Daily Eular 2025 Recap Day 4 Save

You're listening to a RheumNow podcast coming to you from Barcelona, Spain, and you are twenty twenty five. Hope you enjoy it. Hello, everyone. Welcome to RheumNow's daily recap. It's day four here at you are '20 25.

We're in Barcelona. The meeting has wrapped up, and we've got a lot to talk about in what was a pretty substantial day for the last day of a meeting. Usually, last day of the meeting sort of like a half day and a wrap up of a few sessions that nobody attends, and people are looking at their, phones and trying to find cabs and whatnot, but there was a lot presented today. And, and so, I'm joined here by good friends and faculty who've been covering this. I'm Jack Cush with RheumNow.

Adela, introduce yourself.

Hi. I'm Adela Castro, assistant professor of rheumatology, University of Tennessee, Memphis.

Excellent. And David?

David Lee, Melbourne, Australia.

Excellent. Okay, folks, you know the rules. We're going to talk about our favorite things of today. And I think we're going to be kind of all over the map. We're going to begin with Doctor.

Castro.

Hi everyone. So as Jack was saying, this was an amazing meeting. So it was so many things to cover. My favorite two things from today were number one, late breaking abstracts LB001. These are the results of the phase three poetic PSA one, which evaluated to pravacitinib, as you guys know, TIG1, TIG2 inhibitor in psoriatic arthritis.

These patients, they included patients had to have diagnosis of psoriatic arthritis, They had to have active disease, more than three swollen, three tender joints, the high elevated CRP levels. Something very interesting, they also had to have at least one erosion related to psoriatic arthritis. And the primary endpoint was ACR20 at week sixteen. Of course, as we were waiting and hoping for, ACR20 was achieved significantly more patients treated with ducaracitinib compared to placebo. And then it also met its secondary endpoints.

And in general, it was a very safe medication, no significant, major safety events, as we were expecting. So very, very full trial and very, I'm very hopeful for this medication to come out.

So what was exciting and new about this study other than, you know, do crabacitinib working like we kind of sort of expect from this psoriasis literature and other studies, there were a few things that were controversial, were they not?

So there was a very controversial thing. Think was like definitely a little bit of high plus low response rates, but then I didn't, what I really like about this study is kind of like its efficacy, not only in psoriasis, which we already know that the patients are already using it for, but also, you know, in significant, not only in psoriatic arthritis, and then also in the secondary endpoints, you know, kind of like the patient reported outcomes, fatigue, spores, and without significant safety even.

So the two things that I thought were interesting, this was Desiree Vanderheide presented this, right? Two things that

were really

interesting about this was one, the enthesitis scores. So it was a really positive trial. It looked really good. It had really good numbers, but there were two things that didn't hit on their pre specified endpoints. Was the emphesitis and the other one was the

X-ray So

why don't we go into that a little bit?

Yeah, so in the initial analysis, the actual x-ray, this x-ray progression was not significant. So they ended up doing a post hoc analysis and in this post hoc analysis, they ended up doing like some imputation of the data. And in the end, it did show a significant kind of like effect on stopping, on delay in radiographic progression in patients with tucravacitinib.

So yeah, and of course, Desiree is the queen of one analysis and two X-ray outcomes. I mean, it's the it's the Vanderheide Sharpe score named after her and her modifications and many many years of work on that. But what she pointed out to the audience was that in the analysis that was prespecified, it was they assumed that the X-ray data would be normally distributed, and she pointed out that's usually not the case. It's it's it's not normally distributed. So they had to change the methodologies of of of analysis to an ANCOVA that would allow for sort of a nonparametric.

And when they did that, as an originally analyzed, the differences in sharp score progression, which was a little bit there but was not significant. Now when it was, reanalyzed the correct way, and there were two different ways that they looked at it, It looked much better, and it was now significant. And what was really significant about that was this is a week sixteen

Right. Showing

evidence of X-ray, retardation, if you will. And I think that that's impressive. And I would never have actually expected that with any drug at week sixteen, no less a new drug, no less a drug that's a different mechanism such as, the the TYK2 inhibitor. So I thought that was exciting. David, what do you think?

Yeah, I mean, obviously it's the kind of thing we've had a little bit of experience with already. I don't know about what it's like for all of you in Australia, the label is psoriasis, but rheumatologists can prescribe it. So make of that what you will. It seems like it's been, in practice, it's been great to use. I guess I still ask the question.

