RA Topic Podcast compilation Save

You're listening to a RoomNow podcast coming to you from London in EULAR twenty '26. Enjoy. Hi, everyone. Welcome to EULAR 2026. I'm in London.

We're gonna do a little preview of the meeting that starts tomorrow, Wednesday, and, we've been over the program. There's a lot of really exciting stuff. I'll just give you some highlights of things I'm gonna be looking forward to, things that I think are maybe game changing in rheumatology. Two late breakers, actually there's a bunch of late breakers that come to mind. The Be Bold data is going to be presented by Joe Marola on Saturday.

There are other late breakers that also look really, really good. I like the, Jack Spare study, that's, LB005. This is a, phase three trial of baricitinib, given to people with early PMR. They have less than three weeks. It's a 46 patient study, it's not a big study, but they, either get Barrie four milligrams or placebo for sixteen weeks, and then part two, they either continue or they crossover.

The primary endpoint is glucocorticoid free remission, and Barry is a clear cut winner. And it's not surprising that a JAK inhibitor would work. There's a lot of other data out there about other JAK inhibitors working, in polymyalgia rheumatic, and I think it will be something we'll see more of in the future. Another really important abstract that's coming up, as part of the late breakers is a long awaited study as a follow-up to oral surveillance, where we found out that JAK inhibitors don't do as well as TNF inhibitors when it comes to cardiovascular outcomes and cancer and infection in high risk individuals. The follow-up to that, another big study, not with tofacitinib but with baricitinib, was a regulatory commitment by Lilly to study baricitinib and its venous thromboembolic risk.

So, they set up many years ago these studies called RA Bridge and RA Branch, it's baricitinib versus TNF inhibitors in over, three thousand five hundred patients who have risk factors for VTE events, DVT, PE, and so we're talking there age, BMI, are the main risk factors, oh, and having had a prior event. And the bottom line on that study is that it confirmed what we already know. Baricitinib was the first of the JAK inhibitors to be, labeled, and right out of the gate, labeled with a VTE risk and warning, and this study confirms it, but interestingly, again, another high risk population, they were average age around 60, but it did not show, this study did not show that baricitinib compared to a TNF inhibitor was associated with either a risk of, cardiovascular MACE events, cancer events, or, it did show infection, serious infectious events, but did not show an increased risk of, of, opportunistic infection. So, in some ways it argues against the data for the oral surveillance study, but those are two very important studies that I think will be coming up this week as late breakers. There's a lot of data that I'm going to be covering with my colleagues on ILD.

The bottom line there is it looks like all the risk factors everyone's saying, suggest, yeah, risk factors for ILD in RA is being male, being older, being seropositive, throw in their smoking, throw in their disease activity, and now you've got the profile. The question is, who needs to be screened? There are a number of studies here this week that look at that issue they and all say the same thing, ACR guidelines says you need to have one risk factor, the, ERS UR guidelines from last year say you need to have two risk factors, but the bottom line is that almost all RA patients have one or two of these risk factors. Does that mean you do high risk CT in everyone? Well, remains to be seen.

I like this report, it's going to be, an oral presentation maybe tomorrow, on, it's called the Sun Star Study, and it is a head to head study of, Tocilizumab or abatacid after someone fails a biologic or targeted synthetic, and turns out in this study ninety five, ninety six percent of people were TNF inhibitor failures, and it looked like there was no real difference except for when you do the analysis a new way, a different way, there was an edge for Tocilizumab, but we need to cover that to see where that's gonna go. Other things, there are a lot of studies that have been recently published that are going to get big airtime at this meeting. The Together PSA study, that's the combination of, tirazepatide and the IL-seventeen inhibitor, ixekizumab. That data is going to be presented in full here, the AFFINITY study of, with golimumab, the what else? There's another one that's out there that's going to be presented, again, but I like this, data on, there's going be follow-up data.

There's a lot of CAR T cell therapies and B cell depletion therapies, and everybody's excited about it except for me, because one, we're a long ways off from seeing CAR T cell in the clinic. Two, I'm not seeing studies that are of good controls and are blinded. I'm seeing, you know, 12 people with Munchausen Syndrome getting CAR T and being cured. I'm making that up, that's a joke. But it looks very good, as you would imagine, in lupus, and, somewhat good in scleroderma, maybe not so good in the synthetase myositis patients, and a big question about what it's going to do in RA.

The early report on the what's going be presented here is a small study showing that not everybody gets better but a few people do, and the question is who are they and why are they getting better? The Neptunus study, in Sjogren's Syndrome, there'll be a number of Sjogren's presentations. Neptunus was presented at ACR, that's, enalumab showing its success, now they have some long term data that they're gonna, look at. They have teletacept in Sjogren's, it's also gonna be presented here. And what else?

An anifrolumab study with Sjogren's. And then the, Phonics study was just recently presented, and that's going to be shown here as well, and that seems to look good as far as the data goes. So, this is how you can best follow, EULAR, when you're not in London with a few of us who are here. I think the best way depends on how you like to learn. The Twitter feed's gonna be active, the RheumNow faculty is gonna be out there, they're gonna do, you know, six, seven, 800 tweets, you can follow that.

There'll be daily recaps starting Thursday night, we're gonna do a day one, day two recap that will, play Thursday evening, probably 7PM, and then there'll be a day three recap on Friday and a day four, final day recap, on Saturday. The recap is where a few of the faculty and myself get together and say, what was great today, and what do you want everyone to know about? There'll be great articles that you can follow on your phone and, on the website, and they'll come to you as emails. And the other way to follow is, to look at take the quiz at the end of the week. Do the weekly quiz on this Saturday and next Saturday, and you'll learn just by doing 20 or 30 quiz questions about, what the take home message from the meeting was.

Anyway, it's gonna be a fun time in London. Hopefully, you'll have fun listening to our coverage. Take care.

Hello, my name is Rinalini Day. I'm a fellow in rheumatology and internal medicine working in King's College London in The UK. And I'm delighted to be reporting from EULA twenty twenty six for RheumNow from here in London. And today, I would like to highlight one of the imaging abstract, imaging abstracts being presented at ULA twenty twenty six, and this comes from the Mayo Clinic. It's OP zero three four eight.

So this work used advanced CT based body composition analysis to better understand how rheumatoid arthritis alters fat and muscle biology. So we know from many prior studies that body composition does change in rheumatoid arthritis. And most of these studies have relied on the use of BMI or DEXA scans, for example. But importantly, these approaches can miss important differences in where fat is distributed and how healthy muscle tissue, actually is. So here, the investigators analyzed, abdominal CT scans from almost 900 individuals using a validated deep learning segmentation approach to quantify subcutaneous fat, visceral fat, intermuscular fat, muscle area, and muscle radio density.

