EULAR 2026 PsA Update What's Changing in P Save

You're listening to a RheumNow podcast coming to you from London in EULAR twenty twenty six. Enjoy. Hello, everyone. Welcome to RheumNow. We are post EULAR, and this is the psoriatic arthritis panel discussion.

I'm joined today by three of our faculty who are at UR twenty twenty six in London last week. We covered the meeting, had a lot of great discussion, a lot of great presentations. Now we get together after the meeting and sort of rehash what was of interest to each of us on a specific topic, this topic being psoriatic arthritis. Let's start with introductions. I'm Doctor.

Jack Cush from Dallas, Texas. Nelly?

I am Nelly Ziadle from Beirut, Lebanon.

Anthony.

Hello, I'm Anthony Chan from Reading, United Kingdom.

And Peter.

Hi everyone, Peter Nachter in beautiful Downtown Brisbane in Australia.

We are totally global and again, these folks did a phenomenal job last week. They were all over the meeting. Their coverage was just stellar. So it'll be interesting to see what they chose as being highlight presentations for them. I'm gonna ask them to give us their presentations along with the abstract number or citation so that you may follow along at home.

Let's start with Nelly.

Thank you, Jack. Think

Wait, wait, Peter wanted to start.

Let's start with Peter. I did that wrong. It's okay.

Well, thanks, Jack. It was really very, very good meeting. And in PSA, we had three that we're gonna cover tonight of the key presentation, I think of the whole meeting. So to set up the one of the most important ones that Nelly is going to cover, I wanted to throw out the two little ones, OP o one eight seven by Garamond and o P and sorry, OPO seven o by Lily Lehi Eder. And the Garamen's very interesting because this whole question that you have brought up many times, GLP one agonists, and how we should take the ball and lead by examples what I feel.

So Garman looked at the predictors of response at one year from the speed trial in PSA, which was early PSA. It was step up conventional synthetics or combo conventional synthetics or a TNF arm. And they said, what are the predictors of a good response at forty eight weeks? And treatment came in number six. But what won it?

It was BMI was the most important predictor of who is going to do well, if you can do something about that BMI at forty eight weeks. So it's setting the scene for this whole area of GLP-1s and Lehi even just use diet. And she used a, in a PSA multicenter study, she used standard of care versus two diets. One was Mediterranean, one was low calorie. Turns out that the diets didn't matter which one you chose, but if you're able to bring the BMI down, in addition to what they were normally on, because they had moderate reactive, PSA when they went into the study, you can make a significant difference in dapsa at twelve weeks and twenty four weeks.

So Nelly's going to tell us about this important study of a seventeen inhibitor with a GLP-one agonist. But we're seeing time and time again in PSA with metabolic syndrome, and all the other risk factors, we have to start using these medications, and leading by example. I'll wait to hear what Nelly has to say about her excellent presentation.

Well, we get into, the Together PSA study, Peter, do you think that the BMI is, we know it predicts, first off, obesity is a risk factor for getting arthritis. It's a risk factor for poor responses to drugs. Is BMI as important, is it more important in psoriatic disease than for instance, maybe RA? And, what do you think about that?

So I think we underestimate the deep kerbner phenomenon part of PSA. So if you're carrying increased weight, and we're talking BMIs of over 30, and even up to 35 in some of these studies, that affects, sacroiliac joint MRI pictures of bone marrow edema everywhere. It affects hips, knees, ankles, feet. It makes it almost impossible to examine small joints of hands and feet. So I do think it's very different to rheumatoid arthritis, because of this deep curvular aspect carrying weight and the effect that has on joint disease.

I have the impression though, that it's almost like a unidirectional negative, meaning if BMI is a problem, only bad things are going to happen. Certainly in psoriatic arthritis, there's great data that losing weight gets better responses, unlike in other diseases. But is it just unidirectional just that this obesity is such a weighty factor that, you got to do something about it? Is it bidirectional meaning that being thin is a good thing and losing weight is a good thing?

