Day 3 Recap- ACR Convergence 2025 Highlights Save

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Hello, everyone. Welcome to the daily recap from ACR twenty twenty five in Chicago. This is the day three recap. This is day three at ACR twenty twenty five. Hump day is the last day of full posters, full presentations, full exhibit floor with all the bad coffee.

This year, they had pizza and cookies and popcorn and snacks. It was kinda good, you know? So, maybe we should do a snack report from the convention floor, but I'm not sure the audience would enjoy that. So instead, we'll cover our favorite abstracts from this third day at ACR. I'm Jack Cush, Dallas, Texas.

I'll have everyone introduce themselves. Doctor. Reyes.

Hi. I'm Sheila Reyes, and I'm from The Philippines, and I'm joining live here in Chicago for coverage.

Mike Putman.

Hi, Mike Putman from the Medical College of Wisconsin, also here in Chicago, still at the McCormick Place.

Bella.

Hi, this is Bella Mehta. I'm from New York and happy to go over some of these exciting abstracts.

Yeah, we've got a, it was an interesting day. Know, it began with a, I think, a strong plenary session. I think that's where we're going to begin is that what you're to cover, Doctor. Reyes, as your first one?

Yes. I'll start with that since that's also the first session that was covered this morning. So I'm gonna talk about abstract that's abstract seventeen twenty two. It's entitled defining safe hydroxychloroquine blood levels by the group of doctor Shivani. And the primary objective was of their study was to validate the upper threshold for therapeutic hydroxychloroquine blood level monitoring.

And the second objective was to identify kidney function thresholds associated with potentially toxic hydroxychloroquine blood levels. So they pulled data from three large SLE cohorts from the SLEC, Wisconsin, and three French studies. And then baseline levels of hydroxychloroquine either from serum or blood were taken, and that was studied too. And so the results showed that they had a pretty big population. So 1842 patients were studied, four point four percent developed toxicity, majority of which was retinopathies from hydroxychloroquine.

And what they found is that for levels more than 1,150, this was a super therapeutic threshold, and there was really no added therapeutic benefit with potential for more toxicity and less than that would mean increase in flares. And also in terms of kidney function thresholds, they found that for CKD patients stage three and above, they had twice higher odds of supratherapeutic levels of hydroxychloroquine. And that was even despite weight based dosing of five of less than five milligram per kilogram. So I think, again, it validates some of the previous findings regarding the toxicity thresholds of hydroxychloroquine. And I guess it tells us, you know, the importance of trying to find a way to include this in practice and monitoring therapeutic blood levels as well as toxicity level.

And I think I got curious or interested more with that of the CKD because honestly, I don't necessarily adjust hydroxychloroquine that much. So I guess with these findings, we maybe we which we should be watching out more in terms of monitoring hydroxychloroquine levels.

Yeah. So I think this falls under, you don't know what you don't know. And, you know, monitoring makes a lot of sense here. Bella, what's your take on this data?

I don't know. I I feel like this hydroxychloroquine has gone like like a pendulum. First, they said don't give too much. Now they're saying don't give too less. I mean the five milligram threshold now to monitor like how often to monitor.

Understand. I mean, think we're all going in a very small range. Most patients we are doing fine with. Patients are getting scared and physicians are getting scared. So let's come up with one thing that we can go with.

But I think they were black and white about the numbers. You know? Less than seven fifty, no good. More than $11.50, no good, and be in between. Mike, what's your take?

Yeah. This is a funny one where I feel like we went to the same and we had totally opposite takes on it.

All I'm saying is that how often do you do this? Patient's compliance is changed for these drugs. So it's fine to do it once and then making sure that this is okay. I don't expect this to be doing this every three months. That's expensive.

That's not useful. Once you know that this is an okay dose, then I would just, like it's a one time thing, from a cost perspective also.

