EULAR2025 Topic Podcast PsA 1 Save

You're listening to a RheumNow podcast coming to you from Barcelona, Spain, and you are twenty twenty five. Hope you enjoy it.

This coverage is sponsored by Johnson and Johnson, the organization that believes health is everything.

Hi, everyone. This is Adela Castro from Memphis, Tennessee, reporting from EULAR here in Barcelona. I wanted to, go over a representation. The abstract number is 102, and it's called the efficacy and safety of a new IL-17A blocker called selegakimab in patients with ankylosing spondylitis. This is a Chinese study performed in four sixty five patients with ankylosing spondylitis and the primary efficacy was to achieve ASAS 20.

And then after week sixteen, it showed a significant proportion of patients achieved the primary outcome. And this was also noticed that this efficacy was sustained up until week forty eight in both doses of the medication. As far as safety, there was no major significant safety events. It did show a little bit of high proportion of mild elevation of LFTs, but in general it seemed really safe. Something that is very interesting about this medication is that it's a fully humanized IgG4 antibody, which seems that one of the benefits is that it can last a little bit longer on the body and it can also minimize the drug antibody production.

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Hi, I'm Jack Cush. I'm coming to you from Barcelona and you are twenty twenty five. This is an early look at a new problem that we're dealing with and that is at risk RA, clinically suspect arthralgia, preclinical RA. The question is, when do you treat these folks? How do you treat them?

So we've had a few trials demonstrating the efficacy of a few drugs, but in general it's not that clear. There's a sort of a collision now of several sets of data that I think are somewhat instructive. We reported this week on RheumNow the results of a twenty twenty five ACR ULAR risk stratification criteria. This is a paper that was published that gives us some insight as to maybe who should get treated with more aggressive therapies when they just have arthralgia and may be at risk because of ACPA or being positive, for family history. So, that paper says that the criteria, a point based system, is based on morning stiffness, patient reported swelling, inability to make a fist, C reactive protein, rheumatoid factor and ACPA levels.

And there's high and low points for low levels of morning stiffness or high levels of ACPA and that seems to be a reasonable approach but that's very different than what's being reported here at EULAR. Specifically, are two important long term follow-up studies to the Epipra study and the ARIA study. So, the ALTO study OP-four is a long term follow-up study of the Epipra study. Apipra was a two year trial where patients with at risk clinically suspect arthralgia ACPA positive but a positive MRI or ultrasound, so they didn't have synovitis, right? Two hundred plus patients were either given abatacept subcutaneously or placebo for a year and then followed for a year off of that.

In that study, we do know what the primary endpoint at week fifty two, six percent who received abatacit went on to develop RA but if they received placebo, it was twenty nine percent. But after a year, another year of follow-up off of drug, didn't seem to make much difference. It was 3040%, small difference. They followed those people out to as long as six years, and what they found in the two year study holds true in the six year study, and that is the patients who had the best responses were the ones with an extended auto antibody profile, meaning they had ACPA and rheumatoid factor, several ACPAs, and a number of different antibodies, anti acetylated protein antibodies, anti carbamylated protein, if they had all five of them, you are likely to have an extended response. In a two year study, it was fifty percent of the placebo patients went on to develop RA but if you had this five serotype profile, only ten percent.

That was at two years. That same result is carried out to two years and four years and as long as six years and four years, the extended autoantibody, it was forty seven percent of abatacept developed RA versus sixty seven percent. So, there's still some protection is the point and that's just with one year of treatment. So, the profile being not what the ACR ULAR risk stratification said but here it's being ACPA positive and really high titer plus five other autoantibodies for RA. This is a little bit different than what was shown in the ARIA study.

The ARIA study was another abatacep study. About 100 patients were enrolled in a six month trial abatacep versus placebo, and then they were followed for another twelve months. At the end of six months, eight percent of abatacep and thirty five percent of placebo developed RA. In this study, they followed them initially out to eighteen months where kind of the lines start to come together suggesting that the delay is being lost thirty five percent versus fifty seven percent, but what they found in their prolonged study at five point three years, the people who never developed RA were those who had lower SED rates, lower rheumatoid factor, lower pain scores, better functional status, meaning that the opposite of that might be the people who are at high risk, and maybe those are the ones that you do want to treat and maybe that you do want to treat them with abatassa. So, from these three studies, we're getting a picture of the people that we may want to treat more aggressively with abatassa, right?

So the extended autoantibody profile and maybe the people who had high risk disease, not low risk disease from the ARIA study. One more caveat and that is the TREAT earlier RA trial with methotrexate only showed in past publications that it worked only in seronegative, actin negative patients. So again, these are sort of rules as to who may need treatment in this hard to manage group. Do you treat them, do you not when they have clinically suspect arthralgia but no arthritis? Tune in for more great abstracts and presentations from UR twenty twenty five.

