ACR2025 Day 1 RECAP Save

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

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Hi, everyone. Welcome to ACR twenty twenty five. This is the day one recap where we, me and my friends here who've been in Chicago, are going to talk about the things that we saw today that we thought were worth bringing to your attention as what you may have missed. We're going to begin with introductions. I'm Jack Cush from Dallas, Texas.

Arlie?

Hi, I'm RheumNow, I'm from Glasgow, Scotland.

And Joost.

Hello, my name is Joost Yusuf. I'm from Leeds, but I'm reporting live in Chicago.

Leeds, a lot of things going on in Leeds these days. We'll talk about maybe here. We're going be joined in a few minutes by Doctor. Janet Pope. She, like the rest of us, were scurrying back from the convention center to get on this call.

So in this day one recap, we're each going to share our thoughts and impressions on impactful research, things with clinical impact, things that are certainly worthy of some discussion. So why don't we begin with Doctor. Youssef?

Yeah. Thanks, Jack. So the one thing that I want to cover today is pertaining to the update of the American College of Rheumatology guidelines of a nonrenal SLE. So as you may be aware, the previous guideline was back in 1999. So there was definitely an urgent need to update all this guideline, particularly with all the new licensed therapies in lupus.

So essentially, those presented in a session today. So it's really good because initially it presented how the guideline was developed, and after that, what were the key recommendation, and followed on after that, they actually make some practical sessions. So for example, they broke down, know, for example, if you have refractory cutaneous manifestation, how would you do then we'll apply the guideline to clinical practice, and then to pleural pericarditis and so forth. And so just in terms of the guideline themselves, so there were 65 recommendation, but only three really the one that was strongly recommendation means like with the highest inequality of evidence. So the three key messages from this non renal SLE guidelines were one hydroxychloroquine for everyone unless contraindicated.

Secondly, if you're using glucocorticoid, make sure you taper them and also to the lowest possible and at least, less than five milligram per day. And also the third one, the strong recommendation one, was to escalate therapy if the initial therapy fails. So these are the three main things that were strongly recommended. And then after that in the flowchart diagram for recommendation, you've got all these features management, but most of them were conditional management. And you can see that from using immunosuppressive therapy and also biological therapy.

So I think this will be really useful for people to then start applying this. And also maybe people can also do some audits after that to see whether it will be adopted in the practise.

Certainly, they're always needed and desired. It's a little distressing that they still have so many conditional recommendations coming from the experts like yourself. But nonetheless, without good evidence, they can only be conditional, can they not? I'm surprised that there isn't, a recommendation in there about hydroxychloroquine monitoring. Is that in there or is that discussed?

Yeah, so I think it was, it didn't mention about monitoring. It mentioned about the starting dose where you can ideally you'll be within five milligram per kilogram, but you can actually start higher dose temporarily before you bring it down in patients who are resistant with really severe disease. But yeah, I couldn't see any monitoring there. So perhaps we need to dwell into it, you know, when the full manuscript will be published in a few months.

Yeah, I think there's another presentation at this meeting again on hydroxychloroquine monitoring. It seems to be the standard by the leading centers, and I would strongly advocate for it. Orly, you have any ideas or suggestions here?

Yeah, I was wondering is did they follow the whole systematically literature review process? Was there any specific challenges considering that it's almost like in Lupus, it feels like there is very old evidence and then a whole bunch of very new evidence and kind of nothing in between. So how was that addressed?

Yeah, so I think that's a good point. So I think this is what Jack was mentioning just now, because it's slightly a bit disappointing. Out of 65, there were only three strong recommendations. It was because we have a separate guideline for the lupus nephritis, which was recently published. So in there, so you had more strong recommendation because you had more clinical trial, know, very high quality evidence trial on that one, but not so much in the non renal because it tends to be with non renal, they lump it all non renal.

So it's quite difficult to do like a subset analysis. But even if you do like a subgroup analysis, it's still not powered to answer all this. So hopefully maybe in the next guideline, because currently they are planning quite a few trials, they're doing a target specific, organ specific trials. For example, there are phase three trials in cutaneous lupus on its own. So perhaps after this, people will do lupus arthritis trials and so forth.

