Day 1 Recap: ACR Convergence 26

Hi everyone, I'm David Lou and this is the day one daily recap from ACR Convergence 2026 in sunny sunny Orlando. Thank you for joining us today on our first of the four daily recaps going through what is good and great at this meeting. As always, there's plenty going on. Day one is always jam-packed, and I'm really glad to be joined by four friends here to talk about what has been going on, what they found interesting out there on the floor today. So, maybe we'll go around the screen to say who everyone is. Mike, do you want to introduce yourself? Hi, I'm Mike Putman, Medical College of Wisconsin. Thanks for having me, Akil. Hi, I'm Akil Suda, Washington University in St. Louis. Derek, hi — Derek Mueller, PA from Detroit, Michigan. And Janet, hi everybody — Janet Pope from London Western University in Canada.

And it's really neat to have our group here because Derek's a newbie and he's going to tell us so much stuff. Oh, he did very well in the campaign, in the PA campaign. Very eloquent. So we're glad that he can join us today. But Janet, don't shake off the opportunity because we do have to congratulate you on yesterday. Big name up in lights — Distinguished Clinical Investigator Award, incredibly prestigious award, recognition from the ACR of your lifetime of achievements. So many congratulations to you from everyone at RheumNow. And thank you, I'm honored.

So, Mike, what did you find interesting today? Tell me about what really made a big — love to jump right in. I'm actually going to start with one of the plenaries from this morning that I think is just really cool. So this is abstract 0871. This is the results of the TRIUMPH 4 study, which is kind of a rheumatology study. The background here is that we're all used to these GLP-1s now. They've exploded. I'm prescribing them myself and the 2026 guidelines for OA recently conditionally recommended them for osteoarthritis. But we have no actual approvals. We need a big phase three study for that. So this study presented the results of a large phase three study on retatrutide, which is a new GLP-1 — for everyone who's used to the Ozempics, this is a different, probably stronger version of that. It actually beat semaglutide head-to-head with nearly twice as much weight loss. Pretty impressive things we've already seen; we think this one might do more.

I have to say, I actually heard about this first on a podcast. There's a bunch of people who think it's going to cut weight and you're not going to lose any muscle mass, but in the studies, people also lost muscle mass. So keep an eye out for that. Now, in this randomized trial, they had retatrutide at two doses versus placebo. People couldn't have diabetes. They had to have an elevated BMI. Most of the patients were in their mid-50s with a BMI around 40. And then they had to have osteoarthritis with the WOMAC pain score kind of in the middle range — they had some real pain here. And so what they did is they randomized these people to go on to placebo or retatrutide. And it's really impressive results in my opinion. I mean, there was as usual a huge placebo response as in every single osteoarthritis trial. But there was also an even bigger response. They met their primary endpoint at week 24 and then that persisted for a really long time throughout the trial. Three-quarters of patients had a 70% reduction in pain compared to 26% in the placebo group. So that's a number needed to treat of literally two humans. You give two humans this drug and they'll improve their osteoarthritis pain by 70%. That's really impressive.

The participants dropped their weight 26%, which is a big number. You can imagine how that's going to help your osteoarthritis. And then lipids got better, high-sensitivity CRP got better — everything kind of across the board improved. And I wonder how much of this is just, you know, you've lost weight, you're in a great mood, you're at the beach, you're active. Maybe that's why you're feeling better. Or is there some additional — like the pleiotropic effects of statins — something more to the GLP-1s? At the end of the day I'm not too worried about it because boy, we've had so many randomized trials in OA that failed, and seeing one with just a clear convincing delta was pretty exciting. There are some side effects — one in 20 people had the kind of GI things that made them stop it, one in five people had nausea and vomiting but they kind of powered through. So nothing is without side effects, but I thought this was really exciting — finally a strongly positive trial in OA.

So really quickly — I mean, there's a lot of talk about when we look at these, is it all mechanical offloading? Is it just about the weight loss, or do you — what do you think? I know it's very hard to say at this point, but what are the clues? What do the tea leaves tell us? Yeah, so you're inclined to say it's just about the weight loss. I mean, cutting 26% of your weight — that's like, for some people, 50 pounds. And you can imagine how much better a knee would do with that. And we've always been telling people you should lose weight and exercise; it's just hard, but this makes it possible. So I think that's really exhilarating. But the placebo-controlled response in these studies is huge, and you would imagine that if you are cutting weight, that's going to contribute to it. So I wonder if some of this is also the psychosocial burden of pain just kind of being alleviated, or maybe some additional pain-sensing signaling effects of GLP-1s. We know that they rewire your brain in different ways related to addiction and things like that. So I could see it being a little bit of all three, which would be great. Whatever the case, it's real benefit. And we talk about 5% weight loss being meaningful for knee osteoarthritis, so 26% is substantially more than that.