Well, fat's very active metabolically, but you should argue that for rheumatoid as well as for PSA, shouldn't you? So that doesn't make a hundred percent sense. But I do believe that the data on inflammation being contributed to by obesity, whether it's gout flares, whether it's knee OA, whether it's post joint replacement, whether it's even lupus nephritis flares, there's something in adipose tissue that drives inflammation on top of metabolic syndrome in PSA, on top of the deep curve phenomenon as well.

Anthony, you're a spondylitis maven, is it as big an issue in axSpA as it is in PSA?

Certainly the response to biologics would be much less with the higher BMI's, but this is played more so out in PSA. I think a lot of these patients have a metabolic syndrome. In the early stages we see they have fatty liver disease and more difficulty with glucose control, with insulin resistance as well. So I think that is very inflammatory. We know that the immunological pathways and defects in NK cell signaling, for example.

So I think there are many more pathways that will be dissected once we understand this whole aspect of trying to reduce adiposity.

Jack, can I throw something out there? We've got to think about safety if we're going to use these GLP-1s willy nilly in the water supply. And if anybody wants to have a good look, there's an article by Zhang twenty twenty five in the journal Gastroenterology, where they looked at one hundred and five thousand patients treated with these drugs from 55 randomized controlled trials, and most of the adverse effects were nuisance GI. Pancreatitis very rare, the rest pretty harmless. But I have now come across a couple of instances, and I'm just throwing it out there, of mesenteric ischemia, and mesenteric thrombosis that is possibly associated with these drugs if you lose a lot of weight fast.

So if you're going to do it, you should do it in a controlled situation and not an excessive rapid amount of weight loss, because there's some effective GLP-1s on the splanchnic circulation. I'm just throwing it out there as kind of a coming out of left field now, a couple of these funny case reports of mesenteric ischemia and thrombosis.

A lot is written about and said about the tolerability of these medicines, and I think that Doctor. Nash is correct in that it's mostly nuisance, but the fact is there's fifteen percent who can't take the drug can't tolerate it. They don't like the nausea, the abdominal discomfort, or the GI symptoms of constipation, or throwing up, whatever. And then there's this rare stuff, you know, blindness and pancreatitis, and now, but those are all rare events that you only see in a 100,000 or something like that. The benefits far outweigh the risks.

And I think that most people don't know what they don't know, but like Doctor. Nash is intimating here, we got to know about these drugs because they're going to be in play. And you have to know, you know, because it goes in play and your patient's on azathioprine. You blaming azathioprine for the belly issues, or are you going to blame it on the GLP -1s? There's many of them.

So without further ado, we want to get to Doctor. Zayed, who has this really interesting study. Go ahead, Nelly.

Yeah, so we have a lot of buzzing around GLP-one, but I think it also makes sense a lot in PSA in particular because of the metabolic syndrome. So there were at least three abstracts about it. I will talk about Together PSA study, OP069, presented by Laura Coates. It's a Phase 3B study. So they compared the impact of tirzepatide plus ixekizumab compared to ixekizumab alone in achieving measures of PSA disease control.

So this was a 3B multicenter assessor blind, so not randomised controlled trial, it was only assessor blinded, open label trial that included patients with PSA and obesity. So obesity BMI more than 30, or patients with overweight, so less than 30 plus one additional weight related comorbidity. So this is a very particular population. All the patients also received counselling for healthy diet and exercise, and the primary endpoint was a composite one achievement of both ACR 50 and more than 10% of weight reduction at week thirty six, which is a little bit weird because we don't expect weight reduction with ixekizumab alone. So they had one hundred thirty eight patients in the combo arm and one hundred thirty three patients in the monoixekizumab arm, mostly seventy percent females, BMI thirty seven, high disease activity dapsa was around 50 in both groups.

Now at week thirty six for the primary endpoint, thirty one percent of patients received the COMPO therapy achieved the study primary outcome, so ACR50 and loss of 10% of weight, compared to 0.8 in ixekizumab alone, which is mostly expected. Now, if we want to look at the data that's important to us, so at the joints, ACR50 response was different as soon as week forty. So eleven point one percent ACR50 percent in the combo arm and 3.9 at the monotherapy arm. And this difference also continued until week thirty six, thirty three percent for the combo arm and twenty percent for the monotherapy Also other measures were significantly different, especially dapsa, LDA and the remission rates at week four and at week thirty six, forty percent compared to twenty six percent. No adverse events, mostly mild, moderate and what is known, and so they think that we should use this comprehensive treatment strategy in patients with PSA and obesity.

