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Hi, this is Eric Dine from RheumNow here in Washington, DC for today's first day of the ACR convergence. One of the big topics of conversation has been bimekizumab, and I'm honored to be here with Doctor. Anna Maria Orbi of the Johns Hopkins Arthritis Group. Tell me about, abstract 600 and what we learned about bimekizumab.

First of all, thank you, an honor as well. So our abstract analyzed long term effects of pimekizumab on psoriatic arthritis life impact in people with psoriatic arthritis using the PSA12 patient reported outcome measure. Bimekizumab, as we know, is a selective dual inhibitor, it's looking 17A and F, and it is labeled for psoriatic arthritis. The B OPTIMAL and B COMPLETE are randomized controlled trials, phase three trials of Rheumatuzumab in TNF naive and TNF experienced patients respectively, and we are looking at the long term extension for this these trials. Now, about PISA-twelve, it's a patient reported outcome measure that is validated in multiple languages and it is a composite scores of pain, physical function, sleep, emotional domains, and it has a score range of zero to 10.

A difference of three is a meaningful improvement at patient level, and the score of one is almost no symptoms or life impact, whereas a score of two is a low level, and these would be desired targets in our patients. So, with bimekizumab, about half of the patients, whether they were TNF naive or TNF experienced, achieved no to low disease impact in these clinical trials, and this was maintained at one year in the clinical trial as well as our longest data go as far as two years where patients maintain this stage. And I think that this is very important because life impact is related and a determinant of achieving and maintaining treatment targets in psoriatic arthritis. Yeah,

and it's really the things that the patients want to hear the most is the things how they experience and not necessarily those objective numbers that we're always following in the office so that's great when we have those patient reported outcomes. That's wonderful I think that's a great study. Thank you very much I appreciate you sharing your abstract with us today.

My pleasure thank you.

Alright. Good morning. My name is Akhil Sood reporting for RheumNow here in Washington DC. Today I have the pleasure of speaking with doctor Chris Winkup from King's College London. Hi Chris.

How are you today?

I'm very good. Thank you very much. It's nice to be here with you.

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

think CAR T cell is an area of rheumatology that we're just getting to terms with. We're learning a lot from our colleagues hematology with regards to this treatment. When I try to describe it to people I say that this is a drug but it's almost a living drug. What we're doing with CAR T cell therapy is we're asking patients to typically donate their own blood particularly their T cells which we all know as rheumatologists are important in the immune response of many of the autoimmune conditions we treat and these T cells are then taken to a lab and genetically reprogrammed to target something else in many case CD19 or BCMA which we see on B cells. So it's a very very extensive precise way of B cell depleting.

These new genetically modified cells are then reinfused to the patient where they don't just stay dormant they expand they grow and they find their target so for example b cells and they deplete and kill those b cells leading to a very profound b cell depletion and what we're seeing in many of the studies and bear in mind these are very small numbers in open label studies is significant clinical response following that treatment so it's a hugely exciting area we're learning a lot from our colleagues in hematology but one of the things that I'm talking about here an awful lot is how can we change this treatment how can we look at using this treatment en masse for autoimmune conditions so it's a really exciting to be in this field and doing this type of work.

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

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

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

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

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

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

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

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

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

Hello everyone, Lihye Heather here from the University of Toronto reporting from RheumNow. The abstract that I decided to present today, number six zero three, cycling versus switching after first failure of TNF inhibitors in patients with axSpA. So this is a very relevant question to us because of the limited options that we have. This is a study from a big check registry that evaluated patients who failed their first TNF inhibitors, and they evaluated whether persistence on a TNF inhibitor versus IL-seventeen inhibitor is better in one or the other. The bottom line is that there is really no difference.

The retention was similar for TNF inhibitors and IL-seventeen inhibitors, but uniquely there was a difference in response. So the study did have information about ASDAS and response to treatment, and they showed some superiority of TNF inhibitors compared to IL-seventy inhibitor. On the other hand, there was a little bit of more safety issues, including severe adverse effects in the TNF, inhibitor group compared to the IL seventeen inhibitor group. So even though the retention was similar, there were some differences in terms of efficacy and safety. So I think for us as clinicians, both options are available, either switching to a different mode of action or staying within class of TNF inhibitors.

