PsA Topic Podcast compilation Save

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

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

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

And it's not surprising that a JAK inhibitor would work. There's a lot of other data out there about other JAK inhibitors working, in polymyalgia rheumatic, and I think it will be, something we'll see more of in the future. Another really important abstract that's coming up as part of the late breakers is a long awaited study, as a follow-up to oral surveillance, where we found out that JAK inhibitors don't do as well as TNF inhibitors when it comes to cardiovascular outcomes and cancer and infection in high risk individuals. The follow-up to that, another big study, not with tofacitinib but with baricitinib, was a regulatory commitment by Lilly to study baricitinib and its venous thromboembolic risk. So, they set up many years ago these studies called RA Bridge and RA Branch, it's baricitinib versus TNF inhibitors in over, three thousand five hundred patients who have risk factors for, VTE events DVT, PE, so we're talking there age, BMI, are the main risk factors on having had a prior event.

And the bottom line on that study is that it confirmed what we already knew. Baricitinib was the first of the JAK inhibitors to be, labeled, and right out of the gate, labeled with a VTE risk and warning, and this study confirms it, but interestingly, again, another high risk population, they were average age around 60, but it did not show, this study did not show that baricitinib compared to a TNF inhibitor was associated with either a risk of, cardiovascular MACE events, cancer events, or, it did show infection, serious infectious events, but did not show an increased risk of, opportunistic infection. So, in some ways it argues against the data for the oral surveillance study, but those are two very important studies that I think will be coming up this week as late breakers. There's a lot of data that I'm going to be covering with my colleagues on, ILD, the bottom line there is it looks like all the risk factors everyone's saying suggest, yeah, risk factors for ILD in RA is being male, being older, being seropositive, throw in their smoking, throw in their disease activity, and now you've got the profile. The question is, who needs to be screened?

There are a number of studies here this week that look at that issue, and they all say the same thing. ACR guidelines says you need to have one risk factor, the, ERS UR guidelines from last year say you need to have two risk factors, but the bottom line is that almost all RA patients have one or two of these risk factors. Does that mean you do high risk CT in everyone? Well, that remains to be seen. I like this report, it's going to be, an oral presentation maybe tomorrow, on, it's called the Sunstar study, and it is a head to head study of, tocilizumab or abatacid after someone fails a biologic or targeted synthetic, and turns out in this study ninety five, ninety six percent of people were TNF inhibitor failures, and it looked like there was no real difference except for when you do the analysis a new way, a different way, there was an edge for tocilizumab, but we need to cover that to see where that's gonna go.

Other things, are a lot of studies that have been recently published that are going to get big airtime at this meeting, The Together PSA study, that's the combination of, of tirazepatide and the IL-seventeen inhibitor, ixekizumab, that data is going to be presented in full here, the AFFINITY study of, with golimumab, the, what else? There's another one that's out there that's going to be presented, again, but I like this, data on, there's going be follow-up data. There's a lot of CAR T cell therapies and B cell depletion therapies, and everybody's excited about it except for me, because one, we're a long ways off from seeing CAR T cell in the clinic. Two, I'm not seeing studies that are of good controls and are blinded. I'm seeing, you know, 12 people with Munchausen syndrome getting CAR T and being cured.

I'm making that up, that's a joke. But it looks very good, as you would imagine in lupus, and, somewhat good in, scleroderma, maybe not so good in the synthetase myositis patients, and a big question about what it's going to do in RA. The early report on the, what's going to be presented here is a small study showing that not everybody gets better but a few people do, and the question is who are they and why are they getting better? The Neptunus study, in Sjogren's syndrome, there'll be a number of Sjogren's presentations. Neptunus was presented at ACR, that's, enalumab showing its success, now they have some long term data that they're gonna, look at.

They have teletacept in Sjogren's, it's also gonna be presented here. And what else? An anifrolumab study with Sjogren's. And then the, Phonics study was just recently presented, and that's going to be shown here as well, and that seems to look good as far as the data goes. So, this is how you can best follow, EULAR, when you're not in London with a few of us who are here.

I think the best way depends on how you like to learn. The Twitter feed's gonna be active, the RheumNow faculty is gonna be out there, they're gonna do, you know, six, seven, 800 tweets, you can follow that. There'll be daily recaps starting Thursday night, we're gonna do a day one, day two recap that will, play Thursday evening, probably seven p. M, and then there'll be a day three recap on Friday and a day four, final day recap, on Saturday. The recap is where a few of the faculty and myself get together and say, what was great today, and what do you want everyone to know about?

There'll be great articles that you can follow on your phone and, on the website, and they'll come to you as emails. And the other way to follow is, to look at take the quiz at the end of the week. Do the weekly quiz on this Saturday and next Saturday, and you'll learn just by doing 20 or 30 quiz questions about, what the take home message from the meeting was. Anyway, it's going to be a fun time in London. Hopefully, you'll have fun listening to our coverage.

Take care.

I'm Anthony Chan, I'm reporting here from London at EULA twenty twenty six. And there have been a lot of interesting abstracts and presentations today in the field of psoriatic arthritis. And I want to highlight to you an interesting, abstract that was just presented. I've just come out of this session right now. It's oral presentation OP068.

Now we've all been here before. We have done psoriatic arthritis clinics. We've examined the joints. There is nothing swollen. There's nothing that is tender, but the patient still reports having pain.

Is there any inflammation there? What can we do if we can't see it? And I think today we had some interesting result from this presentation. The study comes from India and it's using Gallium sixty eight PET scan. Now, what's interesting about this is understanding the molecular signals behind this presentation where patients are complaining of pain when we can't see it or feel it when we examine the patients.

So this is a study where they looked at the use of Gallium sixty eight PET scan to look for inflammation in patients who clinically didn't find any tendon or swollen joints. Now we know that in psoriatic arthritis there is a subclinical inflammation that can happen, where there's inflammation but maybe not visible or not something that we can examine. And what happens is there's synovial angiogenesis, a new blood vessel is being formed, which is the early pathogenic event in psoriatic arthritis and often this precedes the onset of joint symptoms. We know that there are cytokines of HF, TNF alpha, IL -seventeen, and also an important integrin, which is alpha V beta-three. Now in this study, the Gallium sixty eight PET scan is able to detect the alpha V beta-three integrin.

In this study, they had fifteen patients with psoriatic arthritis and in total, they examined around ten twenty joints, so a lot of joints. Now what is interesting is that they found that in fifty two percent of these patients, the PET scan lit up, as in the PET scan was positive, but the examination was negative, as in there were no tendon or swollen joints. So these were clinically quiescent in this group of patients. There was good correlation in terms of the examination finding and the negative examination finding and the positive PET scan and also the PET scan results correlated with DAPSA, with swollen joint count, CRP and also the NAEP C score, the NAIL score. Now, I think what we are saying here is that the PET scan is not yet going to be used in our clinics.

We certainly would not be using this routinely in our patients. But what is telling us that there is this concept of subclinical inflammation that can be seen using other imaging modalities such as this Gallium sixty eight scan compared to our traditional examination, where we know that in psoriatic arthritis damage can happen as early as six months in early disease and uncontrolled disease. So they also were able to use a latent class analysis where they found that there are patients who are very PET positive. So these are patients who they call PET predominant, where the scans were positive but clinically they were found to have no tender or swollen joints. And these were in thirty five percent of patients with positive joints, where they actually had one hundred percent PET positivity, but zero percent clinically tender joints.