Now this is very important, it answers a very important clinical question. These are patients who are TNF inadequate responders, so they have already difficult to treat patients. However, the study is open label. Difference between the two ACR50s is only thirteen percent, so it's not really huge. It is statistically significant, but I don't know how clinically significant it is.

They didn't study skin. And the main question that we heard also in the halls, what will happen on long term? So how long will we continue these GLP-one agonists? Will we continue them forever? What will happen if we stop them?

Will we use this benefit? So I think that we need more time to assess really the value and the place of this combination.

Yeah, it's sort of the big issue with GLP-1s and their plethora of benefits, beyond diabetes control, weight loss, sleep apnea, cardiovascular outcomes, and death. Those are the gigantic return on investment. And the question is, once you lose your 33, and get control of your disorder, do you stop it or you continue it? What's going on, I think in the real world is, it's often mandated by insurance. Sometimes they'll only allow it for a certain amount because they can't have everybody.

The number is something like eight percent of The US population is taking GLP-1s, the last number I looked. Another way of looking at this is that these are so popular, the companies that make this made $19,000,000,000 in the first quarter of this year, dollars 19,000,000,000. When Humira was doing fabulous, it was making 22,000,000,000 annually, dollars 19,000,000,000. So this is big. And the question is, are societies and municipalities gonna pay for this?

I think what will happen is that we'll go on modified regimens, micro dosing and whatnot. Peter, what do you think?

So exactly right. So two things, Lilly who make a tirzepatide have their oral. So they've already done a study where it's injected for a number of months and then continued with their oral tablet. That's if you have to stay a longer term. And to be fair, it's not always very well tolerated, as you said, you know, one in five get this, one in four get that nausea, diarrhea, constipation.

But I always get in our neck of the woods is not covered for obesity, only diabetes. So I get people to pay for their own for six months, lose 15 kilos. And then I say, now you can stop and fight to keep it off. And if you can't, then we have to microdose. And I think that's what people are going to do.

I think even weight watchers are suggesting we microdose this stuff. So it really should be in the water supply, but it's got to be used carefully.

So Nelly, how much weight did these folks lose? To have the combined endpoint, they had to lose 10% of their body weight along with the ACR50. But how much weight did lose? Because the argument was always going to be, are they better because they lost weight, or are they better because these GLP-one drugs actually are immunologically active and possibly anti inflammatory?

So I don't have this data in the abstract, but I can tell you that there are two other abstracts that really looked into it. One by the team of Vincenzo Benelito from Italy, and they found that there was a quick drop in CRP even before the loss of weight. So they hypothesized that it is really also an anti inflammatory effect. And another study also presented as an oral abstract by Punktin Mehta, she also said that they did an adjusted analysis. Adjusted for weight loss, and also they found there was a benefit.

So we hear some studies like here and then saying that it's also beyond the weight loss and not everything is explained by the weight loss.

And in the Together study, they were big people. They had a mean BMI of thirty eight. They're seriously overweight.

But these are the people who lose the fastest and the most.

And they had serious arthritis, tender joint counts at 25, swollen joint counts were over 10 So or again, I highlighted this on RheumNow just with the press release when it came out in April, I think it was, or maybe March when there was no data. Then again, a month later when they released some of the early data, only at week sixteen, think that, and the other important thing is that there was another trial called the Together PSO trial, which was done just in psoriasis and really showed the exact same sort of outcomes. Although the outcomes there were read out as PASI 100s and only skin only, and they did very, very well. So this is exciting stuff and I do think that rheumatologists, as Peter has suggested, need to be keen on this and know what's going on here because whether you prescribe it or not, and when I'm in an audience full of people and I'm talking about this, I ask how many of you have prescribed a GLP-one, and you know, ten percent of the audience raises their hands, and I have, and there's no reason that we can't. Because if it's gonna help the arthritis and they're gonna lose weight, are you not constantly saying you gotta lose weight, you gotta exercise, you gotta do pushaways the ice cream table and get better.