And hopefully we'll get more evidence based on more disease specific.

It's driven really by the trials and the trials are driven by drug development. So we have lots of new lupus drugs, all seeking a lupus nephritis indication, as opposed to a general lupus indication, which is actually harder to achieve. I think that now there's sort of a pathway forward to do CLE, chronic lupus, skin disease clinical trials with, a classy endpoint that maybe we'll get some clarity there. But I mean, we want these guidelines to help us in other areas, hematologic lupus, CNS lupus, you know, articular lupus, etcetera. So, it'll be good to review these and if anything, it draws a line in the sand on future research.

And as you say, if we do an audit, you know, the audit will tell us how good are we at doing at least what the experts suggest that we might do. Fortunately, we're joined by Doctor. Janet Pope. Janet, introduce yourself to everyone.

Hi, Janet Pope, rheumatologist, Western Uni in London, Ontario.

Excellent. All right, so we just heard from you his favorite starting abstract was the ACR, new ACR guidelines on non renal lupus. Orly, you're next.

Yeah, so I wanted to talk about this presentation. I saw the plenary session seven seventy five. There was quite a whole bunch of presentations about, you know, at risk patients, and who's going to develop clinical RA, and can we predict, and it's almost like we could take all of these talks together and make a prediction model or a score to test. This one in particular, why I looked into it further, so it's the bacterial RNA, so the TDR1. So basically they took plasma from patients from the studies of vitrology of rheumatoid arthritis.

So it's an old cohort. And some of them, some of these patients were at risk for rheumatoid with high CCP titers, and none of them had clinical synovitis. However, it was not clear, and even looking back in the literature in some of the early publications of this cohort, whether they had had any form of imaging to look for synovitis, and that might be a caveat of the study, but we can talk about that a bit later. But ultimately what they did is this microbial RNA they're particularly interested in because they demonstrated that in people with RNA already, they had a better response to the biologics, and they had a less severe kind of phenotype if they had high levels of this specific RNA, which is considered to be regulating genes expression, epigenetically. And so they looked at sixty patients at risk and they compared to over double the amount of patients seronegative.

And first of all, one of the things that I noticed is almost half of the patients converted, which is not our typical ratio of patients that convert. That's why I think that might be another caveat here, but ultimately what they showed is that after adjusting for smoking and a whole bunch of autoantibodies, the presence of this RNA was massively associated with the lesser risk of converting into clinical array. And they presented this array under the curve, which was like 0.86, which was actually higher on its own than a model that had associated rheumatoid factor, smoking status and HLA, like shared epitope status. And then when we're combining all together, it was 0.9. So it was very close on its own than with all the clinical parameters.

And that is something that really that I found quite impressive, because usually, you know, it adds a little bit maybe to the strength of the prediction, but a biomarker that on its own has such a strong prediction was pretty impressive to me. Now, there's a bit of caveats to that. So as I said, they had a very high percentage of converters, maybe because some of them already had subclinical synovitis, maybe it wasn't checked. And also, it's not been validated in any other cohort. And we know very well that sometimes we have these amazing biomarkers, and then you test them in a different cohort and it doesn't do as well.

But if this on its own is able to be such a strong prediction factor, because it's not hard to look for it in the blood, it could be quite promising if it's validated. We don't know how though. They did some in vitro stuff looking at transfecting this RNA into cells, and it does seem to affect interferon pathway, but it's also bacterial kind of RNA anyway. So maybe because interferon's associated with response to germs, and it could well be that. So difficult to say how, but if it does get validated, then I think it's exciting.

Yeah, this one caught me by surprise. It wasn't on my list of things I wanted to see, but a lot of the correlations here were interesting. Again, these are sRNAs that are, you know, appear, you know, and she made a point of these being probably of bacterial origin, but they don't have to be, and they can be endogenous as well, but they have a regulatory function. They impair protein synthesis and certainly get in the way of alpha interferon signaling, which they say seems to be an early event in RA and maybe RA progressing or, you know, clinically suspect arthralgia progressing. So they made it, they tied up a nice little loop on this and now turn this into, you know, most sRNA kind of research kind of goes nowhere in the past, I think that this is, looks very interesting, and I think there's a lot to be learned still.