But we obviously need to take into consideration issues like safety, and some patients might benefit from maybe IL-seventeen inhibitors if safety issues are a major concern. So personalized treatment still remains intact until we have biomarkers that could help us predict response. Thank you.

Hi. I'm doctor Sheila Reyes from The Philippines, and I'm here at Washington DC reporting live for RheumNow at the ACR Convergence twenty twenty four. I'm joined this afternoon by Doctor. Dennis Padavni from the University of Toronto where he will be talking about abstract number eight nineteen regarding the newest definition of difficult to manage axial spondyloarthritis. So Professor Padavni, thank you for joining us this afternoon and congratulations on your paper.

Thank you. Yeah, so could you like walk us along how the criteria came about or the definition, what criteria you used or how you came about with the consensus definition?

Well, so that was a long process. It took about three years in total to find a consensus among experts on what's difficult to manage spondyloarthritis is about. So we started this initiative some time ago and there was clear there is an unmet need in the field. We see everyday patients coming to us not responding to the most advanced treatment and rheumatologists are very well aware of various problems which might lead into treatment non response or insufficient response to the therapy. It can be a biological non response so inflammation is not controlled well but more commonly these are other problems like chronic pain not related to inflammation, so called, nociplastic or neuropathic pain.

It might be a bit surprising but this fact is not really reflected in the management guidelines. If you look into the management guidelines you will see that in a patient who is not responding to the treatment the recommendation is to check the diagnosis and to change the treatment. But the problem is much deeper so you need to understand what is the structure of reasons behind this treatment non response so that is why we decided to develop this consensus definition to define the group clearly to be able to study this. And in addition to that and that what was the development during the whole process, we came across a definition of a narrow smaller group of truly treated refractory patients or patients where we have uncontrolled inflammation despite effective or presumably effective anti inflammatory treatment.

Okay, thank you. Interesting to note because it's giving more of a practical application that we can also use in our clinics, right, and not just in research as defining difficult to manage spondyloarthritis.

I think this is the first important step on that ways. We certainly will need to study these patients, to manage patients to understand what is the best approach, how to address all the problems outside of inflammation to find an appropriate way how to manage those patients. I think many rheumatologists have ideas how to deal with those how to manage pain in this patient, but there is no unified approach. This is something that will come as a next step.

As a next step, okay. So before we wrap up, could you give us the different elements, the important elements of the definition that you came up with?

Absolutely. So there are three main pillars in that definition. First is a history of treatment with sufficient number of advanced treatment options. In the case of extra spondyloarthritis we define that as a history of at least two biological or targeted synthetic DMARDs given appropriate amount of time to see a response. Second pillar is presence of signs and symptoms indicative of uncontrolled disease that can be defined by a composite outcome measure like ASDAS, it can be defined by the presence of symptoms such as fatigue, extra musculoskeletal manifestations, it can be defined by rapid structural damage progression, or it can be defined even by other symptoms not mentioned here, but still bothering the patient.

And of course, it can be uncontrolled inflammation as reflected by CRP or MRI. And then the third pillar is that this situation, so having signs and symptoms with a history of previous treatment is perceived as problematic by a physician and or by a patient. So all three should be fulfilled cumulatively. Then we can talk about difficult to manage situation. Treatment refractory is a fraction of this big patient population, difficult to manage population, where we ask for treatment failure and presence of objective signs of inflammatory activities as obligatory criteria.

Okay, alright, so thank you very much for giving us insights on the definition of difficult to manage and the refractory type of spondyloarthritis. Hopefully we get to know more about or we get to use the definition and also that will help us in the management of our patients, and also, you know, control disease activity and even improve quality of life. K. So there you have it. Tune in to RheumNow for more updates and use of the a on the ACR convergence twenty twenty four.

Follow me on Twitter at RheumAreampa, and have a good day.