Akil, do you see much of this? Have you seen many patients walking in your door on GLP-1 — well, on incretin-targeting therapies for weight loss — and how's that affecting them? Yeah, absolutely. I think the GLP-1 class of drugs has just been a game changer and we're starting to see a lot of the downstream benefits beyond just diabetes with this weight loss. And I do wonder sometimes if it's that drop in weight and then the reduction in weight-bearing joints that is having the benefit, and that's where we're seeing this improvement in knee function. But I think it's really impressive results and really impressive findings. I'm definitely curious to see how it affects other aspects of joint pain as well, especially in these weight-bearing joints where we put a lot of pressure. I do wonder if the GLP-1 is having a lot of benefit in those aspects and how it helps in other areas too.

It'd be really cool if we knew about their erosive OA, because some of the folks might have had it — not everyone, of course — but then we'd say, well, it's not offloading weight. So is it, you know, the downregulation of the pro-inflammatory cytokines from fat? Because fat is pro-inflammatory and anti-inflammatory depending on what you measure and where it is. I wonder if the weight of the hands actually gets worse because people are out and about playing pickleball and stuff. [laughter] So it could go either way. Yeah, don't know. But I guess what we saw — I think a lot of the discussion together around PsA and psoriasis where we saw a GLP-1/GIP receptor agonist added on to an existing DMARD — I guess it's about the kinetics and trying to understand whether some of the benefit outpaces the weight gain. We don't really have those clues in this study right now.

No, I guess, and I mean the other thing I'd ask — and Derek might have seen a bit of this — but retatrutide feels like one of the drugs where we don't have it registered yet but all of a sudden there's a whole lot on the market floating out there, coming in little packages from China or elsewhere. I don't know — have you seen that, Derek? Has that come up in your practice? Oh, it's all over the place and I'm just trying to understand how people get their hands on these drugs. But yeah, people are demanding these products and they're going to get them whether it's retatrutide or one of the other existing products, and people are clamoring for these things. And I think that just makes it such that we need to understand these drugs and the safety and the efficacy so we can make some recommendations that are sound. Yeah, absolutely. I mean, this is one of those things where the evidence is getting well and truly outpaced by practice. So it's good to be able to get some evidence to back it up and to understand where the strengths and benefits are.

Akil, let's talk a little bit about what you've seen on the floor today. What have you got? Yeah, absolutely. Thanks, David. So I want to talk about abstract 0922, which essentially evaluates the utility of the PREVENT calculator in patients with lupus. The American College of Cardiology and the American Heart Association have guidelines that recommend the use of the PREVENT calculator to predict ASCVD risk. But the bigger question is how well it applies to certain populations — like lupus — is not really well understood. And so abstract 0922 seeks to explore this. This was a single-center cohort of females with lupus ages 40 to 60 with no cardiovascular disease or no history of cardiovascular disease. They inputted their clinical and laboratory values to calculate the PREVENT score and then they were classified as low, intermediate, or high risk. And then separately they calculated — they screened them for coronary artery calcification using a multidetector CT scan. And essentially what they found is that based on the PREVENT score, about 70% of the women were classified as low risk, and among those classified as low risk, about 20% actually had detectable coronary artery calcification. And among those with detectable coronary artery calcification, this encompassed more than half of all the participants. And when it came to looking at ASCVD risk versus age, it didn't really perform well in detecting coronary artery calcification, with the receiver operating curve analysis of about less than 0.7.

I thought this was really interesting — the major takeaway I got from this was that ASCVD calculators alone do not really apply well to individuals with lupus. There are likely other components in lupus that may contribute that really weren't accounted for in the risk calculator. I think when it comes to lupus, one has to think about antiphospholipid status and even the role of antibodies like double-stranded DNA and endothelial damage, and even thinking about how lupus largely affects women — think about the role of estrogen and how it can drive inflammation, but how it kind of fits in the bigger schematic of things, and even thinking about hormone replacement therapy and its role especially in this age group and the use of contraceptives and the type as well. There's definitely still a lot of questions to uncover what can drive this. There's actually another abstract on Tuesday, another oral abstract looking at a different database evaluating the PREVENT score — that's abstract 2861 on Tuesday.