And this certainly will help that in a major way. All right, they're very exciting. Doctor. Chan, what do you have?

I've got the late breaking one, the B Bol study. This was presented at the last day. The moment the slides went up, all the cameras came out. It looked like everybody was waiting for this moment of the reveal. And essentially they looked up to twenty four weeks, and it was superior, to bimekizumab was better than, risankizumab.

The changes were seen very early at four, you had about threefold improvement and that sustained at sixteen weeks and then up to twenty four weeks. Now that was the primary outcome. Well they didn't achieve MDA when they looked at both groups so all the subsequent secondary outcomes were therefore only for analysis rather than showed any significant change. So why what did I gain? It's the first head to head study in PSA.

We have a lot of head to heads in our in PSO but this is the first one in PSA with joint specific. It shows quite rapid onset of action and up to twenty four weeks certainly seems to be more superior for the ECR fifty but didn't achieve MDA. So I think we will need to kind of see how this goes on for longer.

Yeah, so again, this was another phase three, two seventy seven patients, randomized, and they had to be, refractory or active disease. The number was like twenty percent, twenty five percent were on TNF inhibitor before. That didn't seem to make a difference, they got standard doses. Peter, you brought to my attention the issue of dosing. And what was interesting about the result here was that the primary endpoint at week sixteen, a very significant difference between the bimekizumab and rizenkizumab.

That same difference was maintained. It was forty nine percent versus thirty eight, eleven percent difference. And that was maintained out to week twenty four. But the other endpoints that we looked at, as Anthony said, the skin endpoints, MDA, DAPSA, they might've numerically been better, but they weren't significantly better, at those two time points. But while rizenkizumab had one dose, bimekizumab had two different doses.

Peter, do want to address that?

Yes. So I'll get into trouble for talking about this, but, I heard it presented by Jose Scheer, I heard it presented by Joe Merola, and both of them didn't think it was particularly significant, and I'm sure they can correct for this and fix it and prove that the difference is very real. So I'm just waiting to see that analysis. But really, said if you had moderate to severe PSO, or you had a greater than 10% body surface area or IGA above three, you're considered moderate to severe, and the label says you can start with three twenty milligrams, and you can do that monthly after week sixteen, and then it goes out to every, extended, right? So eleven percent of the patients got that.

So that was double dosing three twenty mgs monthly for up to sixteen weeks, and poor old Riz got one dose at baseline, one dose at week four, and the next dose is gonna be week sixteen or week twelve. So they got a couple of doses. So I just need to be reassured that that eleven percent of the high doses wasn't the reason why these two separated quickly early and whatever, but they stayed separate. And to be fair, that might have had an effect on skin. But what we saw in the registration trials of bimekizumab, the higher dose didn't have a better effect than the lower dose on joints.

If you remember, it was quite unusual, the one hundred sixty had a better response than the three twenty. So maybe it doesn't count for joints. And it's so simple to pull those 11% out, do the analysis again, they've answered the whole question. And Joe and Jose didn't think it was particularly relevant and they presented the data to us all. So we will wait and see, but that's just the only tiny thing that I'd like to get clarified.

So we don't, again, we don't know that the 11% that were better were the same 11% who took a higher dose. We don't know that that's same. We're to find out at some point. But the other interesting thing here is, in psoriasis,

there

is a clear cut hierarchy on which is the better drug because they have tons of head to head trials. And TNF inhibitors were boom, the new thing. But then, we got IL-twelve twenty three that did better than that. Then we got the IL-17A inhibitors. Then we got the 23s that were better than the 17s.

And now the most recent, I believe, bimekizumab versus a twenty three shows the dual AF inhibitor is better at skin only. So there's a hierarchy. And here we are in rheumatology and nothing's ever better. Everything's the same, sixtyfortytwenty ACR, whatever. And so I think the hardest question I could have, if there was time to ask questions for Doctor.

