PsA Topic Panel: EULAR 2026

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 were at EULAR 2026 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 Dr. Jack Cush from Dallas, Texas. Nelly, I am Nelly Zad from Beirut, Lebanon. Anthony, hello. I'm Anthony Chan from Reading, United Kingdom. And Peter, hi everyone. Peter Nash 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 going to 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. I think Peter wanted to start. Let's start with Peter. I did that wrong. Okay.

Well, thanks Jack. It was really a very very good meeting and in PsA we had three that we're going to cover tonight of the key presentations I think of the whole meeting. So to set up one of the most important ones that Nelly is going to cover, I wanted to throw out there two little ones. OP0187 by Garman and OP0070 by Lilli Lehi Eda. The Garman one's very interesting because this whole question that you have brought up many times — GLP-1 agonists and how we should take the ball and lead by example is what I feel. So Garman looked at the predictors of response at one year from a 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 48 weeks, and treatment came in number six. But what it was — BMI was the most important predictor of who is going to do well, if you can do something about that BMI at 48 weeks. So it's setting the scene for this whole area of GLP-1s. And Lehi just used diet, and she used 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 active PsA when they went into the study — you can make a significant difference in DAPSA at 12 weeks and 24 weeks. So Nelly's going to tell us about this important study of an IL-17 inhibitor with a GLP-1 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. And I wait to hear what Nelly has to say about her excellent presentation.

Well, before we get into the TOGETHER PsA study, Peter, do you think that the BMI — 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 enthesopathy phenomenon as 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 with 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 enthesopathy 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. And 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've got to do something about it — or 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 100% sense. But I do believe that the data on inflammation being contributed to by obesity — whether it's gout flares, whether it's NASH, 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 enthesopathy phenomenon as well.

Anthony, you're a spondylitis maven. Is it as big an issue in axSpA as it is in PsA? Certainly the the
response to biologics will be much less with the higher BMIs, but this is played more so out in PsA. I think a lot of these patients have 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 there are pathway 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 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 2025 in the journal Gastroenterology where they looked at 105,000 patients treated with these drugs from 55 randomized controlled trials and most of the adverse effects were nuisance GI, pancreatitis very rare, the rest 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 with an excessive rapid amount of weight loss, because there are some effects of GLP-1s on the splanchnic circulation. I'm just throwing it out there as kind of coming out of left field now, a couple of these funny case reports of mesenteric ischemia and thrombosis.

So a lot is written about and said about the tolerability of these medicines and I think that Dr. Nash is correct in that it's mostly nuisance, but the fact is there's 15% 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 mesenteric. But those are all rare events that you only see in a few hundred thousand 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 Dr. Nash is intimating here, we got to know about these drugs because they're going to be in play. And you have to know, because it comes into play and your patient's on azathioprine — are you blaming azathioprine for the belly issues or are you going to blame it on the GLP-1s? And there are many of them. So without further ado, we want to get to Dr. Zad who has this really interesting study. Go ahead, Nelly.

Yeah. So we have a lot of buzzing around the GLP-1, 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 the TOGETHER PsA study OP069, presented by Laura Coates. It's a phase 3B study. So they compared the impact of tirzepatide plus etanercept compared to etanercept alone in achieving measures of PsA disease control. So this was a 3B multicenter, assessor-blinded — so not a randomized 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 counseling for healthy diet and exercise, and the primary endpoint was a composite one: achievement of both ACR50 and more than 10% weight reduction at week 36, which is a little bit weird because we don't expect weight reduction with etanercept alone.

So they had 138 patients in the combo arm and 133 patients in the mono etanercept arm, mostly 70% females, BMI 37, high disease activity, DAPSA was around 50 in both groups. Now at week 36 for the primary endpoint, 31% of patients in the combo therapy arm achieved the study primary outcome — so ACR50 and loss of 10% — compared to 0.8% in the etanercept alone arm, which is mostly expected.

Now if we want to look at the data that's important to us: at the joints, ACR50 response was different as soon as week 4. So 11.1% ACR50 in the combo arm and 3.9% in the monotherapy arm. And this difference also continued until week 36: 33% for the combo arm and 20% for the monotherapy arm. Also other measures were significantly different, especially DAPSA low disease activity and remission rates at week 4 and at week 36, 40% compared to 26%. No adverse events mostly mild to 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 already have difficult-to-treat disease. However, this study is open label, the difference between the two ACR50s is only 13%, 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 uh the main question that we heard also in the halls what will happen long term so how long will we continue these GLP-1 agonists will we continue them forever what will happen if we stop them will we lose this benefit so I think that we need more time to assess really the value and the place of this uh combination.

