EULAR 2024 SLE Daily Topic Podcasts Save

This is the UR 2024 podcast with daily reports on lupus. This lupus podcast is sponsored by Bristol Myers Squibb. Enjoy.

Hello. Hi, everyone. My name is Youssef. I'm from Leeds. I'm reporting for RheumNow at EULA twenty twenty four Congress in Vienna, and I'm reporting live today.

This is day one of the congress, and we have had so many fantastic presentation today. But one abstract that caught my eye in the field of systemic lupus erythematos is an abstract OP zero zero seven seven. So this is an abstract pertaining to longitudinal assessment of biomarkers from the obinutuzumab, which is a type two c d 20 monoclonal antibodies in phase two randomized controlled trials called nobility. So I'm privileged today to be accompanied by the main presenter, doctor Edward Vital. Hi, Ed.

Hi. Hi. Hi, Cush. Yeah. Thank you for joining us today.

And and would you like to tell us, about the background of

the studies? Yes. So, B cell depletion has been around for a long time. We've been using it for about twenty years for lupus in the form of rituximab with variable efficacy, sometimes good. And what was shown a long time ago when I did my PhD was that it was the depth of depletion achieved that determined whether rituximab was clinically effective or not.

And what that led to is attempts to make other therapies that would deplete B cells more efficiently. And one of those is abinutuzumab. It depletes B cells better than rituximab does by a variety of mechanisms. And that's been shown to be effective in a phase two trial in lupus nephritis. Nobility, as you say, the purpose of this abstract was to show do differences in depletion and other biomarkers explain those responses.

And can you just describe a bit how do you measure the depletion in this study?

So, yeah, B cell the best way to measure B cell depletion is with something called highly sensitive flow cytometry that we've used for some time, which is a more advanced flow cytometry protocol. You have to look at subsets, naive memory, plasmablast, the plasmablast subset that have to be measured. And that was applied not on every patient in the study, but a substantial number of patients in the study got high sensitive flow cytometry at several time points up to two years.

Okay. And what was the main findings? So the

main thing was that so basal depletion was profound with abinutuzumab. Abinutuzumab was dosed at baseline at six months, and then no more abinutuzumab was given, but the patients were followed up for a total of two years. And what you see is that obviously while avenetuzumab is being given, there's profound depletion, but after you stop giving it, the depletion remains for quite a long time until they eventually repopulate similar to the placebo arm for two years. But when you look at the B cell subsets, see a different story, which is it's naive B cells that come back by two years. The memory bases and the plasmablasts remain suppressed even two years.

So eighteen months after the last dose of abinutuzumab, the memory bases and the plasma blasts remain low. And that is the pattern that we previously showed is predictive of best response to rituximab. So with rituximab, you see it on certain patients. They get that really good repopulation pattern, good long term outcome. In here, it's being seen at a group level because of the more profound depletion.

Oh, that's fantastic. So, again, this validate the importance of achieving deep depletion to obtain sustained and good clinical response. So just in term of implication of clinical practice, I know that we're all waiting for the result of phase three trial in the post nephritis that will may come out soon. In the meantime, what is your view in terms of context of, you know, how can we achieve best using the B cell depletion?

There's several interesting things here because one is, as you say, should this drug be in the clinic, phase three trial reporting quite soon, is fully enrolled. So if that comes through, we are expecting to get it as a license. We would expect to get it as a license drug for lupus derived. It also tells you something about what you need to do with B cell depletion in general, whatever drug you're doing with a condition like nephritis, it might not be just keep depleting forever and ever. It might be more like it's part of the induction phase of therapy.

And that forms part of a more wider idea about lupus nephritis in particular, which is this kind of inverse pyramid strategy where patients might start on a number of drugs. I think it's no longer correct that a single immunosuppressant like mycophenolate is correct. I mean, all patients have combinations. So, you might have mycophenolate, steroids, and then a combination drug. We've already got bulimia, lactose sporen, lysis maybe a bit of two twenty two and hydroxychloroquine, and then you start tapering things down as time goes on.