I think it's still that the studies haven't really answered this as to whether we can consider it at the same line as a biologic. And that's fundamentally the big question that we're all asking. I guess the claim that I suspect they want to make is that this is as effective as a biologic, but safer and more convenient. I don't know if we can say that.

You're not gonna get safer. You're not gonna usually get better. You're not going to get cheaper. So but what would make it akin to a biologic for you, David, and for you, doctor Castro, Adela? What would make it so that you would consider it equal to any of your biologic choices in PSA?

What would you like to say?

No, I would definitely, I think it's amazing kind of like the safety profile of it and the rapid effects and also like the secondary outcomes met. So definitely I would use it, you know, instead of, or even in combination with a biologic, you know, in patients that are not responding what I'm expecting, or like there are other subsets of the disease that are getting active. So I think in combination it will be a great medication as well.

Yeah, combination's got a hot area and there's a lot of work being done on that, but it's all pretty much off label at this point.

Right.

But you know, yeah, I think people are considering that. I think that for me, the benchmarks that are gonna get you to biologic equivalent is going to be, you know, the same level of ACR twenty fifty seventy, and the same effects on dactylitis and enthesitis and radiographic benefit. And they kinda showed that here with with the reanalysis on the X rays. Their ACR twenties were really strong and high, not not like thirty percent. I can't remember the number, but it was very it was up there.

And and the the other thing

was the

well, how much was it?

Fifty four point two percent compared to over like twenty percent.

And placebo is how much?

34, it was like over 20 points over placebo. And then the ACR 50 was like over 10%, you know, over 10 points above placebo. So

So that's impressive. Yeah. I'd like to see a little higher, but that's still, you know, it makes you in the game. They the pre specified analysis on enthesitis, they use the leads enthesitis index, LEI, which wasn't significant. Dactylitis was significant as measured, but the leads and the site is index wasn't, but, Philip Meiss and, Desiree have told me they don't like the leads because it's too stringent, doesn't perform as well, and they like the spark which is being, as being more dynamic and more really representative.

And the spark, enthesitis index was significant. So, David, is this bothering you that the pre specified don't work and the reanalysis do work or is it doesn't Oh,

no, it definitely matters. I mean, we'll see the full paper, won't we? But the I think it's a super competitive environment in psoriatic arthritis right now. I mean, you're going to have to this if you if you want this to be competitive with biologics, you're saying this is as good as bimekizumab and giselkumab and the other agents that we have, and knowing as well that the field is moving on as well, and there's been a lot of talk about nanobodies at this meeting. I think it's progressing.

I guess I worry for ducraft and synov that it's maybe there are just some questions as to whether it is competitive at that level, especially extraterpillar manifestations. And I think, yeah, I guess if that's the case, then exactly where will it slot in in terms of our treatment algorithms? That's been the question all along. I guess that was the question with the premilast and it found its place. So I'm sure there is a place.

I'm sure there'll be uptake. And I'm sure we've already all had some success with it. It's just it may not be able to do exactly as the manufacturer hopes it might.

So, the success of Aprimolast in the psoriasis dermatology world is in many ways based on the fact, based on the safety, that there's no monitoring and there's no safety signal. So far, ducravastatin has really enjoyed almost the same degree of safety, and that's, again, that's been so in other psoriasis and PSA trials with ducravastatin and certainly in this one. The safety data looks really nice. So I think that that's encouraging. It'll be exciting to see where this goes.

And and, again, I I like asking the question that, that Adela answered was how do where do you see this fitting in and whatnot when doctor Vanderheide was asked, where do you see this fitting in? She was really smart in saying, we need to see. Meaning, she wants to see more data. You know, this this is just, you know, a large trial that, that's encouraging, and I think she's encouraged by that. But she's not going out on a limb and saying it's her second favorite, third favorite, or whatever.

I think I do think we need more clinical trials, and we need to get it on the market and see where people actually start to slot it in. Is it gonna be, you know, above methotrexate, above Epimelast, above secukinumab? Again, there's the advantages of oral versus, injectables, and we'll see where this goes. David, what was your favorite for today?

Yeah. I mean, there's a lot of great stuff. And I have to agree with you. The last day is getting punchier and punchier. I love the late breakings, though.