I think that the group that does a lot of it, Michelle Petrie's group, it's not a one time thing, but it's periodic thing and it's done early on, you know, when you're just doing that dosing. Now, one of the points of the paper was that even when you're doing the prescribing guidelines of less than five milligrams per kilogram, fifty two percent were sub therapeutic, and seventeen or eighteen percent were super therapeutic, even though you're in that nice guideline window. So, again, you might assume if everyone's doing well and you don't know the levels, then you assume everything as well, but, why not optimize things, with a tool? And it's not like this is a thousand dollar test and it is commercially available. The fact is, it was not available at my medical center before I left there.

It is commercially available in a number of places. I don't know the cost, but more than a rheumatoid factor and less than a biologic is what I would say at this point, but unless someone knows the actual cost. Mike, why don't you give it a try for a comment?

Yeah. It's funny. This is one of those abstracts where we each went to the same session and we had totally opposite impressions from it. The thing that I thought was the most interesting was actually that levels under 700 and 50 were associated with an increased risk of flares, and a dose under five milligrams per kilogram was associated with an increased risk of flares. And for me, that's just the most important thing.

Hydroxychloroquine retinopathy is rare. It happens about ten percent of people over ten years, and it's completely preventable from a morbidity perspective. The eye doctors see it. You stop the drug. Very few people actually develop long term issues with it.

And so from my perspective, I am much more scared of lupus flares. And my take home from it was that I want to get people up to eleven fifty. I actually want to go the other way on it. And my preference from seeing the abstract would be to air on the high side.

And I think that that was, that's what I learned a few years ago. I remember the first report on this at Madrid in EULAR over five years ago, maybe six years ago. It was pre COVID when Michelle presented this. All right, let's move on. Bella, why don't you give us your first one?

So I I went to the session with the, SJIA guidelines. These guidelines were updated from 2021 to 2025. A lot of changed in systemic JIA. Specifically, they're they're trying to give recommendations on drugs, which ones to use. So patients with MAS and without MAS is the big two brackets that they sort these patients in.

And those without MAS, I think they're saying go with any IL one or IL six. No real preference. Try not to do a lot of glucocorticoids. Of course, those with the MAS, you have to add glucocorticoids. But overall, I think the guidelines were trying to minimize steroids as with all our guidelines.

But the other things that they were not recommended were NSAIDs upfront, glucocorticoids upfront, or even initial oral DMUDs. Also, for patients of you know, after taking care of the initial phase for subsequent therapy, either try you know, they were preferring biologic DMUDs or JAKs instead of some of the other ones. And, again, they were preferring IL one or IL six agents compared to JAK inhibitors. And sort of for persistence, MAS, they did add imapalumab for, MAS, and I think it does, work well. So it's good that they added it.

And then sort of the big takeaway for this guidelines was that all patients they are recommending screening for lung disease because that's a big problem in the pediatric population. Not as much in the adults but screening probably might be a good thing. It's not really put in practice as of now for adults at least, but now there's a strong guideline recommendation. And then the last thing they said is for clinically inactive disease. I like that they want to say, hey, strongly recommend decreasing glucocorticoids, which we all do, but also conditionally recommend sort of tapering or going down on biologic DMARDs.

Again, we'll see what the data is, but if it's monophasic or something, it probably does make sense. Think from nine to 15, the guidelines, they have expanded. They're trying to go in-depth. But, all of this is mostly on recommendations, not huge evidence for a lot of the recommendations. But, I think it's an important one, to talk about.

Oh, the only strong recommendation is this recognition that they have already had, which is first line treatment is an IL-six or an IL-one inhibitor. That was already out there, that's in EULAR, and that is a recommendation. And then they throw in these, they throw the curve at you about don't use nonsteroidals. Actually, it's very old, ways of thinking about this and that's fine. It really doesn't work.

Although the

old And most people aren't using it. Yeah.

Well, it used to be 60% of the therapy, and whatnot. But the idea of not using steroids is, you know, first off, that's conditional. You know, I'm sorry, everybody with Stills that ends up in the hospital is gonna get steroids, but they're gonna, you know, theoretically, they're gonna get parenteral. And if you're sticking with, you know, liberal use of parenteral in the early phases, then they can go home not on parenteral, not on oral if they're on a biologic that is as effective as we think IL-one and IL-six is. So I think that makes sense.

