therapy would include low dose cyclophosphamide plus belimumab and glucocorticoid pulse or steroid taper less than five milligrams. Now, the reason why the they chose triple therapy over just the dual therapy is because of the evidence from RCT specifically BLISS LN and AURORA and that triple therapies showed improved outcomes with in patients with lupus nephritis and also to save the kidneys because ongoing, continuous ongoing lupus nephritis loses nephrons and time is kidney. I think that were the important points that really struck my mind and also the guiding principles. You should not forget that we have to collaborate with our nephrologist colleagues in the treatment of lupus nephritis and that we have to remember that treatment of lupus nephritis, treatment of lupus in general should be a shared decision making between the patients and the physicians. Follow me on x at RheumNow for more updates of the ATR convergence twenty twenty four.

David Liu from Melbourne here as part of RoomNow's ACI twenty twenty four coverage, getting right across the meeting. And I want to talk to you today a little bit about vaccine responses and what DMARDs mean for that. And we've started to be conscious about the DMARDs that we use as levers on developing a vaccine response, it makes perfect sense. The therapies we use to try and change an immune response might actually, as part of autoimmunity, may well change an immune response to a vaccination. We became very conscious of that during COVID.

We saw especially with rituximab patients getting very poor immunogenic responses to COVID vaccination and the consequences at a time when they really needed protection against COVID. At the moment, I think we've become particularly conscious about the recombinant zoster vaccination and responses to that. We are very conscious about what our patients experience as far as shingles is concerned, and about the consequences of that postherpetic neuralgia and beyond, I think is a good example for thinking about vaccinations and DMARDs going forward. And we've seen a number of different abstracts at this meeting looking at this. One of the a pair that is really interesting are 24048.

They're from a Brazilian randomised controlled trial looking at zoster vaccination in rheumatic disease patients. And what they saw is that actually, once again, rituximab patients do quite badly as far as developing a response or concern. They actually saw as well, they looked at mycophenolate patients. And so, got a decent response, but they got a better response when you were withheld for two weeks after the mycophenolate dosing. So, there were things that you could do there.

But overall, most people got a response. What about other mechanisms which might be relevant to developing a vaccine response? Well, we've seen at this meeting that patients with upadacitinib seem to do reasonably well with developing a zoster response, a zoster vaccine response, particularly important knowing that they've got an increased zoster risk. What about nipocalimab? So, nipocalimab is an FcRn inhibitor that's just had a breakthrough designation for Sjogren's by the FDA.

And by nature of what it does, it reduces IgG, clears IgG, but potentially, well, you know, maybe it might not necessarily affect the vaccine response quite as dramatically. And so what we saw in abstract number nineteen eighty eight was actually data on nipocalimab and vaccine response. And we've that actually, naturally it reduces diodesitis as it should as part of its mechanism of action. But actually, eventually patients get there. Patients eventually get that response.

And I think that gives us enormous reassurance as we start to use that. What I think was particularly depressing was data looking at a batacept. And I guess it makes sense once again, a batacept co stimulation might be important in terms of the way that we develop an immunogenic response. So, abstract number 1,009 looked at patients with recombinant zoster vaccine and nabadacept. And unfortunately, that's really depressing.

It's a bit of a swing and a miss. I think we've got to think about strategies in those type of patients when we're vaccinating them. We can't just go with a normal two dose strategy. We've got to think about how we can improve the immunogenicity, either by withholding a Baticep like we've done with microphenolate and methotrexate before then, or potentially extra doses. Somehow trying to get these people some response, otherwise we're probably wasting our time to some extent.

We've got a bit more to figure out in this space, but it gives us pause for thought, especially as we start to think about other vaccinations that have come the near future. No doubt the same is going apply for RSV, and it's still worthwhile thinking about influenza, COVID vaccination, and other vaccinations really to try and reduce any infective burden that our patients face. For plenty more on the whole meeting, you know where to go. Rheumnow.com.