And there's a few there. I wanted to talk about first Neurandormalast because I think we've been waiting for this. Is it? Was, I should say- David,

before you go on, say the name really slowly, because it's a new big long name. Go ahead.

Yeah, Nerandomolast. Ust. There we go.

Nerandomilust. Thank

you. They're enunciated. Definitely not perfectly. Having to look at the word while I'm doing it. Doesn't quite roll off the tongue like Nintendonib does.

But with due course, give it. Because the whole idea is that this is a success attempt to nintedinib. I think all along, with the time from when we've started to play with nintedinib and after the in in build results, you know, over the last four years, I guess at the poster they've always been saying, well, just wait until this next molecule comes along. It'll come along, it'll be better tolerated and it'll be more efficacious. So this is a molecule which has been just like INBUILD it looks at an indentinib in, I guess, what we now call it's progressive, the fibrosing subtype of ILD that's not IPF but still kind of in that vein.

We saw the main paper published last month in the New England Journal of Medicine. That's the overall group. But of course, when we look at these things, we feel that our patients are different to the overall cohort. And so that's what we saw presented today by Doctor. Hoffman Vold very eloquently about the subtype of where just under a third of patients in that overall study actually had a background to connective tissue disease.

And so it was interesting to see how the performance was. And I mean, the bottom line is good. I guess the question and you got up and asked very good questions, Jack is in the detail. So headlines are: There is a mortality benefit for our patients from this drug. There is a you can see there, there's a significant, you know, at least a statistically significant difference in terms of FVC, the primary measure.

And as well, it's quite well tolerated. So I mean, I guess we always question about diarrhoea with this, and that was always one of the problems with entendinib. Still there's one of the problems with entendinib, and entendinib hitting fifty percent or more getting diarrhoea. So in this one, we're talking about thirty percent in the placebo and kind of with Nerandomolast in the kind of high 30s as well. So, I mean, not that much different.

Of course, we want to see the detail. I think there's a few questions about this you raised about the background Pembrolizumab sorry, background of Indatinib going on at the same time and where that interaction sits. I think there's some questions about that. I can't imagine us using this as combination anti fibrotic therapy, but maybe I'm just not imaginative enough. I think we want to see the exact detail.

We didn't see the exact details in this about the interaction with background immunomodulatory therapy. I was just trying to look at the slides later on and do the numbers. It seems like most patients were on some immunomodulatory therapy within the sub cohort, but I can't really say for certain. And there's a big difference between a little bit of hydroxychloroquine and then a heap of mycophenolate. So I think we need to try and understand where those interactions sit.

Yeah, a lot of them are on DMARDs for their autoimmune disease, RA scleroderma inflammatory myositis making up about, that was about eighty almost eighty percent of the autoimmune group. But then there was that one third who are also on entedinib made by the same company making this new drug, but they wouldn't allow tocilizumab, and their explanation was that entedinib is actually approved in patients, the patients that they were studied. Whereas, not all the other ones that are their competitors are approved, but yet they allowed immunosuppressive. So I think that for me, I don't care that they really had the nantentenib other than it complicates the diarrhea numbers. I mean, diarrhea numbers were 35%.

And at the start of their presentation, they were trying to say that, you know, that nantentum, we know is a problem because of that, and we and we are looking for, a, a more effective drug and b, a better tolerated drug, and that's what they were trying to tout, but yet they still had high diarrhea numbers. Now, again, not having used the drug or tried it or with a patient to know how big a problem it is, we'll find out. But they say they're going to do studies in the future that they'll get to a more pure answer, on what this drug can do. But I agree with David. The big news was whereas nantetinib sort of flattens out that rate of change on FVC and that's its primary efficacy.

In this case, it actually made those numbers better and made the mortality numbers better and did so in pretty short order, which was surprising too. Adela, what'd you think of the data? I think you were there, right?

Yeah, I was there. You know, I agree. I really like the the data on mortality because not only we see the difference in the high dose in the eighteen milligrams, but also in the nine milligram doses, we see that significant prevention of mortality, which we've never achieved with other medications for ILD in the past. So that's definitely very important. And then I also like the results on prevention, I mean, kind of like prevention for acute exacerbation of ILD, because we know that these patients can exacerbate by kind of like out of nowhere, and then the more exacerbations they get, the more risk for mortality.