But the algorithm that I think that Susan Chenoy presented was you get an IL-one or an IL-six. If you're not doing one, you get the other one you didn't get. And then after that, you're going to get a jacked. And then, after that, if you've got, you know, joint stuff, you use joint demards or joint biologics in in the mix but yes, they want you to stay away from steroids. The other thing about these guidelines was that these were an update to both the 2019 and 2022 JIA treatment guidelines.

So they also had guidelines on treatment of polyarticular, oligoarticular, enthesitis related disease, new on dactylitis, and new comments on what they call deselection, that you could start to withdraw therapies, which seems reasonable, especially with stills. I don't know how reasonable is when you have polyarticular JIA. So I like some of the things that they said. I think I have, you know, as usual concerned about a lot of this being expert opinion and conditional recommendation. Any other comments on this?

My one cautionary note on on this disease area is that I think we extrapolate a lot from the child side onto the adult side, and I'm really cautious about that. I think they're somewhat different diseases. I think on the adult side, a lot more of it is triggered by some other underlying autoimmune disease, and there's a lot more malignancy. And so I I I I think that often on adult side, we take our cues from the from the kiddos. But I think that it's qualitatively different.

We have to be careful Mike, you

have to move yourself. I don't know what that was about.

Yeah. Yeah. But I I guess some things are different, but a lot of things, at least in stills, can be extrapolated. Like there is some level of evidence, but yeah.

Doctor. The FDA obviously considers them the same and the nomenclature is it's Still's disease. And the only differences are, in my opinion, the prodromal sore throat is seventy percent of adults and uncommonly seen up to fifteen percent of kids. Everything else looks the same except this issue as Bella points out about lung disease. And they're carrying that banner, and they want to look for lung disease.

And I don't know, they didn't say how, you know, so you're going to get a chest CT or an MR on everyone with Still's. Again, I treated, you know, I don't know, over two hundred patients with Still's and seen over 500 consults. I have three great cases of bad lung disease in Still's disease. And I'm very tuned into what they're doing and they get a lot of pleural pulmonary manifestations to begin with. So I think we in the adult world are aware of this.

However, I don't know that recommendation is going to carry through. We need to move on. Mike, what's your big one?

Yeah. My big one was the great debate. Really enjoyed the great debate this year. It was between Wolfgang Schmidt and Tanaz Kermani. So pretty pretty expert people in the field, and they they they covered a lot of ground that I thought was interesting.

Wolfgang always puts on a good show. He established that, you know, ultrasound is available. It is fun to do as a rheumatologist. You can get a lot of information that you can't get from a biopsy such as axillary involvement, and then you can use it to track over time.

So what was the tell us now tell the audience what the great debate was.

Oh, it was about ultrasound. Oh my god. Oh my god. God. It's the ultrasound or biopsy and giant's arteritis.

Sorry. I jumped right ahead. Yeah. Yeah. Ultrasound or biopsy in giant's arteritis.

And they covered a lot of great ground. You know, the argument was really around a couple of things. One is how good ultrasound is at finding GCA and being confident about it. You know, the pro ultrasound for giant arthritis diagnosis side of it said, Hey, ultrasound is 100%. You know, we find it in the axilla.

You can't do that in the temporal arteries. It is easy. It is available. Patients love it. It's fun for rheumatologists.

And then the other side said, you know, ultrasound misses a lot. You know, the specificity for a biopsy is nearly a 100%. And, you know, if you compare ultrasound to that, you wind up missing a fair amount. And that the biopsy winds up giving you other important information. And then most importantly, there's just not a lot of centers in The United States that can do ultrasound to to a sufficient quality for compared to what they're doing in in Europe.

You know, Wolfgang was sharing his cohorts of over 500 people that he'd done ultrasounds on. And, you know, there's very few people in The US who have done anything anything like that at all. So I really think that it was a fun debate because it sort of synthesized how I feel about this, which is that ultrasound's a great modality if you can do it, can help you risk stratify people. For folks who are really low risk, a normal ultrasound kinda rules it out. People who are really high risk and a positive ultrasound may maybe enough to rule it in.