Now what does this all mean to us? I think it helps us to dissect the molecular imaging of angiogenesis a bit more and this perhaps one day could serve as a way for us to identify and detect, psoriatic arthritis earlier and perhaps start treatment a bit earlier and also to monitor the response certainly in this early phase of disease. So in PSA I think what we are saying here is that the clock starts much earlier than we think as in we can examine the patients, but in fact the inflammation and the angiogenesis might be happening much closer and much earlier than we think. So I think this adds to our understanding of the importance of this pathological process, namely angiogenesis and how more detailed scanning such as the sixty eight gallium scan hopefully in the future might be able to help us to detect these conditions much sooner. I'm Anthony Chan reporting for RheumNow here at EULA twenty twenty six in London.

Peter Nash reporting for RheumNow, Eula, London twenty twenty six. This is another interesting PSA abstract further to the one I previously presented, OPO seventy led by Lehi Iida. And she took patients with moderately active PSA, and she gave them and their BMIs were between twenty five and forty. A lot of them were quite heavy, over thirty, thirty four. Stable on treatment, many on a biologic, and they either got a Mediterranean diet or they got a weight loss diet or they got standard of care with some leaflets about diet.

And guess what happened at twenty four weeks? The patients nearly all lost weight. There wasn't any difference between the different diets, but their disease activity improved significantly just by losing weight. And by, week 12, they've improved MDA, they've improved PASTAS scores, and the amount lost was proportional to the clinical improved outcomes. So the first abstract talked about that weight reduction and and the BMI predicted who'd respond.

This abstract talks about weight loss. Then we move to another couple of abstracts that looked at the GLP one agonists. O p o six nine, Laura Coates, we've now seen the together study published and reported the IL-seventeen inhibitor, execizumab, combined with the GLP one agonist, tirzepatide, compared with ICSI alone, and they had significant improvements in outcome, ACR 50 plus PASI one hundred in those patients that were on the combination, and the weight loss was significant and made a difference to outcome, particularly pain and function. And then there were two real world studies. One POS, double o, 50 by Venereto, which looked at the same combination, but in a real life study with propensity score matching.

So they took a small number of patients, and they started them on a biologic plus the GLP one agonist and matched them with patients who were just starting the biologic. And, again, the outcome was significantly improved if you started the weight loss drug, and there was another small study that looked at the same thing. Rheumatologists need to get on board with these drugs, learn how to use them, take them back off the endocrinologists and the weight loss doctors, and act to start the first script and talk all your patients with a BMI over 30 into a short period of time, maybe six months, lose 10 or 15 kilos. If it's unaffordable, then stop and try and fight to keep the weight off. Many people are now microdosing to keep the weight off.

Hello. This is Nelly Zade reporting from EULARG 2026 in London for RheumNow. I had the pleasure to attend today to be part of a session called This is a Woman's World. So the EULAR Congress dedicated an entire session to women's health and rheumatic diseases. It was one of the most clinically rich sessions at the meeting.

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

So this was a multinational effort. We found that fertility and pregnancy outcomes were largely preserved with a live birth rate of eighty seven point nine percent and rates of miscarriage, pre eclampsia, and preterm birth comparable to the general population. The median time to pregnancy was four months and only eleven percent had subfertility. The single most important modifiable determinant of prolonged time to pregnancy was smoking. So women with axSpA reported a higher desired versus achieved number of children compared to men and more frequently cited their rheumatic disease as a limiting factor.

This data provides strong real world reassurance and underscore the importance of proactive reproductive counseling and smoking cessation in axSpA. So let's move to rheumatoid arthritis. Some good news for RA. Two large registry studies painted a broadly reassuring picture of RA during pregnancy. From Norway, Ingoon Sagberg, OP0242, presented data from the REV NETOS registry covering five ninety eight pregnancy and four seventy five women.

Most women maintained stable low disease activity during pregnancy, with remission rates climbing from sixty four percent in preconception to seventy five percent in the third trimester. The catch: postpartum flares were common, with twenty percent of women flaring at the first postpartum visit at six weeks, and remission rates dropped back to fifty nine percent. Seropositive women showed the most pronounced pregnancy related fluctuations and the highest postpartum disease activity. Importantly, temporal trends showed markedly lower disease activity in pregnancy after 2020, paralling broader uptake of biological DMARDs. Another study from Japan came from Shizuku et al.

February, who analyzed data from the NINJA National Registry across nineteen twenty one women of reproductive age. They found that pregnant and breastfeeding women had lower STI scores and fewer swollen joints than non pregnant counterparts, but were significantly more likely to be on corticosteroids and had near zero methotrexate use, which reflect appropriate but challenging medication adjustment during this period. Now let's move to France. RheumAboutin et al. OP0242 analysed twelve year data of follow-up from the French SPAR cohort, six twenty four women with early RA.

Among the three thirty nine women at risk at baseline, seventeen percent experienced at least one pregnancy during follow-up. Younger age, absence of NSAID use and absence of teratogenic treatment were independently associated with pregnancy occurrence. Among eighty nine pregnancy captured, seventy five percent resulted in full term delivery and nineteen percent had adverse outcome. NSAID use in the six months preceding pregnancy outcome were associated with a 6fold increase risk of adverse outcome, which is a really striking signal and adds to concerns about NSAIDs in the preconceptional period. Now to autoinflammatory disease in pregnancy.

So Isabelle has OP0244 presented data from the German registry on fifty one pregnancies in women with autoinflammatory diseases: FMF, STILL, etc. The overall picture was encouraging. Life birth, ninety three percent. No cases of preeclampsia or HELP. Neonatal outcome were generally favorable.

However, flares occur in thirty eight percent of pregnancies and elevated rates of small for gestational neonates warrants further investigation. One concerning observation from this study was that colchicine and interleukin-one inhibitors were frequently withdrawn during pregnancy, despite their established safety profile. So there's a gap between evidence and clinical practice in counselling. Also, Laura Coates presented the safety data on giselkumab in pregnancy, and it was very reassuring. Eleven eighteen maternal exposure cases from the J and J Global Safety Databases, four hundred pregnancies with known outcome.

The majority of exposures were in women with psoriatic disease, While the authors appropriately caution their data limitation, prevent definitive conclusions, these findings add to the growing body of evidence supporting the relative safety of interleukin-twenty three during pregnancy. Now let's move to the other side of the woman's life, to menopause. There were two studies on menopause. First one, Simone Perignola, OP0243, presented data from the Italian Bio Pure Registry, two thousand six hundred and forty five women starting a biological GMAT. They showed that postmenopausal women present with a more severe immunological and radiological phenotype, higher seropositivity, more erosions, higher CRP compared to women of childbearing age, and are significantly less likely to achieve thus 28 CRP remission.

Notably, however, early remission remained achievable in postmenopausal women who were B DMAR naive, had lower inflammatory burden and did not have comorbid fibromyalgia. The message here, menopause is a risk modifier, but not a treatment barrier if the disease got early. And the last study also in menopause in psoriatic arthritis, Lihi Adder OP0246 prospectively tracked four seventy seven women over more than twelve years and found that perimenopause was independently associated with a significant rise in dAPSA scores, tender and swollen joint counts, and PASI scores compared to both pre and postmenopausal age. Fatigue partially mediated this effect, accounting for twelve to eighteen percent of the dAPSA change, whereas BMI was not a mediator. So they suggest that hormone replacement therapy warrants consideration in perimenopausal women PSA, which is a really thought provoking conclusion that will likely spark further studies.