Well, coronary calcium scores have really — they're right out there and that's changed the game a bit in terms of trying to assess who might be at risk and who might not. They've got their strengths and weaknesses. Janet, I feel like you've spent a lot more time than me thinking about lupus and comorbidities. What do you think about this? Does this surprise you? How do you think this is going to play out? Right. So I think in general most of the calculators we use — we were doing fudge factors back in the EULAR days for RA, etc., for our inflammatory chronic inflammatory diseases, and the fudge factors both over- and rarely undercalled what the real risk was. So I think we have to still be pretty cognizant that the most important risk factors are the major risk factors we're aware of for coronary artery disease — family history, smoking, diabetes, hypertension, that kind of stuff — and then our drugs, like disease activity and glucocorticoids because they're intertwined. And so I suspect at some point we're probably going to have a less expensive one-view coronary calcification that'll be sort of like as inexpensive as maybe a rapid CT, and that's probably what's going to happen in people of moderate risk, because if you're high risk it doesn't really matter — we're going to treat. I mean, it matters if we think they need a stent or something, like if they need an angiogram because they've had what could be angina or not, because they can present atypically. But I think the bottom line is the medium-risk people — you want to know, do I raise them or keep them there or do I lower it? And you don't really know till you look. So I'm not against calculators; I think they give us an idea. But I think you just have to kind of do even like a Framingham or a Reynolds or something like that and just say, "Okay, this person's medium risk, but I kind of have a gut feeling they're low risk — so do I look further?" Or, "I have a gut feeling they're higher risk because glucocorticoids aren't doing good things to the rest of their body and so I'm wondering what it's doing for accelerated atherosclerosis," because risk factors are only risk and low-risk people still get events and high-risk people get more events.

Yeah, this screening is hard to navigate — trying to make sure you pick the right people and you're not over-calling or under-calling. I feel like Mike might have some thoughts on this — coronary calcium scores and estimations in general in lupus. What are your thoughts, Mike? Yeah, two thoughts. I also love fudge factors. And my favorite fudge factor that I heard — my buddy Ali Duarte gave a grand rounds one time where he said, you know, if you just take folks with lupus and pretend that they have diabetes, that winds you somewhat close to where they ought to be. So for one, that's really sad because diabetes is such a strong cardiovascular risk factor. But then also I think it's kind of useful, because if you reran this study and put diabetes into the PREVENT calculator, I'm positive that those risk numbers would have been higher and I think you would have been closer to the truth with it. So speaking of Janet's fudge factor, I think my favorite fudge factor lines up. It's also sad because — oh yeah, I was just going to say, often in the note I'll say, "Because this patient has systemic lupus and they've already had it for however many years, please use the targets that you would use in a type 2 diabetic." So I don't know that that's true, but it makes me feel better, because then you really are trying to treat to a target of both decent blood pressure that's a little bit lower than the general population and also good cholesterol that would be a bit different from the general population. So it's funny you're saying that, Mike, because that's what I kind of say — treat them like a type 2 diabetic, because then the family doc knows the targets. Yeah, it gives an easy framework for them.

The other thing I'd add is that coronary calcium scores — a lot of folks with lupus already have CT scans. So a quick call to a radiologist can get you half of the way there for identifying some of this cardiovascular disease calcification that you wouldn't have otherwise expected. So keep your eyes out for that. Derek, how do you find these conversations with patients? I feel like it's one thing for us to make these assessments, but then sometimes it also feels like different patients respond differently to these conversations about screening or about comorbidity management. I think this is a very important conversation to have especially in young adult lupus patients — to use that as a door to have them understand that they are at much higher risk for cardiovascular complications, and having these conversations about how we can optimally screen them and evaluate them and use even just simple existing tests to understand what the risk is. That's very key for this patient population. Yeah, absolutely. Great abstract.

So Janet, what did you find out there that was good and great on day one? Right, so my major one will cover almost an entire session because I can't report in detail on all of it, but I went to the myositis session and there's a lot of interesting stuff. Some I'm going to talk about just bottom line, and I'll talk a little bit about one of the studies that kind of impressed me on maybe what I might change in my practice. So there were two FcRn inhibitors in this session — 0904 was, sorry if I say it wrong, efgartigimod — I'm sure it's kind of close to what I'm saying but not quite — and then the next one was on nipocalimab. So both of them in inflammatory immune-mediated myositis, I guess is the best way to call it. So on 0904 it was really saying that efgartigimod both decreases the antibodies that are probably pathogenic and not bystanders — but some people might call me on that — and can give hypogammaglobulinemia, and that's well known with the FcRn inhibitors. The main reason I was looking at that is as a side effect profile, because on Wednesday with the late-breaking abstracts the phase three RCT is going to be presented of this FcRn inhibitor in inflammatory myositis, and spoiler alert, I think we'll be happy to see the results. So I thought I should probably know a little bit about benefit and risk. And nipocalimab didn't have much extra to say, but we do know that these FcRn inhibitors can give hypogammaglobulinemia — they're lowering IgG — and that for the short term it doesn't seem to have a lot of infection issues, but in the long term who knows, so time will tell.