Great to see those axillary arteries. But then people in the middle, I'm still doing a whole lot of biopsies. And I think that's gonna remain the gold standard in The United States for some time to come. But kind of a fun debate, I always like that format for learning.

I think that the idea on this is that not that everyone's going to change their practices right away, there are technical limitations to not having great ultrasonographers that do a lot of this and are good at this. But I think this coming up and being debated this way lets the rheumatology world know that this is where we're going, that you need to push for this in your environment and where you work. And maybe you're not the ultrasonographer that's going to do it, but having that conversation. At my center, I remember having this conversation going back ten years when they said we can do it, but we don't know how good we are at it. And now they're reasonably experienced and they can do it.

So, let me ask Sheila and Bella, is this being done where you're practicing, Sheila?

Yeah, so I think, you know, the difficulty or the challenge really lies in the expertise or the being able to do the ultrasound or even the biopsy. I mean, my center, all, for example, not all radiologists would be trained in doing ultrasound of the arteries and that being said, even the biopsy. So I guess there really is a challenge in terms of how to use these diagnostic tests. And especially, for example, if it's the biopsy, most of the time patients have already been on treatment before they even get to do a biopsy if there would be one. However, ultrasound is, at least in my country, it's relatively cheaper than doing a biopsy.

Bella, what about HSS?

We you know, in theory, there is somebody who can do an ultrasound, but it really doesn't happen. And the quality, it depends. It's so user dependent, I feel like. And, you know, it's easier. Like, there's a protocol in place.

There's a way a system in place to get the biopsies. So I still think that most people are sending patients out for biopsies, like, even if it's bilateral. You know, changes takes time.

That's

right. And then there's like all these newer sort of CT and MR protocols which look at the arteries. So those are also done in these iffy cases.

Yeah, well, and I mean, they should be done with a new diagnosis. You should be looking for the, you know, the extra temporal, other vessels and being involved anyway. But making the diagnosis by one method or another is still is going to be the ongoing debate. So my first presentation is going to be a late breaker from today. It was LB15 and it was from Geneva, two centers in Geneva, I think, and one center in Australia.

They did a small pilot study looking at the role of dietary fiber on microbiome and DMARD responses in RA. Forty nine patients, yeah, it's small. One month trial, that qualifies as pilot, right? An unknown number on methotrexate, you know, it was more than a dozen. And what they found was that, when they looked at the, and it was double blind, randomized, placebo controlled, forty nine patients, that those who receive fiber, had improvement in their UR good scores and, and in their DAS scores.

Now let's say right off the bat, these were mild patients. Their average number, mean number of tender joints was six or seven. Mean number of swollen joints was one point eight and two in the two different cohorts that we looked at. The CRP was roughly seven milligrams per liter. So, you know, modest activity.

But to have like fifty three percent develop a UR good on fiber versus 20, I wanna say twenty three, twenty four percent on placebo, that's a little eye opening. And then when they looked at where the benefits were seen, it was in the methotrexate population. Methotrexate treated patients who were taking fiber had a minus one point zero drop in their DAS score, their DASH 28 score, which would have been low, although I don't know what that number was. It would have been fairly low, but it dropped minus one. The placebo population dropped minus 0.38.

The numbers here are too small to be significant, but it still is an interesting concept. Now they have a comparative group of like six patients on other DMARDs, mainly sulfasalazine or leflinamide, where they showed that being on, again, the fiber didn't change their clinical outcomes. If anything, they got a little worse, you know, and the same thing for the placebo. So I like this as a proof of concept. Goes to, you know, in learning about the microbiome from Jose Share and others, one of the things I've learned is, the microbiome is cool, but maybe the real secret to the whole microbiome story is what the microbiome does to pharmacokinetics and pharmacodynamics.

And we know this to be true in oncology studies where it's really a big issue. And they're looking for tie ins, you know, as to how we do it and why not start with methotrexate. So anyway, the authors of this who were great in their presentation and fending their choices at the poster side, are embarking now on a larger 100 patient trial. Bell, what do you think?