So the bottom line from this is a woman's world session at EULA twenty twenty six in London, that it delivered a clear and urgent message. Reproductive stage hormonal transitions and sex specific disease phenotypes must be integrated into how we assess and treat inflammatory rheumatic diseases in women. From the postpartum flare and risk risk in RA to the perimenopause driven disease spike in PSA, to the safety of biologic in pregnancy, rheumatologists now have richer data to counsel their patients and stronger reason to act on it. Thank you very much for your attention.

Hi guys, this is Aurelinage from Scotland, live from London, EULA Twenty Twenty Six, day two. I wanted to talk about something I feel like I talk to you about every year. Every year I talk about synovial biopsies. This year though, I'm talking about synovial biopsies in PSA as a way to potentially inform therapeutic decision in people with PSA. However, I'll say it straight away, it is it is not an abstract that I think will be life changing for now in terms of PSA, but I wanted to talk about it because it has the potential to make us reflect a little bit of what we want to do with these biopsies now that they're becoming increasingly popular.

So it's oral presentation 71. And so obviously with all the work done before with randomized controlled trials in RA, with biopsy and strap and therefore RA and so on, there was a feeling that maybe it wasn't ideal or it wasn't something we could use for prediction of response to treatment in patients. And so the idea of this trial in PSA was to look into whether we could inform terrapatec decision using tissue. A lot of the times in these really fancy studies, there's a lot of transcriptomic proteomics going on, things that you can't really do in clinical practice. So this one wanted to be a bit more pragmatic, and so what they did is they took biopsies from patients, sinovial tissue in thirty five patients, and then they looked at two different things in the tissue which are actually easy to look at.

One was the Crenn score, which is basically the levels of inflammation, and another one was the expression of CDR17 positive cells, which are myeloid cells in the tissues. So and it's a simple marker you look at nor a whole complex thing. And so fifteen patients within this 35 had a high amount of cells, these specific CD117 positive cells in their biopsy, and then the question was, in that case, first of all, do they respond as well to the drug, and what drug should we give them? And so basically it seemed that those patients that had higher inflammatory cells in the tissue, if they were receiving an IL-seventeen inhibitor or an IL-twenty three inhibitor, they were more likely to respond and to have a dapsa low disease activity or remission at six months than if they were receiving TNF. Also, and that's something that I think we kind of know by now, is that the more inflammation in the first place, the better the response, which means that if you do give drugs that have anti inflammatory action, it works better when there is inflammation, which that's pretty straightforward.

But the fact that IL-seventeen or IL-twenty three inhibition was better in people with a specific cell signature within their tissue, which is easy to see histologically, was interesting. Now this being said, it kind of also reflects the fact that in some patients they will respond better to IL-seventeen or IL-twenty three anyways, and whether it's because they have this specific subset of cells, it's really, really hard to tell. The sample size was extremely small, nothing was randomized and it was a single center study. So before getting really excited about this and biopsying every single patient in clinic, I think we really do need to decide whether or not we want a randomised clinical trial. I personally don't know if I would go ahead because I don't think I believe strictly in biopsy to guide therapeutic decision, but certainly if that could help us identify biomarkers that can be found in the blood, I think it would be something extremely helpful in the future.

I think you should look into rumnow.com, rumnow on Twitter or orallyromo if you want more content about EULA twenty twenty six. See you later!

Hello everyone, this is Nelly Ziade. I'm reporting from EURA, London for RheumNow, and I'm joined today by Doctor. Uta Kilsk from Germany, And we are here to talk about the SELENA study, which is a poster 51 presented at the Congress yesterday. So, Uta, welcome. Happy to have you here.

Thank you.

Can you just tell us briefly about the study?

Yes, sure. So the SERENA study is a non interventional study conducted in 19 different countries, included more than one thousand of patients with psoriasis, skin psoriasis, but also PSA and axSpA. I will report here the skin psoriasis data and the post hoc analysis on prevention of PSA in those patients.

Okay and what were the main findings?

So the main findings, they investigate the results over the period of five years and the main question was the proportion of patients that remained free of PSA in this SO population. And the short answer is ninety six percent of the patients remained free of PSA resulting in a very low incidence of new PSA development over five years.

Yeah, that's amazing. So you're saying ninety six point nine percent of psoriasis patients remained PSA free after five years on secuclumab. Exactly. Yeah, so how confident are you that this reflects a true disease modifying effect rather than just masking early musculoskeletal symptoms?

Yeah, this is a non interventional study so we have several limitations to discuss. However, I'm quite confident because we have other independent data on prevention of PSA in abso patients that are treated by biologics. So I think that it's really a true prevention because we have data on this biomechanistical approach but also translational data. However, because this patient population might not be the typical SOAR patient population, We have some limitation here, as we also can see in the patient characteristic where distribution compared to other typical populations.

Yeah, so I see in your study that sex and psoriasis duration emerge as the two significant predictors of PSA development. Yeah. However, classic risk factors like nail involvement, BMI and PASI did not. So were you surprised by these findings? Do you think they change our clinical risk stratification?

No, I don't

think so because if we as a rheumatologist think about prevention, we will see another population in our patients. In this non interventional trial, it was able to include so patients that are already on secukinumab and as you know in non interventional trials we did not have a very robust documentation of clinical findings like nail involvement, all these other clinical findings. So I think that's a limitation here and we cannot compare our observational study data to the more prevention study data.

Yeah, so do you think now that dermatologists should consider PSA prevention as an explicit treatment goal when initiating interleukin-thirteen inhibitors in patients with BSO?

Yes, absolutely. I think that is one of the goal. First of all, they should have an effective treatment on the skin psoriasis, but on the long run prevention of PSA is one of the main important goals.

Yeah, this reminds me of a study presented by the Greek team by Kukas et al. OP072. They showed that non TNF biologics, interleukin-twenty three and interleukin-seventeen were associated with lower odds of developing PSA compared to TNF, and they had a longer follow-up with a median of twelve years. So does this mechanistic make sense to you? So the positive response was interleukin inhibitors, but not with TNF?

Yeah, absolutely. So we have, first of all, we have other data that shows that prevention, the risk reduction in prevention is more pronounced in interleukin twenty three inhibitors, for example, and interleukin seventeen compared to TNF. So that's underpinning the existing evidence. And also when we are looking from a translational perspective on that, the inhibition of the cytokines that appear very early in the disease development process. I think that one of the key features here that gives the rationale really that this is a true prevention.

Yeah, so it's very exciting that to know that we can now prevent a disease from happening, and I'm sure there will be more data of like biomarkers and indicators about how to select these patients and to identify them early. So, thank you, Doctor. Kilts, for being with me for this interview, and thank you all for listening.

Hi everyone, this is Aurelie Najm from Scotland reporting live from London, EULA 2026, and I have exciting news for you. And the exciting news is there was a late breaking abstract presenting a head to head trial of two different mechanisms of action in PSA that are not TNF. So effectively, the presentation, which is LB0001, was the trial called Be Bold, and B BOLD was boldly comparing bimekizumab, so dual IL-17A and F inhibition, to rizenkizumab, which is IL-twenty three inhibitor. I'm actually really excited about this trial because it's giving us information that we can directly take home and potentially implement into our practice, or that certainly will be implemented into updates of recommendation for management of PSA. But certainly what was interesting was this phase 3b study recruited five fifty three patients that were randomized with active PSA, they were TNF naive or TNF inadequate responders and the study had a primary endpoint of ACR50 at week sixteen.