Then abstract 0907 was a subanalysis or secondary planned analysis of the VALOR RCT, and that's brepocitinib — again, if I don't say it right, I apologize. These drugs — we have to learn all these names because they have positive studies. Anyway, they already presented that it's a positive RCT; I think it's already published and it's gone through the FDA. But this was looking at some patient-reported outcomes and physician outcomes. So first of all, they kind of made up the outcomes because they said they wanted to look at LDA — low disease activity — and that was kind of more like a physician global. They wanted to look at clinical remission, sort of physician and MD global. So we don't really know that these are remission-remission, but low scores — physician global less than or equal to two out of ten — and they wanted to look at the improvement in HAQ or the delta HAQ, and whether these are validated or not. Surprisingly, the active treatment did moderately better as you would expect than the placebo, and a lot of the placebo and the active were on standard of care that was failed or partially responsive. So I thought that was kind of cool and interesting and kind of validates that it does work in other ways that you might slice and dice the data, even if it's not validated.

And then to spend just a couple of minutes on 0906 — so that's ruxolitinib, and hematologists have used that JAK inhibitor for a long time. This was an open-label study of severe MDA5 patients — most were in the ICU, very very severe and progressing — and the use of ruxolitinib. They tried to do controls so it wasn't randomized, it wasn't blinded; they looked at some basically historical controls or even over the time frame some who got the drug and some who didn't. And what was really important — although there's maybe channeling bias and stuff — it improved mortality short-term and even at 3 and 6 months. So you know what, when I have a person in the ICU with MDA5, which is quite highly active, am I going to reach for that drug, or am I going to say, well, maybe brepocitinib because it's a JAK1/TYK2 inhibitor — should I use the approved drug? And someone asked the question: if you had a patient like that in the future where you have access to an approved drug, are you still going to use ruxolitinib? And you know, it's not really for a researcher to answer that question — I think we'll use whatever we get access to. But I was impressed that this could maybe bail out patients, and whether it's a class effect or that drug in particular, I don't really care. What I want to know is that we can bail out patients. So that was sort of my takehome. There were some other talks within that session that were good, but those were my clinical takehomes.

I'll throw to Derek a second because I know he's a myositis guy. The um — I mean it's exciting, isn't it — I guess I grew up thinking maybe rituximab would just fix everything in myositis, but it doesn't. So we've got now these two FcRn inhibitors — efgartigimod, I think I've got that right, or we'll keep saying it until we get it right — and nipocalimab as well. Both of those obviously have gone through development in other indications. And then ruxolitinib — the hematologists are right on top of that JAK1/2 inhibitor — and then brepocitinib, which we've seen of course in that big VALOR study, the JAK1/TYK2 inhibitor as well. So interesting seeing those two sets of mechanisms of action play out. Derek, do you think there's a real unmet need in terms of different mechanisms of action in myositis?

Yeah, absolutely. I think this advancement reflects our growing knowledge about the pathophysiology of this whole conglomeration of diseases. So — with effort, I practiced that one ten times in a mirror — we know that this may reflect that these autoantibodies in this disease state are somewhat pathogenic, and maybe that's part of the reason why this molecule has also been studied in Sjögren's, so we understand more about the antibody story with these diseases. And then also the interferon pathway is unfolding in this disease state and I think that's of particular importance in MDA5 disease. And as we all know, these are very sick patients — a lot of times these patients will require multiple mechanisms of action of therapy. And if you have a patient in the ICU, you're going to throw what you have at them. You'd rather expose them to therapies that you've used more and that you understand the toxicity profile of better. In the past, maybe these are patients who would have been dealt cyclophosphamide and tacrolimus or what have you, but now we have these understandably less toxic therapies that can bail out these patients.

Well, it's obviously an exciting time to have multiple options. Akil or Mike, maybe I'll ask both of you in terms of where you see us being able to stratify these therapies. We've seen the challenge in a few different diseases now when you have no therapies and all of a sudden a lot of therapies. How do you pick what you're going to choose for — lupus, Sjögren's — I guess that's coming, a few others. What do you guys think? How are we going to pick? You can jump in. I mean, I think it's hard to stratify even within just dermatomyositis. The cool thing about the efgartigimod data — hope I said that right — is that they actually have data in immune-mediated necrotizing myopathy, which is a huge unmet need. These HMGCR and SRP patients often have very refractory disease, so I thought that was really welcome. The vast majority of trials right now are in dermatomyositis and are not going to give you anything in that area. So I thought that was pretty cool. How that relates to IVIG is kind of an open question — are we going to keep giving IVIG? Like, where do we land there? Even within each disease space, it's hard to see where they're going to land in a crowded landscape.

