EULAR 2026 Daily Podcast Day 2c Save

You're listening to a RoomNow podcast coming to you from London and EULAAR twenty twenty six. Enjoy.

Hi, everyone. This is Aurelie Najm from Scotland reporting live from London, EULA twenty twenty six, and I have exciting news for you. And the exciting news is there was a late breaking abstract presenting a head to head trial of two different mechanisms of action in PSA that are not TNF. So effectively the presentation, which is LB0001, was the trial called B BOLD, and B BOLD was boldly comparing bimekizumab, so dual IL-17A and F inhibition to rizenkizumab, which is IL-twenty three inhibitor, and I'm actually really excited about this trial because it's giving us information that we can directly take home and potentially implement into our practice, or that certainly will be implemented into updates of recommendation for management of PSA. But certainly what was interesting was this phase 3b study recruited five fifty three patients that were randomized with active PSA, they were TNF naive or TNF inadequate responders, and the study had a primary endpoint of ALCR50 at week sixteen, and so quite interestingly the results are clear fifty percent of ACR50 response at week sixteen in the bimekizumab arm versus 38 in the rosenkizumab arm, so quite effectively demonstration of superiority of bimekizumab.

More patients also achieved secondary NPONS such as ACF50 by week four twenty versus seven, DAPSA lower disease activity remission sixty five percent versus fifty four percent, and then the combined joint and skin response as well. The minimal disease activity was not statistically superior, but numerically higher. The safety profiles really were quite similar, or at least as expected, with obviously more candida infection due to IL-seventeen inhibition, but we know that really. But there was no new safety signal, and I think there's been a lot of head to head trials we've seen, especially in RA, where it's actually quite unclear. For example, this one that was presented in the RA session earlier at the conference, OP0205, which was a non inferiority trial of tocilizumab versus cebatacept, and the results are, you know, you can sway one way, you can sway one other, but I think this is a trial that has very clear results and I'm just quite excited for us to see how this is going to shape the recommendation and the way we care for people with PSA in the future.

In the meantime, I invite you to follow me on twitter orilyromo and follow RheumNow for more EULA twenty twenty six related content. Bye!

Peter Nash reporting for RheumNow from EULA, London twenty twenty six. The first abstract I want to cover is one of my favorite topics. Jack has talked about it very frequently, I think it's time for rheumatologists to step up and get involved. My attention to this was drawn by Canadian abstract of 10,000 diabetics who had autoimmune diseases, PSA, axSpA, lupus, RA, and the diabetics who are on the GLP ones had less death, less stroke, less heart attack, I started getting interested. PSA metabolic syndrome, it's common and important and very important to patients' outcomes.

Now there's an o p o one eight seven by Gurai Man presented at this meeting, which looks at the predictors of the one year response to disease activity using AI tools from the SPEED trial. Now the SPEED trial compared three arms, step up conventional synthetic DMARDs, combination of conventional synthetic DMARDs, and early TNF use, and guess what the predictors of response were at forty eight weeks. They looked at all the usual things, age, gender, disease duration, treatment, BMI, smoking, alcohol. And number one predictor of who would respond in those three arms of treatment was BMI. Guess where treatment came?

Number six. Age was number two, and baseline disease activity was number three. Now the people with the worst outcomes were those with the highest BMI, the longest disease duration, polyarticulin age. So this is trying to tell us that BMI is important and even more important than treatment arm, including TNF, in patients, with this active disease looked at in this study.

Hey there. My name is Al Kim. I'm at ULAR twenty twenty six in London, UK, and I want to bring up another topic within the cellular therapy space that I found very interesting. Two different abstracts about how what happens when CAR T cells don't work, right? And then how do you manage their disease recurrence?

So again, there are these two abstracts. The first one is OP-seventy six, oral presentation 76. It was provided by Doctor. Andreas Vershing, named The Management of Relapses After Autologous CD19 CAR T Cell Therapy and Lupus, Scleroderma and Inflammatory Myopathies, a case series. And then second one, another oral abstract, OP-three 33, that was presented by Doctor.