And so quite interestingly the results are clear: 50% ACF50 response at week sixteen in the bimekizumab arm versus 38% in the rozankeizumab arm, so quite effectively demonstration of superiority of bimekizumab. More patients also achieved secondary NPOWNS, such as ACF 50 by week four, 20 versus seven percent, dapsa, lower disease activity remission sixty five percent versus 54 and then the combined joint and skin response as well. And the minimal disease activity was not statistically superior, but numerically higher. The safety profiles really were quite similar, or at least as expected, with obviously more candida infection due to IL-seventeen inhibition, but we know that really. But there was no new safety signal, And I think there's been a lot of head to head trials we've seen, especially in RA, where it's actually quite unclear.

For example, this one that was presented in the RA session earlier at the conference, OP0205, which was a non inferiority trial of tocilizumab versus sabatricep, and the results are, you know, you can sway one way, you can sway one other, but I think this is a trial that has very clear results and I'm just quite excited for us to see how this is going to shape the recommendation and the way we care for people with PSA in the future. In the meantime, I invite you to follow me on twitter orilyromo and follow RheumNow for more EULA twenty twenty six related content. Bye.

Peter Nash reporting for RheumNow from EULA London twenty twenty six. The first abstract I want to cover is one of my favorite topics. Jack has talked about it very frequently, but I think it's time for rheumatologists to step up and get involved. My attention to this was drawn by Canadian abstract of 10,000 diabetics who had autoimmune diseases, PSA, axSpA, lupus, RA, and the diabetics who are on the GLP ones had less death, less stroke, less heart attack, I started getting interested. PSA metabolic syndrome, it's common and important and very important to patients' outcomes.

Now there's an OPO one eight seven by GuraiMan presented at this meeting, which looks at the predictors of the one year response to disease activity using AI tools from the SPEED trial. Now the SPEED trial compared three arms, step up conventional synthetic DMARDs, combination of conventional synthetic DMARDs, and early TNF use, and guess what the predictors of response were at forty eight weeks. They looked at all the usual things, age, gender, disease duration, treatment, BMI, smoking, alcohol, and number one predictor of who would respond in those three arms of treatment was BMI. Guess where treatment came? Number six.

Age was number two, and baseline disease activity was number three. Now the people with the worst outcomes were those with the highest BMI, the longest disease duration, polyarticulate age. So this is trying to tell us that BMI is important and even more important than treatment arm, including TNF, in patients, with this active disease looked at in this study.

Hello. I'm Jonathan Kaye reporting from EULAR twenty twenty six at the Excel Center in London, England. Today, on the third day of EULAR, there was a very interesting, debate, between Maya Book, Maya Butch and Jacques Eric Gottenberg about combination targeted therapies for the treatment of rheumatic diseases. This is a very interesting area because doctor Gottenberg, who's from France, suggested that there are a number of combinations that might be safe and more effective for the treatment of rheumatologic diseases. And in France, he has no difficulty getting approval or having dispensed to his patients the multiple targeted therapies.

There are recent data in psoriatic arthritis of the combination of ixekizumab and a GLP one agonist compared to ixekizumab alone, and this was more effective achieving PASI one hundreds greater with the ixekizumab and the GLP one agonist than with ixekizumab alone. In rheumatoid arthritis, the potential for combination therapy is most interesting with the combination of a JAK inhibitor and a TNF inhibitor. JAK inhibition does not block signaling of the through the TNF receptor so that a patient who is inadequately responsive, to a JAK inhibitor might benefit from the addition of a TNF inhibitor. Now with biosimilars of adalimumab, available at a lower cost, this might become a feasible therapeutic option in rheumatoid arthritis. The addition of GLP-one agonists to biologic therapies is very promising, especially in patients with peripheral spondyloarthritis where an IL-seventeen inhibitor might be inadequately effective alone, but the addition of a low dose of a GLP-one agonist for its anti inflammatory effect may potentiate the effect of the IL-seventeen inhibitor.

Maya Butch said that she agrees with the idea of combination biologics, but the data are not yet there, and we need to learn more about mechanism, before embarking on this. This is a very interesting potential topic. More on this to come. For more about this and other topics at EULAR twenty twenty six, go to rheumnow.com. I'm Jonathan Kaye.

See you again soon from

Hi. This is doctor Artie Kavanaugh from UCSD coming to you for RheumNow. I'm at EULAR twenty twenty six in beautiful London, and, of course, a tremendous amount of material being presented here. I'll talk about one oral presentation and that was by Mikhail Ostegard. The abstract is OP186, and this was on an important study.

This is a combination therapy study called Affinity. Now this follows on the VEGAS study in ulcerative colitis, very successful, showing that the combination of the IL-twenty three inhibitor gazelkumab and the TNF inhibitor glimimumab did what we had always hoped the combination therapy would do, and that is get greater efficacy and yet not have increased toxicity. Based on the results of that study, there's great interest in psoriatic arthritis looking at combination therapy, and this is one of the first studies to do that. Affinity looked at two of those groups, looked at gazelkumab and galimumab versus gazelkumab alone in psoriatic arthritis. Now the primary outcome was a very stringent one, and that was minimal disease activity or MDA, and while numerically superior, it did not reach significant statistical significance in this somewhat small study.

This abstract, was presented by Mikhail Ostegard, looked at MRI findings. So they looked at the SAMRUS, the, OMRAC way to look at MRIs in, hands and feet of patients with psoriatic arthritis, and they also looked at the hemorrhage which looked at enthesitis. They looked at inflammation and they also looked for structural damage, and what they found is that in the subset of patients treated with the combination therapy, there was a statistically significantly greater reduction in overall inflammation in the hands and feet than with just the therapy with gazelkumab, the IL-twenty three inhibitor alone. So I think that raises some interesting questions. This is yet another way to look at the efficacy of therapy, and in this case, an important question about combination therapy.

The study was short, and as you probably would have expected, no difference in structural changes in the MRI. I think this points out that MRI imaging may be a very useful adjunct in studies to get proof of concept, and that the combination therapy is certainly an idea worth exploring more in psoriatic arthritis. So coming to you, ULA twenty six in London for RheumNow. This is Artie Cavanagh.

Hello. I'm Anthony Chan reporting here from ULA twenty twenty six in London and today there are important presentations on dual therapy or combination therapy in SpA Spondyloarthritis. There have been more studies in psoriatic arthritis but today I want to focus on SpA Spondyloarthritis. First Oral presentation OP351 which is a study from Spain. So the first thing in order for us to treat patients is we need to do what we call treatment to target or T2T.

That measurement allows us then to escalate the treatment into combination therapy. But what was very interesting from this presentation this morning from this oral abstract is that in SPAR only forty percent of patients had documented measurement of their S test or the outcome measure that allow you to escalate the therapy compared to seventy percent over in PSA and rheumatoid arthritis. This means that in most of the time these documentation did not take place. And what was quite interesting is that there's a treatment inertia that results as a result of not calculating your ASH test. In about a third of patients there was reassurance more than escalation of therapy compared to seventy percent in the PSA group.

So while we have guidelines and while we have the approach to treat to target, most of the time the problem is structural. The problem is documentation rather than clinical. And so they suggested prompts to get people to do the S test to be able to check the CRP prior to the patients coming. Many are ways for us to escalate the treatment. And then going into that, the next oral presentation is OP352.