Hi everyone, this is Adela Castro from Memphis, Tennessee reporting from Barcelona, and I am going to present the abstract OP0096, which is sonilocumab in psoriatic arthritis. What is very interesting about this medication is that it's a novel IL-17A and IL-17F blocker but it's actually a nanobody which makes it different to the previous one already we are using. And this was studied in patients with psoriatic arthritis. This is a phase two study, so the population that's been studied is a little bit smaller, so only like forty two patients. In this study, it shows that the patients with both doses, sixty milligrams and one hundred and twenty milligrams with induction achieved its primary endpoint at week twelve, and they also achieved significantly higher rates of ACR 50 compared to placebo, and it was also noticed that this effect was sustained all the way through week twenty four.

It was also very interesting that the proportion of patients achieving important outcomes like minimal disease activity as well as other important outcomes that we like to see in patients with psoriatic arthritis. Something that is interesting about this molecule is nanobody technology seems to enhance efficacy given the smaller molecular weight, and it can also seems to be better kind of like penetrating tissues. So for more information, please stay tuned at RheumNow.

Hello, it's Doctor. Janet Pope reporting at ULAr twenty twenty five in beautiful Barcelona, Spain. I tweet for RheumNow and my handle is janitburdope, so I hope you'll be following the meeting. It was off to a great start, ULAR was, and I'm going to talk about some seronegative arthritis breakthroughs. So there were three areas that I thought were kind of novel.

The first one was using bite cells for the treatment of axial spondyloarthritis. So to remind you, bite cells are bispecific T cell engaging antibodies, and they've been looked at at least theoretically and with a little bit of data, particularly in lupus, little bit and difficult to treat other more seropositive autoimmune diseases and connective tissue diseases. So I looked at this poster, it was on the poster discussion and I was really intrigued. Why? This was a BiTE or a bispecific T cell engager targeting this area called TRBV9 positive autoreactive T cells.

So why would they ever pick this? Well, was an off the shelf BITE cell or T cell engager that was actually in an area where HLA B27, particularly HLA B2705 binds. So it would stop this autoantigen problem from happening. Now this came out of Hopkins. It was in poster board B33, and it's too early to know if something like this will work, but I thought it was really interesting and something I hadn't thought about.

Okay, what's the next cool technology? So I looked at an oral TYK2. Now we already have one for psoriasis and PSA to be approved in some jurisdictions already approved, do cravasidenib. So this was called Zazosidenib and their claim to fame as needing another TIC-two was that they might be able to fully spare Jack, which Deukre does, but also they're in late stage development in psoriasis. And what they looked at was that the clinical doses of this molecule, the oral Tik2, Zazza, I'll call it, that they found high inhibition of Tik2 and it didn't affect the other JAK pathways.

So it was a pure TYK2. There was no one, two or three JAK changes. And they compared it to do cravasidenib, and what they found was a far higher maintenance of inhibition. So is this going to be better, same or worse? First of all, no head to head trials.

This is an early pharmacokinetics, pharmacodynamics of how this mechanism of action might be different than DUCRA, but time will tell if it pans out clinically to see if it has a different benefit and or a different safety effect than DUCRAVASYDNIB. So this is poster 15. The last sort of cool thing was another novel antibody, and this is novel because this thing called ORKA slash zero zero two, so I'm gonna call it ORKA, but it's not a whale. It's ORKA. This is a novel platform technology that when we think of the monoclonal antibodies, the ends of the monoclonal antibodies have been changed to change the signaling.

So what there is, is technology of homo and heterodimer signaling, and this monoclonal change at the tips of the antibodies will make it stay in the system longer. And you could say, well, what's the advantage of that? Well, what they've done is they've put in an IL-17AF inhibitor. So as you know, we have bimekizumab as one of the inhibitors that's already on the market. So they used an IL-17AF inhibitor and they found that they could probably or possibly dose this monoclonal antibody with the neat technology, the ORCA-two technology in the platform.

They could dose it once every, listen to this, six to twelve months. And this is poster 16. So again, would this be able to really help adherence, would have a long term effect? Well, all of us in rheumatology, we know another mechanism that will prolong an antibody and that's PEGylation. And PEGylation would be an idea like Circulizumab pegol or as we know it as Cynzia that prolongs it in the circulation and you get less anti drug antibodies.

We know another PEG, a PEG uricase, that's highly antigenic, prolongs in the circulation, but you get a lot of antibodies to the PEG. So I think this pathway and platform is really cool. All of these things I've talked about today might not be ready for prime time, but I think will help my patients with seronegative diseases. See you at the next blog and RheumNow presentation. Thank you.

Hi, this is Eric Ritterrand from Northwestern University in Chicago, and I'm coming to you from the EULAR meeting in Barcelona for RheumNow. I've been looking at, a lot of the abstracts on psoriatic arthritis at this meeting. And one interesting thing that I've seen has have been some abstracts really looking in detail at using combinations of DMARDs to treat psoriatic arthritis. The abstracts in particular are, OP0093, o p o one zero six, and a poster, poster o one 06. What these are looking at is the idea of using combinations of a conventional DMARDs rather than going to a biologic in order to get control of disease.