Marola, which he ran out of time strategically so I think, at the presentation, I would have asked, why did this suddenly work? Why do we have a head to head in arthritis that now looks good? Because I really wanna know the answer to that question. Does anybody, I mean, I'm sure all of you are happy about a head to head that works out for arthritis, but Nelly, does this information, is this going to change how you treat PSA?

Actually I was happy to see the rapid separation of the curves, but for joints I think the longer term is the more important one. So I would like maybe wait for longer data.

You want to see 50 For two

the joints it's not the same as for the skin. Yeah. You know we are used to like slower drugs and we are used that curves may may be joined afterwards. So I I would wait.

But I do think we need to insist on active comparative studies. Just like the derms do, because we love making treatment algorithms based on no evidence. Right. And that's why everybody was so happy with this study, because we could start making a treatment algorithm and actually had a bit of evidence to it.

Yeah. Anthony, do you You play a lot with the IL-17s. Do you think that this Is there a mechanistic reason why an AF inhibitor would be better than a twenty three or better than an IL-17A inhibitor alone like the other ones, secukinumab, predalumab, ixekizumab?

I think we need to understand the kind of pathogenesis and where in the disease is the patient. I think probably those who are more early phase, early in the diagnosis, the IL-twenty three possibly could be more effective, and later on in disease, I would think the 17 or 17 ANF probably has a bigger role, once they kind of have more established disease. The anthesis for example may have already been primed by 23 and then producing more 17. So this obviously in this study there was no separation between early and late disease. But not to forget that the 23s have a long story to it as well.

There was another poster 47 which I also looked at, the Keepsake study, which went on to two forty four weeks with risankizumab and still showed achievement of good joint and skin scores. So I think we just have to see whereabouts in these patients are they are and I think which I'm going to come in my second abstract, I think the use of, biopsy would actually help us to differentiate, the types of patients who should have certain treatments.

I think the dosing is important because, the derms use much higher doses than we do with these drugs, with safety and the gastros as well. So I think the registration trials often start off with conservative dosing, and they wish they'd have used either a higher dose or a more frequent dose once, but it's too late once the registration trial's done. And because of the axial difficulty of IL-twenty three to show efficacy, there are other pathways that make IL-seventeen. The IL-thirty six, IL-thirty eight, these are the things that are proposed to explain why the 23s don't work so well in the spine, that there are other things driving 17 apart from IL-twenty three.

Yeah.

One interesting abstract also presented was by Nicola with Skogas, and they compared actually in a joint clinic of derma and rheumato the effect in psoriasis of different biologics on the appearance of psoriatic arthritis. So of course they found that anti interleukin were better than TNF inhibitors, so they will intercept more PSA, but also a small preference for anti interleukin 23 compared to anti interleukin 17 in patients with PSO. So, they had a little bit less of development of PSA and a median of twelve years. So, maybe it's also support to what Anthony was saying, like maybe in early disease, interleukin 23 may have a more important role.

So I can tell you that I've covered that report from six other authors in the last two years many times, that there's plenty of literature out there that says aggressive intervention can prevent, PSO progressing to PSA. But then you put that in front of, you know, Alexis Oddi and statisticians, and they tear it apart Because it's observational data, you don't know the channeling bias that goes into it. My only comment, and I like that data, it means that you can modify disease by being appropriately aggressive. And my comeback to Alexis, and she's given a great lecture on this, it shows you the six different ways that you can be led astray here. But the fact is, I've got like seven or eight studies now that say the same thing.

And they're very consistent on that. And the bottom line though, is observational data like this, registry data like this, claims data like this, is never proof of principle. It's actually hypothesis generating and you have to consider as such, but who's gonna do this study? I don't know who would do the actual disease prevention study. Actually, think there is a study going on on this, and process.

Okay, so let's do a quick round. I'll begin. These should be faster presentations. Mine is POS0668. It's called Sharp AI.