And here is the study looking at the use of combination therapy in spa. And this includes people with peripheral spondyloarthritis as well. What they found is the biggest combination was the TNF and IL12 stroke twenty three followed by TNF combination of IL17 and then finally TNF with IL23 combination. The results were quite startling that if you did combination therapy and you escalated the treatment, more than fifty five percent of these patients would achieve S test remission or S test low disease score compared to the other patients who are on standard types of treatment. When we think about combination therapy, obviously we think about the safety, whether this is safe.

In this cohort of patients that they studied, there were no new safety signals. There were no unexpected results as a result of the combination therapy. So these are very refractory patients. The median number of biologics either targeted synthetic or BD marts were a median of four. So these are truly refractory patients who are not achieving the S test.

Putting these two together, think the first thing is to be able to measure. If we don't measure these, then we are not going to be able to escalate. And when we do measure and the patients do not meet the standard for remission, then the ability now to escalate into one, there will be two biologics. And we need long term data to know how safe would this be in the long term or whether we de escalate patients down the line once they achieve the target. So very interesting presentations today.

I'm Anthony Chan from RheumNow, EULA twenty twenty six.

Hello everyone, this is Nelly Ziadev from Beirut, Lebanon. I'm in London reporting on EULAAR twenty twenty six for RheumNow. Today I will talk about combo therapy. R2 better than one. This is a case for dual pathway blockade and refractory psoriatic arthritis.

Psoriatic arthritis is by nature a disease of multiple inflammatory pathways, joints, and diseases, skin, dactylitis, there's a role for TNF, interleukin-seventeen, TNF 23, TYK2, and no single agent controls all of them optimally in every patient. Actually, forty to fifty percent of PSA patients on TNF inhibitors monotherapy fail to achieve minimal disease activity. So this treatment gap has long prompted a question among rheumatologists: what happens if we block two pathways at once? And I will talk about two abstracts at EULAR that explore these questions from different angles. One is reporting MRI data from a complete phase 2a trial, and the other is just a starting study of a phase four entering recruitment.

So the first abstract is AFFINITY OP086 by Wallen et al. They explored MRI findings from the phase 2A affinity study. They randomized 91 TNF inadequate responders, PSA patients, two to one. First arm is guselkumab associated, so an interleukin twenty three inhibitor plus golimumab HNF inhibitors compared to the other arm of guselkumab monotherapy over twenty four weeks. So the rationale is mechanistically elegant.

Interleukin 23 and TNF may play a complementary non redundant role. And so if you block both of them, you could have interesting results. And this is reporting the MRI data which they scored using the OMRACT framework. So in the hand pharyngeal joints, they found that the combination therapy produced a numerically greater reduction in the composite inflammatory score compared to monotherapy. So change minus five compared to minus 0.4.

However, the P value did not reach statistical significance. However, the FUT results were more striking and they reached nominal statistical significance. So, the composite foot inflammation score improved by minus 3.5 in the combination therapy versus a worsening of plus 2.7 with monotherapy. Structural damage scores were stable in both groups, which is reassuring, knowing the basal crema established effect on radiographic progression. And Hill antizitis scores showed no significant differences between the groups.

So this is an exploratory study, it was not powered for more endpoints, so we need to be cautious. The sample size was modest, we didn't find any significant difference for the hands, but it was important for the foot, and it is biologically coherent. So we look forward to have more data on this combination. The second abstract by Merola et al, poster four ninety nine, is a different approach. So this is a combo trial pairing dotravacitinib, a TYK2 inhibitor, with ongoing TNF therapy.

So target population is a patient with PSA and partial response to anti TNF, defined by persistent skin involvement or active joint, despite at least six months on TNF. So this is the, like the classical scenario where the patients are okay with TNF, but not really well enough to reach the treatment goal. So the trial is ongoing. They were randomized one hundred twenty eight adults to clavacitinib once daily plus TNF or placebo plus TNF for twenty four weeks and followed by a twenty four week open label extension where everybody will receive the combination. The primary endpoint is a composite skin joint target, BSA less than 1% and swollen joint count less than one, less or equal to one at week twenty four, which is a bit stringent, but this is what our patients ask for.

They have also interesting secondary endpoints, MDA, very low disease activity, and the full PROs battery, also cardiometabolic biomarker profiling, adding in a new dimension. So recruitment is just beginning and also we look forward for the result. So I have two concerns to address when I see this combo treatment. First, the safety data of both agents. So when used individually, the safety is well established.

However, the incremental risk of combining both of them is still unknown. And the second one is the cost and the cost effectiveness of this combination, which also needs to be addressed. So the question is whether this is ready to move from hypothesis to practice in psoriatic arthritis. Thank you.

I'm Anthony Chan reporting for RheumNow here in London in EULA twenty twenty six. One of the areas that had been discussed in this conference is the use of combination treatment or dual targeted therapy in the field of both psoriatic arthritis and also axospondyloarthritis. One of the presentations was the AFFINITY study, which is OP0186, which is the study of gusilkomam in addition to golimumab in patients who had failed one or two TNF inhibitors. This was a phase 2A study which tested the IL-twenty three inhibitor gusilcumab combined with golimumab, which is a TNF alpha inhibitor, versus gusilcumab monotherapy in patients who had failed, one or two prior TNF inhibitors. Ninety one PSA patients were studied in this study and this earliest, report is about the MRI findings, as an exploratory outcome.

The key findings is the combination therapy. Patients who had received both gusilcumab, in addition to golimumab, did better with regards to some of the MRI findings compared to patients who had just received the TNF inhibitor alone or with the gusilumab monotherapy. The combination therapy produced numerically greater reductions in the hand inflammation, compared to the monotherapy group. And also the foot MRI showed a statistically significant reduction in the total inflammation versus the monotherapy group. The structural damage was stable in both groups.

The combination did not accelerate any damage. And there was no obvious difference in the heel and ascites data that was seen. So the question is what is the significance of this? This is very early data. It's looking at MRI changes.

So it's very much looking at the imaging outcomes and the MRI data, certainly in the hands and feet would support, the clinical signals, the dual pathway, the dual blockade of IL-twenty three and TNF, may actually raise the ceiling with regards to reducing joint inflammation in patients who had failed TNF or TNF inadequate responders, particularly the ceiling in the foot. And it does not appear to increase our structural risk. So this is, I thought was interesting because it's using in the exploratory phase, the MRI result rather than the typical outcome measures that we would use in standard reporting. Obviously, we'll await further data as the study is carried out in the longer term. But we are increasingly seeing in patients who had failed one or two TNFs that we are going for more the combination treatment in these patients to try to get, the treatment refractory patients and to get them into a more better clinical state and also, hopefully reduce structural damage in the long term.

I'm Anthony Chan reporting here in London at, EULA twenty twenty six.

Hi, everyone. Peter Nash reporting for RheumNow, London, EULA twenty twenty six. There's many abstracts on variety of different treatments, new TYK2 inhibitors, combination therapies, etcetera. But probiotics are very popular, and this is p poster two ninety, where because of the microbiome in the gut joint axis, people are very interested in whether adding a probiotic has any efficacy in psoriatic arthritis. So they took a number of people who had moderately active PSA.

They gave them a lactobacillus and a bifidobacterium, probiotic and compared it to placebo. And over twelve months, the primary endpoint was their PASTAT remission or low disease activity, and unfortunately, they were unable to show any difference in controlling or improving disease activity whether you took a placebo or a probiotic. So probiotics look like they aren't the answer. We are working on a lactobacillus probiotic ourselves. We've done it in rheumatoid with some modest efficacy, and we're about to do it in PSA, but that study really argues against it being of efficacy.

