ACR 2025 RA Topic Podcasts Compilation 4 Save

This is an ACR twenty '25 podcast coming to you from Chicago. Hope you enjoy it.

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Hi, everyone. This is Oily Naj reporting live from Chicago ACR twenty twenty five. I'm from Scotland, Glasgow, by the way. So today is an important day. Today is the day where finally after many, many, many negative studies, we had a positive vagal nerve stimulation trial that was positive.

So what does it take to make a positive trial in vagal nerve stimulation? It takes to implant it inside of the patient. So a lot of the studies we've seen that were negative were studies with external stimulation and in this specific case, so that was presented in the RA session, abstract sixteen seventy five. So in this specific study, it was an implantable device and so it was quite interesting. So the study is called RESETRA.

They had randomized patients. So everyone had the implantable device placed through surgery, but half of the population, so it was two forty patients in total, half of them had the device turned off for three months. And then after three months, everyone had the device on and it was this open label studies that continued for another sixty six weeks. So, it was really interesting to see that the inclusion criteria was a bit surprising to me because usually you want a DAS calculation that is above 3.2 to define active disease. In this case, it had to be what they call moderate to severe RA, but then it was minimum four tender and swollen joints.

There was no other criteria, which was fairly surprising to me, but the good thing is the population was already resistant to one biologic at least and very importantly in this population, fifty percent of the people or actually thirty had not responded inadequately to two or more and thirty five percent had responded inadequately to at least three biologic. So we're looking at a resistance population which is good because these patients are not usually included in trials that much. So, primary outcome, three months ACR20, so quite soft primary, but even then, it seemed to be very efficient, or at least more efficient than the placebo, the control, the sham control group, which wasn't placebo, forty two percent versus ninety percent. And then at twelve months, once people had kind of all gotten to the active group, it was sixteen percent of ACR seventy, which you know is not that high, but equally these are people that are mainly resistant to multiple biologics anyways. The good thing as well is that at twelve months, there was no need for rescue therapy or change of biologics in eighty two percent of the people, which again, I think it's a good result.

Persistence was good. There was one severe adverse event though that was admitted to be related to the implant and it took that they had to remove it from the patient, but aside from that, there was a question I think in the audience about whether or not the sham was an actual sham because does the patient know if their device is on or off? But aside from that, I think it is promising, but it is invasive. So I think it's definitely a conversation to have with the patient. If we were to develop that, would you want to have this device implanted considering you know the improvement is moderate, but it's still better than nothing.

So that's something definitely to keep an eye on. And then there's a poster that's presenting the structural data, 2614, showing that apparently at three months, the active group had less erosions or had less radiographic progression using the MRI Ramray score, and it was forty percent versus nineteen. So, I found that surprising that so quickly in three months you can see such an important difference in the imaging. So I would be quite careful with that one, but definitely something to keep an eye on. The authors explain it by saying that vagal nesting relation can reduce rank ligand which is a protoaclastic cytokine and therefore reduce bone damage.

That's I think that's seductive, but we need to definitely keep an eye on that and see if that's confirmed in larger studies. That was me for today. Tune on rheumnow.com for more content and follow me on Twitter aurelieremo.

David Lu here for rheumnow. ACR twenty five day two, and there was a really fantastic RA abstracts, oral oral abstract session. A lot of fantastic work, some of which we'd heard a bit about before, Kevin Dean's work on hydroxychloroquine and stop RA, which of which there was negative. We heard Mandy Cope talking about the Alto study, the continuation of epipipra and the benefit that upfront abatacept can deliver in people with clinically suspect arthralgias and high appetizers. But in fact, one of the things that I think was particularly interesting that we hadn't heard much about in terms of the most recent results was actually data from Leeds presented by Tusk Toyota.

What he showed was looking at a cohort of people who had upfront TNM inhibitor for a year at the time of rheumatoid arthritis diagnosis. What effect could that have? I think a lot of this go through a process which has been reflected in the data up until now, where we start conventional synthetic DMARDs for the first period of time after a rheumatoid arthritis diagnosis and escalate up. But especially in places like The UK, we are getting the temptation to think about whether maybe upfront biologics might have an advantage, especially because with biosimilars, they are getting a lot cheaper. And if you come up with that upfront hit, whether you might have a legacy effect going on, especially thinking about whether we hit that difficult to treat rheumatoid arthritis, which we become more and more conscious about.

So that's exactly what this has looked at over greater than ten years follow-up after an initial one year of TNF inhibitor. It's not a randomized trial, they've looked at a cohort that they treated and compared it to controls from their clinics, but you can get an idea as to where the potential benefit is. So at five years, I saw that in fact, that upfront TNF inhibitor treated group had less difficult to treat rheumatoid arthritis. We saw more remission at ten years in that group as well. We saw that in fact, more people had come off, had actually come off DMIs altogether at five years.