So decreasing the risk for exacerbation was also very important. For me, I agree with you guys that the nantatinib, a third of the patients being on nantatinib kind of like, you know, mask all the other results. Do you think this result will be because of the combination with nantatinib or, you know, and then the side effect profile also can be affected by nantalanem. The background immunosuppression, I don't think it was that doing that major. There were not so many patients, you know, that much about batch immunosuppression, mostly were kind of like hydroxychloroquine were the most patients on it.

So I don't think that was doing that many difference, but I do agree that I want to see the results, you know, when the patients are treated appropriately with, you know, like mycophenolate or like IL-six inhibition.

David, I don't know if you saw the data as it was going by and I'm trying to find it on my phone, but the one thing that stood out to me on what seemed like it was a effective intervention in a well done trial was, on safety. The serious adverse event rate was like thirty percent, which is really, really high, but it was equal to the placebo population. And that made me think, you know, is that because of the population we're dealing with? These are autoimmune patients who also have ILD that's progressive. They're on very aggressive medicines.

They're probably on steroids too. You know? So I wanna know more about that. But, other than that issue, well, it's a big issue, serious adverse events, meaning

I do have the numbers.

Right. You get hospitalized. You or you die or you and actually, they had a fair number of deaths, which is that's immediately a serious adverse event. Did you see any other safety concerns with this?

Oh, look, I mean, I firstly want to emphasize that I think these are quite unwell patients, like you're getting at, really. I mean, thinking about that group, thinking about my patients in clinic that would fit in there, this is the kind of thing where you let it run and I guess we used to just assume that these patients want an inexorable march to death a lot of the time. So I think it's and they fail a lot along the way. They get, like you say, they get hospitalised a lot along the way. So maybe the serious adverse event rate is not entirely surprising.

And yes, it was pretty, I think Adela was mentioning it, it was similar. I've kind of got the numbers in front of me. Placebo, serious adverse events was thirty nine percent, the lower dose of nerandolamolast was thirty three percent, and then the higher dose was thirty nine percent. So very comparable. I think obviously as well, I think we do want to watch for safety signals with this in terms of the PD-four.

I think that that will come out but you won't be able to tell it from this kind of short term follow-up. We I mean I I think the the key thing from the Entebnib was always I I feel like talking amongst ourselves. The issue why we didn't feel like we were using it more and maybe patients often came off quickly or maybe didn't want to start it in the first place really came down to the diarrhoea. And you have to say that isn't that isn't so much of a problem when we look at it in this group. Yeah.

And I also found that, you know, interestingly, like the fatal adverse events were like more in the placebo, but they were all very minimal, but they were more in the placebo group compared to like the ones in the neurandomimbus.

Okay. I'll I'll give a little more perspective on my negative comment. If I wanna get under the skin of a rheumatologist, I I I challenge them to manage a patient with scleroderma. If I really wanna get under their skin, scleroderma with ILD. So, yeah, this is a a tremendous unmet need area, and so that's why I think you're hearing, us, discuss this with such passion because we certainly need something like this.

I wanna go over what I thought was a really interesting. My two that I'm gonna present our classification criteria. I was sort of surprised by the presentation on, the ULO R crestification criteria for hemochromatosis arthropathy. And, it was presented by, doctor Patrick Keeley from The UK, and he gave a little bit of history as to how all this evolved, you know, discovery of this. Ralph Schumacher's role in this pointing out that hemochromatosis had a significant arthropathy component to it, and that in the last sixty one years, there's still a tremendous amount that's not known about this.

Hence, the convening of a classification criteria committee. And, you know, the doctor Kelly went over the importance of, you know, the genetic testing and the iron overload state and joints and the other organs being involved. So they went through a process as to how they, came up with their their criteria. I immediately tweeted, you know, the this one, the iron fist. Let me do a camera right there.

Where if you make them someone with hemochromatosis make a fist, the first two knuckles are rising up because they can't fully get them down like you and I get them down. They're kinda up here somewhere, And that's just basically indicating that sort of osteoarticular involvement of MCPs two and three, and they call that the iron fist sign. I've never heard that before. David Adela, did you know that?