Yeah, it's sort of the big issue with GLP-1s and their plethora of benefits uh beyond diabetes control, weight loss, sleep apnea, cardiovascular outcomes and death. Those are the gigantic gigantic return on investment. And the question is once you lose your 33 pounds um 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 um it's often mandated by insurance. Sometimes they'll only allow it for a certain amount because they can't have everybody and the number is something like 8% of the US population is taking GLP-1s. The last number I looked at — another way of looking at this is that these are so popular the companies that make this made $19 billion in the first quarter of this year. 19 billion — when Humira was doing fabulous it was making 22 billion um uh annually. 19 billion. So this is big and the question is are societies and and um municipalities going to pay for this?

Um 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 — 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. Um that's if you have to stay on it longer term and to be fair it's not always very well tolerated as you said you know one in five get this and one in four get that — nausea, diarrhea, constipation — so but I always get — in our neck of the woods it's 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 could stop and fight to keep it off and if you can't then we have to micro dose and I think that's what people are going to do. I think even Weight Watchers are suggesting we micro dose this stuff. So it it's really uh 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 um along with the ACR50. But how much weight — did they in fact — because did they lose — because the argument was always going to be are they better because they lost weight or are they better because these GLP-1 drugs actually are immunologically active and possibly anti-inflammatory.

So I 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. Uh one um uh by uh the team of Vincenzo Benito 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 uh effect and another study also presented as an oral abstract by Puncta and she also said that they did an adjusted analysis so they 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 are big people — they had a mean BMI of 38 so they're seriously overweight but these are the people who lose the fastest and the most and they had serious arthritis — you know tender joint counts of 25, swollen joint counts were over 10, 11. So um uh again I 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 and then again a month later when they released some of the early data but only at week 16.

Um you know I think that uh um and 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 uh and only skin only and they did very very well.

So, uh, this is exciting stuff and I do think that rheumatologists, as as Peter has suggested, need to be, um, keen on this and 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-1?" Uh, and you know, 10% of the audience raises their hands. And I have, um, and there's no reason that we can't. Um because if it's going to help the arthritis and they're going to lose weight, are you not constantly saying you got to lose weight, you got to exercise, you got to do pushbacks from the from the from the ice cream table and um and and get better. And this certainly will help that in a in a major way. So all right, they're very
exciting. Dr. Chan, what do you have? I've got the late-breaking abstract 001, the BEBOP study. This was presented on 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 24 weeks. And it was superior — bimekizumab was better than risankizumab. The changes were seen very early at week four. You had about three-fold improvement and that sustained at 16 weeks and then up to 24 weeks. Now that was the primary outcome. Well, they didn't achieve MDA comp 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 — this is the first head-to-head study in PsA. We have a lot of head-to-heads in PsO, but this is the first one in PsA, was joint-specific. It shows quite rapid onset of action and up to 24 weeks certainly seems to be more superior for the ACR50 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, 277 patients randomized, and they had to be refractory or not — active disease number was like 20, 25% were on TNF and one TNF inhibitor before, that didn't seem to make a difference, and they got standard doses. But 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 16 showed a very significant difference between the bimekizumab and risankizumab. That same difference was maintained — it was what, 40, 49% versus 38%, an 11% difference — and that was maintained out to week 24. But the other endpoints that we looked at, as Anthony said, the skin endpoints, MDA, DAPSA, they might have numerically been better but they weren't significantly better at those two time points.

But while risankizumab had one dose, bimekizumab had two different doses. Peter, you want to address that?

Yes, so I'll get into trouble for talking about this, but I heard it presented by José Scher, 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, they said if you had moderate to severe PsO, or you had greater than 10% body surface area, or IGA above three, you're considered moderate to severe. And the label says you can start with 320 milligrams and you can do that monthly out to week 16 and then it goes out to every extended. Right? So 11% of the patients got that. So that was double dosing — 320 migs monthly for up to 16 weeks. And poor old Riz got one dose at baseline, one dose at week four, and the next dose is going to be week 16 or week 12. So they got a couple of doses.

So I just need to be reassured that that 11% of the high doses wasn't the reason why these two separated quickly early. And whatever — 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 160 had a better response than the 320. So maybe it doesn't count for joints.