The key finding from their study was that patients with rheumatoid arthritis had a very distinct body composition profile compared with matched non RA controls. So they had significantly more subcutaneous fat, more intermuscular adipose tissue, and essentially fat infiltration, between muscle groups, and lower muscle radio density, which is a marker of reduced muscle quality or myosteatosis. Now, what is particularly interesting here is that overall skeletal muscle area and visceral fat were not significantly different. So, rheumatoid arthritis seems to be associated with a qualitative remodeling of muscle and fat tissue that conventional metrics like BMI, which we are so used to measuring, may completely actually fail to capture. And that matters because clinically, intramuscular fat accumulation and myosteatosis are increasingly associated with frailty, disability, insulin resistance, and cardiovascular risk.

So this does have important implications for our rheumatoid arthritis patients, for the development of comorbidities, which, of

course, we know that they are already presusceptible to. It may help explain why some patients with rheumatoid arthritis appear metabolically unhealthy despite having relatively normal body weight. Another important aspect is the imaging methodology itself. So the use of deep learning CT segmentation allowed detailed phenotyping, in this case, from

routine clinical imaging, suggesting that opportunistic CT analysis could eventually become a scalable way to identify high risk metabolic and musculoskeletal phenotypes in people with rheumatoid arthritis. So overall, this study shifts that conversation away from simply looking at just obesity or sarcopenia, but towards understanding how chronic inflammation may fundamentally alter tissue composition and muscle quality in ways that are very clinically meaningful. So if you want to know more about this particular work, it is OP0348 in the imaging abstract session. And if you'd like to know more about everything going on here at ULAr twenty twenty six, do be sure to follow us along on RheumNow.

Hello. I'm Jonathan Kaye reporting for RheumNow from London on first day of EULAR twenty twenty six. The meeting got off to an excellent start with many interesting presentations. As expected, there are many presentations at this meeting about CAR T cell therapy for a variety of rheumatologic diseases. Georg Schetz Group in Erlangen has published their impressive and dramatic results with CD nineteen CAR T cell treatment for lupus, scleroderma, and idiopathic inflammatory myopathies.

At the plenary session this afternoon, Fredrik Albach of the Department of Rheumatology and Clinical Immunology at Charite in Berlin presented the phase one results of their COMPARE trial, which evaluated mivoc aptagene otilucel, a human CD19 CAR T cell treatment, in six patients with ACPA positive treatment refractory active rheumatoid arthritis. Patients received lymphodepletion with cyclophosphamide and fludarabine followed by infusion of the CAR T cells. The primary endpoint was safety, and secondary endpoints were clinical and biologic efficacy and a reduction in ACPA. All patients were followed for at least thirty six weeks, and two were followed for fifty two weeks. There was robust CAR T cell expansion with depletion of CD19 positive B cells from both peripheral blood, bone marrow, and synovium.

All six patients experienced a rapid decrease in disease activity with a median DAS28 CRP reduction of nearly 50%, and imaging confirmed the reduction in joint inflammation. By thirty six weeks, four of the six had achieved an ACR 70 response. All patients were able to discontinue DMARR therapy with continued control of disease activity. Only one experienced a flare that required a brief period of treatment with corticosteroid. The treatment with CAR T cells was well tolerated.

Cytokine release syndrome was limited to mild to moderate events, and there were no unexpected toxicities or cases of neurologic toxicity. There was a marked reduction in ACPA and rheumatoid factor, but not in antibodies to tetanus, suggesting that there are different mechanisms for the development of autoantibodies and protection from vaccination. These results in rheumatoid arthritis are similar to the early results in lupus and other rheumatologic diseases. However, this phase one study treated only six patients and was open label without a control arm. Phase two is ongoing, in which five patients will be treated with CD19 CAR T cells, and five others will be treated with rituximab as a comparator arm.

It is most impressive that CD19 CAR T cell therapy results in deep tissue depletion of B cells and allows for complete discontinuation of DMARD therapy. The prospect of long term drug free disease control may make this treatment attractive to patients with difficult to treat rheumatoid arthritis. However, it requires leukapheresis and generation of the CAR T cells as well as pretreatment lymphodepletion. Availability of off the shelf allogeneic CAR T cells should make this approach to treatment more feasible. I look forward to seeing the results of additional studies of CAR T cell therapy in rheumatoid arthritis and in other diseases.

For more information about this and other studies presented at EULAR twenty twenty six in London, go to RheumNow dot com. I'm Jonathan Kaye reporting from London. I look forward to seeing you tomorrow. Thanks.

Hello. This is Nelly Ziade reporting from EULAR twenty twenty six in London for RheumNow. I had the pleasure to attend today to be part of a session called This is a Woman's World. So the EULAR Congress dedicated an entire session to women's health and rheumatic diseases. It was one of the most clinically rich sessions at the meeting.

From pregnancy in RA and axSpA to the impact of perimenopause on PSA, this session titled This is a Woman's World made clear that sex and reproductive stage are not just footnotes in rheumatology, they are central to disease management. I will start with the talk of my team, AHPRA fertility and pregnancy. So this is OP0245, the ARCH group study. The ARCH group included five nineteen patients with AHPRA who had ever attended conception, recruited from 26 centers across 15 Arab countries. So this was a multinational effort.

We found that fertility and pregnancy outcomes were largely preserved, with a live birth rate of eighty seven point nine percent and rates of miscarriage, preeclampsia, and preterm birth comparable to the general population. The median time to pregnancy was four months and only eleven percent had subfertility. The single most important modifiable determinant of prolonged time to pregnancy was smoking. So women with axSpA reported a higher desired versus achieved number of children compared to men and more frequently cited their rheumatic disease as a limiting factor. This data provides strong real world reassurance and underscore the importance of proactive reproductive counseling and smoking cessation in ACPA.

So let's move to rheumatoid arthritis. Some good news for RA. Two large registry studies painted a broadly reassuring picture of RA during pregnancy. From Norway, Ingo Sagberg, OP0242, presented data from the RevNetOS registry covering five ninety eight pregnancies in four seventy five women. Most women maintained stable low disease activity during pregnancy, with remission rates climbing from sixty four percent in preconception to seventy five percent in the third trimester.

The catch: postpartum flares were common, with twenty percent of women flaring at the first postpartum visits at six weeks, and remission rates dropped back to fifty nine percent. Seropositive women showed the most pronounced pregnancy related fluctuations and the highest postpartum disease activity. Importantly, temporal trends showed markedly lower disease activity in pregnancy after 2020, parallellying broader uptake of biological DMARDs. Another study from Japan came from Shizuku et al. February, who analyzed data from the NINJA National Registry across nineteen twenty one women of reproductive age.