I mean, it's the kind of thing which I guess you hear about maybe gets mentioned, to I don't know. You don't really see as much of an I guess so I think the thing that was really stunning for me out of that, apart from the fact that I'm biased towards Patrick Healy because he on he's in my hotel and on the we're in the lift together and he told me how good my talk was the entire lift ride down. He can do whatever he wants really. The hemochromatosis, the most common manifestation that bothers patients that affects patients, apparently, is arthritis. That was stunning to me.

It's true that we are not organised at all, and I don't think we know at all how to manage it, really. And I think probably the most touching moment of it was the patient partner lead for the organisation getting up at the end and basically thanking the group for doing something about it, because I think that really hits home. Gets me where you feel it. But, yeah, I guess my point out of that, to your answer to question, the kind of thing that I feel like I've never really actually seen properly in clinic, maybe apart from squinting once or twice when that's happened to have come across my desk, you know, in my clinic room. So I guess I need to start looking better and I feel bad that we're not servicing these patients better.

Yeah, given the frequency of this in the population, at least genetically, we probably should be seeing more than we are. And I might even go as far as to venture that if rheumatologists stayed involved in telemedicine, we might make more of these diagnoses because you can't do a really good exam. But you do a number of these camera moves, and one of them can be show me your fist, and you start seeing that iron fist sign with those two knuckles raised up, it's like, oh, let me let me look into that a little further. Maybe we'll identify this a little more. Before I get a Adela, your your opinion on this, I wanna go over the the criteria that they came up with.

It's a point system. Everything gets a point except for, the onset of joint symptoms before age 50 gets two points. The absence of any PIP involvement gets two points, and then everything else gets one point, including iron fist, hip or ankle surgery, which I really would like to know more about. MCP two, three, or four, five tenderness, which, they extended it to beyond just two and three. X-ray abnormality with joint space narrowing of grade three or more at the MCP, X-ray of, ankle joint space narrowing and, hook osteophytes, which are, we know a part and parcel of the diagnosis.

Again, sensitivity of 93, specificity 93%, sensitivity 71% if one has, a score of five or more out of a potential 11 points. What I was surprised at is why isn't ferritin or an iron measure in there? I think that they were assuming that maybe you already had that information and then you were going to use the criteria to affirm that they would have this diagnosis. But then again, remember, this is classification, not necessarily diagnostic, and classification may be more for the importance of studying the condition and doing clinical trials. Adela, what do you think of this, this presentation?

So I've never heard the iron fist before, know, I'm bad with eponyms. I've seen patients with this condition before and I've seen the classic signs before, but I didn't know the name of it. And I think it's very helpful because I agree that sometimes you wanna make sure that the type of arthritis you're seeing is related to the condition as opposed to something else, you know, because sometimes these patients can be misclassified with other conditions like, you know, seronegative gray or like some other inflammatory arthritis. So you really wanna know, you know, is this hemochromatosis related arthropathy? So I think it's important to have this classification criteria.

Yeah, I really think it's a significant unmet need. Like I was there honestly at the class, there was a whole bunch of classification criterias that were presented today. And I was there to hear the RA ones, which I'll talk about next. So I was listening to the hemochromatosis and I thought, oh, this is good. He's very good.

Wow. That's new. I didn't know that. Why? I just started taking pictures because it was I needed to talk about this.

So anyway, let's move on to our second of the day. Adela, what's your next that you'd like to discuss from today's presentations at day four UR 20 '25?

This was very interesting and we all were there. This is also another late break in abstract, two. And this is the efficacy of Akcea, which is an app based intervention that combines home exercise programs, patient education, comprehensive disease management for patients with axial spondyloarthritis over a twelve week period. And in this study, which was done in Germany with German patients, they included in general 200 patients, and then they kind of like randomized one to one, placebo one to the app, and then they measured the outcomes after twelve weeks. Interestingly, as you pointed before, know, there was a lot of female patients in both groups, which we were wondering, did this represent the true or like the common axial spondyloarthritis type of population?

But also interesting is that a significantly higher proportion of patients kind of like achieved the primary endpoint, which was predominantly kind of like patient reported outcome of like FAST die. But they also, the responses for ASAS twenty and ACES forty were very, very high, which I was very impressed about because we've never seen kind of like these high responses, even with like biology people, but also other the question. So I found that the app was very helpful because any intervention that kind of like gives the patient the ownership of the disease is of course helpful and can help the patients do better. But the impressive results compared to placebo, because there were very minimal placebo responses as opposed to the effectiveness response. It's kind of like raised my question if there was any potential bias, including the health or aesthetic of patients having the app.