The JAK inhibitors were pretty interesting — I've been trying tofacitinib since that kind of peculiar pre-post study that was published in the New England Journal, a small case series from China a while back. And I can't say it's been amazing, but people with MDA5 are quite sick, so I don't know what your expectation should be there. So it's really funny — in a lot of these areas that were kind of orphaned before, all of a sudden we have sort of an embarrassment of riches, and how they play together is becoming increasingly complicated. I don't have it yet — help me out, what are we going to do? [clears throat]

Yeah, it's the exact same point, Mike — just like now that we're having this growing armamentarium of drugs, which to pick, which to use. I've definitely had this question for some of my patients with myositis in the past as well. And I guess maybe one thought comes to mind is just kind of seeing which are the really active domains involved in myositis and the subtype as well. At least with some of the subtypes they tend to correlate with certain manifestations and even like the malignancy-associated ones as well, and kind of seeing risk-benefit, maybe considering one option over the other — like brepocitinib versus a JAK inhibitor. I mean, for me my algorithm has always been mycophenolate, rituximab, IVIG — but I think now, as Derek alluded to, we're understanding the interferon pathway and its role and pathogenic autoantibodies. These may even be considered earlier on in the treatment course depending on how severe the disease is and which manifestations or domains are really active, and kind of thinking of treatments targeted towards that.

Well, I think we're getting better and better at phenotyping myositis. We've long gone past the days when we used to talk about polymyositis as this kind of amalgam of all sorts of different evils. And I'm sure as we get better at it in different modalities, we'll get better at picking therapies. Derek, what's been good out there today for you on the floor?

So I've got abstract number 0351 — this is the BIMVAC study. This is looking at in real-world spondyloarthritis patients — that includes axSpA and psoriatic arthritis — exposed to bimekizumab as part of real-world data. This piqued my interest just because bimekizumab has been out on the market now for PsA and axSpA for two years, and I think when the drug was first released a question that we still have is: is this really — is this a me-too drug, or is there something truly different? Is there some substance here to say that the dual IL-17 inhibition mechanism of this drug makes a difference? And I think when this drug was released, maybe people can chime in here, but I think a lot of the experience of this product was in patients who had already been through multiple mechanisms and possibly an IL-17 inhibitor in the past.

So what we're looking at here is an observational cohort of patients with PsA or axSpA over the course of two years who had been previously exposed to IL-17 inhibitors or other mechanisms. This looked at drug persistence over time and therapeutic response at several intervals using EMR data. So this is a population of 260 patients — 36% axSpA, 63% PsA roughly — diagnosed with standard criteria. Of this population they received a mean of three previous biologic or targeted synthetic DMARDs, and 54% of this population already had a previous IL-17 exposure. In this population, bimekizumab was initiated as a third or later line treatment in almost half of patients, and these patients did have quite high disease activity at baseline.

So the retention data — in these bimekizumab-initiated patients, 83% of patients were still on the drug at 6 months, 68% of patients were still on it at 12 months. There were no differences depending on if the patient had axSpA or PsA, and there were no differences in retention depending on the number of previous targeted synthetic or biologic exposures. And then looking further at those prior IL-17 inhibitor-exposed patients — either secukinumab or ixekizumab — looking at the retention rate, it still looked quite favorable no matter if they were compared to IL-17-naive patients, at the six-month mark. But there was a little bit of a dropoff when it came to a year. Of those who discontinued, 48 patients — it was because of loss of efficacy. There were 20 patients with discontinuation due to adverse events, but most of those adverse events were not serious. And the top adverse event was fungal infections — 26 patients. [snorts] So I think the takehome is this is real-world evidence of patients who've been exposed to IL-17 inhibitors in the past. This kind of gives us a little bit of a glimpse into that question of using this specific product in those patients exposed.

Yeah, really nice rundown there. I think it's always — I mean, we've got this plethora of choice now in psoriatic arthritis and in axSpA as well, and just trying to make sure you pick the winner with the next therapy that you rotate to is a really active question. Janet, maybe I can ask you — do you see there being this role for these — I'm really interested in these IL-17A inadequate responders, whether it's primary or secondary, and then potentially thinking, well, maybe I'll hit it up to IL-17A/F as well. Is that something you think about? I guess what type of patient would you think about doing that in?