They found that pregnant and breastfeeding women had lower STI scores and fewer swollen joints than non pregnant counterparts, but were significantly more likely to be on corticosteroids and had near zero methotrexate use, which reflect appropriate but challenging medication adjustment during this period. Now let's move to France. RheumAbhosan et al, OP0242, analyzed twelve year data of follow-up from the French cohort, six twenty four women with early RA. Among the three thirty nine women at risk at baseline, seventeen percent experienced at least one pregnancy during follow-up. Younger age, absence of NSAID use and absence of teratogenic treatment were independently associated with pregnancy occurrence.

Among eighty nine pregnancy captured, seventy five percent resulted in full term delivery and nineteen percent had adverse outcome. NSAIDs used in the six months preceding pregnancy outcome were associated with a six fold increase risk of adverse outcome, which is a really striking signal and adds to concerns about NSAIDs in the preconceptional period. Now to autoinflammatory disease in pregnancy. So Isabelle has OP0244 presented data from the German registry on fifty one pregnancies in women with autoinflammatory diseases: FMF, STILL, etc. The overall picture was encouraging.

Life birth, ninety three percent. No cases of preeclampsia or HELP. Neonatal outcome were generally favorable. However, flares occur in thirty eight percent of pregnancies and elevated rates of small for gestational neonates warrants further investigation. One concerning observation from this study was that colchicine and interleukin-one inhibitors were frequently withdrawn during pregnancy despite their established safety profile.

So there's a gap between evidence and clinical practice in counselling. Also, Laura Coates presented the safety data on giselkumab in pregnancy, and it was very reassuring. Eleven eighteen maternal exposure cases from the J and J Global Safety Databases, four hundred pregnancies with known outcome. The majority of exposures were in women with psoriatic disease, While the authors appropriately caution their data limitation, prevent definitive conclusions, these findings add to the growing body of evidence supporting the relative safety of interleukin-twenty three during pregnancy. Now let's move to the other side of the woman's life, to menopause.

There were two studies on menopause. First one, Simone Perignola, OP0243, presented data from the Italian Bio Pure Registry, two thousand six hundred and forty five women starting a biological GMAT. They showed that postmenopausal women present with a more severe immunological and radiological phenotype, higher seropositivity, more erosions, higher CRP compared to women of childbearing age, and are significantly less likely to achieve thus 28 CRP remission. Notably, however, early remission remained achievable in postmenopausal women who were B DMAR naive, had lower inflammatory burden, and did not have comorbid fibromyalgia. The message here, menopause is a risk modifier, but not a treatment barrier if the disease got early.

And the last study also in menopause in psoriatic arthritis, Lihi Adder OP0246, prospectively tracked four seventy seven women over more than twelve years and found that perimenopause was independently associated with a significant rise in DAPSA scores, tender and swollen joint counts, and PASI scores compared to both pre and postmenopausal age. Fatigue partially mediated this effect, accounting for twelve to eighteen percent of the data change, whereas BMI was not a mediator. So they suggest that hormone replacement therapy warrants consideration in perimenopausal women's which is a really thought provoking conclusion that will likely spark further studies. So the bottom line from this is a woman's world session at EULAAR twenty twenty six in London, that it delivered a clear and urgent message. Reproductive stage hormonal transitions and sex specific disease phenotypes must be integrated into how we assess and treat inflammatory rheumatic diseases in women.

From the postpartum flare and risk in RA to the perimenopause driven disease spike in PSA to the safety of biologic in pregnancy, rheumatologists now have richer data to counsel their patients and stronger reason to act on it. Thank you very much for your attention.

Hey there. My name is Doctor. Al Kim. I'm one of the leads for the cellular therapy topics at UR twenty twenty six in London, UK. And today I want to highlight one abstract which was predictable, but there was a really interesting surprise that was very much unexpected.

And so this abstract is oral presentation or OP two zero three entitled Immune Dimming with Low Dose Blended Tumumab Reverses the Treatment Resistant State in Rheumatoid Arthritis, a very provocative title. So Doctor. Laura Abucci from Erlangen, Germany presented this abstract. And so the background here is that when we're doing these trials of T cell engagers and CAR T cells in autoimmune diseases, almost all the protocols, actually all the protocols, were first developed and used in oncology. And so basically, we're using oncology high doses, in this case of a T cell engager, blinatumomab.

And remember, blinatumomab is the very first T cell engager FDA approved for B cell lymphoma. And it's not the best T cell engager that's out there, no doubt. And an additional reminder, blinatumomab is a T cell engager that binds to both CD3, that's going to be your T cell engager, and then CD19 molecule, which you're obviously on B cells. When that binds to both, both are brought into close proximity and then the T cell kills the B cell. So Laura Bucci previously published a couple of years ago that high dose blinatumomab in treatment resistant rheumatoid arthritis did reduce disease activity, but there was some toxicity.

There was some cytokine release syndrome observed. And again, because we're using oncology dosing, they asked the question whether or not a lower dose of lunatuzumab can maintain efficacy but reduce adverse events. Alright? So, they had fifteen participants with treatment resistant rheumatoid arthritis. Blinatumumab was given at least in two cycles and these cycles are not trivial.

So, it is a continuous ninety six hour infusion of blinatumomab. This low dose was nine micrograms a day. Followed by a five day holiday. Now, five of these patients received a a second dose at a higher dose. Twenty eight micrograms a day, and one patient even received a third dose also at twenty eight micrograms a day.

Everyone is premedicated by high dose dexamethasone, sixteen milligrams. And again, this is to mitigate the severity of any adverse events. So, again, the safety issue was one of the questions they had, they were asking. And indeed, there was some cytokine release syndrome, but it was only three out of fifteen, all grade one. It's pretty encouraging.

There was no ICANS, no hypogammaglottinemia, something we would expect with this type of T cell engager which is relatively low potency and it's not targeting plasma cells in the bone marrow. So your antibody levels remain pretty stable. Now the pharmacodynamics of data that they had was interesting too. They were able to completely remove B cells from the blood by three months. And in fact they also had five patients that got synovial tissue biopsies post blunetumumab and four out of five had no B cells in the synovial tissue.

We had chatted before about the potential importance of deep depletion of B cells, I. E. Tissue level depletion of B cells and this may be being a requirement for this immune reset of B cells. So four out of these five patients that were part of the study and were elected to get synovial tissue biopsies did have no B cells in their synovium. But everyone that was participated in the lymph node aspiration part of it, every single participant had incomplete B cell depletion in the lymph nodes.

This actually is interesting because this opens up the possibility that you may not have durable responses, Right? Now, looking at efficacy in terms of clinical responses, the ACR20, fifty and seventy were through the roof, 100% ACR20, 73% ACR50, 53% ACR70. Well, the problem though is that very few patients hit remission using the DAS28 CRP. Only five out of fifteen hit remission at three months. What's even more concerning and again, maybe not is that at month four, ninety three percent, IE eleven out of the fifteen relapsed, alright?