Denae Mona Nutheng entitled The Phenotypic Changes of the Peripheral B Cell Compartment Precede the First Case of Relapsed Lupus After CD19 CAR T Cell Therapy. Okay. So this is two reports coming from Erlogen. Alright? So Erlogen has probably the most patients, at a single center that has treated autoimmune diseases with either CAR T cell, CAR NK cell, or a T cell engager.

And in this case, we're focusing just on CD19 CAR T cells from a CD19, yeah, CD19 CAR T cells that is an autologous source. And so here, from a single product, they have fifty patients that were treated. And out of those fifty, pretty remarkably, only six has demonstrated a relapse. And it's not the same across all autoimmune diseases. Here in lupus, they had one out of twenty eight with a relapse.

In scleroderma, they had two out of fourteen with a relapse. And in the inflammatory myopathies, they had three out of eight with a relapse. So the median time to relapse across all these diseases was thirteen months. And what's interesting here is what they did in order to get these people back into complete remission. So for the three patients that had myopathies and relapsed, one of them at nine months, another one at ten months, another one at eighteen months after getting the first CAR T cell therapy.

Two of them got a BCMA CAR T. So remember, CD19 does get one type of antibody producing cell called a plasmablast plus every single cell that is preceding a plasmablast, including the pre and pro B cell in the bone marrow. If you did BCMA, this takes care of some of the plasmablast but also primarily the longer living antibody producing cells called plasma cells that are living in the bone marrow. And you can start thinking already the differences that you would have in terms of why you would want to do one or another. If you are targeting CD19, you're making an argument that the pathogenic autoantibodies are coming from plasmablast or that there are pathogenic B cells that aren't making antibodies.

And lupus is the best example of this. And again, this Erlagan experience highlights that, that only one out of twenty eight relapsed with a CB19 approach. But if you think that your autoantibody that's pathogenic is coming from a plasma cell, you have to use a BCMA approach. And again, with inflammatory myopathies, two out of the three received a BCMA CAR T cell and then one of them had a sustained drug free remission. The second one actually initially started on tofacitinib before getting the BCMA CAR T, relapsed after three months of TOFA therapy, got the BCMA CAR T and it's too early, unfortunately, to report whether or not they went into remission based off of the abstract submission.

The third one actually got a completely different regimen. This participant got obinutuzumab plus natezumab, which is going to be your anti fibrotic. And this person actually interestingly improved. The lupus patient relapsed at nine months after getting CAR T cells and then got BCMA CAR T and significantly improved with exception of a mild rash. That was treated with anifrolumab and then the patient went into remission after that.

The two patients with scleroderma, one of them relapsed sixteen months, the other one twenty four months after getting their CAR T cells. Both of them got BCMA T cell engagers, and they both improved. So I think what this is telling us is that you could potentially rescue these people by using a BCMA approach because the the whatever is creating the pathogenicity of their autoimmune disease is coming apparently from this bone marrow compartment. So using BCMA may be the best choice for this. Now, you can argue, why not just target BCMA right after that or even a CD19 and BCMA dual targeting either CAR T cell or T cell engager?

I will tell you the toxicities are not trivial with BCMA across the board. You will one hundred percent have hypogammaglobulinemia and a higher rate of infections. I guarantee you that. Right? Is this something that your patient will want to sign off on when the majority, alright?

We're talking nearly ninety percent of patients treated across the spectrum, at least in the Erlogen experience across different diseases, responded to just CD19 where you don't have to worry about hypogammaglobulinemia or those infections, right? So it's an interesting question. So the second abstract presented by Doctor. Nithing was a case report of one of these lupus patients in a different study. There were 11 patients with lupus that received CD19 CAR T cells.

One of them relapsed at day two twenty six clinically after getting CD19 CAR T cells. Now, interestingly in this particular person, several days before, she actually had a routine per protocol collection of her blood and they did immunologic analysis of that preclinical FLAIR blood sample, they actually found pathogenic B cells, memory B cells, atypical memory B cells in that patient before the clinical FLAIR. So here what you are showing is that there pieces of information that suggest immunologic flare that then actually preceded the clinical flare here. So this actually opens up a really interesting and important opportunity for patients that want to think about CAR T cells or T cell engagers is that there may be a way through labs to predict and detect pathogenic B cells or even rises in autoantibody level that then end up having, you know, allow you to anticipate clinical relapse, right? So, you know, again, this is a we've been waiting for these type of data to show up because I think there's been so much discussion about how CAR T cells in particular is kind of a one and done therapy.