Anybody else have a thought on this?

I think you're sorry.

Yeah. Cush, what did you say? What did say, Cush?

I think Janet was on mute, sir.

Oh. I was just gonna say, all I would say is we always have to do beware. It's hypothesis. I think generating and not testing a lot of different analyses were done. However, it's kind of quite interesting.

Yeah, absolutely. And that's why I think it's I'm glad it was a plenary session because I don't I think this if this was a poster, it may have gotten buried and, hopefully this will spurn more research in this area. Doctor. Pope, what do you have for us?

Right. So Jack, I picked something that you really like. I looked at adult onset Still's disease. So this was a poster, and again, there's lots of little pearls in the posters for sure. So it's 01/1963, and it was by a third year internal medicine trainee, RheumKeener.

So Doctor. Mohamed Akram, et al. So what was it? It was looking at trends in hospitalization with outcomes and adult onset Still's disease from The United States from 2016 to 2022. So you would say, why on earth would I pick that?

Like, Still's is pretty rare and everything, but here's why. This is a giant database of multiple hospital records throughout the country. It's Medicaid, Medicare, a whole bunch of stuff, national database kind of stuff. There were hospitalizations really got so many the n is so big. It was eighteen twenty seven unweighted and nine thousand one hundred and thirty five weighted hospitalizations in The US for adult onset Still's disease.

So, some of these I would speculate were first diagnosis and some were recurrence or who knows what. So, the first thing is, who is more apt to do poorly in hospital? Men more than women, ethnicity identified as black versus others, and those on Medicaid because they're possibly older. So, not all of that kind of made sense to me, but here's where I found it really interesting. So, the most common reason they said for hospitalization in Otto Onset Still's Disease was infection.

So I asked him, like, how many were culture positive? Because, of course, Still's is high temperature, rash, high ferritin, high CRP. How do you know it's not Still's? And the answer was, who knows? This is what they were coded as, is infection.

So the good news is only about two point four percent mortality. The bad news is I'm not sure well, not bad news. The equivocal news is not sure that these patients were no, I'm not sure that these patients actually had infection, or was it infection and stills because it's really hard to differentiate, and they couldn't get as granular as you would like to see if they you know, how many were culture positive or lots probably got antibiotics. And if the fever didn't settle, they probably got glucocorticoids. But as I say, the reason I was interested in it is this is the largest amount of data on adult onset Still's I've ever seen.

And I guess I can ask each of you, like, what how many stills patients are in your practices? Jack, you had an interest in it when you were doing a heavy practice. What what number would it be?

Oh, I always carried about 30 plus, 30 to 40.

Yeah. And that's and that's a lot. Yeah.

Yeah. But that's but I get to see people from all over the country and sometimes outside of the country. I probably in my career have seen over 500 stills consults. I think I've only seen, about somewhere between 3040% of the consults actually had stills for the reasons that are apparent in this report that they get called Still's because they don't know what it is. It gets admitted as infection and certainly infection, everything from, you know, tularemia to Lyme disease could actually look like Still's.

But, you know, I I don't know that you're going to get this from hospital ICD-nine codes and whatnot, but it still is interesting. And if only to look at the absolute number and then also the mortality rate. I mean, I always teach that nobody would, should die from stills. They die from stills, they're going to die from MAS, Yes. But real or they're gonna die from steroids.

So you gave them too much steroids.

Right.

You got the steroid complications Right. And Yep. So

Yep.

But they Yeah. You shouldn't die from stills.

So Right. But I mean But Yeah. And and I mean, because you you have had expertise in this, I probably only have less than 10 true adult onset SILS. I have some kids that mostly grow out of it where we follow them as adults. Or Lee and and Yus, about how many SILS patients would you have?

Yeah, so I think it's very rare. So I probably see about once every six months if that.