And again, you may have been able to say, okay, that's interesting and but I would expect it. This is a lower dose of a compound of a T cell engager that doesn't work very well in the first place. And on top of that, we aren't getting rid of B cells in the lymph nodes despite the fact that we're getting rid of B cells in the synovium, right? Now, this is the surprise here. Remember, this is difficult to treat rheumatoid arthritis or treatment resistant.

And they failed a ton of medicines. And so the physicians at Erlogen didn't have many choices to go back to in terms of getting their flare under control. So, they had to start using medicines they had failed before. Most of the patients had to follow this and the interesting thing is after blinatumumab, the medicine they had failed before was reused and they actually were able to restore responses. IE, if they were on a TNF inhibitor and failed it before getting blinatumumab, After getting blinatumumab and then after relapsing, they responded to TNF inhibitor.

They also found this with the JAK inhibitors. This is a really difficult observation to explain and it opens up a really interesting question whether or not this is a drug specific effect. This is only applicable to glutamate. And I can't imagine that being the case. Or is it more of a class effect in therapies that engage T cells or maybe even NK cells that kill B cells?

Is this possible with more potent B cell depleting agents that are monoclonal antibodies like obinutuzumab, right? I think, again, this opens up a really interesting question about how you can remodel the immune system response to the point that their prior resistance to a therapy actually works. So kind of in summary, right, you have this

low

dose blinatumomab, which got initial efficacy. People did get better, but not all the way. Almost everyone relapsed but then they had these restored responses to failed therapies. So the group at Erlakin calls this immune dimming because you're not really resetting the immune system. You're just kind of stunning it.

But again, how that translates to restoration of responses to previously failed therapies is absolutely wild to me. All right. So thanks for listening.

Hi guys, this is Aurelie Naj from Scotland live at day two of EULA twenty twenty six 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 OP0204. 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, but 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, the 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 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 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 percent, so twenty eight people wanted JAK inhibitor oral, twenty three-forty five percent wanted the injection, so it's about fiftyfifty 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 RubNow 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 2026 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, our NK cells are 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 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, well, I I think I've heard about this before. The type two monoclonal antibodies like obinutuzumab, inebilizumab, those are antibodies where there's a few codes missing, I.

E, they're a few costly ligands 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 lymphodeplane chemotherapy, both 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? 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 in about six to twelve months later. So what's interesting is when you look at therapies that they were on, three out of four were able to discontinue their background therapy 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 ULAAR 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.

E, the blood. Lymph node B cells, tissue based B cells, they aren't touched by lymphodepleting chemotherapy. This is the reason why the NK cell is needed. And then the second issue is, okay, yeah, we talked about how complicated this regimen. Why not just use obinutuzumab, right?

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 going to act on the obinutuzumab. Maybe, maybe not. And then the other thing you might be thinking is that why not just combine AB101 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.

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.

Hey, everyone. This is Bella Mehta reporting for RheumNow from London for EULA. And one of the most practical and immediately relevant abstract at EULA was this one which looked at cost effectiveness of digital patient education in newly diagnosed rheumatoid arthritis patients. This is o p zero zero five, and this builds on a web RA randomized control trial where patients with newly diagnosed RA were randomized either to digital patient education or standardized face to face education and followed over twelve months. In this economic evaluation, they analyzed data from one seventy five patients, eighty four in the digital group and ninety one in the control group, and both groups who are matched in terms of demographics, disease characteristics.

Again, the average age was mid to late fifties, and about sixty percent were females. And all of these patients had some amount of disease activity, very moderate, with DAS 28 scores about 4.4 to 4.6. They what they looked at was not just clinical outcomes, but also cost and quality of life or QALYs, quality adjusted life years, which was their primary outcome. And they took a broad societal perspective, which is important because it's it included not just health care utilization, but also things like productivity loss, transportation, and municipal services. And the results are quite interesting.

The digital education group had overall mean health care costs compared to the face to face group by around 500 or €600 and slightly improved quality or quality of life. And the quality quality adjusted or life year gain difference. So quality gain difference was 0.013. It's a small number, but it's still in the in the right direction. When they calculated the incremental cost of effectiveness ratio, the digital intervention was actually dominant, meaning better outcomes at a lower cost.

And then they ran, like, probabilistic analysis. Again, this seems like a lot of math, but, you know, we they did simulations and which which fell into the best case quadrant, better outcomes at lower cost, and overall probability of cost effectiveness was around 70% even at a zero cost willingness to pay threshold, increasing slightly to about 71.5 at standard thresholds. So, again, most of the cost savings were driven by hospital utilization, which was reduced, which I think is a key thing that a lot of patients, physicians, insurances care about. And, you know, for the secondary outcome self efficacy, the results were mixed, and it's difficult to interpret in a small RCT, but it is in a small trial like that. But mainly what this suggests is that structured digital education tools can reduce cost without compromising outcomes and potentially improve access and efficiency in early RA care.

In a setting where we are facing workload shortages, increasing patient demand, this might be highly useful. But I think there's nuance here again that it's not about replacement. It's about augmentation. Digital education can standardize and scale information delivery, but it does not account or does not take care of individual concerns or health literacy differences or nuances of shared decision making. Again, this ties to the broader shift that we are seeing that patients are increasingly willing to engage with digital tools, whether structured education platforms or informal AI based systems.

But even if these tools improve baseline understanding, they don't replace the need for a contextual interpretation, which we as clinicians can do. So, you know, with these tools, this I don't think they'll replace us, but they will change how we spend our time and focusing more on complex decision making. But, again, all I when I see these abstracts, it makes me think that, slowly, the spectrum of how we are trying to treat these diseases and patients, is changing, and there's a lot of food for thought here. So with that, signing off. This is Bella Mehta at RheumNow, and please follow me on Twitter at Bela underscore Mehta.

Thank you.

Hello. I'm Jonathan Kay reporting from EULAR twenty twenty six in London, England. This is the second day of the EULAR meeting, and there were a number of interesting abstracts presented today. I'm gonna talk about abstracts OP zero two zero six and OP zero two zero seven, which were about optimizing treatment of rheumatoid arthritis with methotrexate. At the American College of Rheumatology meeting last fall, there was an abstract presented as a plenary from India of a clinical trial that compared split dose methotrexate twenty five milligrams given in a split dose once weekly to single dose twenty five milligrams of oral methotrexate.