Right. So first of all, let's be honest that we don't know what to do post-IL-17. If it's your first advanced therapy, maybe we'd go to a TNF. We'd look at the other problems with the patient, because in my opinion — which is only an opinion because data will tell me otherwise — I believe the IL-23s are not as strong, and there have been some head-to-heads suggesting they're not as strong. So I'm kind of looking: am I going to go another IL-17, a TNF, or a JAK? First I'd probably be more apt to go out of class, but that's just because who knows why they've broken through on secondary loss of effect. I mean, sometimes we're going to push the dose anyway, or if it's bad skin, derm will push the dose for us. But have I had people who have done IL-17 to IL-17A/F — so secukinumab or ixekizumab over to bimekizumab? Have I had some respond? Yes. Do I have the same durability as if I would have gone out of class? I don't think I really know. So I think really it's almost like patient preference, safety, comorbidities — obviously if there's anything GI remotely, we're not going to stay in an IL class, but we probably wouldn't have chosen it to begin with if they had even inactive IBD probably. So the short answer is I think I've done all of the above, moving them around, keeping them in the class. And I do see responses irrespective almost of what I do. And I'm not so certain how different, after you've done an IL-17A, how different an AF will be versus going out of class. I really don't know. I'm not convinced that it's really a lot different.

Another disease where we'd like to phenotype a little bit better, right? And I think as we go on it feels like we have these conversations year after year, but it does feel like we're getting closer on a few different counts, and choice drives that. I might just quickly talk about one thing that caught my eye today — it's from the poster floor, the METEORICS study, which is abstract 0179. I think this is a really interesting question about methotrexate and giant cell arteritis. We know tocilizumab works; I think it's been the mainstay of therapy. We're getting some extra choices now. Choice is good. But I guess how long do you keep on going with these therapies? For some people, some would like to believe that GCA is a phasic disease and that it might disappear away at some point. Do you eventually try and transition these patients off to something else? And there's a lot of appeal to trying to go to a csDMARD at some point after tocilizumab, maybe on the basis of immunosuppression, or cost, financial cost, or something else, in different settings of course as well.

So we saw a little bit last year from the French — the METOGIA study — looking at outright methotrexate versus tocilizumab for the first 52 weeks of giant cell arteritis. Methotrexate didn't achieve non-inferiority to tocilizumab, but it certainly did something — it wasn't a complete bust, though underwhelming. At the same time, you'd be hard-pressed to say it's as bad as placebo. And so what we saw on the poster floor this year today was the METEORICS study, which is from Valentine Schaefer's group from Germany. I was just saying before we got there that there's a photo circulating of Valentine Schaefer — possibly the best-dressed man in rheumatology — wearing Minnie Mouse ears because we are in Orlando after all. I think that was possibly forced upon him. But his group did this double-blind randomized controlled trial looking at, after at least six months of tocilizumab, whether methotrexate would compare against placebo. The headline suggests that methotrexate and placebo were no different according to the primary outcome, and I think that's a legitimate important conclusion out of this.

At the same time, I guess the question is — is there something in there? Because these patients stopped tocilizumab and went straight to starting methotrexate — so no real ramp-up time, no crossover time. And what we saw was that in the first 26 weeks of methotrexate versus placebo, there were quite a few flares in both arms. That second 26 weeks — once the methotrexate had a bit of time to bed in, maybe the disease is a little bit different as well — at that point, we only saw one relapse in the methotrexate arm versus 11 in the placebo arm. So I think this raises all sorts of questions about where methotrexate sits, if at all. I think it depends a lot on what the individual patient situation is and what the access is like. Mike, I know you've got thoughts on this — I mean, does methotrexate feature at all in your giant cell arteritis practice, and if so or if not, where would it go? What does this tell us?

Yeah, I don't use a lot of methotrexate in giant cell arteritis. I just don't think it's the right drug for the area. I mean, we do have trials using methotrexate upfront and they were mostly a whiff. I think the best one by Hoffman back in the day was a negative trial, so I don't use it up front. I thought the METOGIA study presented last year by the French Vasculitis Study Group was useful, and I would quibble — I am not sure that that curve looked very different from a longer steroid taper. So I thought the METOGIA trial was a strong argument against using methotrexate, or at least a strong argument in favor of tocilizumab upfront for those people.

This study was really interesting and I'm really curious to see the full data. A big question that I had is: how long had people been on tocilizumab? They had to be on for six months to get into this and to be randomized. But if someone was on for six months and then flipped over, I'm not surprised that you saw a few flares later on in the course. If someone's been two years on tocilizumab and then flipped into this, it's a different story — those people I feel like are less likely to flare. I think from the SELECT-GCA data that we saw recently, when you stop people after one year of therapy in GCA, they flare — they flare a lot. So I think people need two years of an IL-6 inhibitor, and then after two years things get a little more complicated — some people might be able to fly. But I think my takehome from this one is that it's another argument against pushing methotrexate very hard. Certainly there are folks who truly can't afford tocilizumab and are having glucocorticoid-related side effects — I will reach for a conventional synthetic DMARD, and I actually like leflunomide better. But methotrexate has no role, I think — despite the best efforts of the French Vasculitis Study Group, its role has not been resuscitated in recent years.