And I wouldn't even see a new

one in And this I know one of my colleagues called Professor Suneja Savage, he does the auto inflammatory clinic, so I think he picked up a lot more of

this. Yes.

I don't think that his cohort is as big as reported here as well.

Yeah. In Orly, pretty rare

for you? Oh, yeah. Definitely. Definitely.

So Right. Sounds quite

unique to me.

Exactly. Yes. So I wondered about misclassification, but I think the teaching point for the people listening is certainly you wanna see the fever be monophasic every day and that it peaks and goes back to normal. Whereas a septic patient, they don't usually go back to normal and they can peak more than once a day. And that often the rash comes around the time of fever, but you don't have to have a classic rash, and it can be macular papular.

It can be that salmon non raised. If it's bad enough, it just looks like a macular papular. And that, you know, we would tend to try to avoid steroids once we can get them on an Aisle 1 or an Aisle 6 or something. But that's why I picked it. It was a large n, and I don't know the amount of misclassification.

But I don't think people just rush to saying stills unless someone's confirming it on a consult. Because we get consults every week. Is it stills? Because they're CRPs, and we go, it's infection, infection or cancer. Probably not stills.

Right. Alright. That was interesting. I want to talk about abstract. I wanna pay honor and homage to the University of Leeds, an abstract eight thirty two from the lead author was Sherrick, I think was the name.

And this was about predicting those Sanisherik at Leeds predicting those who will progress from clinically suspect arthralgia to RA. So this is banking on the well known voluminous experience in early arthritis at the LEAD Center. And in this particular study, they looked at the factors that may influence those who might progress. So they looked specifically at PADI two and four, the enzyme that is involved in citrullinization. So both PADI two and PADI four, very important here.

They had sort of data before and they followed people and they looked at levels in seventy nine CCP positive at risk individuals who did not have, inflammatory pruritus. Thirty four with early, CCP positive RA and forty four healthy controls. And then, you know, they looked at the clinical parameters, obviously a difference between RA patients and and far as the controls, you know, controls not having any serologies, the RA and the at risk had serologies by definition to get in. And they looked at PADI two and PADI four levels. And so while both PADI two and PADI four were elevated in RA, the only one that was seemed to be really interesting here was PADI four in the at risk individual.

So you could find PADI-four and PADI-two in early RA, but the patients who were CCP at risk had a lot of people who had high PADI-four levels. Now they're just measuring PADI-four. There are a lot of studies out there about antibodies against peptidyl, arginine, DMNase, and that being associated with ARA risk and worse disease or progression. But here they're actually just measuring PADI-four. And so the idea is that there's more PADI-four and there's more PADI-two.

I asked the question, what's the mechanism here? Is it driving more citrullinization? Are you having higher and more CCP levels? And we do know more CCP and multiple autoantibodies increases risk as well. She didn't quite answer my question because they said they had to have CCP to get in the study over a 100, as if to say that that's a lot.

I don't know that a 100 CCP is the same of what we usually get, which is CCP greater than two fifty. You know, you of get, you get three reports on CCP, and now I'm really getting into a tangent here, but you either get a negative CCP or a very, very high CCP, and then some other number that's like thirty to one hundred. Who are those people? And are they at risk to progress or have worse disease? And no one really knows much about them.

Anyway, in this study, they all had CCP. She wasn't able to answer Again, if you did have PADI two and PADI four and high levels, you were more likely to, higher than they had a high PADI four versus low PADI four, high PADI two versus low. The high levels were people who are going to progress to RA more quickly. So the point is, unlike some other studies that we've seen here today, PADI-four has predictive ability and augments the number of people who will progress from clinically suspect arthralgia to actual inflammatory arthritis, where we know if you just have arthralgia and you're CCP positive, you have a one third risk. And when it's more than that, you wonder about the data set and whatever, but here it clearly augments the number.

So, I think this was really, this is why it was an oral presentation. It was well done. I think it's important work. Okay, why don't we go on and do one more round? You have a quick one that you want to point out to the audience?