And it's so simple to pull those 11% out, do the analysis again, and they've answered the whole question. And Joe and José 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 the higher dose. We don't know that that's the same. Sure. We're going to find out. We're going 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. You know, TNF inhibitors were boom, the new thing, but then we got IL-12/23 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 23 — 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 — 60, 40, 20, ACR whatever. And so I think the hardest question I could have asked, if there was time for questions for Dr. Merola — which he ran out of time, strategically 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 want to 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? Uh, actually I was happy to see the rapid uh separation of the curves, but for joints I think the longer term is a more important one. So I would like to maybe wait uh for longer data. You want to see 52 weeks for the joints. It's not the same as for the skin. Yeah. You know, we are used to like uh slower drugs and we are used to curves that may be joined afterwards. So 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. And that's why everybody was so happy with this study, because we could start making a treatment algorithm that actually had a bit of evidence to it.

Yeah. Anthony, what do you — you play a lot with the IL-17s? Do you think there is a mechanistic reason why a TNF inhibitor would be better than a IL-23, or a bit better than an IL-17A inhibitor alone, like uh you know the other ones? Secukinumab? I think we need to understand the kind of pathogenesis and where in the disease the patient is. I think probably those who are more early phase, early in the diagnosis — the IL-23 possibly could be more effective — and later on in disease I would think the IL-17 or IL-17/TNF probably has a bigger role once they kind of have more established disease. The entheses for example may have already been primed by IL-23 and then producing more IL-17. So obviously in this study there was no separation between early and late disease.

Um, but not to forget that the IL-23s have a long story to it as well. And there was another poster 0047 which I also looked at — the KEEPSAKE study — which went on to 244 weeks with risankizumab and still showed uh you know achievement of good joint and skin scores. So I think we just have to see whereabouts in the disease these patients are, and I think — which I'm going to come to in my second abstract — I think the use of biopsy would actually help us to differentiate the types that 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, but it's too late once the registration trial is done. And because of the axial difficulty of IL-23 to show efficacy, there are other pathways — IL-17, IL-36, IL-38 — these are the things that are proposed to explain why the IL-23s don't work so well in the spine, that there are other things driving IL-17 apart from IL-23.

Yeah. One interesting abstract also presented was by Nicola Covas, and they compared actually in a joint clinic of dermatology and rheumatology 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 interleukin-17 in patients with psoriasis. So they had a little bit less development of PsA over a median of 12 years. So maybe it also supports what Anthony was saying, like maybe in early disease an IL-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 many times, and there's plenty of literature out there that says aggressive intervention can prevent psoriasis progressing to PsA. Um, but then you put that in front of, you know, Alexis Ogdie 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 kind of like that data — means that you can modify disease by being appropriately aggressive. But my comeback to Alexis — and she's given a great lecture on this — shows you these 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.

So 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'd have to consider it as such. But you know, who's going to do this study? I don't know who would do the actual disease prevention study. Actually I think there is a study going on on this, in process — obviously. Okay, so let's do a quick round. I'll begin — these should be faster presentations. Mine is poster 0668, it's called SHARP AI. Yes, that's right, artificial intelligence. It's a longitudinal assessment of radiographs using artificial intelligence. And in this particular study they collected the radiographs and the data from three
fairly large PsA trials, a total of 1,401 patients with over 17,000 X-rays that were used to develop a training set and then have a validation set to see how this would perform compared to expert analysis. And you know, when you look at the graphs 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 12 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 comparisons, and it can be not only just qualitative but quantitative reviews. I think this is where radiology is going, and I think radiologists are not going to get paid much in the future because AI is going to replace them.

Well, I think AI will get rid of the normals and they only have to look at the abnormals, Jack. Yeah, there's no dermatologist in Rockhampton, a city of 300,000 people. So the local derm down an hour away put the vector machine in Rocky. You walk in, take your clothes off, 360-degree photo. The AI is better at diagnosing a benign nevus 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, a 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. And he was a medical student, took anatomy, and the story was that the ER physician said, you know, skull X-rays — 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's going to happen with AI, but it's still going to be more accurate, I think, than human readings, unless you're dealing with someone who's an expert, for instance, at orbital X-rays. 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 there's going to be a downside to it. But you're right — how is that going to play out medically, 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. All these X-rays get looked at by AI and then it picks up and gets 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. That's right. It's like — if you use AI — I mean, we use AI on RheumNow to research things, organize things, start first drafts and whatnot, but we acknowledge it, and 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.

Dr. Nash, what do you have as a quickie? As a quickie, I went to a lovely symposium — I'm trying to find the abstract for it — talking about the role of the fibroblast in chronicity in patients that can't get to remission and the different pathways that drive rheumatoid arthritis, because we were very disappointed that Cartabri couldn't make a huge significant difference in a positive rheumatoid arthritis if it was a pathogenic antibody. And Chris Buckley pointed out that 15% 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 fibroblast as an inflammatory fibroblast, then turns
into a fibrogenic fibroblast, and the fibroblast 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 in lupus, rheumatoid, psoriatic synovium.