Yeah, and we've got a lot more choices in GCA now. I definitely always take tocilizumab over methotrexate given the choice. I saw you write about tofacitinib in the US costing the price of a burrito, so I think cost-plus drugs is changing the game a little bit possibly. Let me just kind of ask this panel — does anyone use methotrexate in giant cell arteritis? How much? Right. So I use far less. Back in the day before we had tocilizumab, I used it occasionally because I think in long-term need for trying to get the steroids down there's an occasional patient where it really helped. But I think it's another nail in the coffin now. And I do think that if I'm going to reach for a csDMARD — because we have both obviously tocilizumab and sarilumab, and a lot of countries have tocilizumab as a biosimilar which might make it a bit more cost-efficient — if I was going to pick a csDMARD, I would probably go leflunomide. But I sort of sometimes forget to use it and it can be highly effective in some people. Like, say if we're worried about serious infection, zoster, Bell's palsy — maybe somebody's really quite fragile and I don't want to use either advanced therapy. I might go to leflunomide. So to me it's a nail in the coffin. I wish that it wasn't, but it is. Fair enough.

Well, let's do a bit of a quick-fire round. Go around and give us a 30-to-60-second little snippet of some of the other good stuff that's going on. Mike, what have you got? All right. So I talked about a big success for the retatrutide study earlier today. I'm going to bring it down for a trial that did not meet its endpoint, and that is abstract 0927 — the low-dose naltrexone vasculitis study. This is a randomized trial of low-dose naltrexone. It was a basket study among patients with various types of vasculitis — mostly ANCA — and you know, a couple years ago I think a lot of us got excited about low-dose naltrexone. I actually was giving people compounded 4.5 milligram dosing for the sort of non-inflammatory symptoms that people experience — the fatigue, the non-inflammatory muscle pains. This is a big problem for folks with vasculitis. And so I was trying that out. There was a trial published in Lancet Rheumatology — it was a negative study and it kind of tempered my hope. And then this is, I guess, another nail in the coffin. There was a great effort — it is a really good study. I think it was a big question. It was driven to a large degree by patient organizations and patients who felt like it was helpful. And at the end of the day, it didn't meet its primary endpoint. There didn't seem to be a substantial benefit to going on low-dose naltrexone for these types of symptoms. The primary outcome was PROMIS — a cool patient-reported outcome measure, which I love. I love everything about this study except for the outcome. Now, the one saving grace — in the abstract presentation today, the primary author was asked, "What are you doing about this now?" and he said, "We told the patients in the study that it didn't work and half of them wanted to continue therapy." So I don't know if that's like a silver lining that it did make people feel better, but unfortunately in the randomized trial framework it did not. Wouldn't be the first drug to fit into that category. And you've got to take a swing at these things every now and then.

And Akil, what did you like? Yeah, on a similar kind of wavelength — common questions my patients often ask are, you know, what can I do to control my inflammation, especially when it comes to joint pain? And one of the things centers around diet. We have the ACR guidelines around use of integrative health, including diet — Mediterranean diet — as a way for anti-inflammatory control. And abstract 0948, which was one of the late presenters this afternoon, evaluated the role of diet on inflammatory control in patients with rheumatoid arthritis. They essentially had two groups — one group that received the Mediterranean diet and another group that received something called the ITIS diet, which essentially is the Mediterranean diet with specific components that are anti-inflammatory in nature, tailored for RA patients. And essentially what they did was look at the clinical response over a three-month period and also look to see, as an exploratory endpoint, if there are any signatures that can come up from these dietary changes.

Essentially, they found that at the three-month mark, the number of patients with high disease activity measured by CDAI had decreased by almost about 30% in both groups — both the Mediterranean diet group and the ITIS diet group as well. And then when it came to the signature changes, they essentially used unsupervised machine learning methods and found that there were some unique signatures in both groups that correlated really well with the change in disease activity at the 3-month mark. I think these findings are really interesting, but it's also a small cohort with short follow-up. I think we need a larger population-based study with longer-term follow-up to really evaluate the changes, and even some things like adherence to the diet and how that can impact both short-term and long-term are really important. But I think it definitely opens up the conversations — as rheumatologists we really should be thinking about diet and its role in inflammation, just even understanding the details when it comes to specific components that can help or not help in terms of inflammation control. We're starting to see more essentially biological data that can explain the impact of how anti-inflammatory diets can play a role in inflammatory arthritis like rheumatoid.