Yep, so just as the quick one from plenary again. So this abstract number seven seventy six. So this is actually data from two years study of select GCA. So as you know, that April this year, both the FDA and EMA have approved, the use of upadacitinib, for remission induction of giant cell arthritis. So in this trial, so they just take on a little bit further.

So what happened after the fifty two weeks trial, so I think it's about eighty percent people are eligible for this extension studies. So what they've done was whoever's in the placebo still remain in the placebo for another fifty two weeks. For people who are on upadacitinib, either seven point five milligram or fifteen milligram, which is a dose that was licensed, then been re randomised, whether they then switch to placebo or they will maintain the drug. So what they found at, so the following fifty two weeks, so it's like two years altogether, they found that those who continued the upadacitinib, so they had a higher remission rate as their definition, so sixty nine percent compared to only twenty nine percent for those who were initially on upadacitinib fifteen milligram who switched to placebo. So it is really interesting to say, initially we all thought like, similar as tocilizumab as well trials.

So when they first initially did the fifty two weeks, then people asking whether is it safe to stop and then see how it goes. But I think in this case, we were asking the same question again. So, you know, you had an initial remission induction, whether it can be stopped after one year or or should we continue? But so so this data, you know, may may suggest that, you know, we need to to continue. And in terms of a safety perspective, although this is like a sort of an ageing population where you are concerned about the use of JAK, so they found that the risk of serious infection is actually lower in upadastineb continuous for two years, likely because of the steroid, know, becoming really less.

But also there are some, you know, as you expected increased risk of herpes zoster and also some slight Race CK. And there was one VTE occurred in upadacitinib continuous group for two years. So I think it's really interesting, but the studies add more value that I think we probably need to continue upadacitinib after one year. But then again, how long? So probably the story will continue, you know, for the execution studies probably.

Yeah. So did they, did they feel the question about, since this is only a two year study, they couldn't really say much more about what to do, but did anybody bring up the issue? How long do you treat?

Yeah, no one actually brought the question up actually. Yeah. So

you wonder, I mean, the whole issue here is to justify the ongoing use of a new JAK inhibitor. You got to show this kind of data. You've got to show the safety of it. I guess relapse rates would be the other primary outcome. At some point they're going to have to get into a cost effectiveness analysis.

You can avoid that kind of analysis if you start looking at things like death and hospitalization as outcomes. But I guess with these kinds of therapies, these people shouldn't die and shouldn't end up in the hospital. So I don't know what else they can do. The interesting thing about these, the development of drugs for GCA, and for that matter, PMR, you know, I think it's great, but we still use tons of steroids. We still aren't using much IL-six inhibition.

We're not rushing to, I don't know what the numbers are on the use of, OPA or JAKs in GCA right now. But, you know, we have IL-seventeen drugs that are looking good to some extent. And there are others in the wings. They're all expensive and you're going to have to justify their use. Janet, what would you recommend to these people who are going to develop Right.

These

So just a couple of things, I guess, to kind of clarify is that the first interestingly, secukinumab negative in GCA phase two positive, phase three neg, but just had a positive study in PMR. So that makes it complicated. Cirilimumab is PMR, and then we've got tocilizumab in GCA, and now, you know, eventually soon to to come, I hope for all of us, the ability to prescribe regular dose upadacitinib in GCA. So with that being said and done, I think we have to learn from these protocols that if we use a steroid sparing drug, I'll call it for I'll be a bit provocative. I'll say the majority of patients.

The majority might not be the majority in my practice or your practice. It might be the majority in someone else's. But in these patients, then you have to do this rapid steroid tapering or how much bang for the buck are we getting? And what was really interesting in the second part, the second year of of GCA with OOPA, you stop drugs, they stop working. We already learned that with tocilizumab that this is a chronic disease at least for a while.

You need more than one year of treatment. But that overall, you are saving at least on average, not everyone, a few grams of glucocorticoids if you got upa year one and year two than if you didn't get it. So you can 3,000. It's a median. I mean, the mean is a bit different, but that's a lot of steroid experience.

