EULAR 2026 Daily Podcast Day 4c Save

You're listening to a RheumNow podcast coming to you from London in ULAR twenty twenty six. Enjoy.

Hi. This is Jiahao Li from Michigan reporting for RheumNow for ULAR twenty twenty six in London. Today I'm going to talk about two posters that are actually updates to the APeX trial which involves guselkumab which many of you may be familiar with. This is poster number four eighty and four seventy one that are looking at slightly different aspects of the same trial. So this trial involves patients with psoriatic arthritis and it 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 question of is gloselumab 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 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, Gazelka Mab is a fully human monoclonal antibody that selectively inhibits the IL-23p19 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 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.

Then the comparator group was towards 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 POS four eighty 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. Question of whether concomitant methotrexate as or deters from the effectiveness of guselkumab. 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 ACR20 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 a 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 on that nail 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 to forty percent I should backtrack just a little bit of all the trial enrollees sixty percent met the criteria for having at least mild to severe skin disease.

Of those thirty to forty percent on guselkumab achieve the endpoint of having clear skin and that is compared to twelve to fifteen percent of placebo. 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 two 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 our 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 gozalcumab 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. And 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 be 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 is Jeehaw Lee reporting for RheumNow for EULAR twenty twenty six in London.

Hello. My name is RheumNow, and I am a rheumatology fellow here in London. I'm delighted to be reporting from ULAW twenty twenty six also here in London. I am joined by doctor John Giles from Cedars Sinai Medical Center in California in The US. And we are going to be discussing the very last abstract to be presented at this congress, l b zero zero zero nine, which is looking at the long term safety data, really exciting stuff from looking at baricitinib versus TNF inhibitors in an enriched cohort.

Specifically, we're gonna be discussing results of VTE. So, doctor Giles, thank you very much for joining me. Can you just give us a brief overview of the study?

So this is a phase four safety trial. It was mandated by the FDA. The FDA had a lot of input into the design of the trial. Primary outcome was venous thromboembolic events based on some signals from, their randomized clinical trials, some of, issues about class effect as well. There were 36 more than 3,600 patients who were randomized, two doses of baricitinib, two milligrams, four milligrams, versus TNF inhibitors, which could be a Tannercept or adalimumab.

The trial, there were two different trials put together. One was a standard global randomized clinical trial.

Mhmm.

And then the other was a more of a pragmatic trial that was done in The US with less data collection, but still adjudicated events.

Okay.

There it was an events based trial, so there were a certain number of, venous thromboembolic events that were supposed to occur. It turned out that, the trial was stopped, early because if if the trial had continued and they had accrued all those events, they still would not have had been underneath the non inferiority margin of 1.8 for the upper bound of the 95% confidence interval. Okay. So there was there was numerically higher venous thromboembolic events in both of the arms of baricitinib, and it was basically equal for the two milligram versus the four milligram. But it was not statistically significantly higher, but certainly, did not meet the criteria for non inferiority.

Okay. Great. And I guess we're all looking at this through the lens of oral surveillance and the warnings we've been receiving, since that study came out. How do you think clinicians should view the data from RA Bridge and RA Branch now that we have this, for their clinical practice?

Well, think it's important to note that that this is really a very adventurous trial because the population was enriched for venous thromboembolic risk factors. They could even have had a venous thromboembolic event in the past. Now that was the minority of patients that had had those, but they are included in that group. And then the other risk factors like higher BMIs and older ages are included there. So I think this gives us an idea about what the actual risk is.

And this is comparative risk too. So we're talking about the difference between TNF inhibitors and baricitinib. We're not talking about overall risk and we're not talking about compared to not treating people with anything or treating them with other things. So I think it gives us a good idea about what the actual numbers are. And subsequent analyses will be able to interpret what the risk factors for those people who had the venous thromboembolic events are.

We'll be able to look at the other outcomes of secondary interest that were there. We'll be able to come up with numbers needed to harm and what the bounds on those are. So I think there's more to come here. I think when we're trying to put the baricitinib as a single drug into context, and then also put the greater context of the risks of JAK inhibitors as a class, I think this is very, very important information, because we've been talking about oral surveillance for, five years now.