Hello. I'm Adela Castro at ACR twenty twenty four in Washington, DC, and I wanted to, talk to you about the sex related differences in responses of biologic, which is abstract number five ninety nine. So this was a very interesting study that was a systematic review and meta analysis of over 11 studies that included over 11,000 patients. And the intention here was to evaluate if there was any difference between female or male in responses to efficacy of biologics predominantly TNF inhibitors and IL-seventeen inhibitors in terms of VASD I50, ASDAS, and ASAS 40 responses rate. Over here in the study, the majority of the patients with ABA were predominantly male, sixty percent, and more of the male patients had also HLA27 positivity.

So in the in terms of efficacy, it seems that in terms for VAST I50 and VASTAS low disease activity responses, male patients were actually higher in achieving these response rates compared to female patients. Whereas as far as the ASA stories, there was no difference between male or female patients in achieving this response rate, which makes us wonder whether do females have higher disease activity versus should we be utilizing a more gender neutral efficacy measure for these patients. Thank you for more information follow-up on RheumNow.

Hello, my name is Rinalini Day. I am a clinical fellow and trainee in London in The UK, I'm delighted to be reporting for ACR twenty four here in Washington for RheumNow. There was a fantastic session earlier today on RAILD. I'd just like to highlight one particular abstract, eight zero three, which was on serum adipokines and the risks associated with RAILD. So as we know, adipokines have been associated, of course, with metabolic syndrome, but also they have been seen to be associated with the incidence of idiopathic pulmonary fibrosis, which is obviously closely related to ILD, but the evidence within RA ILD specifically is still lacking.

So in this particular study, this was conducted in the Veterans Affairs rheumatoid arthritis cohort and there was just under three thousand patients who had prevalent ILD and they found that while there was no association between adipokines and prevalent incident ILD, there was an association with prognosis. So specifically fibroblast fibroblast growth factor 21 was associated with a poorer prognosis in people with RA ILD. So why is this important? So we know that metabolic dysregulation in our patients with rheumatoid arthritis is an important topic. Extra articular manifestations in general and comorbidities, we know that they should be managed better in order to improve outcomes in our patients with rheumatoid arthritis.

So this just adds to that growing database of evidence that we have on this topic. And actually, the fact that adipokines are so closely associated with the prognosis in RAILD tells us that we should be doing more to manage aspects such as healthy living, obesity, weight management in our patients in order to improve outcomes not just for their disease activity and their quality of life but also aspects such as their extra articular manifestations such as RAILD. If you'd like to know more that was abstract eight zero three and you can also check out the RheumNow website for further updates or you can follow me at doctor mini day on x as well during the conference. Thank you.

Hello, everyone. I'm Catherine Bakewell. I'm reporting from ACR 2024. I'm standing next to my colleague and friend, Leahy Adder, and we're going to talk to you a little bit about updates from this ACR on ultrasound and psoriatic arthritis. There are two sessions that I wanna highlight today.

The first one was session, and I've got the number written down, 16 s o six. This is the ACR proposed, guidance statements for the use of musculoskeletal ultrasound in both rheumatoid and psoriatic arthritis. I would like to refer you actually to an interview with Anthony Chen, that was done earlier today, but the bottom line is that ACR combined with USONR is trying to put out everyday practical application statements for the clinician for the use of musculoskeletal ultrasound in both rheumatoid and psoriatic arthritis. How do we define, these diseases diagnostically by ultrasound, how do we look at treatment response, remission rates, and how do we make this applicable in day to day clinical practice. I also have next to me, doctor Lihi Ader who presented an update on Duet, a diagnostic ultrasound tool, a combined international collaboration with GRAPA, a group for research and assessment for psoriasis and psoriatic arthritis.

And I'm hoping she can tell us a little bit about what you taught us today.

Okay. So DUET is really aimed to develop a new diagnostic tool for enteritis sonographic enteritis. We know that it's very hard to accurately diagnose enteritis in PSA and we hope that this new tool will help us, with early diagnosis of the disease. So this was really an international collaboration. We spent a lot of time training people, and, there was also a unique component of central scoring, which is not usually done in ultrasound studies.

We presented today the preliminary analysis, and, we what we found is that, first of all, many of the or some of the elementary lesions are not unique to PSA. I think this is known to people that are doing ultrasound. Things like thickening, hypoecogenicity, and tesophytes can be found in in older individuals, and and so this is one thing to to keep in mind. Secondly, lesions that seem to be more specific, like power Doppler erosions, were not very common in patients with early disease, but when they do appear, they seem to be very discriminative. Yes.