And they found that split dose methotrexate was more effective than one single dose of methotrexate twenty five milligrams weekly, probably because the methotrexate receptors in the gut are saturated at a dose of fifteen milligrams weekly, and doses higher than that are not absorbed as well. So this abstract, o p zero two zero six, reported on the SCOOT study, a study comparing oral split dose methotrexate to subcutaneous parenteral methotrexate in patients with active rheumatoid arthritis. This study randomized two hundred and fifty two patients with rheumatoid arthritis that was in at least moderate disease activity, one to one to receive either parenteral methotrexate twenty five milligrams subcutaneously weekly or oral split dose methotrexate twenty five milligrams once weekly in two divided doses, fifteen milligrams in the morning, and ten milligrams in the evening. And this was a noninferiority study with the primary noninferiority outcome being minus fifteen percent noninferiority margin for achieving a EULAR moderate or good response at week sixteen. This study failed to demonstrate noninferiority of oral split dose methotrexate to subcutaneous parenteral methotrexate indicating that probably parenteral methotrexate is the way to go when you need to use doses of methotrexate more than fifteen milligrams once weekly.

The oral split dose methotrexate also had a higher incidence of elevated ALT and AST compared to the parenteral methotrexate. So not only was the parenteral methotrexate more effective, but it was also safer or at least better tolerated. So this study suggests that when one is escalating methotrexate above fifteen milligrams orally weekly, it's better to go to parenteral methotrexate administered subcutaneously despite the preference of many patients to take an oral medication rather than a parenteral medication. The other abstract that was presented at this session that I'm gonna discuss is zero p zero or o p zero two zero seven, which was a study from Montpellier in France that looked at dietary fiber supplementation in addition to methotrexate to see if dietary fiber supplementation might improve methotrexate clinical response. The rationale for this was that dietary fiber supplementation increases short chain fatty acids, which may decrease t h 17 cells compared to t regulatory cells, decreasing the pro inflammatory effect and also alter the microbiome, perhaps leading to a change in the metabolism of methotrexate resulting in greater efficacy.

This study randomized forty nine patients, who were randomized essentially one to one to receive either twelve grams of inulin daily as fiber or placebo, which was a different powder. And the primary endpoint was the EULAR moderate response at thirty days. In this study, the patients who received inulin fiber had a greater response to methotrexate than those who were given placebo, suggesting that the administration of fiber with methotrexate improves the clinical response. And the exploratory analysis of the microbiome showed changes in the microbiome with dietary fiber supplementation compared to placebo supplementation, suggesting that this might change the metabolism of methotrexate, resulting in greater efficacy. So taken together, these two abstracts, o p zero two zero six and o p zero two zero seven, suggest that there are ways to change the way in which we administer methotrexate, giving doses of fifteen milligrams or higher once weekly as a single subcutaneous parenteral dose rather than split dose oral administration, and that perhaps administering dietary fiber supplementation with methotrexate may alter the microbiome, increase short chain fatty acids, and decrease t h 17 cells, increasing the t h seven or decreasing the t h 17 to t regulatory ratio, thereby improving the efficacy of methotrexate.

So these two rather straightforward alterations in the way in which we administer methotrexate, subcutaneous rather than oral at doses of greater than fifteen milligrams once weekly and along with dietary fiber supplementation, may potentiate the effect of methotrexate, which is our anchor drug and which is incredibly important in the treatment of rheumatoid arthritis for virtually all of our patients. For this and more from EULAR twenty twenty six in London, I'm Jonathan Kaye. Go to roomnow.com, and I look forward to seeing you again soon.

Hi, it's Doctor. Janet Pope. I'm reporting from London, England, ULAr twenty twenty six for RheumNow. And I hope you've been following us. There's a lot of exciting reports coming out.

I wanna talk about treatment of RA with ILD, are we failing? And this is based on guidelines that have come out over the last two years, but also on a hot topic, which is how to treat for HOT by Doctor. Phillip Dayud. And it was on 06/05/2026. So I think the first question is, are we failing in the treatment of RA ILD?

So why did I frame it that way? We've come a long way where ILD is sometimes being screened for patients. We can ascotate their lungs in the lower bases. We can do PFTs when they go on an advanced therapy, they're getting chest imaging and periodically in high risk patients maybe will even be doing CT scans. So I think there's an awareness.

And what is different about rheumatoid arthritis ILD is that more people than say scleroderma associated ILD, more people with rheumatoid arthritis have a UIP or a usual interstitial pneumonia pattern. More men with RA relative to women will have ILD and they're older and often long standing disease. So older men smoking is a risk, more UIP pattern, they kind of look like IPF patients. So for a long time, number one, we might have been failing because immune suppression was not always used with the drugs that treated progressive pulmonary fibrosis, such as Nintandanib. Although MMF can be used in RA ILD, but it doesn't really treat the rheumatoid arthritis joints very well.

Number two, the use of anti fibrotic is probably not optimal. Some of it might have been from a lack of treatment, tolerability, some of it might have been access, and some of it frankly might have been not case finding, lack of awareness from the rheumatologist or the pulmonologist. So the anti fibrotic classes of drugs currently are the PDE 4 B inhibitor, Neurandolamast, which has been approved in The US, fast tracked and will be approved in many other countries in the near future we think. And then Nintendenib. Nintendenib is a tyrosine kinase inhibitor.

There were some abstracts and some of the review that we heard from the professor who gave this lecture suggests that treating obviously RA effectively is helpful and using concomitant immune suppression. What I did learn, and I thought that this was maybe a failure of my understanding, is that RA disease activity might not change the pulmonary functions, but it will change the overall mortality. So we need to get RA disease activity under control. I always understood that area under the curve of more rheumatoid arthritis active disease increase the chance of both getting ILD and RA and worsening ILD. And I think a bit of a shadow was put on my understanding of that.

I don't think the answer is totally clear. The final thing is I think we have to look at the things that can prolong our patient's survival. Giving oxygen if they're hypoxic and testing for that. Using shared care so that the patients are vaccinated so that they get smoking cessation, so that they get in an exercise program, and using a common sense algorithm so we know what would be the cut point within this individual where I will trigger a change in therapy for their RA because they have ILD and for the ILD itself. Who should get on a pulmonary fibrosis drug or are we actually putting them on too late?

Now one area where we're not failing, and this will be my final point that was a take home message, was once you treat the RA ILD, you often can level the worsening PFTs for at least over the next one to two years. And there was an abstract that suggested that as well in rheumatoid arthritis. So I don't think we're failing, but I do think there's a care gap and we can do better. Please again follow us at RheumNow. It's Janet Pope reporting JanetBurdope.

Thank you.

Hello. I'm Jonathan Kaye reporting from EULAR twenty twenty six in London, England. This is the third day of EULAR twenty twenty six, and there were lots of interesting posters and some very interesting oral presentations. I was going through the rheumatoid arthritis poster session, and I came upon a poster that was being exhibited by Eleanor Bolton, a PhD student from University of Leeds in Yorkshire in England. She's working with Paul Emery and Culver Manckea and looking at the prearthritis group.