More work needs to be done because nothing changed. The microbiome didn't change, the gut permeability didn't change, and the composition of the immune, subsets didn't change either with the probiotic. Now everyone is talking about late breaker one, which is going to be presented tomorrow by Joe Marola. This is the sixteen week data, and it's a head to head study between bimekizumab and risankizumab. He'll present the twenty four week, and we look forward to hearing about that tomorrow.

But we don't have many head to heads in psoriatic arthritis. We have two head to heads TNF versus, 17 inhibitors, one with and one without methotrexate, and that was very educational. It helped us, increase discontinuations in the, TNF group. The TNF group had much more serious adverse events than the 17 group, but this was a head to head for the first time, a active comparator study, including superiority, and they looked at a 17 versus a 23. Sixteen week data presented, twenty four weeks tomorrow, and these patients were all be DMARDs naive, or they had one TNF, and up to about twenty percent had one TNF.

And they used the labeled dose. The risankizumab dose was one hundred fifty, at baseline four weeks, and then week sixteen, whereas the bimekizumab dose was the one hundred sixty milligrams that was dosed as per protocol, but up to sixteen percent who had moderate to severe psoriasis or body surface area greater than 10% or, an IGA greater than three, we're allowed to use the label dose, which was double the dose, and that was about sixteen percent of patients. The primary endpoint was ACR fifty at week sixteen, and a whole series of secondary endpoints including MDA. And there was significant difference at week sixteen, forty nine percent versus 38% ACR50. They looked at a whole series of other endpoints, including PASI 100.

There was a difference of 53 versus 47. Because the second endpoint MDA didn't reach statistical significance, but just numerical significance, all the other endpoints were nominal, and they couldn't work out confidence intervals and significance there. But, dapsa, low disease activity and remission, numerically in favor of the 17 inhibitor, and all the way down the line, we didn't see any major differences in safety. There was a candida signal, is known with the 17. So first, head to head 17 to 23 in favor of the 17.

We look forward to the twenty four week, results, and they'll hive off the percentage of patients with double dose and see if the significance is maintained, whether you can whether that was a a reason for the difference or not. So we look forward to hearing about that tomorrow.

What does it mean to you?

To me, I think we're starting to get a treatment algorithm that has evidence based rather than elderly bull fat men in a room sitting around a table deciding which drug should be used before which other drug. Hi, everyone. Peter Nash reporting for RheumNow from EULA London twenty twenty six. I've got a little theme, a couple of abstracts, and a couple of presentations talking about the transition of psoriasis to psoriatic arthritis, how we can prevent it perhaps, and how we can, use some imaging to help. So the first is an Austrian group that have put together a nice prospective longitudinal program where they've taken a couple of 100 people who are at risk of developing psoriatic arthritis but don't have any synovitis, don't have any swelling, negative inflammatory markers, they only have PSO, and they have some morning stiffness, and they have an improvement with NSAID, but that's about all.

And they have done a nice lot of work with this group, and even at the baseline, they find four percent have rheumatologists diagnosed PSA, and they're gonna follow this group over a length of time. Now we did a similar thing in eight dermatology clinics, and we turned up about nine percent of pay PSO patients hiding amongst the p the hunt eight percent PSA patients hiding amongst the PSO population. Now the next transition is is anything can stop that transition from PSO to PSA. So the Greeks have done an, OP o seven two. They have done a retrospective observational cohort study where they took PSO derm diagnosed, but no PSA, and they were all on a biologic for over six months.

And they looked to see, and they followed these patients up over seventeen years and they looked to see how many developed rheumatology diagnosed PSA. Again, three forty patients, three ninety four patients, sorry, and in the seventeen years twenty two percent developed frank PSA and of that twenty two percent, given that they were all given a biologic by their dermatologist for their rash, forty five percent of them happened to be on the TNF when they developed PSA, fourteen percent on an IL-seventeen inhibitor, ten percent twenty three, and eleven percent on a twelve twenty three. So these are three hundred people, twenty two percent actually have PSA that evolves and they diagnose it, and they had been on a variety of different biologics. And there was a hazard ratio difference adjusting for the disease time on a biologic and methotrexate background. And the 17s and the 23s and the eleventwenty, 1223s, there's no difference between them, but you're more likely to prevent and not get progression on those agents compared to a TNF in a group, all of them on a biologic.

So that was of some interest. People, including Lihi Ida, have presented ultrasound to help pick the PSA in the PSO population. But previous meetings have shown, and this is abstract two six one three, that if you use a technique called FAPI PET, you can show fibroblast activation. And the fibroblast is gonna become very interestingly more important as a measure of chronicity in rheumatoid, in PSA, in people who are not responding and not going into remission. And it's a watch this space as a number of companies are developing anti fibrotic drugs.

But this FAPI PET CT, if you have a high index compared to if you don't, you're six times more likely to develop psoriatic arthritis whilst you started off with psoriasis compared to those who do not have an elevated FAPI PET CT. It's an expensive research tool, but people are looking for ways to pick PSA in a PSA population and do something about it early.

Hi. I'm Sheila Reyes from The Philippines reporting here in London for ULUR twenty twenty six. Joining me today is professor Marina Magre from, Case Western. And in in this video, she will be talking about two of her abstracts, which she presented in the oral abstract sessions on the safety and, major adverse cardiovascular events of biologic DMARDs and JAK inhibitors in patients with, AS and psoriatic arthritis. These will be abstract zero p zero one zero six and, abstract zero p or o p, rather, zero one eight one.

Doctor Magrath, thank you very much for joining us.

Hey, Sheila. And thank you for giving me an opportunity to present these abstracts, which were two oral presentations. These abstracts, they were actually some real world data, which, work we had done answering some real world questions. So the risk of, you know, cardio major cardiovascular events in patients with psoriatic arthritis is high. There was actually a meta analysis done several years ago.

We showed that the risk was around, like, forty percent in the psoriatic arthritis patients on major cardiovascular events. We have multiple therapeutic classes now available for treatment of psoriatic arthritis. However, you know, there is no direct compare to, you know, studies in real world showing their, cardiovascular safety profile. So we decided that we're gonna, compare the cumulative MACE risk between the biologic classes like TNF inhibitors, IL-seventeen inhibitors, IL-twenty three inhibitors, IL-twenty three, IL-twelve inhibitors, versus JAK inhibitors. And the reason we chose that is because there is always a concern of increased, MACE risk with JAK inhibitors based on the oral surveillance study, even though the study was in RA, but those results are then extrapolated into other rheumatic diseases.

And so, that was the reason why we wanted to look at these data. So, we used the TriNetX database, which is a large federated database and has, medical records from at least, more than 100 healthcare organizations, and somehow it has more than 100,000,000 patients in it. So, question was to look at cumulative MACE risk of these, in medication classes versus this, and our primary outcome was incident MACE. The MACE was defined in this study as myocardial infarction, stroke, pulmonary embolism, and venous thromboembolism, so we combined them together. We did not include, sudden cardiac death in this because those data were not available in this database.

And in order to, balance the baseline characteristics of these, subjects, since it's a large database, we did inverse, proportional, treatment weighting because, to balance these groups. It was a large, group of patients, about, 21,000 patients together, and predominantly majority of them, at least 11,000 to 12,000 were on TNF inhibitors, followed by IL-seventeen inhibitors, then IL-twenty three inhibitors, and there were about six hundred patients on JAK inhibitors. We matched the baseline demographics. However, in the JAK inhibitor group, still, there were more females than males. There were about 69 females, male, and then, and only 30%, males.