Yeah, so again, the audience, Axia is spelled A X I A. I kept looking at this in the program saying, what in the world is this? It's a an intervention. It's nonpharmacologic and whatever, but it's it's an app. It's a it's digital instruction.

And half the group were using this app developed by two medical students to guide them in their exercise routines. The other half, the placebo, and by the way, there's supposed to be a crossover. We don't need to hear anything about the crossover in this. But in the other group, they got nothing. They got no app.

They got no instruction. So this was as Adela is pointing out, there's a bias in that one group is getting an active intervention. The other group was doing the same old same old. And on one hand, they showed these significant reductions in bas die, bas fee, a s q o l, but also a s s 40, a s s 20. I mean, really kinda like I wanna say it was like 30% ASAS 40 and, and like, I mean, really big time separation.

But then again, the placebo group didn't get any intervention. So I would expect their placebo rates to be low. And the question is, if I made these people, you know, ride the merry-go-round, you know, every day, Monday through Friday, as part of their therapy, would they do results like this? Meaning and merry-go-round being a passive activity, but you're involved in something and you're measuring something. Or was it the fact that they were in fact, doing active exercise, which we know makes everyone better.

But to me, the bothersome part of this data, and I went to this presentation wanting to believe this, and many, many people have said just as Adela has said that this was kind of exciting. This was kinda new. This was the surprise of the morning, and they really like this data. You know, I looked at it and said, wait. The placebo group was fifty four percent female.

The, active intervention group was seventy percent. The seventy two percent female. Wait, isn't this ankylosing spondylitis? And then when you looked at the other characteristics, thirty two and thirty three percent of these people were active in sports. How many of my patients, I don't care what disease we're talking about are are playing soccer on the weekends or playing cricket on Tuesday night or skating up and playing in an adult hockey league.

I don't know what kind of sport these people. So, it's a lot of women. They're active in sport and what the speaker when I asked him these questions, number one, he denied that spondylitis is a male predominant disease. He said it's one to one. I'm sure you can find some study that proves that.

Sorry. That doesn't exist in the real world. And if you go scraping for women, yes, you'll find a lot of women who are undiagnosed and not considered properly. I get that. And women don't do well in spondylitis.

So I don't wanna understate their importance and their and how much we need to go after them. But to make them the dominant population, he pointed out that women are better at apps. Women are better at performance in clinical. So if you do clinical trials, get more women and you're and you're doing an app, get more women involved. So, I I immediately, now have some worry about this data and obviously it's been done in one center, it's got to be done again.

David, what do you think of this?

Yeah, so look, think every, you know, a lot of early positive studies are always done in favorable situations and then they get good outcomes. And of course, then you repeat them in a broader stage and they don't do quite as well. But I guess I want to put aside the actual app itself. And I guess for me this is a proof of concept as to what we should be thinking about. Whether it's Axie or something.

And Adele, like getting up and asking that question about attention bias. And I think that's obviously very true. But part of it is that we don't have ways of scaling up giving our patients attention when they're not in our clinic room. This is a fundamental thing, and we all pay too much attention to our phones. And we need to find ways to harness this, to deliver the non pharmacological impact, because I think we can do that better.

Every day I do Duolingo on my phone. And so there's a few lessons from that to try and learn a bit of Italian, right? I do it every day even though, you know, life is busy and everything. Somehow I still do it every day because it's gamified and I think I'm sucked into it. But then is my Italian getting better?

Well, it only really gets better when I'm actually forced to do other things on top of that as well. So when I'm actually, you know, the times I've been in Italy or trying to speak Italian and then pushing myself, that's when it builds on this. And I think it's the same with this app. I think that maybe if you put this up head to head over the biologic, it would get drowned. No question.

Right? No one's really suggesting that. But if you as as add on therapy to an otherwise favorable environment, I could see this adding further value. Maybe not the kind of, you know, what we saw ASAS forty twenty to nothing type of thing here. But this I think conceptually, we need to start thinking about this kind of thing.

I guess the final thing is would I pay the big money for this, Which is, I guess, possibly what's being proposed. I think it depends on how much kind of money.