So drug free remission in that TNF inhibitor upfront group. And we did see as well that actually the patients in that upfront TNF inhibitor group were slower to actually need a biologic later on. The median delay there was actually eleven months. And so it raises a question whether actually this might actually make sense from a cost point of view, as well as in terms of the clinical point of view. And in The UK, they are certainly focused on that.

It did seem from these data that it would support a pharmacoeconomic benefit from giving upfront TNF inhibitor. And with the cost of TNF inhibitors dropping down and down and down, the question will be, as biosimilars take hold, should we be giving a little upfront burst to try and get these patients to a better track than it would have otherwise been? It isn't quite enough to act on yet, but certainly raises some important questions that I'll bring back to the clinic and think of that with my patients. For plenty more about rheumatoid arthritis, everything else at this magnificent conference, you know where to go, roomnow.com.

Hey, everyone. This is Jeff Sparks from Brigham Women's Hospital in Boston, Massachusetts, and we are here at Chicago for day two of the twenty twenty five ACR Convergence Annual Meeting. Today, I'm gonna be talking about new paradigms for the treatment of rheumatoid arthritis. Obviously, we have a lot of great treatments for RA, but a lot of our patients are still suffering. And there haven't been a lot of advances over the past decade.

Certainly, a lot of other diseases have benefited from this, but I think RA has languished a bit. But luckily, there's three trials I wanted to talk about here that are really paradigm shifting, at least potential to be paradigm shifting for rheumatoid arthritis. The first I'll talk about is RESETRA, which is an implantable left vagus nerve stimulation. So, obviously, this is very different from any other treatment that's ever been approved for rheumatoid arthritis before. This involves a surgical procedure, overall relatively minor, but certainly different to refer your patient to a neurosurgeon to have this implantable device.

And this periodically stimulates the left vagus nerve, which has been shown to decrease inflammatory markers. So there were two abstracts that were interesting from this RESET RA study. The first abstract sixteen seventy five reported the primary results. And the primary outcome was an ACR twenty at month three. And this was randomized to basically turn the device on or to have a sham.

Basically, the the procedure was implanted but not turned on. So in 1675, showed that the ACR twenty was hit in around forty percent of patients compared to less than twenty percent of those with the sham intervention, and this was statistically significant. And this showed that this neuroimmunomodulation could be helpful and efficacious to treat RA, and many of these had failed several biologics. I think a particularly interesting part of this is that there continued to be improvement in month three where all patients crossed over into the active arm, and it seemed like this was overall pretty well tolerated. There were some patients who had some hoarseness and dysphonia, but overall not thought to be too severe.

A corollary subgroup analysis of this was twenty six fourteen, and this was looking at, basically, radiologic progression, looking at MRI scores. And this is not something I necessarily expected that a neuroimmunomodulator would actually, decrease the progression of structural damage in rheumatoid arthritis. And overall, there was a trend towards statistical significant and the intention to treat analysis. However, in a subgroup analysis where they restricted it to people who are high risk of developing or worsening ROSENS, particularly if radiographic features at baseline, it was statistically significant. So this is a real proof of concept that this could be a very different therapy to offer our patients.

The next, study I'll briefly highlight is the Rinnoir study at l b 19, a late breaker. This is a phase two b study looking at rosinilimab. This is a study that depletes pathogenic, T cells. In one of my previous videos, we talked about T peripheral helper cells, T follicular helper cells, which seem to be present in higher numbers, particularly in people at risk for rheumatoid arthritis and those that are seropositive. So this study randomized people to rozanolimab versus placebo, and this also hit its primary outcome of hitting an ACR twenty, and, also had differences in ACR 70 as well as many other secondary outcomes and was also very safe and well tolerated.

And I think that, should lead this towards, maybe perhaps a phase three study that would really needed to be established efficacy and safety. The last study is l b 23 that I'll highlight, and this is a CAR T study. However, it's a different kind of CAR T study because the T cell that they use is a Treg. And because this cell is, relatively, a peacemaker, if you will, this one doesn't actually need chemotherapy. It isn't expected to have much side effects.

And it's also, targeted against citrullinated antigens that are specifically implicated in RA pathogenesis as opposed to CD 19 that many of the other CARs. This is a a different kind of CAR T trial. And this is very early study, just phase one, and there did seem to be some transient benefit. I'll say that compared to the c d nineteen, this was not as efficacious. However, this is a dose finding study and perhaps a higher dose might be needed for more lasting effects.

But, again, I think this illustrates how CAR T could be used in many different ways besides just a c d nineteen CAR T effector cell. So these are just, three examples of some potential paradigm shifting studies within rheumatoid arthritis. To highlight, we're talking about neuroimmunomodulation with an implantable device. We're talking about depleting pathogenic T cells, and we're also talking about actually using CAR T regs as a anti inflammatory in a CAR T environment. So again, thank you for your attention, and hopefully, you're learning a lot at ACR twenty five.

And I'll look forward for more reports. Thank you.