So that kind of remained as a bias that we could not balance that, which also balanced their baseline, comorbidities, hypertension, diabetes, anticoagulation use to make this, cohort uniform. Interestingly, what we found was that up to two years, there was no difference in cumulative MACE risk between, IL-seventeen inhibitors, TNF inhibitors, IL-twenty three inhibitors versus JAK inhibitors. However, based on time to event analysis, the risk for JAK inhibitors increased and over time, the risk accrued for all the medication class, but the most accrual was for JAK inhibitors compared to TNF inhibitors or IL-seventeen inhibitors, and this accrual was seen after two point five years of JAK inhibitor use. So, we concluded that saying that the risk of MACE events increases over time in these, patients, and JAK inhibitor was most commonly associated with these events, particularly after two point five years of use. Now the city does have some limitations.

You know? Obviously, there has there was we tried our best. We have very strong team of, you know, clinical, these statisticians with clinical research training. We tried to use mutually exclusive datasets. We included patients only that were only on one class of TNF inhibitors, but there is definitely there had to be some residual confounding, and we did not account for adherence to the medication.

Mhmm. Okay. Thank thank you for that, doctor Nagre. So since these are real world data, right, I was wondering if based on your results, how could how could these results translate to considerations in clinical practice, or are there implications in clinical practice?

So, you know, one one thing I wanna make clear is that the it's just an association, not a causation. So from these data, we cannot imply that this is the JAK inhibitors are cause of it, just an association. So, we thought that with the with this, you know, answering this question would enable clinicians for a risk stratification at the time of treatment initiation and choose which patients would be appropriate for JAK inhibitors and which patients would not be appropriate.

Okay. So it still, is important to do risk stratifications for our patients and considering individualized treatment and what associated risk or comorbidities that they may have.

Exactly. Yeah. I think it's very important for a clinician to, you know, take into account these factors, as you mentioned, comorbidities, age, other risk factors, smoking, and then have a good you know, it should be, like, a good discussion with the patient, and it should the decision should be made both taking into account patient's preferences, where the patient understands the risk and benefits, and then combined decision between the two would, you know, make it a better way of treating our patients.

Correct. And, do you have any plans to further, institute, research on this area or, like, make more?

Mhmm. This since this database is a it's an electronic medical record database, most of these, comparative, safety studies in real world have been done out of claims database. So we wanted to do it out of real EMR. But still, these, you know, these are not, like, prospective studies. So they are basically hypothesis generating studies, and I think it's worthwhile, like, with you know, now that we saw these these results from this database, it's worthwhile doing a proper prospective study and seeing if this you know, is this information going to be same as what we saw in this retrospective cohort study.

I agree. And, so let's go on and, discuss, your next abstract, which is on real world data now comparing the safety and adverse event adverse event profiles of biologic therapies and targeted synthetic DMARDs in patients with ankylosing spondylitis. So what can you say about the your study, the results, and, its significance in clinical practice?

So in in ankylosing spondylitis, we do use the same database, but here, we want compared the safety profile and adverse events between the TNF inhibitors, IL-seventeen inhibitors, and JAK inhibitors. And the, you know, we the primary outcome was, again, looking at overall safety profile, onset adverse events between three months to five years after treatment initiation. We again selected the patient population. These had to be patients greater than 18 years of age with a diagnosis of, ankylosing spondylitis based on ICD 10 code of 45, it's 45.9. And then, these patients had to be only treated with a single class of medications.

There was no, crossover allowed between the groups. If a patient was had taken more than two classes, they were not included in the study. Within that treatment class, they could have used multiple medication. Like, if they were on TNF inhibitor class, they could have been on dalimumab, changed etranercept, but they could not have crossed over to, like, an IL-seventeen inhibitor or a JAK inhibitor. And then we also wanted to make sure that these patients, adhere to their medication.

So medication adherence was also accounted for, and how that was done was these patients had to have at least two exporters to the same medication class, and at least the second prescription had to be ninety days beyond the initiation of the treatment.

Mhmm, I

get And those patients, yeah, who actually had more than, two classes of medications were excluded, and we also excluded those patients who had infections, like oral infections, pneumonia, skin infections, candidiasis that happened either before the start of the medication index date or within ninety days of medication initiation. And these patients that they who that had, like, you know, these adverse events of interest, like if they had had myocardial infarction, stroke, DVTP, they were all excluded before the treatment, so if they had them in the past. So, we try, at the baseline, the cohort, you know, included mostly TNF inhibitor patients, followed by IL-seventeen and JAK inhibitors. And the patients were, the TNF inhibitor and the, IL-seventeen, that the TNF inhibitor had had, age group was lower compared to the IL-seventeen inhibitor and JAK inhibitor group. The JAK inhibitor and IL-seventeen had older patients, and, they were also predominantly males in those two groups.

So, we then tried to balance these baseline characteristics by doing a propensity score matching between the two groups. And, time to event analysis was also done using a Cox proportional hazard ratio and, Kaplan Meier curves. And what we found was in these propensity matched scores, the adverse events between the three therapeutic classes were variable. So those patients that were on IL seventeen inhibitors, that they actually showed a lower odds of, major cardiovascular events compared to TNF inhibitors. The odds ratio was point six four.

So there was about, six percent patients on IL-seventeen inhibitors that showed an increase. The MACE risk was six percent in these patients in IL-seventeen inhibitors compared to nine percent in TNF inhibitors. However, there was no difference in all cause mortality, malignancy, depression, overall infections, candidiasis between IL-seventeen inhibitor and TNF inhibitor group. On the other hand, the MACE risk was higher in JAK inhibitor. The odds of MACE were higher, two point four, compared to TNF inhibitor group, but there was no difference, again, in all cause mortality, malignancy, depression, infections between JAK inhibitors and TNF inhibitors.

And then in time to event analysis, we found out that the the even though IL seventeen inhibitors had shown lower odds of MACE compared to TNF inhibitors, but in time to event analysis, we did not find a statistically significant difference between the two groups. So the Crocs proportional hazard, the hazard assumption failed. And, but in contrast, the JAKs over time continued to show an increased hazard, compared to TNF inhibitors, the hazard ratio was around 3.4. So in conclusion, we said that in this real world study in patients with, you know, using the real world ankylosing spondylitis population, the risk of MACE increased over time, and the risk was more in JAK inhibitors compared to TNF inhibitors. However, there was no difference among the classes in all cause mortality, malignancy, depression, and infections.

And, again, you know, the study has some limitations. You know, there are studies, like any retrospective cohort study, there is still possibility for residual confounding. We tried to account for medication adherence, but the cohort of JAK inhibitors was small, and, it was only two hundred and forty five patients in that group. And so that kind of limits this generalization of these results. And, even though and then we only included infections after ninety days of treatment initiation, which also lowers some generalizability.

Mhmm. Okay. So it the the results are still interesting. And, you've mentioned about infection. So was were there any particular infections or safety signals that stood out in your, in the study, in the patient and the participant?

We looked for pneumonias, specifically skin infections, candidiasis, and none of them showed any difference between the treatment groups. There there was not one one more than the other. They were there was no increased signal showing in any of those treatment groups, which is reassuring to us as clinicians and patients saying that, you know, there is there is not one has any more more risk than the other, at least. The association, we would say there was no association of those infections within this. So that was kind of a that is reassuring for us, both Okay.