And she used artificial intelligence to identify two distinct preclinical phenotypes among patients with anti CCP antibodies, but no clinical synovitis. And she looked at this prospective cohort of 451 individuals who were recruited from Yorkshire. They were adults over the age of 18. All of them had anticyclic citrullinated peptide antibodies and musculoskeletal symptoms, but no clinical synovitis. And she fed this cohort information about this cohort into machine learning, and she came up with two clusters.

There was a low risk cluster and a high risk cluster. And they differed in that there was a higher sedimentation rate in the high risk cluster than the low risk cluster, higher tender joint count, higher rheumatoid factor level, higher patient global health assessment by visual analog scale. And then when they looked with ultrasound for synovitis, there was more synovitis among those in the high risk group than in the low risk groups. They had more morning stiffness. Anti CCP antibodies were higher, tighter.

They were older, slightly older, 53 years compared to 49 years. And they had more tenosynovitis. The tenosynovitis difference wasn't significant, but all of the other differences were highly significant between the two groups. So she clustered these into two groups and then looked at a Kaplan Meier survival curve looking for survival without arthritis and found that in the high risk group, they developed arthritis more and more rapidly or sooner than those in the low risk group. So this was a very interesting use of machine learning, artificial intelligence, to feed in this cohort that had been collected of four fifty one patients with musculoskeletal symptoms but no clinical synovitis and presence of anti CCP antibodies, putting them at risk for possibly developing rheumatoid arthritis.

And then when she looked at these two groups and plotted Kaplan Meier's survival without arthritis, it turned out that the high risk patients developed arthritis sooner, and more of them developed arthritis than did the low risk group. So she found, she validated our clinical suspicion that patients with higher levels of acute phase reactants, patients with higher levels of rheumatoid factor or anti CCP antibodies, patients with worse global health assessment, patients with more tender joints and more tenosynovitis are going to be more likely to develop arthritis from the pre arthritis phase. So I congratulated her on this work, which she's done as the beginning of her first year of her PhD. And I asked her what she plans to do to take this study further. And she plans to look at this cohort longitudinally and prospectively, which will be very interesting.

So her retrospective analysis found a separation between these two groups. But if she looks prospectively at patients who meet these criteria to see whether there's still a difference in the rate of progression from a preclinical phase to a clinical inflammatory arthritis phase, that will be very interesting. So we've heard more about artificial intelligence at this meeting, but I found this a very intriguing and useful and informative and practical application of artificial intelligence to also study this preclinical phenotype of rheumatoid arthritis, which is really the most exciting area to me of trying to identify who's at risk and then looking at ways to prevent progression to rheumatoid arthritis. So look forward to seeing more work from this group and other groups about progression from preclinical arthritis to arthritis, and especially more studies of prevention For more from ULUR twenty twenty six in London, go to roomnow.com. I look forward to seeing you again soon.

I'm Jonathan K.

This is Jieha Li from Michigan reporting for RheumNow in London for EULAR twenty twenty six. I'm going to be discussing what is adjacent to my passion, which is aging and rheumatology. This is poster number 1326 looking at to show that treat to target works in elderly onset RA. And if anything, that they need less to get there. Older adults with RA are often undertreated.

And in clinical practice, there's a tendency to kind of be hesitant about prescribing for concerns about tolerability risk because older adults have more comorbidities and there's some assumption regarding safety and efficacy. Although there's been a number of studies to show that our drugs, even the biologic and targeted synthetics are pretty well tolerated in older adults. So I was really excited to see this study to really get at the question of does treat to target work? So by ways of a little bit of background, elderly onset RA is defined as already diagnosed on or after the age of 65. And I want to put in a little bit of a plug here because the American College of Geriatrics tries to avoid words that catastrophize aging.

So their preferred term is late onset rather than elderly onset. So it's really interesting to see there's some difference regarding terminology. I think this is one way in which having a unified term approach is how we can also improve care of our aging population. Because the population is aging. In Europe, they're saying by 2050, at least one third are going to be over the 65.

I believe in The US that number is by 2030 we're going to be one in four are going to be older adults. So this is going to be the norm of our study. And I think Rise actually shows that forty percent of all clinical patients are 65. So this is our reality and our challenge. So it's really important to understand and get data on these because older adults often are not included in trials that actually inform our guidelines.

So with that, there's also some clinical differences between those with late onset forgive me if I say late instead of elderly late onset versus younger onset, in that these patients tend to have more abrupt systemic presentation, tend to be more seronegative. There tend to be less of a gender difference. So instead of the typical three to one or four to one, it tends to be two to one. So it's important not to under diagnose our older male patients. And also there has been some studies to show that have higher levels of IL-six and lower levels of TNF-one.

So clinically, physiologically, they tend to be a little bit different. And also at the time of diagnosis, they're more likely to have comorbidities and polypharmacy adding to the challenge of treating these patients. But the question, like I said, for these authors, and they're from The Netherlands, was can older adults receive achieved disease remission or low disease activity with a treat to target approach? To really challenge the assumptions, as I said, that some physicians have because there was a study on ageism, where interestingly most rheumatologists said they were not ageist, but those who did have tendency were less likely to prescribe RDMRs and more lean towards symptomatic management with glucocorticoids and NSAIDs. So with that, let me set up the study for you.

So this data is from what they call a T REACH trial. It's a multicenter stratified single blinded randomized control trial that was conducted in The Netherlands. And it was enrolling patients who met classification criteria for RA. And they were either categorized as elderly onset or young onset depending on the age at which they were diagnosed with RA. And out of, I believe they had a total of just over three hundred.

So ninety eight patients had a mean age of 73 at the time of diagnosis meeting the elderly age onset criteria and the rest were younger onset and their age ranged between 18 to 65. And that means roughly about twenty five percent were late onset. In The US in the Medicare population, that number is about thirty percent. Again, I think that's reflective of The US being slightly older in general than the European populations. For all of these three twenty seven patients where the overall mean age was 48, they were followed doing a fixed protocol of a treat to target approach of treatment.

Their DAS trajectories, their DMARD use, glucocorticoid use, biologic drug survival, and DMARD free remission along with adverse events were assessed over a two year period of time, which I think is very nicely set up and impressive. And then they looked at stratified analysis based on autoantibody status at the end. So taking each of the outcomes, so for disease activity trajectories, they were actually similar between the two groups. The mean DAS difference between elderly onset and young onset was only 0.03, which is very clinically negligible. And both groups actually achieved comparable rates of low disease activity over the follow-up period of two years.

How did they do that? Did the treatment intensity differ? I think this is where the importance comes and the authors note that appropriately as well. So for elderly onset RE patients, they need a significantly less intensive therapy to achieve the same low disease activity with an odds ratio what they put as like zero point three. So like sixty percent less intensity compared to the young patients.

So they were less likely to require biologics. And I think the value here is that this was a perspective data collection, whereas in US when we look at Medicare, it's often a cross sectional retrospective. So we find that they get less biologics. And we don't know if that's because they didn't require it or that it just wasn't given to them. So I think it's reassuring and informative to see that in this type of study, they really did not.