So I think we have to be bold and do rapid tapers if we're gonna use these advanced therapies, or I would say as the payer, then you tell me what the what the outcome and benefit is because increased hospitalizations occur from their glucocorticoids. So there were less hospitalizations in some databases observationally if you're using an advanced therapy, which in the observational data so far have been with tocilizumab. So we need more than a year of treatment, and we need to get those steroids down quickly. But it gives me the ability to say, I think I wanna do that, and I don't know what to where to put an IO -seventeen in until we have even more data for GCA.

Orally use, are you using these newer, either tocilizumab or, any other therapies right now to steroid spare in GCA?

So in The UK, we can only use tocilizumab. That's the only one that currently, but even then in the initial approval for a year. So, you know, for continuation beyond that, it has to be discussed in the in a multidisciplinary team, you know, to to to approve that for patients with severe, severe refractory and also high dose steroid and yeah.

You know, I think it's not a bad idea that you should have to defend your decision, when the decision is an expensive one.

But also, and now we have the tocilizumab biosimilar, so that probably will change thing for regulatory as well.

Absolutely. All right, Orly, what's your quick hit?

Yeah, well, in the topic of glucocorticoid toxicity, seven ninety. That was quite interesting because it looks specifically at skin toxicity in people receiving glucocorticoids. Always have patients coming in and say, oh, you know, since I've started I'm bruising and this and that, but I hadn't really seen a lot of work looking specifically at that. So they had this cohort of patients. It's a cohort that is prospectively enrolling people that are taking glucocorticoids.

And first thing, you know, disclaimer, these people were on average thirty milligrams. So it's not the typical, it's not really the typical, you know, rheumatoid population, clearly, but it's mostly people with myositis and so on. But the thing that I found quite interesting, in their 90 patients that they followed up, they wanted to assess baseline and month six, and what factors were predictive of skin toxicity. So obviously, those people that were older, and that had higher dose and more severe disease and higher disease activity, were more likely to develop skin. But the thing that I found really interesting is that there was a really strong association between people who developed skin toxicity and neuropsychiatric toxicity.

It was basically very similar, and muscular toxicity as well. And I think one thing that I certainly haven't really done in my practice is, oh, if there's skin toxicity, let me look specifically for neuropsychiatric toxicity, or let me look specifically for muscle toxicity. But apparently they come together a lot, and so the main message in a nutshell is if there is skin toxicity, look for all the toxicities as well.

Sage advice, I like that. Janet, you got a final one?

Yeah, and just on that point, Arlya, I wouldn't have thought it either, so it might just be a cumulative dose effect. If you're already having one organ, think of others. So I I love that. So I just have a really quick one. So it's kind of because patients ask me this stuff.

The the this is poster zero one six four, and it was saying, do do patients with rheumatic diseases flare with extreme weather? So first of all, patients don't ask about extreme weather. There's lots of data so far from basically Vienna and and in US and elsewhere that seem to suggest that a subset of patients because we'll get to extreme weather in a second. But in regular weather changes that a subset of patients reports at least self reported flaring under two conditions: when the barometric pressure has big changes, so it gets damp, and or when the temperature gets a big change mostly for the colder. So big delta temperature, big delta barometric pressure, and not everyone, but maybe up to a third of patients flare.

And in my opinion, and I think what some of these other studies have shown, is that this flare is fairly self limited. It might be subjective because they don't come in all the time for that, and it could be multifactorial. People don't feel as good if it's sort of damp, rainy weather, etcetera. This question, though, this was a a large survey. About a 180 people, I think, were surveyed, and the response rate for a survey like this was pretty good.

It was over fifty five percent. But it was a survey on what happens to you during extreme weather. So we're talking like hurricanes, your power being out. In Canada, snowstorms, but this is a California study, so it wouldn't be snowstorms there. But, basically, extreme weather.

And so what was kind of interesting is that at least the people that completed the questionnaire said, yeah. They do flare, but they're flaring even ninety days after. So I talked to the presenter, seemed very knowledgeable about this. The first author was there presenting the poster. And I said, but do you think maybe it's biphasic that maybe the shock and and this big extreme weather change like a hurricane or a tidal wave or something comes through that maybe your joints do hurt more?