Yes, that's right, artificial intelligence. It's a longitudinal assessment of radiographs using artificial intelligence. In this particular study, they collected the radiographs and the data from three fairly large PSA trials, a total of fourteen oh one patients with over 17,000 x rays that were used to, one, develop a training set and then have a validation set to see how this would perform, compared to, expert, analysis. And when you look at the graph showing correlations, man, they're really tight. They're very tight.

And why I think this is important is the following. I am one of these contrarians, much to your surprise, to people that want to do x rays in rheumatoid arthritis, as some sort of validation of what you're doing. And my point is, you don't know what you're doing. You weren't trained in x rays. You don't know how to read I mean, you think you know how to read x rays.

And yes, you are good at reading x rays, but you don't know how to score them. And when you do a repeat x-ray, the old x-ray is never available for you to compare it to. So who are we kidding here by doing x rays every six months or every twelve months? In an ideal situation, only Peter Nash lives in the world of ideal medicine, where all that's at your disposal, it just is foolish. But now, if AI is going to take the place of my community radiologist who sends back a report, no fracture seen, it's coming from the arthritis clinic with a history, and I want to know what the cause of the fifth metacarpal pain is, and you get back useless reports.

Now with AI, you can get detail, you can get precision, you can get comparison, and can be not only just qualitative, but quantitative reviews. I think this is where radiology is going, and, I think radiologists are not gonna get paid much in the future because AI is gonna replace them.

Well, think AI will get rid of the normals, and then only have to look at the abnormal check. Yeah. There's no dermatologist in Rockhampton, a city of 300,000 people. So the local derm down at our way put the vector machine in Rocky. You walk in, take your clothes off, three sixty degree photo, the AI is better at diagnosing a benign nevis from a melanoma.

She looks at the pictures, tells the GP which one to biopsy, you don't need a dermatologist in Rockhampton. So I think AI is going to be great for eliminating normals. You only have to look at the abnormals. My concern is who carries the can if they get it wrong?

Yeah, well, when I was a medical student, first year medical student, someone in my class did a rotation during the summer and he was a hero because he identified an orbital fracture in a motor vehicle accident patient. Excuse me. And he was a medical student, took anatomy. And the story was that the ER physician said, you know, skull x rays, you you can read them all as normal because you're not going to find an orbital fracture anyway, and you're going to miss the one in a thousand, and that's an acceptable thing. And I think that's what happens, what's gonna happen with AI, but it's still gonna be more accurate, I think, than human readings, unless you're dealing with someone who's an expert, for instance, at orbital x rays, right?

And obviously, if you really were looking at orbital, you would do a CT or another procedure rather than an x-ray. But I think that there's going be a downside to it, you're right. How is that going to play out medical legally and whatnot? Do any of you have a situation where AI is being used in the hospital? Anthony?

Yeah, we use it to detect vertebral fractures. So this is part of the osteoporosis screen. They're done. All these x rays get looked at by AI and then it picks up and gets sort of notified to the radiologist.

Interesting.

Also in the new MRIs there are integrated AI softwares that can help the radiologist identify, but still the radiologist will have the final word and sign the report.

That's right. It's like if you use AI, I mean, use AI on RheumNow to research things, organize things, start first drafts and whatnot. We acknowledge it. When it's authored, it's authored by Jack Cush, not Claude and Jack Cush. And I have to take responsibility for that which appears in our print.

Doctor. Nash, what do you have as a quickie?

As a quickie, I went to a lovely symposium. I'm trying to find the OP for it, talking about the role of the fibroblasts in chronicity, in patients that can't get to remission, and the different pathways that drive rheumatoid arthritis, because we were very, disappointed that CAR T couldn't make a huge significant difference in ACPA positive rheumatoid arthritis if it was a pathogenic antibody. And Chris Butley pointed out that fifteen percent of rheumatoid synovium when you biopsy it, it's full of activated fibroblasts, but has no inflammatory cells, no B cells, it's a different pathway. And he actually describes the fibroblasts as an inflammatory fibroblast, then turns into a fibrogenic fibroblast, and the fibroblasts pour out cytokines and drive pain, All the things that I was completely unaware of really. So I think there's a whole area of drug resistance, symptoms related to tissue that we're not even aware of.