That's an impact on our practice as well.

It potentially has an impact on our practice and allows us to kind of compare and contrast between the two different trials.

And then just speaking about the risk factors and the fact that it was an enriched cohort, are you able to comment on any of the other outcomes that we were looking at in oral surveillance, may

Well, so the interesting thing that's different from from bridge and branch compared with oral surveillance is that there's absolutely no signal for major adverse cardiovascular events or malignancies.

Yeah.

And they it's they're equivalently powered on those. They're not enriched for those, but they're they have the same number of basically, the same number of patients. They have basically the same number of follow-up times. So there's no real difference there. Now why that is, we don't know.

We'll have to dig into that a little bit more. They're not in risk for those things, but people who have VTEs are also enriched

for response.

Risk factor for cardiovascular disease. So I think as we dig into the data a little bit more, we'll we'll be able to compare and contrast maybe doing some subgroup analyses with more of a subgroup that looks like the inclusion criteria for oral surveillance and see if anything comes out of there. It certainly does maybe lower the concern about those, whether that's a class effect or it's a drug specific effect, you know, we don't know. Remember that, oral surveillance included a standard dose and a double dose.

Yes.

And this includes a half dose and a standard dose.

Yeah.

So may that could be part of what we're seeing too.

And a different target as well.

And a different target.

Yes. Yeah. So really not able to comment maybe on the whole class of how we how we use JAKs in general. So interpret with caution maybe at this stage.

With caution, I think. And it and it really shows that, you know, these are two of the largest clinical trials that have ever been done in RA. Yeah. And and we still have uncertainty about, you know, what they mean. And then when we look over into other clinical trials that have, you know, a few 100 patients, you know, it just makes us realize, especially for safety, that safety outcomes are really require big numbers of patients and some of them that we're not able to actually get to.

Okay. Great.

Well, thank you for taking us through that study. So if you want to catch up on that study, it is the very last abstract in the congress. Thank you very much for joining us here on RheumNow. Do follow along for further coverage.

One of the issues that we face in inflammatory arthritis is the referral from the primary care physician or general practitioner. While we have many modern therapies, the issue that we have is the delays to diagnosis. When patients present late after their symptom onset often they have more comorbidities and often the treatment becomes less effective when instituted at a later stage. So one of the things that is quite important is to try to improve the diagnosis time by improving the referrals that we get from primary care. Here at EULA twenty twenty six in London, there were two posters.

Firstly, Poster twelve eighty four. This comes from the UMass Rheumatology department in Worcester in The United States and this study was presented by Doctor. Carmen Solomon Escoto and Doctor. Jonathan Kay and it was a very interesting study where they used the CARE tool which was first developed in The Netherlands. In this study they validated the CARE tool which is a screening questionnaire that allows us to screen for the probability of inflammatory arthritis.

With a score of greater than four that would increase the probability of inflammatory arthritis. They had two eighty four new adult patients who suspected inflammatory arthritis and they used the CARE tool and the sensitivity from the study was seventy seven percent meaning at least three in four of these patients were screened for possible inflammatory arthritis and the specificity was sixty three percent allowing for these patients to be deprioritized or may be seen less sooner than those who scored positive. What was very interesting was the tool not only screened patients in but also screened patients out as they were deprioritized into urgency if they scored less than four and the negative predictive value was ninety percent. So nine out of ten of the patients who scored less than four could have a more routine appointment. The area under the curve from the study was 0.74.

This showed good overall discrimination from the use of the CARE tool. So this was a very important study. If we have such a tool, then this allows us to select our patients more carefully for the studies. How about the implementation? And this is something that we presented from my group.