So I think that's the future of nephrolis therapy.

Thank you, Ed, for the wonderful insight and and also explaining about your work. I'd like to thank everyone for listening and tune in to RheumNow. You can follow me and also to follow RheumNow reporters and key leaders through social medias, and we'll catch up with more news from from us. Okay. Bye bye, everyone.

Bye.

Hi. I'm doctor Janet Pope. I'm reporting at RheumNow here in beautiful Vienna 2024 Yular. I want to tell you three things that I think might be the cool hot topics in lupus at this meeting. So there's three areas.

One is biomarkers. One is is prednisone poison or not. And the third one is really looking at under treatment of membranous lupus nephritis. Let's talk about membranous lupus nephritis first. That's poster seven thirty two.

That's the Toronto cohort. And what they're finding is that when they've looked back over the years, that membranous also has a poor prognosis, not as poor as GN, but not as good as we might have thought. And maybe that's food for thought that we should be giving more immune suppression to that group. The next thing is what about biomarkers? So there was one biomarker study looking at IL-sixteen in the urine of patients with GCA.

And it has been found in last year and in other years that it's an important biomarker in urine and lupus patients. But there was a soluble biomarker study this year, OP0255 And it really is not ready for prime time in my opinion because it's hard to know is this validated but it did find big differences but you know some of these cytokines can change over time. We'll see. The final thing is prednisone. Is it good, bad, or ugly?

Certainly in all the guidelines, including EULAR guidelines, least amount of prednisone is the best. So Monash and his group looked at the Pacific Australia lupus patients who are a really large cohort now. And what they found was that if they looked at patients in low lupus disease activity of seven point five milligrams a day or less of prednisone, or they looked at a group of five milligrams a day or less of prednisone, The bottom line is they found that damage was no different between the two. There's a caveat though. Of the thousands of patients visits, one hundred and four of the patients only were between five and seven point five milligrams of prednisone.

So everybody else is included twice in the less than five or the less than seven point five. So I don't think we have the answer out. And for now, what I would say is prednisone, the least amount that keeps your patient in a good disease state is the best. Great. Thanks.

Follow me. I'm JanetBurdo. Thanks.

Hi, I'm Jack Cush reporting to you from Vienna and EULAR twenty twenty five. It's the first day of the meeting. A lot of interesting things. I heard a message several times today and the message being our thinking on steroids and lupus is changing. One such abstract where that's portrayed is this abstract, OP 59.

It was an oral presentation, in a lupus session, presented by, Doctor. Askenazi with other authors being Ken Colounian and Maria Gallara talking about how we treat lupus nephritis patients. This is a reanalysis of data already presented. One study being the ALM study and two other studies were the Aura LV study and the AURORA-one. In this study, they did a propensity matching, and they compared the ALM study to one hundred and seventy nine patients to one hundred and seventy nine in the Aura LV plus AURORA one study.

And they wanted to look at outcomes, renal outcomes, which is the primary endpoint, but also side effects and whatnot. The main differences were A) in the immunosuppression. Study received either up to three grams per day of mycophenolate or IV cyclophosphamide and a higher dose of steroids starting out at sixty milligrams per day, lowering every two weeks until they got to ten per day, but with not a lot of success and a lot more overall steroid exposure in the ALM study. That was compared to the ORA LV and the AURORA one, where the patients received, two grams of mycophenolate plus voclosporin, the lower daily dose, plus steroids starting at twenty five milligrams per day, and then decreasing down over sixteen weeks to two point five milligrams a day. That second group, the oral LV or oral one had less steroid exposure, but also had the addition of the voclosporin.

They call that triple therapy. I don't know if I agree with that. Mycophenolate and voclosporin, that's double therapy. Adding steroids to that, I don't think that we're using enough steroids to consider for this to be truly immunosuppressive, but they called it triple, with the third big drug in there being steroids. The end result of this was that there were more side effects AEs, in the ALM study than in the other two.