At the same time, just as a benchmark number, in The US about thirteen percent to fifteen percent of older adults are on biologics. And in this study for them, I have the number, give me one moment. I think that number actually was higher in terms of the biologics. So yes, their numbers were actually up into prescribing rates of like twenty five to thirty percent. So they required less however yet their overall prescribing rates were much higher than in The US.

Sorry, continuing on with that. So again, in terms of the treatment intensity, they were left. But in terms of drug survival, in terms of discontinuation, they were very similar in that older adults or elderly onset RA patients were well tolerant of biologic therapy as well. In terms of adverse events. Again, this is important because safety is something that we very much care about.

So elderly onset patients had higher rates of bone marrow depression or osteoporosis, understandably, fifteen percent versus seventy percent. Elevated creatinine, it could be from methotrexate intolerance or underlying CKD, that number being eight percent to two percent compared to the younger onset. Younger onset patients did report more mood related disorders than anything. In terms of the continuity of treatment, though, DMARC switches or the dose adjustments due to the adverse events, it did not differ overall between those two groups indicating again that the overall drug tolerability is comparable, although in terms of absolute experiences older adults may report more. So what does this mean clinically for us?

I think this finding makes a clear case that treat to target is not only feasible in elderly onset RA, that it may work better than we expect with less treatment exposure, especially in this group they did some stratified analysis that's seronegative patients. But again, just keep in mind I think that seronegativity is just coming from the nature of what elderly onset RA patients usually present with. And it's reassuring to know that the adverse effects are really not different between these two. So the practical message I hope to share with you, and for me as well, is that we are progressively caring for an older generation of patients. So let's not withhold treat to target strategy from these patients based on age alone.

There's a saying in the geriatric role that chronologic age does not equate to physiologic age. So there are other means and assessments that we can bring in. There was actually a number of abstracts at EULAR about sphericality sarcopenia being a risk stratification model or even an outcome model for older adults. Oh, and yes, there was actually I was very pleased to see this. There was actually a whole entire session about aging.

And I think what was most powerful is the patient voice. So there was a patient who had been diagnosed, was 17, who came and shared what the patients want. And what they want is to be able to independently age at home, to be able to have conversations about treatments and understand that within the context of their competing comorbidities and devise a plan that fits in with their goals and priorities. So I think this information and this study gives us some reassurance that our usual treat to target approach helps so that we can have better shared decision making. In terms of just do want to point out just a few limitations in that it is relatively small.

Again, like for prospective cohort I think three thirty is good. But again, the numbers are somewhat small for certain subgroup comparisons, especially with the smaller disease or drug specific measurements as well. And this is a trial setting. So like they had intense monitoring and hands on. So in real world where adherence is different for our patients, there may be some variance in terms of the findings as well.

With that, this was Jeehali reporting for RheumNow in London for EULAR twenty twenty six. Thank you for listening.

Hello. My name is Runaalini Day. I am a rheumatology fellow here in London. I'm delighted to be reporting from ULAW twenty twenty six also here in London. I am joined by doctor John Giles from Cedars Sinai Medical Center in California in The US, and we are going to be discussing the very last abstract to be presented at this congress, l b zero zero zero nine, which is looking at the long term safety data, really exciting stuff from looking at baricitinib versus TNF inhibitors in an enriched cohort.

Specifically, we're gonna be discussing results of VTE. So, doctor Giles, thank you very much for joining me. Can you just give us a brief overview of the study?

So this is a phase four safety trial. It was mandated by the FDA. The FDA had a lot of input into the design of the trial. Primary outcome was venous thromboembolic events based on some signals from their randomized clinical trials, some of issues about class effect as well. There were more than three thousand six hundred patients who were randomized, two doses of baricitinib, two milligrams, four milligrams, versus TNF inhibitors, could be a Tannercept or adalimumab.

The trial, there were two different trials put together. Yeah. One was a standard global randomized clinical trial. And then the other was more of a pragmatic trial that was done in The US with less data collection, but still adjudicated events.

Okay.

It was an events based trial. So there were a certain number of venous thromboembolic events that were supposed to occur. It turned out that the trial was stopped early because if the trial had continued and they had accrued all those events, they still would not have had been underneath the non inferiority margin of 1.8 for the upper bound of the 95% confidence interval. Okay. So there was there was numerically higher venous thromboembolic events in both of the arms of baricitinib, and it was basically equal for the two milligram versus the four milligram.

But it was not statistically significantly higher, but certainly did not meet the criteria for non inferiority.

Great. And I guess we're all looking at this through the lens of oral surveillance and the warnings we've been receiving since that study came out. How do you think clinicians should view the data from RA Bridge and RA Branch now that we have this for their clinical practice?

Well, think it's important to note that this is really a very adventurous trial because the population was enriched for venous thromboembolic risk factors. They could even have had a venous thromboembolic event in the past. Now that was the minority of patients that had had those, but they are included in that group. Yeah. And then the other risk factors like higher BMIs and older ages are included there.

So I think this gives us an idea about what the actual risk is. Yeah. And this is comparative risk too. So we're talking about the difference between TNF inhibitors and baricitinib. We're not talking about overall risk, and we're not talking about compared to not treating people with anything or treating them with other things.

So I think it gives us a good idea about what the actual numbers are.

Yeah.

And subsequent analyses will be able to interpret what the risk factors for those people who had the venous thromboembolic events are. We'll be able to look at the other outcomes of secondary interests that were there. We'll be able to to come up with numbers needed to harm Yeah. And what the bounds on those are. So I think there's more to come here.

Okay.

But I think when we're trying to put the baricitinib as a single drug into context and then also put the greater context of the risks of JAK inhibitors as a class, I think this is very, very important information, because we've been talking about oral surveillance five years now.

It's an impact on our practice as well.

It potentially has an impact on our practice and allows us to kind of compare and contrast between the two different trials.

And then just speaking about the risk factors and the fact that it was an enriched cohort, are you able to comment on any of the other outcomes that we were looking at in oral surveillance may

capture Well, so the interesting thing that's different from bridge and branch compared with oral surveillance is that there's absolutely no signal for major adverse cardiovascular events or malignancies.

Yeah.

And they're equivalently powered on those. They're not enriched for those, but they have the same number of basically the same number of patients. They have basically the same number of follow-up times. There's no real difference there. Now why that is, we don't know.

We'll have to dig into that a little bit more. They're not in risk for those things, but people who have VTEs are also enriched So for risk factor for cardiovascular I think as we dig into the data a little bit more, we'll we'll be able to compare and contrast maybe doing some subgroup analyses with, more more of a subgroup that looks like the inclusion criteria for oral surveillance and see if anything comes out of there. It certainly does maybe lower the concern about those, whether that's a class effect or it's a drug specific effect, you know, we don't know. Remember that, oral surveillance included a standard dose and a double dose.