It's not something we do a lot in The US, but I think in other parts of the world, either because of availability of drugs, or because of, their healthcare system that requires, use of conventional DMARDs before going to a biologic, it's an issue that's come up a lot. A couple of papers have come out of, The UK looking at, an early inception cohort of psoriatic arthritis, and looking at their treatment. They pulled out in one of those patients who were treated on two different DMARDs before going to biologic. And while on the one hand, it suggested that those patients did not always respond to DMARDs and many ended up on a biologic. It really is sort of a glass half full, glass half empty proposition, because about fifty percent of the patients on a combination of methotrexate and sulfasalazine, or methotrexate and leflunomide, did well enough that they didn't need to take a biologic.

I don't know that it's something we routinely do in The US, but it's certainly something that's a possibility, and certainly raises the question about whether we really need to move straight to a biologic. The dermatologists often do that because of the control of skin disease. But for joint disease, we may do okay with combination therapy. One of the abstracts here actually came from a Dutch study that looked at combining methotrexate and leflunomide. And they had presented that study previously, but at this meeting they talked about some of the longer term data.

And again, many of the patients did well, but about fifty percent of them had to go on to a biologic. And interestingly, it was the glass half full, glass half empty proposition, because their conclusion was that that wasn't all that successful. So, I think it depends on how you look at it. But in my mind, people switch off of biologics all the time. So, patients who do well 50% of the time, that's not a bad track record.

And I think in many cases, it may be worth at least thinking about combining DMARC and not going straight to a biologic, certainly for cost reasons that make sense. You know, it's challenging these days, certainly in The U. S, when biologics are more available and patients want to go straight to the target. So, that may be a difficult proposition to persuade them as we talk to them about it, but certainly worth thinking about. Anyhow, that's, one of the issues I'm seeing here at the meeting at ULAr in Barcelona.

And again, this is Eric Ruterman coming to you from RheumNow. Hello. This is Eric Ruderman coming to you, for RheumNow from the EULAR meeting, in Barcelona. I wanted to talk about, a semi new drug, a drug called ducravacitinib, a TYK2 inhibitor, that's been approved for about a year now for treatment of psoriasis. And we've seen phase two data in psoriatic arthritis and assume that eventually this is a drug that will become available.

At this meeting, two abstracts were presented with the two large phase three clinical trials of about 700 patients in each one, looking at ducravacitinib versus placebo to treat psoriatic arthritis. The upside of this drug is that it, is an oral agent. It's given once a day. It's very specific, for TYK2 as opposed to other members of the JAK family, which seems to reduce the risk of toxicity. Certainly, it seems to reduce the risk of some of the laboratory abnormalities that can see be seen with other JAK inhibitors.

And so far, it has not been associated with some of the other issues, the cardiovascular issues and so forth that have been associated potentially with other JAK inhibitors. They presented two large phase three trials at this meeting, both run, in parallel and and largely similar protocols. One, compared ducravacitinib to placebo, and they included a a safety reference arm of a premilast, not for, efficacy, but just to look at some of the safety. Dugravacitinib was effective. It was statistically better than placebo, though the placebo response, interestingly, was quite high in that trial.

It was more effective, at least nominally, than Apremilast, though it wasn't powered to really test that statistically. And it did have actually fewer side effects. It did not have the GI side effects that are often seen with premelast, the nausea and the diarrhea. The second trial looked at ducravacitinib versus placebo and selected for patients who were at higher risk for joint damage. These are patients who had at least one erosion upon entry into the trial, and they able were able to look at X-ray data in the trial.

The prespecified X-ray analysis did not meet its endpoint, but they presented some secondary analyses that have looked at that and suggested that looked at another way, this may, in fact, halt or at least slow radiograph progression. What I don't know is where this drug is gonna fit in. It it appears to be effective. We really have no comparative data, including no really statistically valid comparative data against the premilast. It does seem to be effective.

Is it, more effective than a premilast? Probably. Is it as effective as, some of the other biologics we're using? Don't know. Probably not, but we don't know.

And I think it'll be really interesting, when this gets to the clinic, which it will at some point probably within the next year based on these trials for psoriatic arthritis. It'll be interesting to see where people want to fit this in. It's intriguing to think about a once daily oral medication with very few side effects, and and sort of stack that up against some of our other options, other oral drugs that may have more side effects or require more monitoring like methotrexate or against injectable drugs. I think that as people begin to use it, where it fits in will become more clear as they try to understand, you know, which patients respond, which patients seem to want an oral agent. So it's an area to stay tuned in, but I think it was really intriguing at this meeting to see the phase three data, to see that this is a drug that's going to work.

And it's definitely a drug that I think will become part of our toolkit. Where in the toolkit it fits has yet to be seen. And, with that, this is Eric Ruterman again coming to you for RheumNow, from Barcelona, the EULAR meeting.

This coverage was brought to you by our EULAR sponsor, Johnson and Johnson. Check out their new data this week on the first and only IL-twenty three inhibitor proven to significantly inhibit progression of joint structural damage in active psoriatic arthritis by visiting RheumNow's virtual poster hall at roomnow.com.