Hi, I'm Quellin Connolly reporting at ACR24 with RheumNow. I am accompanied today by Doctor Lisa Christopher Stein, who gave a phenomenal talk yesterday during the great debate on the topic of mixed connective tissue disease. So Lisa, thank you so much for joining me today. Tell us what is MCTD? You know, Quellin at the end of

the day I'm not sure after the Great Debate that I can tell you cohesively. What I can tell you is that in preparing the Great Debate and in hearing from my colleagues, I learned a lot. So we classically think of MCTD as a mixed connective tissue disease. The name suggests that it is a mix of many different diseases. Classically, know that lupus, systemic sclerosis, myositis, and even maybe to some extent rheumatoid arthritis is represented in the syndrome.

But I think the reality is that it's not the right way to think about it. It's not just a mix of other things, that it is in its own right a disease. And I think what I try to convey, and hopefully swayed some who might not have thought that way is that we now understand that many autoimmune diseases that we see are a mix of several other features. We can easily say that Raynaud's phenomenon, which is found in one hundred percent of mixed connective tissue disease cases, is seen in scleroderma, myositis, lupus. It doesn't mean that in fact it's not its own disease, just because it shares features with another disease.

I try to use an example of a platypus, right. So in a platypus, we say that it can lay eggs, but it's not a chicken. It has a bill, but it's not a duck. It can actually even secrete venom. It's not a snake.

It has fur, but it's not a dog. And it seems kind of funny when you think of this analogy, but a platypus is a platypus. And what I found is that many people did not properly identify their medical platypus. So MCTD was often not identified in the beginning. It was either undifferentiated connective tissue disease, and so one thing to remember is that UCTD does not equal MCTD.

Or, it was probably always lupus or systemic sclerosis and was mislabeled. So, what happened is that many people tried to discern, if you follow people who are well characterized over time, does MCTD, this entity, stay the same? The answer is that in some studies, between sixty and seventy one percent of people maintain that diagnosis. So I think the key is to properly identify the patient in the beginning, and in fact this is its own disease. What I would say the take home for me at the end of the talk that I'm not sure I really realized as much is that we owe something more to our patients.

I try to make that point, but when a patient who was attending the conference came up to the microphone, it was a really wonderful moment, something I won't forget, where she said that she herself had, I believe as a patient of Gordon Sharp who originally described the syndrome, and she told us that she felt like she kind of never had a home because someone tried to call her maybe lupus but not quite. And I think that she represents how we should do better. The answer is whether we decide that the name is not a great name, whether we say this is U1 RNP disease, because one of the main features of the disease that is required is to have the U1 ribonuclear protein antibody. We If say this is U1 associated disease, usually in very high titer, then maybe we can start naming it. We don't even have an ICD-ten code here in The United States for that disease.

It biases against the patient, they can't be part of clinical trials, and they can't often get the medications they deserve because we don't even have a code for them. So for me at the end of the day, it was a wonderful spirited debate. I think my colleagues did great. We had a lot of fun there on the stage, but the patient at the end of the day is our focus, and I think that the woman at the microphone who came to tell us not to forget her is how I will remember the debate.

Fantastic and really helpful for all of our patients. Do you think giving people the diagnosis of MCTD, does that improve treatment or overall outcomes or not so much?

I think that's exactly the problem. I think that we actually don't have the ability to do that because we're still debating on how we even name this entity. So I think that if we can come to an agreement, ever we decide to call this overlap syndrome, then we could in fact improve treatments and improve outcomes. So I'm actually glad you asked that Doctor. Connolly because that's what we should be doing.

We should be doing better so that we can actually find those answers. I don't think we have them today. We just haven't done a good enough job.

So maybe we're getting caught in the weeds a little bit about what we're calling this but ultimately we need to characterize the patient, characterize the disease manifestations that are going to drive of our immunosuppression that will improve outcomes.

A 100% and I think we actually have precedence for that. That's what we do beautifully as rheumatologists. I think we phenotype people well. We're visual people. We take good histories.

We're very knowledgeable and observant. And I think we deserve to have this conversation to do better for the patient. Fantastic. Well, Lisa, thank you

so much for your time. And Lisa is the three hundred and thirty fourth female professor at Johns Hopkins and an inspiration for us all, particularly in the world of myositis, but medicine in general. So thank you so much, Lisa. Pleasure to speak with you as always.

Thank you very much.

So that's it for for me. Can find out more at rheumnow.