EULAR2025 Topic Podcast IL-17 Save

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

Hi, everyone. This is Adela Castro from Memphis, Tennessee, from EULAR here in Barcelona. I wanted to go over a representation. The abstract number is OP0102, and it's called the efficacy and safety of a new IL-17A blocker called selegepimab 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.

For more, please follow RheumNow. 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 ACR50 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 penetrating tissues. 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, Euler 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 this was an off the shelf bite cell or a 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 tick to was that they might be able to fully spare Jack which Duker 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 TYK2, Zazza, I'll call it, that they found high inhibition of TYK2 and it didn't affect the other JAK pathway. 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 ducravisindib. So this is poster 15. The last sort of cool thing was another novel antibody.

And this is novel because this thing called ORKAtwo, 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 use 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 was 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, I'm Anthony Chan reporting here for RheumNow in Barcelona at EULA twenty twenty five. And there were interesting presentations on novel therapies in axial spondyloarthritis here at EULA twenty twenty five and I wanted to share with you some highlights of emerging treatments in the field of XBA and there were three key developments. One, a new IL-17A inhibitor, Venakizumab, JAK inhibitor, Evamacitinib and then a highly individualized exercise intervention study. So let's, go through these and explore their clinical implications. The first one is, poster two fifty four which is a vunakizumab.

It's a novel IL-17A monoclonal antibody which was studied for, its use in ankylosing spondylitis. In the post op analysis four forty patients both TNF naive and TNF experience were treated. At sixteen weeks the ASUS 20 response in the TNF experience was 67% versus 45% in the placebo and the TNF naive was 65% versus 41% in the placebo. So fairly similar in both TNF experience and TNF naive and ASUS 40 responses were also significantly improved. Importantly the response rates were similar as, in both the TNF exposed and TNF naive groups suggesting quite broad utility of this treatment and, in terms of safety there were mild to moderate adverse events but no serious infections or malignancy seen.

This study suggests that possibly Vunekizumab could offer additional IL-seventy in, A option for those, even those who were exposed to TNF, inhibitor therapy. The second poster was, poster O262 which is, evamacitinib. We are obviously now moving towards a JAK inhibition. Evamacitinib is a selective JAK1 inhibitor. In phase twothree trials in three seventy three patients, They studied this and after twelve weeks the total back pain, visual analog scale, dropped by 25.6% versus 17% and this was significant.

The night pain, visual analog scale also dropped by 25% versus 14.3% in the placebo and morning stiffness also dropped by 24.5% versus 15.8% in placebo all meeting, statistical significance. The, patient global assessment and SQL also improved, significant. These are the quality of life measures. So even, patients who switch from placebo to the active drug after twelve weeks caught up and showed a rapid improvement. So again, I think this supports, the what our current experience and JAK1 inhibition is a highly effective target for XBA offering rapid symptomatic relief, across multiple domains.

So, another, one to add to our list of drugs that we could use to treat, XBAW. Moving away from this drug therapy, there was an interesting presentation, post February and this is about individualized exercise program, beyond medications. I think structured, exercise is crucial. This was an eight week study so quite a short study. They looked at cardiopulmonary exercise, training and also they looked at, trunk strength and mobility exercises using a specialist devices.

And the results were the strength were improved by about 14% in mobility, improved by fifteen percent in people who underwent this, this, treatment and the improvements were in, things such as ventilatory efficiency, the anaerobic threshold and also chest expansion. The best time also decreased from 3.5 to 2.9. So supervised individual exercise program, can significantly improve function, mobility and overall patient well-being, in XBA and this is again shown I think important that we don't just focus on the drug therapies but also the exercise as well. So what did I take away from these, three, presentations today? Firstly, the treatment landscape for XBA continues to evolve.

We have another IL-seventeen inhibitor option, Vunacizumab, another JAK1 option, Evomacitinib, it was a rapid response and also comprehensive. The L17 drug here responded both, in both TNF naive and TNF experience and finally, support and adjunctive therapy individualized exercise remains important and I think these developments underscore and tell us the importance of multimodal personalized treatment approach to our patients. So thank you for joining me for this update on, the latest, developments in XBA and I'm Anthony Chan reporting here at Barcelona at EULA twenty twenty five.