Yeah, there's something there, isn't there? And it's good to see that people are working on trying to understand what in the microbiome and the metabolomics might link up those things. Janet? Okay, so I'm not a biomarkers person, but there were a couple of interesting things. So I was looking at fibrosis, PPF, and also ILD and the systemic autoimmune rheumatic diseases. So very one sentence on each of three abstracts. So one was 0019, and this was looking at — of all things — sarcoidosis, and they looked at fibrosis looking at the TL1A pathway. TL1A — to be honest, one of the drugs failed in their IL trial, but there are three drugs out there, and they're out in UC and Crohn's because they have positive trials, so they are doing something. But what this said was that in the sarcoid patients it was a pro-fibrotic pathway — the TL1A pathway affected the myeloid cells and then downstream you're getting your granuloma from sarcoid, including the lungs but other places as well, and fibrosis. And TL1A seemed to be not a master switch but something that was controlling, in a bad way, upregulating TNF, IL-1 beta, IL-6, IL-17. So it sounds like it could help some of our patients by downregulating this. So I thought that was kind of cool.

The second one — one sentence — 0037. What they did: this was a cohort of patients, 60 with scleroderma and 19 controls — scleroderma and no ILD, I suspect they were matched, though they were kind of a bit sketchy on whether it was matched or not. But what they found was that KL-6, which has long been used in ILD in Japan for scleroderma ILD — if it's high, it's kind of like a CRP but not identical — and they looked at ICAM-1, so an adhesion molecule. And KL-6 and ICAM-1 both predicted moderately well what the FVC percent predicted would be at baseline, but it didn't go forward. So it's not really a biomarker that would change over time, unfortunately.

Then the last one was 0025, which was from UCSF. They looked at progressive pulmonary fibrosis and SARD ILD patients. And the big thing right now that I just learned recently is that a lot of these IPF patients, and then I'll call them PPF probably as well, have these short telomere syndromes — less than 10% — and it can run in families, blah blah blah. So I just learned that recently. The reason this one caught my eye was they were looking at senescence — which is kind of like aging stuff — and they were looking at epithelial remodeling and damage, and that the more of this problem you have — they didn't talk about telomeres, but I thought that was kind of a cool adjunct — if you have this senescent stuff where you remodel inappropriately, you get your epithelial dysfunction, the laying down of fibrosis, but it is moderately at least linked to DNA damage. And they found it not just in IPF; they found it in PPF, but they found it also in SARD before they're even fibrotic. So I think some of these things are not ready for takehome messages, but they might be real potential targets down the road. Yeah, it really feels like it's getting closer to the pathogenic pathways as well, so there's some real promise there.

Derek, what did you see out there? So I think at this time we can all agree we're in a Sjögren's renaissance period — a lot of interesting therapies and research going into this disease space — and specifically understanding more now about the tools that we have available, and also how we can diagnose and phenotype patients, and understanding there's been a retooling of nomenclature. Now we don't have primary and secondary; we have Sjögren's that is isolated and Sjögren's that is associated with another rheumatologic disease. So I found a very interesting abstract — this is 0409 — looking at minor salivary gland biopsy characteristics of those with isolated Sjögren's and those with associated Sjögren's, looking at biopsy minor salivary gland characteristics as well as objective measures of dryness, and specifically in this analysis, unstimulated salivary flow.

So this is a little over 200 patients — the majority were primary or isolated Sjögren's. And looking at the differences between biopsy features, 90% of the isolated Sjögren's patients had a greater focus score — a focus score of greater than one. Only 66% of those with associated Sjögren's had a focus score of over one on their biopsy. There was more frequent acinar atrophy and a higher overall focus score in the isolated Sjögren's group versus the associated. But interestingly, in those patients with associated Sjögren's, their salivary flow rates were lower than the isolated Sjögren's group. So just some interesting snippets here that say, you know, are these the same disease states? I don't think we should discount that just because a patient has associated Sjögren's it's any more benign functionally — that's not the case. I think we should think more elaborately about these potential associated patients. Not every patient with rheumatoid arthritis who has a dry mouth truly has Sjögren's, right?

Yeah, absolutely. Really good to see what's going on at the salivary gland level. I just want to make quick mention of abstract 0869 from the plenary, which was about asking artificial intelligence chatbots about some clinical scenarios and seeing when they concurred with the guidelines. I don't think the outcome's important — I'll tell you that Open Evidence and ChatGPT seem to do better in this test. But by nature of how these abstracts are, these models are ancient now, and there's so much in terms of the way that things are structured and might appeal to specific different training of individual models, and really we need to test them in multiple different ways before we start making conclusions. But plenty more to watch there, and it's a very real question in our practice.

Well, we've taken up a good solid 50 minutes of good discussion here. I'd like to thank the panel — Mike, Akil, Derek, and Janet Pope — for joining us here today. Make sure you go down to RheumNow.com where you'll find all of this incredible content and much more in our comprehensive coverage. Thanks so much everyone. Have a good night. Thanks, Dave. Appreciate it. Take care.