And this is poster seven eighty four, where for the last four years we have been leading rheumatology academy and collaborative network called RheumCan where such tools such as screening tools such as the care tool and many other screening tools can be used but also implemented in a way that the system provides training and education for primary care physicians to use this and the confidence went up by nearly twice the amount from 4.4 a start to 8.6 over 10 in terms of the users being more confident in looking at inflammatory arthritis and ninety five percent of them said they were likely or very likely to change their practice as a result of the training And this was seen where the percentage of referrals that were referred to secondary care or to the rheumatology department three days after presentation in primary care went up from fifty two percent to seventy percent within a year of implementing this program. This compares to the old national average which remains fairly static at fifty percent of these patients being referred within three days of presentation to primary care. So what we are seeing here is if we have a tool that we can use which is validated such as the CARE tool then we need to have a system that allows us to train and also educate our primary care colleagues to use this tool so that they are more confident and at the end of that we will reduce the delays to diagnosis.

So I think these are new ways of us delivering education and training by using validated tools. I'm Anthony Chan presenting here at EULAW twenty twenty six in London.

Hello everyone. My name is Doctor. Youssef. I am associate professor and consultant rheumatologist in Leeds, United Kingdom. I'm reporting for RheumNow to cover the Congress EULA twenty twenty six in London, United Kingdom.

Today, there is late breaking abstract sessions. The room was full. So the abstract that I would like to discuss today is the title LB003. As we all know, B cells play a major factor in the immunopathogenesis and achieving peripheral B cell depletion is important to achieve both biological and also clinical response in rheumatic and musculoskeletal diseases. Currently, there are various ways, including the use of cellular therapies such as CAR T and also bispecific or trispecific antibodies.

However, is there any other method? Well, in this abstract, so this is a Phase 2a basket study to evaluate combination therapy using off the shelf allogeneic NK therapy. This is a non So the compound is called AB101. This is a non genetically modified compound which was developed from the cord bloods. So it is off the shelf so that this is scalable compared to a CAR T cell, which require quite a long process time to manufacture.

So in this abstract, so the use of AB101 is in combination with patient has to undergo conditioning with low dose cyclophosphamide and fludarabine. Secondly, with rituximab, which is given one gram to infusion two weeks apart, and also the compound itself with the allogenic AB101, which was given one dose weekly for three doses. So this is a basket trial encompassing four diseases, including rheumatoid arthritis, Sjogren's disease, scleroderma and also inflammatory myopathies. In this preliminary analysis, the investigators presented data on three conditions. One is severe refractory rheumatoid arthritis.

So majority of the patients have failed at least DMARDs and also have active disease. Secondly, patients with Sjogren's disease who have active disease despite standard care. And as we know, we don't have inoleacin therapy in Sjogren's. And the third one is patients with scleroderma who have active disease despite failure of the at least one immunosuppressant. So the results are quite astounding.

So it shows a very good peripheral B cell depletion achieved with this combination therapy. And they also presented data up to fifty two weeks. And the primary endpoint is at six months. And we can see in people with severe refractory rheumatoid arthritis, for example, the ACR fifty response was seventy one percent. This is like if we want to compare with patients with TNF inhibitor failure in the initial study of rituximab, which is called reflex, the rate was actually around thirty percent.

So this is really interesting that with deeper basal depletion, we can also achieve greater response. In people with Sjogren's disease, the change in SDAI has dropped to about eight point score. And also people with scleroderma, there was improvement in terms of modified Rottman skin score for the skin fibrosis for around nine point reduction. So these are all interesting efficacy preliminary analysis of this study. In terms of safety, there was no icons or any more than grade one GRS that was reported.

And they also reported no evidence of hypergammaglobinemia in the first fifty two weeks. Of course, this is only a preliminary analysis. It would be interesting to also know in the future about the efficacy in also in inflammation myopathies, which I'm sure is going be presented in the next conference. Importantly, one of the advantages of this therapy is scalable. It can be administered in the outpatient settings.

However, with all the studies, this is still early, so we will still keep our card in the chest. Compound need to be investigated in a randomised controlled studies and to have a proper comparator for it before we can use that in the future. So I hope you found my video summary interesting, and follow RheumNow for more content coverage from EULA 2026.