It's a big issue throughout rheumatology, renal biopsies and lupus, rheumatoid psoriatic synovium. I did an abstract on comparing FAPI, F A P I versus FDG PETs. And FAPI picks up fibroblast activity, whereas FDG PET is a metabolic glucose activity. And the FAPI is really turning out to be a better tool mainly.

And it's a predictor. It's a predictor of who's going to get PSA in a PSO population.

Right, that's cool. Nelly, what do you have?

So I have a study, we have them in other diseases, but not a lot in psoriatic arthritis. The AFFINITY study, it's a 2A phase study. Busalcumab and golimumab combination on MRI detected inflammation and damage in pharyngeal joints of hands and feet and enthesis of the heels in patients with active PSA. So they defined the MRI lesion by the OMRACT, PSA MRIs and the antisitis by the haemorrhis. So PSA and TNF inadequate responders randomized to combination therapy guselkumab plus golimumab, justifying this that like there are two different mechanistic pathways compared to monotherapy with guselkumab alone every four weeks.

So ninety one randomised patients, age 49, disease duration eight years. So the result was different in the hand and in the feet. We only have MRI data, we don't have clinical data. So in the hand, patients treated with the combo therapy had numerically greater reduction in inflammatory feature scores compared to monotherapy, and the change was -5.5 in combo compared to -0.4 in monotherapy. And this was also the same for structural damage, however it did not reach statistical significance.

However in the feet there was a bigger difference that reached statistical significance, minus 3.5 in the combo, minus 0.6 in the monotherapy. And for the antisense, there was no obvious difference at week twenty four for the MRI. So it's promising, like for patients who may be difficult, maybe the difference is not that important because already with guselkumab the progression is not that important. So guselkumab alone is doing a good job, but maybe for patients who are refractory to monotherapy, this pathway can be useful adding like an NTTNF. So this is still exploratory, it's not really powered for combined outcome.

What I saw that the clinical results are still on file. Didn't find the publication of the clinical results.

I mean, this is a major study and the other studies that are out there, I thought that the clinical results were presented somewhere and showed that the combo was better and also safe, which is why these combination trials are being done a lot in GI and a lot in PSA. It's really because of the makers of galimumab and gaselumab, same company, they're the ones doing the studies and they're looking very good. The VEGA study in GI and whatnot, because the early days when we were doing clinical trials in RA, the warning came down, you don't combine biologics because when we did that with IL-one inhibition and TNF inhibition, there was no clinical benefit and the SIE rate went from two to six percent. And that was a major issue with the, and so hence all labeling after the first three TNF inhibitors and anakinra said, do not combine biologics, even though that was never tested. Now we're in an era where they're combining them, it looks safe, it looks like it's efficacious.

Peter, do you think that the benefit here is because of the TNF or because of the combination?

It's hard to know, but I think what's driving all this is it's difficult to treat complex to manage stuff. If you can prove that the treatment refractory, they've still got, objective evidence of inflammation, ESR, CRP, the implication is we've got to predict them, we've got to treat them more aggressively at the beginning, and how we're going to do that, we're going to use a combination. So they're trying to drive, to reduce the number of these treatment refractory people, by predicting the worst outcomes, whether it's male sex, smokers, overweight, bad family history, requiring steroid, bad function, erosions, multiple joints involved, whatever the the algorithm is going to be. Let's start them with a combo instead of what we're doing now, which is guessing a drug for six months, followed by another guest drug for six months. So I think that's really what's behind testing various combos.

There's certain combos I wouldn't do and certain combos I would try, and we already are trying in difficult patients.

So, Anthony, do you think that this surge of combination trials in the spondyloarthritis community, I'll include as IBD and AS and PSA, the surge here, is it because those patients have more severe disease or why do you think this came about? It's a fortuitous thing, and we're excited to see it, but it's not happening in RA, it's happening in the spa world.