Yes.

And this includes a half dose and a standard dose.

Yeah.

So may that could be part of what we're seeing too.

And a different target as well.

And a different target. Yes.

Yeah. So really not able to comment maybe on the whole class of how we how we use JAKs in general. So interpret with caution maybe at

this Interpret with caution, I think. And it and it really shows that, you know, these are two of the largest clinical trials that have ever been done in RA. Yeah. And and we still have uncertainty about, you know, what they mean. And then when we look over into other clinical trials that have, you know, a few 100 patients, you know, it just makes us realize, especially for safety, that safety outcomes are really require big numbers of patients, and some of them that we're not able to actually get to.

Okay. Great.

Well, thank you for taking us through that study. So if you want to catch up on that study, it is the very last abstract in the congress. Thank you very much for joining us here on RheumNow. Do follow along for further coverage.

One of the issues that we face in inflammatory arthritis is the referral from the primary care physician or general practitioner. While we have many modern therapies, the issue that we have is the delays to diagnosis. When patients present late after their symptom onset often they have more comorbidities and often the treatment becomes less effective when instituted at a later stage. So one of the things that is quite important is to try to improve the diagnosis time by improving the referrals that we get from primary care. Here at EULA twenty twenty six in London, were two posters.

Firstly, Poster twelve eighty four. This comes from the UMass Rheumatology department in Worcester in The United States and this study was presented by Doctor. Carmen Solomon Escoto and Doctor. Jonathan Kay and it was a very interesting study where they used the CARE tool which was first developed in The Netherlands. In this study, they validated the CARE tool which is a screening questionnaire that allows us to screen for the probability of inflammatory arthritis.

With a score of greater than four that would increase the probability of inflammatory arthritis. They had two eighty four new adult patients who suspected inflammatory arthritis. They used the CARE tool and the sensitivity from the study was seventy seven percent meaning at least three in four of these patients were screened for possible inflammatory arthritis and the specificity was sixty three percent allowing for these patients to be deprioritized or may be seen less sooner than those who scored positive. What was very interesting was the tool not only screened patients in but also screened patients out as they were deprioritized into urgency if they scored less than four and the negative predictive value was ninety percent nine out of ten of the patients who scored less than four could have a more routine appointment. The area under the curve from the study was 0.74.

This showed good overall discrimination from the use of the CARE tool. So this was a very important study. If we have such a tool, this allows us to select our patients more carefully for the studies. How about the implementation? And this is something that we presented from my group.

And this is Poster seven eighty four, where for the last four years we have been leading rheumatology academy and collaborative network called RheumCan, where such tools such as screening tools such as the care tool and many other screening tools can be used but also implemented in a way that the system provides training and education for primary care physicians to use this and the confidence went up by nearly twice the amount from 4.4 at a start to 8.6 over 10 in terms of the users being more confident in looking at inflammatory arthritis and ninety five percent of them said they were likely or very likely to change their practice as a result of the training And this was seen where the percentage of referrals that were referred to secondary care or to the rheumatology department three days after presentation in primary care went up from fifty two percent to seventy percent within a year of implementing this program. This compares to the old national average, which remains fairly static at fifty percent of these patients being referred within three days of presentation to primary care. So what we are seeing here is if we have a tool that we can use which is validated such as the CARE tool then we need to have a system that allows us to train and also educate our primary care colleagues to use this tool so that they are more confident and at the end of that we will reduce the delays to diagnosis.

So I think these are new ways of us delivering education and training by using validated tools. I'm Anthony Chan presenting here at EULAW twenty twenty six in London.

Hello everyone. My name is Doctor. Youssef. I am associate professor and consultant rheumatologist in Leeds, United Kingdom. I'm reporting for RheumNow to cover the Congress EULA twenty twenty six in London, United Kingdom.

Today,

there

is late breaking abstract sessions. The room was full. So the abstract that I would like to discuss today is the title LB003. As we all know, B cells play a major factor in the immunopathogenesis and achieving peripheral B cell depletion is important to achieve both biological and also clinical response in rheumatic and musculoskeletal diseases. Currently, are various ways, including the use of cellular therapies such as CAR T and also bispecific or trispecific antibodies.

However, is there any other method? Well, in this abstract, so this is a phase 2a basket study to evaluate combination therapy using off the shelf allogeneic NK therapy. The compound is called AB101. This is a non genetically modified compound which was developed from the cord bloods. So it is off the shelf so that this is scalable compared to a CAR T cell, which require quite a long process time to manufacture.

So in this abstract, so the use of AB101 is in combination with patient has to undergo conditioning with low dose cyclophosphamide and fludarabine. Secondly, with rituximab, which is given one gram to infusion two weeks apart, and also the compound itself with the allogenic AB101, which was given one dose weekly for three doses. So this is a basket trial encompassing four diseases, including rheumatoid arthritis, Sjogren's disease, scleroderma and also inflammatory myopathies. In this preliminary analysis, the investigators presented data on three conditions. One is severe refractory rheumatoid arthritis.

So majority of the patients have failed at least one biological DMARDs and also have active disease. Secondly, a patient with Sjogren's disease who have active disease despite standard care. And as we know, we don't have inulacin therapy in Sjogren's. And the third one is patients with scleroderma who have active disease despite failure of at least one immunosuppressant. So the results are quite astounding.

So it shows a very good peripheral B cell depletion achieved with this combination therapy. And they also presented data up to fifty two weeks. The primary endpoint is at six months. And we can see in people with severe refractory rheumatoid arthritis, for example, the ACR fifty response was seventy one percent. So this is like if we want to compare with patients with TNF inhibitor failure in the initial study of rituximab, which is called reflex, the rate was actually around thirty percent.

So this is really interesting that with deeper basal depletion, we can also achieve greater response. In people with Sjogren's disease, the change in SDAI has dropped to about eight point score. And also people with scleroderma, there was improvement in terms of modified Rottmann's skin score for the skin fibrosis for around nine point reduction. So these are all interesting preliminary analysis of this study. In terms of safety, there was no icons or any more than grade one GRS that was reported.

And they also reported no evidence of hypergammaglobinemia in the first fifty two weeks. Of course, this is only a preliminary analysis. It would be interesting to also know the future about the efficacy in also in inflammation myopathies, which I'm sure are going to be presented in the next conference. Importantly, one of the advantages of this therapy is scalable. It can be administered in the outpatient settings.

However, with all the studies, this is still early, so we will still keep our card in the chest. Compound need to be investigated in a randomized control studies and to have a proper comparator for it before we can use that in the future. So I hope you found my video summary interesting, and follow RheumNow for more content coverage from EULA two thousand twenty six.