And to telling our patients. It was only the association with, major cardiovascular events and deep vein thrombosis and pulmonary embolism. That was the only thing that, was higher with JAKs. The with the other groups, did not see an association to that.

K. That's very, reassuring to know. I was actually gonna ask about, was were there any incidents or were there any signals on the occurrence of TB or hepatitis in these sets of patients, but I guess there were none.

We know we didn't check. We didn't look for that. So we didn't look for TB or hepatitis. So that was not, you know, in our study question.

Mhmm. Okay. But thank you for thank you, Marina, for sharing your study results with us today. And I think this will add more it will it will add more how do you call it? Like

Yeah. Definitely, there I would say,

you know,

as you're you're alluding to what I was gonna say, that these are very hypothesis generating ideas. It's Yeah. You know, trying to give us tell us that there may be there may be an association, and this needs to be studied further to evaluate further.

Yes. To evaluate further and to have more robust data that we can get generalizations from. But, again, I I guess the main message here is that we really have to prioritize individualized treatments, risk stratify our patients, especially since patients with SPA and with PSA have an increased risk of developing cardiovascular disease. So it's really important that a shared decision making is made between the physician and the patient, taking into consideration, again, their individual risk factors, other fact comorbidities, and even patient preferences, and as well as the local availability of these treatment options. Yeah.

So before we end, Marina, just a quick, like, a a quick message that, you know, our viewers can use as they go back to clinics based on your study results.

So I don't mean, you know, that as you already mentioned it, you know, shared decision making is very important for treatment of our patients, and, we need to, you know, make our patients feel better. We need to improve their quality of life, and we need to treat them, you know, with available therapeutic classes. But I we have to thoroughly discuss the safety profile, adverse events with our patients so they're aware of it and then have the shared decision and, go ahead and treat them.

Okay. Well said. Thank you very much again for joining me, and, we look forward to more, to more researches in this field. And so as I end the interview, follow me on Rheumatra at sorry. Follow me on x at Rheumatra, and tune in to RheumNow for more updates of EULAR twenty twenty six.

Bye. Have a nice evening.

Bye, Rina. Thank you.

Hi. This is Jeehao Li from Michigan reporting for RheumNow for ULAAR twenty twenty six in London. Today I'm going to talk about two posters that are actually updates to the APeX trial which involves gluselkumab which many of you may be familiar with. This is poster number four eighty and four seventy one that are looking at slightly different of the same trial. So this trial involves patients with psoriatic arthritis and involved patients with active disease.

If you may recall, APICS actually enrolled patients with active and erosive joint disease, meaning structural damage was already present at baseline for many of these patients. So they actually enrolled higher stakes population to really get at the question of is gluzelkumab effective in the treatment of psoriatic arthritis across joint, bone, skin, nail. And I think we're starting to get some answers for regards to that, which is really nice because especially the latter two, the skin and nail is something that our patients are really cognizant of and it really affects their quality of life. So just to kind of set up the trial and also just to give some reminders, although many of you may be already familiar, gazelkumab is a fully human monoclonal antibody that selectively inhibits the IL-twenty three P19 subunit. It is approved for moderate to severe plaque psoriasis and active psoriatic arthritis.

And a lot of that was thanks to this APeX trial. It's currently in the 3B randomized double blind placebo controlled study phase. And it was specifically designed to be tested in people who are biologic naive and as I mentioned before with both active joint disease but also erosive damage on radiographic changes according to the hand and foot. So the way the study was set up the participants were randomized to either receive a fixed dose every four weeks or kind of this induction maintenance phase where they would get it in a week zero and four and then every eight weeks thereafter and then the comparator group was porous with placebo. Follow-up was at twenty four weeks and prior reports from this trial have shown that there are improvements in joint disease activity as well as structural protection.

So the two poster presented at EULAR went a little bit deeper and answered two separate questions. So the first one, POS0480 was about subgroup analysis. And in particular, subgroup analysis according to sex BMI, number of joint involvement and complement methotrexate use. And that's because male sex and higher BMI are considered risk factors for progressive disease. And also the joint disease involvement shows you higher disease activity measures and its response to that.

And the question of whether concomitant methotrexate as or deters from the effectiveness of gazelkumab. So overall, the findings were pretty consistent with the overall finding in that regardless of whether you get the fixed dose or the kind of induction ramp up in Q8 weeks, those who got guselkumab about two thirds achieved ACR 20 compared to placebo. And this finding was consistent across the sex BMI joint counts as well as the concomitant method Trexic use. You find similar findings again when you look at structural damage. So again, I think this is just informative in the sense that the overall benefit that you saw in the bigger trial wasn't just with particular subgroups, but in effect for those who are at higher risk for progressive disease and worse disease, this drug holds up.

I think personally what I found more interesting, think I said our patients would appreciate was poster number four seventy one. Because this was actually about the benefit to skin and nail. And I just want to spend a little bit of time about how they identified and set up the disease. So for those with psoriatic skin disease, they identified patients with at least three percent body surface involvement or mild disease according to the investigator global scale, which is a five port scale going from zero being clear and four severe. So they tried to find patients in the middle with at least some mild involvement, if not moderate to severe.

And their outcome was actually the proportion of participants achieving one hundred percent improvement or clear skin, which I think is a really ambitious but also at the same time clinically important endpoint. For nail disease, again, they use validated measures called the modified nail psoriasis severity index. This one goes from zero to one hundred thirty. And then there's also the five point physician global assessment of fingernail psoriasis. Similarly, again, here they identified patients with at least mild disease and their endpoint goal was for patients to have clear or minimal nail disease or at least drop down two scales assessment.

In terms of the results, it was actually very striking and very reassuring and impressive, I have to say. So when it came to the skin, with the drug, thirty eight percent to forty percent I should of all the trial enrollees sixty percent met the criteria for having at least mild to severe skin disease and of those thirty to forty percent on gozelkumab achieved the endpoint of having clear skin and that is compared to twelve to fifteen percent of placebo. So that's actually pretty impressive. When it came to the nail sixty five percent had nail involvement at least mild to severe again according to the definitions I shared earlier. And here about forty three percent on the Q4 week and thirty six percent on the Q8 week was able to achieve that mild to clear definition or at least to valid point drop.

And that is compared to only sixteen percent in the placebo group. It's a little bit interesting that with Q8, the nail finding or nail improvement was less than Q4. So perhaps with patients with severe nail disease that Q4 week dosing may be more benefit. But I think we're going to be seeing more guidance as more data comes through. So kind of putting this together, as I said, I think it's really reassuring to know that goselumab is holding up its efficacy across different subgroups.

But more importantly, showing that there is benefit both for the skin and more importantly the nails. Because I've had some patients ask of me of what their responses may be or what drugs may be more effective and sometimes have been at a loss. So I think I'm looking forward to seeing more follow-up data regarding this as well as safety signals to follow. For those since this was testing biologic naive patients, it'll be interesting to see if this kind of moves up in our chain of prescribing. I will note in terms of the limitation, however, that twenty four week follow-up is still relatively short.

So it'll interesting to see how long this holds up for. And then also this is specifically just for biologic naive patients. So what does this mean a lot of times since our patients are likely to have tried conventional synthetic but also anti TNF or other biologics and how will this finding translate or carry through in those patients as we as physicians will be having to prescribe in real world practices. But I think at least there is more to look forward to from the APeX trial. Thank you for listening.

This was Jeehai Lee reporting for RheumNow for EULAR twenty twenty six in London.