Yeah, we find that these spondyloarthropathies, they fall into these domains. PSA will have your six domains, in XBA you'll have your uveitis, IBD, and we find that if you go down just one way, sometimes you don't get the full coverage. For example, you couldn't use 17, for example, in the gut, but be very good on the joints. What happens then if the patient has another co morbidity uveitis? And so rather than replace it, we are finding that we're actually adding a combination.

The good example and the biggest one we have is the '23 and '17. The patient on '23 might be coming from the dermatologist or gastro and then they still have joint symptoms, but their skin and gut is quite good. Rather than switch them, we add on possibly a JAK or TNF for this type of patient. So that's why we are seeing more and more of this in this field.

I like your answer in that it refers back to, there was a report maybe five years ago, don't know if you remember Peter, think Laura Coates did it or Alexis Agde that if you look at a large cross section of psoriatic arthritis patients, how many GRAPA domains were active at any one time in patients? It was something like out of six or seven domains, the mean or median was like four. That an an idea- this fine. Domains, which maybe is then one, why you should use multiple biologics, but two, more importantly in The United States at least, how you can possibly get it paid for, right?

Yeah. So we're only allowed to write one biologics, so we have to get a second specialist to write the other. But that's what often happens. The joints are fine on your TNF, but they get into current infection and the skin goes crazy. So the derm then adds something on top of the TNF, whether it's Dukra, Apremilast, seventeen, twenty three, the advantage of the new ones, there's no safety penalty.

In Beirut, Nelly, are you able to use combinations?

Yes, it's sometimes difficult to find a monotherapy. That's what I wanted to say. So in low resources countries, like using one is already difficult, than combining two, so it will be very costly for the society. And I think that the payers will prefer to treat like two patients with guselkumab than treat like one patient with a combination therapy.

Well, it's going be interesting to see because these studies are going to come to fruition and all going to be published in a lot of them in '27, and beyond. I think it will become a big topic of discussion. Anyway, our last presentation, Doctor. Chan.

So we're talking about choosing biologics. There was a presentation OP71. This was using biopsy to guide treatment choice in PSA. We've obviously had this in rheumatoid, but this was a PSA study and essentially they found if you had the myeloid CD117 in your biopsy then you respond better to IL-seventeen and IL-twenty three two times better compared to TNF. So maybe something for us to think about with more personalised treatment or we are trying to cycle through biologics, whether we could try to get it right first time.

Linking response to transcriptomes or, you know, epigenetic changes, that stuff is just never, there's always one report linking it to something, but it never gets repeated anywhere. I don't know why people aren't doing more of this. But then again, that's what Pisales tried to do with the R4RA study. And I don't think he successfully really proved the point that you certainly couldn't correlate the histology. You had to get more into the cellular makeup to show some correlations.

But I think that's where personalized medicine is going to be the most yielding. Again, now you're going to have to depend on, biopsies of synovium.

Hopefully we can, if we can get a biomarker that is linked to this biopsy.

Well, Yoshitanak has done a very nice little study with only 64 patients that needs repeating all over the world, where he claims with flow cytometry like the oncologists have with breast cancer, say, you you HER2 positive, you're oestrogen positive, therefore you need that chemotherapy. He claims he can identify phenotypes that are TNF phenotype, 17 phenotype, twelve twenty three phenotype, and a combo phenotype. And then they could pick the appropriate biologic for the appropriate person. And they seem to do better if you did that in the small study that he did. But it clearly needs repeating in big numbers all over the world to see if it's true.

But wouldn't it be nice to have a little flow cytometry before you start your biology, and it should pick the one that would be most likely to be helpful.

Yeah, all right, folks.

In oncology and in lupus nephritis, there's a lot of talk about liquid biopsy, so it makes it a lot easier. So it would be ideal to have it.

Yeah, it's looking good in lupus nephritis. I don't know what the inflammatory arthritis tie in or correlation is going to be there. But you know, more research can only make us better. So I want to thank our panel for a great discussion on some really important presentations from UR twenty twenty six in London. Thank all of you for tuning in and following RheumNow during the coverage.

There'll be more of these topic panels to watch. Thanks everyone.

Thank you.

Thanks, Charlie.