But if you're going ninety days out, I think that's the stress of losing your house or losing your refrigeration or someone being injured or just the cost of all this stuff being uprooted. So I said, I I'm not sure. I said, I think you might have to do a control group of maybe not extreme weather or maybe a control group where, you know, they don't have our inflammatory arthritis and what happens with extreme weather because I think my quality of life would go way down. However, I think the bottom line is it's an interesting area, and I don't know it's the extreme weather. It might be the repercussion of the extreme weather that's gonna make you for ninety days, all that stress involved, still have a lot of rheumatic complications.

And I don't think they asked beyond that. So there you go. It was an interesting study. No take home message yet, but I think more work needs to be done if we want to really, you know, answer this question a little bit more.

Okay. Obviously, always a lot of talk about weather and arthritis and always never enough good information to know. Well, with studies like that, I always think of a study that I looked at during my fellowship that was published in 1957. I think it was five hundred RA patients who had daily exams for a week. And it looked at what happened to the RA exam in seven days.

And there was 20% variation, you know, and you would think that that doesn't make much sense, but, you know, it just shows you and they were done by the same examiner and the same patient. So if you're doing a study on weather, you know, my goodness, the story in Texas is you don't like the weather. Wait a minute. You know, it's going to it changes overnight. I'm sure it's that way where all we live.

So these are really hard studies, but I think it's good to support the patient and tell them it's definitely the weather, you know, you should go on vacation or, you know, just get them through it because you can't do anything about it and moving to Arizona is not going to help. That's been proven to be useless. So anyway, my just quick one is that there were a lot I was interested. I mean, was a lot going on today. We had the year end review, which I heard was great.

We had these markets. We had the year end review for pediatrics. Obviously, we had the plenaries, which were really interesting. I saw a lot of papers or presentations say about this early RA progression to RA thing, conversion to RA. And I think the funniest part of it all was I think I saw no less than eight different cartoon models as to what happens when you go from, you know, the influence of the genetics and environment leading to symptoms, but not arthritis, all kinds of cartoons like that.

I thought that was really interesting. So I covered a number of those, and that was my first report. The second one has to do really the basic science exercise coming out of Stop RA and Kevin Dean's group. They basically looked at two thirds of their patients, a one hundred and forty four patient trial of people who were seropositive arthralgia and could you prevent progression to RA by giving hydroxychloroquine versus placebo? As you know, the trial failed, but they looked at about one hundred of those one hundred and forty four patients to see if a multi omic approach, cellular subset analyses, transcriptomic analyses, single cell SEEK analyses could give you some insights as to who's going to progress.

What they didn't find out from all those studies was who's going to respond to hydroxychloroquine was what we really want to know, and that didn't happen. But they did, with some degree of certainty, show us that if yes, it's still CCP, that CCP three that's high, and especially if it's in the top twenty percent, is more likely to progress. And then the other, I think single takeaway from that is there's a slight elevation in peripheral T helper cells that the number which is really, really low goes up two percent or something. But the people who have higher T helper cells at baseline are more likely to progress and the ones that do progress get more T helper cells in the periphery, peripheral T helper cells. And those two together have predictive value.

But when you look at the AUCs, the added value of going from just looking at clinical parameters, age, sex, CCP, you know, the AUC was like 0.65. And if you add it on these cellular subset analyses, it was better, but the AUC went to like 0.72. So was it worth, you know, all the science? I think the science tells us about what's going on because there are other reports here about peripheral T helper cells and some other T cell subsets that are present at baseline do predict progression. That's good.

That tells us about what's going on in those people. But the clinical utility of that is still high index of suspicion and those autoantibodies and you follow them. All right, folks, that's it for this day one recap from ACR twenty five. I want to thank Orly, Janet, and Youth for their great insights. Tune in tomorrow, same time, 5PM central for the day two recap.

We'll do it again. Take care, everyone. Goodbye.

Goodbye.