It is not. For the majority, maybe, right? But there's an important minority of patients that are relapsing. And it looks like there are ways to be able to get around that. But more importantly, I think there are ways to potentially think about how we can screen in this particular setting using immunologic assays to predict whether or not someone will relapse clinically, and then you can get ahead of the game.

Thanks.

Hello, everyone. My name is Youssef. I am associate professor and consultant rheumatologist in Leeds. I'm reporting for RheumNow at twenty twenty six EULA Congress in London, United Kingdom. Today, I would like to discuss an abstract titled o P076.

So this abstract is about reporting the frequency of relapses after CAR T cell therapy in autoimmunity and also how to manage these relapses. As we all maybe already be aware that back in 2021, the first patient with SLE was treated with autologous CD nineteen CAR T, and the result was presented the year after that the patient was in drug free remission. So we are optimistic about the study initially that this may be a really dramatic changing in the treatment paradigm for lupus. Fast forward five onwards, we now noted some report, small cases that patient had relapsed, particularly a patient with inflammatory myopathies. So in this study, there were fifty patients that were treated originally at Erlangen using autologous CD19 CAR T cell.

A majority of them were patient with systemic lupus erythematosus, second followed by systemic sclerosis and also autoimmune myopathies. So in this longer term data up to over four years follow-up, they reported the frequency of relapses about six out of fifty patients amounted to twelve percent. And the relapses were mostly from the patient with autoimmune myositis, particularly with anti synthetase, three of them, two patients with systemic sclerosis relapse and also one patient with lupus relapse. And when we're talking about these relapses, they were, they were not minor relapse. They were a significant, you know, for example, the patient with lupus had new onset transverse myelitis and also cutaneous lupus, whereas some other patients with anti syphilis syndrome had relapse of myositis and also interstitial lung disease.

So these are really severe relapses. And what they did in this cohort were that they were treated predominantly with the BCMA autologous CAR T therapies. And also two of the patients with scleroderma were treated with BCMA T cell engagers. And these patients responded to all these therapies. So really, the questions you know that that we are wanting to discuss in in this video is one.

We thought that these are all these cardio therapies going to be eternity. Unfortunately this is not the case. Particularly in the field of autoimmune diseases. Secondly, the success of treatment with BCMA therapies might pose the questions that should BCMA targeted at the first instance as an antigen in T cell therapies. And thirdly, these patients have had, to go through, you know, the process of CAR T cell therapy in the beginning and with the median relapse of thirteen months and subsequently had to go different therapies, which is more intensive.

We also have to pay attention in terms of safety profile, particularly long term reduction in terms of IgG level on infections. So only time will tell. So I hope you found my video summary interesting about this progress. Follow us follow RheumNow on the social media outlets for more Congress content. Bye bye.

Hi guys, this is Aurelie Naj from Scotland live at day two of '20 '26 in London. What I really like about EULA this year is that they have very nice abstract sessions, and there are not that many of them, so I had the chance to go and sit for a whole RA therapeutic session looking into different things. And one abstract that really, really caught my attention was OP two zero four. So it's another study from The Netherlands, and it's a randomized controlled trial. But what is very special about this one is that it's about shared decision making.

A lot of the time when you look at shared decision making and what is patient preference, it's a qualitative study or it's a survey. For it to make a whole RCT out of it, thought it was actually quite impressive. It was aiming at answering a very simple question: if you do give people choice of what drug they want to take, is it better for them? And they were looking at that in different ways. Were they more satisfied?

Was it working better? Were they staying on the drug for longer? We know it's important because drug retention in rheumatoid is amazing, you know, especially the first and second drug is not really great. So we want to find ways and means for people to stay on these drugs if they're responding to them. So they took 50 people in each group, one group where they would just get the drug based on the doctor's prescription and decision, and the other one where patients would be given a link to a three minute video.