Yeah. That's another another significant consideration. Alright. Who who's next? David, you got no.

No. Wait. I can't remember who who who who went first here. Yeah. That was Adela.

So now David you.

I'll make it quick. I realise we're running out of time. I really want to talk a little bit we don't talk much about OA here. Feel like I want to talk about the Levi four abstract that Phil Conahan presented. This was a follow on from some data we saw at ACR last year as a late breaking, as a last late breaking oral abstract at ACR twenty twenty four.

So what is LEVIA-four? It's a novel neurotrophin inhibitor. If you look at the different targets that are possible in terms of nociceptors relevant to osteoarthritis pain, this is one of them. It's from the same broad family as friends that we remember from before, NGF and TRKA. NGF, as you remember, had safety issues with rapidly progressive osteoarthritis and TRKA struck out for other reasons.

What I'll say is that this actually looks like there's benefit there, there's clinically meaningful benefit, and it didn't have any other safety issues. Now this is a phase two, we want to see the phase three data. We know that to some extent, tanezumab, the TGF inhibitor from before really only started to stumble when it got to the late stage trials. But we don't have anything in this space at the moment. There are a lot of people affected.

And yes, there might be other things in our armamentarium, including apps and including GLP-one agonists and all the rest of it, which will probably help in this situation. But I feel like we need something for osteoarthritis pain that's better than what we've got right now.

Yeah, how was that delivered? The drug?

How was that delivered? Yeah, that's a good question. That is, I'm pretty sure it's subcutaneous but I can we'll check on that. Yeah. Yeah, IV.

Sorry, IV.

Excellent. Alright, I think that we do need to have clearly OA is the gigantic unmet need in our world, and why not have more. So I just, I'm gonna change in my mind. I was gonna talk about the RA treatment guidelines. Can briefly state that they were presented by Professor Joseph Smallen, did a really good job.

This is an update to the 2022 guidelines and not much change, but what they did do was they paired it down. They kind of simplified things. They dumped, you know, two or three of the overall recommendations. They modified, a number of them. The main modification in my mind was, what happens after you have failed your first conventional DMARD, methotrexate, or substitute.

And if you're not doing well in the old guidelines, what happened was predicated on whether you had poor prognostic factors, And what was important about that was that sort of distinguished one of the differences between the EULAR guidelines, did use in decision making, and the ACR guidelines that did not. And there are reasons for that. Anyway, in the new guidelines, they dropped it. But more importantly, if you failed a conventional DMARD, you're now moving on to adding a biologic or targeted synthetic as the next recommended step. Not a recommendation that you flounder around in another conventional DM or make a sort of sideways move.

I thought that that was a big move but and they were being bold about that. They were bold about saying methotrexate first rules and dominates. And as much as we might talk about, if it's my mother, I'm giving her a biologic and methotrexate. If it's my mother-in-law, she's getting methotrexate. You know, and they're saying methotrexate is where the data is.

So that was one, the one big change. Did anybody have anything else that they got out of the guidelines other than that?

Well, it didn't change my practice that much. You know, that's what I how I do right now. I usually maximize safe, I use as much as possible unless there's a contraindication. Then if the patient is not responding well, I jumped right away to a biologic or a targeted synthetic.

So go ahead, David.

Oh no, no, no. Was just gonna say, it's always interesting to hear the discussion of bad JAK inhibitor safety. And everyone's talking about waiting for the baricitum study that hopefully we'll see next year. And and Joseph Smallman obviously alluded to that as well.

Yes. I think we will stop at this point. I wanna thank the audience for tuning in and following us this week. If you haven't seen any of our daily recaps, there are a few that you can watch or listen to. We have a lot of good videos and a lot of good podcasts coming from this meeting that I think could keep you busy for a few weeks as, this meeting comes to a close.

Since we're coming to a close and since David is using Duolingo, we're gonna end with foreign language, goodbye. So I'm gonna say Did I get that right? Or is I'm doing that wrong? Yeah. It's all wrong.

Alright. What should I what should I have said, Adela?

Adios.

Oh, thank you. Okay. And in Italian, David?

That's Amelia. I live with Eci.

Okay. Della, do you have another language you wanna throw in there?

I also speak Italian, so I was gonna say ciao.

See? I I I I need to get Duolingo. Thanks very much, friend friends. Take care. See you later.