SAEs were the same, serious adverse events were the same. But the AURORA LV and the AURORA one, had urinary renal endpoints and that being a 50% reduction in UPCR and whatnot, and overall had less steroid toxicity. So yeah, it makes sense to use combination immunosuppressors and lupus nephritis. But I think that you're going to hear at this meeting as you get from this particular trial, that limiting steroid use is going to be important in the overall success. And success is not just measured by getting to that renal endpoint, but also how much toxicity you're going to incur along the way.

Anyway, that was an interesting one from ULAr twenty twenty five. Tune in for more at RheumNow.

Hi. I'm at Janet Bourdeaux is my ex name, Janet Pope. I'm reporting for At RheumNow at ULAr twenty twenty four in Vienna. I wanna tell you about JAK inhibitors for new indications. So there's three newer indications that you might or might not be aware of.

Baricitinib has been approved in some jurisdictions for alopecia areata, four milligrams a day, no cardiovascular or VTE signals. And the SALT score, which is the proportion of alopecia left behind, was quite a high level where patients did very well and obviously better than placebo. So there's hope for our patients with autoimmune alopecia. The next thing is upadacitinib has been approved for Crohn's disease. And Crohn's disease has an outcome called C.

Dies. So not our clinical disease activity score, but it's a Crohn's score. And the word on the street is that looking at the positive RCTs of upadacitinib at thirty or forty five milligrams a day for induction is that the scores were rapidly improved and far higher than some of the other comparisons that the Crohn's docs are used to. So keep an eye in that space. Then also hot off the press in June 2024, AbbVie announced that upadacitinib is now indicated for kids greater than or equal to two years with active polyarticular juvenile idiopathic arthritis, as well as psoriatic arthritis in children.

And so that's pretty interesting. Tofacitinib about a year ago in 2023 was also approved in polyarticular JIA. The newest thing is not an approval, but a positive study. So in April 2024, the phase three trial of GCA for upadacitinib usage, which was called SELECT trial, showed positive results in patients with giant cell arteritis. What else is happening in JAKs?

The JAK inhibitor upadacitinib and the tip two depravacitinib are moving into lupus trials. They're already in phase three. The trials are recruiting or maybe are even nearly recruited. So we'll have data in a year or so. Lots of new indications for JAK inhibitors.

Keep your eye on this space. Janet Pope reporting. I hope you'll continue to follow us at RheumNow. Thank you.

Hello. My name is Rinalini Day. I am a rheumatology fellow from King's College London in The UK. And today, I am going to be talking about one of the posters that were presented at EULAR this year. It's 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 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. 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 zero one eight zero. 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 Afava. I'm a physician scientist from Johns Hopkins, connecting here from Euler 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 there has been, 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 they started from a previous experience from a Toronto cohort, the cortical loop trial, in which patients who were on remission but were still on fivoprednisone 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 patient 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 seventeen, 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 patients 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 protected 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 Lucio in which they are looking at the value of per protocol repeat biopsies after one year of treatment to decide eventually how, 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 the 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, 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, 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 monogenic defects 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, other manifestations that are more auto inflammatory, but this concept is expanding, to all other rheumatic autoimmune condition that we treat in our 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, and so we don't get the virus again. And so you can think about that, for example, when we have autoimmunity, like such as autoimmune thyroid disease, where there are antibodies that are targeting one organ that can be directly pathogenic.

Whereas auto inflammation, think about, familiar Mediterranean fever where there are like bouts of fevers that are abrupt at the molecular level, they are 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 a noninflammatory 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 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, 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, a 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, they 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 a 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 serves to, 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 we 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 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 of our diseases 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 precision medicine 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 Jus Yousuf. I'm a consultant rheumatologist from Leeds, United Kingdom. I'm 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 Shet'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 patient 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 would 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, and 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, yes, 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 potential 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.