So it's not like a long education program, it's a three minute video online, and then they get leaflets about each drug, and then the choice was given to them whether they would receive filgotinib, or JAK inhibitor oral, or subcutaneous TNF inhibitor, and one of the worries of the investigators was that potentially patients would not be able to choose. And that's something I've observed in my practice when I say to people, so what do you think? Would you rather do this or do that? They say, oh I don't know doctor, would you tell me what I need to do? So I think it takes maybe a specific population to do that, but also it sometimes takes to give them the information in the first place in a way that is very condensed and digested.

Anyways, in forty eight hours 50 people had made a decision of what they wanted, fifty five So twenty eight people wanted JAK inhibitor oral, twenty three-forty five percent wanted the injection, so it's about fifty-fifty really. But those who had chosen their drug were more happy, more satisfied, they switched their treatments less, they had less side effects, and I think this is a really important one, less reported adverse events over the course of the follow-up, and a better overall survival of the drug, and I think this is also really important. When this started this study, it was before oral surveillance, so obviously they had to refine a little bit who they were offering JAK inhibitors to. But overall, I think it's a very successful study and this is something that for me I will take back home for my practice and try to give people more choice, providing we get adequate information for them. In any case, I invite you to join me on Twitter aurelyromo, join the RheumNow website for a lot more content about the Congress, and I'll see you around.

Hey there, everyone. My name is Al Kim. I'm one of the leads for cellular therapies and cellular approaches to treat autoimmune diseases, and I'm reporting from UR twenty twenty six in both rainy and sunny London, UK. And we have a series of topics that we're going to be able to present over the next few days related to abstracts that are being presented at EULAR. And the first one I want to talk about today is actually going to be four different abstracts, but all related to the exact same product, which is actually a natural killer cell product, and I'll get more into the details of that.

So the title of this presentation is going be Another Way to Leverage NK Cells to Kill B Cells, This Time Without CARs. So what's the background behind the story? So you may remember in our immune system, we have two cells that are cytotoxic, I. E. They can directly kill another cell.

One of our T cells, specifically CD8 positive T cells, you know, these are leveraged in CAR T cells quite successfully in certain diseases. And then the other one are NK cells or natural killer cells. These have been used as CAR NK cells, but in this particular set of abstracts, there are data here that leverages a unique natural killer cell that does not have a CAR, but it's used to deplete B cells. So welcome to AB-one 101, which is the name of this particular product, which is a combination of NK cell therapy plus rituximab in both difficult to treat RA, scleroderma and Sjogren's disease. So the specific abstracts that we'll be covering is going to be poster eleven seventy seven, which is presented by Doctor.

Guillermo Venezuela, late breaker abstract number three, and oral presentation 129, both of them presented by Doctor. Norman Galis. And then poster three fifty five by Doctor. Geratas. So the reason why there are multiple abstracts, I'll get to in a second.

But let me first talk about what AB-one 101 is because this is a pretty ingenious way, if not a little complicated, to be able to leverage the NK cell to kill B cells. So AB-one 101 is a non genetically modified, I. E, it does not have a CAR construct. So it's not a CAR NK. It's just an NK cell That is allogeneic.

It comes from a healthy donor that's given to a different recipient, alright? The patient. Natural killer cell therapy that's derived from cord blood units. What's unique though about this type of cell is that it has a polymorphism in its FC receptors specifically an amino acid 158 that confers enhanced affinity to the FC portion of IgG. Now, you may have thought, I think I've heard about this before.

The type two monoclonal antibodies like obinutuzumab, inebilizumab, those are antibodies where there's a fucose missing, I. E, they're a fucosylated IgGs, that also then confers enhanced binding to Fc receptors on natural killer cells. So instead of modifying the antibody, I. E. Type two monoclonals, we are looking at the same goal but from the opposite lens, I.