The third important message is that the ability to discriminate antisitis by ultrasound between PSA and non PSA patients seem to be dependent on the Entezial site. So there are some sites like the patellar tendon insertions, the Achilles tendon, and the triceps tendon that seem to be more discriminative than areas like the plantar fascia or the supraspinatus insertion. So putting all of these together, these help helps us understand or think about the next steps, which are aimed to narrow down the number of sites that we need to scan, to weight some of the elementary lesions accordingly so those that are more discriminative will get higher weight. And ultimately, we hope to create total scoring system, total score that hopefully will help us make diagnosis early, think about prevention studies and so on.

That's fantastic. I cannot wait for those results. I think this is fabulous work that you are doing and have done already, and I know we're eagerly awaiting the final results. You so much for chatting with us today.

Hello, everyone. I'm Richard Conway reporting for RheumNow from ACR twenty twenty four. What an opening day we've had here at ACR. As you know, I'm a big vasculitis guy, and it's been a great day for vasculitis. In the opening plenary session of ACR, we've two massive vasculitis abstracts have landed.

I've already written an article on the TAPER study, and that should be up on RheumNow. So go check it out there. And that is a landmark study and is going to change clinical practice. But I'm here now to talk to you about the other study that was presented, is the SELECT GCA study. So study of upadacitinib in giant cell arteritis, abstract number seven seventy.

So this study compared upadacitinib on a twenty six week steroid taper to a fifty two week steroid taper on placebo. There were two different upadacitinib doses. There was fifteen milligrams and a seven point five milligrams. The seven point five wasn't really as good, so we'll just forget about that and not talk about it anymore. So we're focusing on the fifteen milligram dose, which is the same dose that we use in rheumatoid arthritis, so the dose that we're used to using.

This study is the largest study ever done in giant cell arthritis, four twenty eight patients recruited. Primary outcome here was sustained remission at week fifty two. The numbers here for the upadacitinib group, it was forty six percent were in sustained remission at week fifty two. And for the placebo and fifty two week steroid taper, it was twenty nine percent. When you first see those numbers, they might not sound terribly impressive.

But if you think back to the GIACTA study of tocilizumab, they are quite similar numbers. And in fact, I would say that these two studies are two of the most positive studies that we have in rheumatology. This is the biggest impact that we see from a drug in changing outcomes for patients. The other thing we saw here, again, very similar to what we saw in GIACTA, is that upadacitinib group got much less steroids. So they were getting twenty six weeks instead of fifty two weeks.

But of course, if they'd been having relapses or whatever else, they'd be going back on steroids. But it ended up that they got about half the steroids, one point six grams versus two point nine grams. So I've mentioned it a couple of times and that this study reminds me so much of the GIACTA study of tocilizumab. The results are very similar. The design is very similar.

And coming out of it, you'd be hard pressed to say which of these two drugs is better. In fact, they look so similar that it could really be a flip of a coin between them. And that brings us to the crux of the potential problem for how this trial will get into clinical practice, in that we have the JAKTA study, which was seven years ago now. It was published. We have tocilizumab available.

We're using it in giant cell arthritis. This drug seems to be as good. But we couldn't reasonably say that it's better. And then there is all the other stuff that's gone on with the JAK inhibitors, regards safety warnings, regulatory issues, and then potential reimbursement issues. And it's quite hard to know at the moment how upadacitinib is going to fit into the giant cell arthritis disease management algorithm.

I think we see with tocilizumab that it's extremely effective in giant cell arthritis. It is unusual that somebody would truly fail tocilizumab or tocilizumab would truly fail them. There are a small number of people that does happen to. There are a small number of patients who do have side effects and can't stay on the drug. There are a small number of patients who do not want to do an injection treatment.

And for these, upadacitinib might be an option. Of course, the other thing is we have other agents coming as well. There's other medications coming relatively soon to the giant cell arteritis treatment space. So it'll be an interesting time ahead. So I'm Richard Conway.

Can follow me on Twitter, RichardPaconway, and tune into RheumNow for all the updates from ACR twenty twenty four.