I think this is something diet trials are hard to do, right? I don't know if it's because of the drug and the fiber itself or fiber itself are doing this. I mean oncology is big on it right now. The recent oncology conferences have separate sessions on these fiber stuff and they are showing improved outcomes, survival even, just by changing the fiber content in the diet. So I don't know if it's completely related to methotrexate or it's just, you you eat fiber and you're just overall healthy and your glycemic control is better.

I'm not quite sure.

Again, as you look at the graphic, the, you know, the placebo methotrexate group is here. The fiber methotrexate group is down here with a negative change in that. So it looks like there's an effect. Again, 12 patients, maybe up to 20 patients in each group there with methotrexate, half on fiber, half on. And the fiber they use is inulin twelve grams a day, which is often used in other fiber trials and in IBD and GI trials.

So, again, I don't think this is proof of anything other than, you know, a head scratcher and let's do this in a big, more solid clinical trial way. What do you think method methodologically about this kind of stuff?

You echoed my thoughts exactly. Things like this rarely translate when you get them bigger. You expect that delta to probably narrow a little bit. The flip side is that, you know, I spend a lot of time recommending healthy diets to my patients, and I'm already trying to encourage them to eat fiber. So this does kinda make me feel good about that.

So I'm gonna I'm gonna take the win while disbelieving the data, if that makes sense.

No. I think that's a it's there's no harm in running with this right at this point. So very good. All right. We're gonna do one more round.

Sheila, do have a quick one?

Okay. So my quick one is abstract two thousand six thirty four, where they look into sex differences and medication discontinuation in patients with axSpA and data was from the RISE registry. And basically what they saw, so patients were on either TNF, JAK inhibitors or IL-seventeen inhibitors. And the results show that women had higher discontinuation risks for TNF inhibitors, but there was really no statistical difference between those taking IL-seventeen or JAK inhibitors. And I guess the main message here is that it reinforces the evidence that gender differences do exist in axSpA and not just in clinical manifestations, but also treatment response.

So that should help us guide our treatment options and individualized treatment.

Yeah, it's obviously a big issue that needs more research, but this certainly helps. Bella, go ahead with yours.

So this is abstract two, five, eight, seven and eight, eight. Basically these were the dissolve trials and data from that in gout. Mainly chronic gouty arthritis were the inclusion criteria and they did administer NAS which is nano encapsulated cerulomas plus pegartigase. Again, this is something that they give for every every month, essentially. And they basically presented data on only patients who were completers.

So patients who at least took six doses of this. A lot of the patients dropped out but they never gave us what numbers dropped out. But this was three arms placebo, low dose sirolimus, and then high dose sirolimus, the nano encapsulated ones. So again, double blind, placebo, randomized phase three, and seems like it did do a great job even at low and high doses. But I guess, you know, the number of flares were low overall, VAS or pain tender swollen joints all of them were low.

The side effects pretty much were similar to what other pegylated uricases have out there. I think it's important to know that they didn't present like an intention to treat numbers. They just presented completion analysis. But I think it's a good option to have. So we'll see.

We need some more data coming up.

I like the technology. I like the advance. I dislike a completer analysis. Why did they I have been unmerciful about that, but why did they do that?

I think they'll, you know, lot of patients, you know, you need to have uric acid lower than two when you're on these pegylated ones. And a lot of patients did not meet that criteria, so they had to stop essentially. And they didn't even present the data of patients who probably took it for three months and how did they do? They just gave us the completion of my analysis. I mean, looks great.

I mean, but I think in way, any RCT, if you just look at the completers, you will feel great about it, right?

Oh, I really, really look great right now on camera on this video. But, you know, there's lighting, there's makeup, you know, there's a team of people behind me that are trying to make this look good. You know, you saw me earlier. I don't look this good in in in real life. So I don't know.

I worry about this kind of presentation. Alright.

Let's do a motion for speculative stuff. That's all. Like, I we'll see. We need more data.

Right. And they're gonna have to put out more data. Mike, what's your what's your last hit?