I did an abstract on comparing FAPI 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 it's a predictor of who's going to get PsA in a psoriasis 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 phase 2A study — guselkumab and golimumab combination on MRI-detected inflammation and damage in phalangeal joints of hands and feet and enthesitis of the heels in patients with active PsA. So they defined the MRI lesion by the OMERACT PsA MRI score and the enthesitis by the HEMRIS. So PsA and TNF inadequate responders randomized to combination therapy — guselkumab plus golimumab — justifying this that there are two different mechanistic pathways, compared to monotherapy with guselkumab alone every four weeks. So 91 randomized 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 minus 5.5 in combo compared to minus 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 enthesitis there was no obvious difference at week 24 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 anti-TNF. So this is still exploratory, it's not really powered for combined outcome, and what I saw is that the clinical results are still on file — I didn't find the publication of the clinical results.

Yeah, I mean this is a major study, and there are 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 you know these combination trials are being done a lot in GI and a lot in PsA. And it's really because of the makers of guselkumab and golimumab — same company — they're the ones doing the studies, and they're looking very good, you know, the VEGA study in GI and whatnot. Because in the early days when we were doing clinical trials in RA, the warning came down: don't combine biologics, because when we did that with IL-1 inhibition and TNF inhibition there was no clinical benefit and the serious infection event rate went from 2 to 6%. And that was a major issue, and so hence all labeling after the first three TNF inhibitors and anakinra said do not combine biologics, even though that was never tested in other combinations. 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 this difficult-to-treat, complex-to-manage stuff. If you can prove that they're 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 are we going to do that? We're going to use a combination. So they're trying 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 steroids, bad function, erosions, multiple joints involved — whatever the algorithm is going to be. Let's start then with a combo instead of what we're doing now, which is guessing a drug for 6 months followed by another guess drug for 6 months. So I think that's really what's behind testing various combos. There are 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 — which 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 it's a fortuitous thing. Um, and we're excited to see it, but it's not happening in in RA. It's happening in the in the SpA world. Yeah, we find that uh these spondyloarthropathies they fall into these domains. PsA will have your six domains. In axSpA, 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 IL-17 uh 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. So the good example and the biggest one we have is the IL-23 and IL-17. The patient on IL-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 that we add on possibly a JAK or TNF for this type of patient. So that's where this is why we are seeing more and more of this in this field.

I I I like your answer in that it refer it refers back to um there was a report maybe five years ago. I don't if you remember Peter the uh I think Laura Coates did it um or or Alexis Ogdie that if you look at a large cross-section of of psoriatic arthritis patients how many GRAPPA domains were active at any one time in patients it was something like the me out of six or seven domains the the mean or median was like four that idea so many domains which maybe is then one 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 biologic, 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 IL-23. the advantage of the new ones. There's there's no safety penalty.

Uh in Beirut, Nelly, are you able to use combinations? Yes, it's it's sometimes difficult to find a monotherapy. That's what I wanted to say. So in low resource countries uh like using one is already difficult than combining two. uh so it will be very very costly for the society and I think that the payers will prefer to treat like two patients with guselkumab then treat like one patient with a combination therapy well it's going to be interesting to see because these studies are going to come to fruition and all going to be published a lot of them in 27 um and beyond and I think it will become a big topic of discussion anyway our last presentation Dr. chair.

So I we were 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 um in your biopsy, then you respond better to IL-17 and IL-23, two times better compared to TNF. So maybe something for us to think about with more personalized treatment or we are trying to cycle through biologics whether we could try to get it right first time.

You know 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. Um but then again that's what Pitsillides tried to do with the R4RA study and I don't think he successfully really proved the point that you could 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 um personalized medicine is going to be the most yielding. But and again now you're you're going to have to depend on biopsies or synovium. Hopefully we can if we can get a biomarker that is linked to this biopsy.

Well, Yoshiak has done a he's 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 know you heard HER2 positive your estrogen positive therefore you need that chemotherapy he claims he can identify phenotypes that are TNF phenotype IL-17 phenotype IL-12/23 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 biologic? And it should pick the one that would be most likely to be helpful. Yeah.

All right. In oncology and in lupus nephritis, there's a lot of talk about liquid biopsy. So which 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 uh um what the uh the inflammatory arthritis uh tie in or or or correlation is going to be there. But you know uh
more research uh can only make us better. So I want to thank our panel for uh a great discussion on some really important presentations from EULAR 2025 in uh London. Um 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, Jack.