E. What you're doing is using a specific type of Fc receptor that has high affinity on the NK cell. So here, what you're able to do is use traditional B cell killing monoclonal antibodies such as rituximab instead of obinutuzumab in order to enhance killing. So the outpatient treatment regimen is complicated, though, and I think this is something that we need to talk about future wise. So first of all, they get lymphodepleting chemotherapy, both of fludarabine and cyclophosphamide, immediately get chased by rituximab.

And then after that, they get three weekly doses of this NK cell, the AB101. It's 1,000,000,000 cells given at day three, day thirteen, and day twenty. So it's a pretty complicated process. But one of the interesting advantages of this particular regimen is that it can be done all as an outpatient, right? And so you don't need to hospitalize patients for this.

So let's focus on the RA, the LB003 abstract that was presented by Doctor. Galis. And in this particular abstract, what they were able to report is six participants with difficult to treat rheumatoid arthritis. All of them were able to continue their conventional background therapy, which is going to be a standard DMARDs. And what they showed were a couple of things.

First, safety wise, there was no cytokine release syndrome, no ICANS, no hypogammaglobulinemia, graft versus host disease, or any serious adverse events. This is exactly what you want if you want a pure outpatient regimen, right? The other thing, nothing that's going make you concerned where you have to give something like tocilizumab and hospitalize them. There were a few adverse events related to the treatment. Six nausea, four headache, three UTIs, two diarrhea, two vomiting, all of them grade one or two.

So they weren't very significant. The B cells that were detected by a highly sensitive assay were completely gone in these patients by day twenty eight. And then B cell reconstitution was observed about six to twelve months later. So what's interesting is when you look at the therapies that they were on, three out of four were able to discontinue their background therapy and all and then three out of three were able to stop glucocorticoids but only four out of six was able to achieve moderate disease activity from high disease activity and that was the best they got. So most patients got better, but they didn't go into remission and they certainly didn't even go into low disease activity.

So efficacy is a bit of concern with this. They also report in other abstracts at EULAR a good response in a single Sjogren's disease patient and a single scleroderma patient. So this is something that may be disease dependent. We've talked about in prior discussions, especially at ACR, where maybe targeting BCMA may be important here for RA versus CD19 and other autoimmune diseases. So, you know, this abstract is interesting because it's a complicated regimen but can be done purely as an outpatient.

The safety confirms that, at least based off these small ends. And it looks like that the issue here, at least with the RA, is going to be the efficacy. And again, this may be a target issue. So this opens up a few questions, right? First of all, wouldn't the lymphodepleting chemotherapy or LDC deplete the B cells themselves, right?

This is chemo. And you're right. The answer is correct. But it only does it in the privy, I. The blood.

Lymph node B cells, tissue based B cells, they aren't touched by lymphodepleting chemotherapy. So, this is reason why the NK cells needed and then, the second issue is, okay, yeah, we talked about how complicated this regimen. Why not just use obinutuzumab, right? Isn't this just obinutuzumab except you're taking advantage of a high affinity Fc receptor on a natural killer cell? Well, you may not get as much cytotoxicity possibly due to the fact that you're not having enough NK cells.

A billion NK cells were injected three times over a three week period. So if you wanted to say, you know, I I think I can make this work with an obinutuzumab approach. You know, I can mobilize highly cytotoxic NK cells from the bone marrow using IL-fifteen superagonist. It's actually called N-eight zero three. So one has to wonder whether this approach, you know, could be used and, you know, be able to completely avoid the need for lymphodepleting chemotherapy because you get the injection of obinutuzumab, you get the injection of the IL-fifteen superagonist, and now you have all of these NK cells coming out that are gonna act on the obinutuzumab.

Maybe, maybe not. And then the other thing you might be thinking is that why not just combine AB one hundred one with a type two monoclonal antibody with obinutuzumab? This might enhance efficacy, but as we've seen with the CAR NK cells and T cell engagers and CAR T cells, when you have a more cytotoxic or better killing product, you may have higher rates of cytokine release syndrome and other related toxicities that render this approach impossible to do completely as an outpatient, right? So that is something to consider. So regardless, though, this is a really interesting approach and the innovation that we're seeing in this field to be able to enhance B cell depletion approaches, that's beyond what is currently available.

Thanks.