My last quick hit is yesterday and today one. This is abstract two two seven eight. They shared some longer term data from RESETRA, which was a study of vagal nerve stimulation for rheumatoid arthritis. So the the idea of this is they implant a little zapper in your neck by the vagus nerve. It zaps you, and then would be some kind of reflex that improves your RA dramatically.

But in the the study itself, the data was relatively mediocre. Only about thirty three, thirty five percent of people met in ACR 12 20, which is not a very high bar, so kind of disappointing. And something about giving people a therapy that zaps them in the neck just feels to me like you're harnessing the placebo effect. Now I actually dropped by the booth today, and I said, hey, guys. Is this all placebo?

And they made an interesting observation, which is they're actually, they surveyed the people who were who got the the treatment, and then they also had a sham group where the treatment wasn't turned on. And they surveyed them to ask, hey. Do you guess which group you're in? And they're going to present that data soon where we get to find out how many people guessed which group they're in. And I think this is really exciting.

Unblinding is a big problem in trials, and we never do this kind of thing where we just try to figure out how much it happened. And I'm I'm genuinely I went from being kind of blase about this to genuinely excited to see how that particular part of it plays out even though I'm overall pretty skeptical of vagal nerve stimulation.

Yeah. It's obviously a new entity just recently FDA approved.

Yep.

FDA approved based on a 40 ish percent ACR 20 at their first time point, which was week 12. Yeah. And a very low placebo rate that was below twenty percent. So that's what made it all significant. This issue of unblinding was brought up in the presentation, and it was discussed and you, I think portrayed it very well.

The other thing is that most of these people are gonna get their one minute of vagal nerve stimulation in the middle of the night while they're sleeping.

The 4AM, yeah.

And company's point of view on this is that, well, how do we know? How do they It's a brief thing and whatever, but I don't know that that's good evidence of maintaining a blind because if you've ever seen nighttime photos of people sleeping and the things that wake them up, dogs and spouses who have a flail arm and whatever, They don't remember any of it, but it happened, you know, and they were subjected to, you know, interferences and whatnot. So anyway, it'll be interesting to see, I think there's enthusiasm about this approach because it's a non medicinal approach, but it certainly has some challenges to it, including it has to be implanted by a neurosurgeon and there are going to be certain centers that will do that.

Well, you know what can stimulate vagus nerve naturally? Exercise, music, meditation. I mean, those things are things that we want our patients to do more than a minute a day and it might have effects too. So, you know, it's those are the cheap ones to do, to ask.

You know, I actually really like that because I've already had a couple patients asking me about that, and I didn't quite know what to say. And so I think that's going to be my take home point that there are many other ways to do this that have other ancillary benefits and no surgery.

All right. I like the idea of the controversy creating a conversation, will make people and patients better. My last one is another late breaker LB06, from Frank Barron's. This was a head to head trial of secukinumab versus ustekinumab in psoriatic arthritis who previously were treated with TNF inhibitors. And the one hundred and nineteen patients with on average 14 tender joints and seven swollen joints randomized to get standard doses of secukinumab or ustekinumab.

And the endpoint here was a week twenty eight response. Secukinumab was better than Ustekinumab at an ACR 50 of forty eight percent versus twenty four percent. Similarly, the Posse 90 scores were better, but a little bit closer here, forty eight percent versus forty percent. Secukinumab over ustekinumab. We don't have many head to head trials in rheumatology, certainly in psoriatic arthritis.

I think it's, and there are no different safety signals here. So, reasonable size trial, I like the head to head study. I think this will probably get published and whatnot, but it looks good. And does this reflect what people will do? Remains to be seen.

Okay? Alright. So, let's move. Let let's close out here. We want to thank our audience for listening to this day three recap.

We're going to conclude the meeting tomorrow with a day four recap. Mike Putman's going to host that because I'm going to be in another meeting but same time, 5PM Central, tune in either here on Zoom and RheumNow or the RheumNow website or X or LinkedIn or Facebook. We're gonna be live streaming. Everyone, thank you very much for your contributions. We loved it.