ACR24 PsA Topic Panel Advancing Care for Psoriatic Arthritis Save

Hello everyone and welcome to the ACR twenty twenty four PSA topic panel. My name is Catherine Bakewell out of Salt Lake City, Utah and I am accompanied today by our esteemed faculty who I would like to allow to introduce themselves. Why don't we start with you, Arty?

Hey, Arty Cavanaugh, University of California, San Diego.

Fantastic. Quilin?

I'm Quilin Connelly from Galway Clinic, Galway, Ireland. Akhil?

Hi, I'm Akhil Sood. I'm at Stanford University in Palo Alto, California.

Fabulous. And last but not least, Anthony.

Hello, I'm Anthony Chan from Reading, United Kingdom.

Fabulous. So as you can see, we literally have folks from all over the globe and we're very grateful to those colleagues across the pond who have stayed up late to do this recording and Arti who is joining us on his lunch break in the middle of clinic. So this is as the world turns, everybody's making this work. So Doctor. Chan, why don't we start with you?

Thanks very much. I want to talk about abstract seven seventy two, which is what's in the plenary session. And this is from Doctor. Andreas Ketschbaum from the University of Vienna. And he looked at the placebo response in psoriatic arthritis over the years.

He summaries that as a one percent increase in the ACR 20 over the last many years and as high as now forty three percent in the placebo arm in arthritis. And when he looked at it as to why this might be, this is linked with the gross national income in these countries. So if you do these trials in developing countries, they seem to have a higher placebo response and they estimate that the if with every £10,000 $10,000 international dollars going up, your ACR then changes by about 5%. So the higher you go, the lower the ACR. He was like a hand stressed rustling moment.

I don't really watch his his YouTube Ted Talk where he talks about how all these socioeconomic factors changes. This was something like this at the ACR. So quite a nice talk. Give you a chance to look at this video and it's worth a look.

Fabulous. What does the group make of this? What do you guys think about these rising placebo responses over time and tying it to socioeconomic status within these countries in which the recruitment is being done?

I think there's a couple of factors. One is the socioeconomic status in the countries. The other is a time effect. Over time, the placebo responses have tended to increase as the spread of the countries in which the studies are being done has also become more diverse. What Andrea showed, and they showed this at EULAR for RA, almost the exact same data.

When you look back twenty, thirty years, most of the studies were Western Europe and US, and now it's spread more worldwide. Not all the placebo responses are in the developing countries though. I think that gets the time effect as well. It seems over time in rheumatoid arthritis now in psoriatic arthritis, it's where the placebo response is increased, which just makes it harder to interpret the results of the studies.

I think so too. Yaquil and Akhil, any thoughts on that?

Well, I just wonder in the developing countries where patients are getting access to care in these clinical trials, if that's impacting their perception of their overall care and that's impacting their responses, their reporting on patient reported outcomes and so on, that they're actually getting access to this care and they're getting followed up very regularly, I think definitely impacts those scores.

I think that makes sense. So one take home that I thought about is, well, maybe we really need to be focusing much more on the delta between placebo and whatever response we're talking about, you know, ACR twentyfiftyseventy 70 or whatever the metric is, rather than just the absolute percentage because we're used to talking about, say, a sixtyfortytwenty percent ACR twentyfiftyseventy response. Well, maybe that's less important than the delta to placebo, right? We would definitely need to be thinking about that as well. Great abstract, Antony, like that.

How about you? You have

to consider the effect size, of course, like you're saying, the Delta plus the standard deviation to account for the variance. Now it's funny, many years ago, we used to talk about psoriatic arthritis studies and say, we were worried that the skin response would unblinded, because if somebody's skin is getting better, they know they're on the real treatment. But I think we don't worry about that as much anymore because most of the, there's mostly concordant responses across scan and peripheral joint domains, but still it's interesting to certainly keep in mind as we look at study results.

Absolutely. And I already, I know you picked out a couple abstracts for us. Do you wanna share what you thought was interesting from the meeting?

Yeah, there are two in particular. So 2640 is one of them and the other one is fourteen sixty. And these are both neither absolutely definitive. The fourteen sixty is from France. They have a registry called Combat, which I thought was a cute name, and they're looking at combinations of targeted therapies in immune diseases, including psoriatic arthritis.

2,000 06/1940 looked at psoriatic arthritis specifically. These are anecdotes, but I think it's super interesting, especially in light of the VEGA study, which showed that the combination therapy with visexelimab and glulimab had achieved what we had always hoped for combination therapy, and that is to have additive or synergistic efficacy without a bigger penalty in terms of toxicity. So since that, I think we have sort of revisited the idea of combination therapy. In the French study, they had quite a lot of various combinations of TNF inhibitors plus JAK inhibitors, TNF plus twenty three, TNF plus vetolemab, of course, in GI disease. In the other abstract, which was led by people at NYU, they looked in a database and mostly, most of the combinations were with PDE4.

And I think we've become so used to that, that I don't think we'd think of that much as combination therapy anymore. In each of the studies, they did find a little bit more in the way of safety concern in terms of adverse events, but these are anecdotes. And as we do in the clinic these days, the people that you treat with these combinations, particularly like those in the French study, those are gonna be the worst of the worst. Those are gonna be people who have failed many other monotherapies and probably on conventional synthetic DMARDs in many cases as well. So it's a very tough population, perhaps not unexpected that you would see infections, of course, as we do with all of our immunomodulatory therapies.

But I think building on the success of the VEGA, and the VEGA study was also presented at ACR. Some beautiful biomarker work from bowel biopsies there. I think combination therapy is resurrected in rheumatology, and I think we may not see it in rheumatoid arthritis, but I think in PSA we will see it, and to me, it's only a question of which combinations we'll use and which are gonna give us the benefit without the additional penalty.

Great points, and I think combination therapy has really been the hot topic lately, and so I love that you brought this forward for us to chat about. And of course, Vega was very exciting and you see, and I believe we have affinity to look forward to in the PSA space looking at that same combination of a TNF inhibitor plus a twenty three, and I noticed that as well in the French study that they really the most common combination actually was a TNF plus a JAK inhibitor, which I think we have extra concern about infection in that combination. But the fact that that was the most common biologic combination, whereas at least in that UT Southwestern, more US based study, you commented, the overwhelming majority was in a premilast combination therapy, which we feel fairly confident with that we are not increasing any safety risk for our patients, but it's maybe not as sort of avant garde. Like we want to see what happens when we combine our biologics or our targeted synthetics biologics for these really difficult to treat patients.

I guess there are fewer lawyers in France than we have here.

Somehow they got it paid for and they were not worried about it,

so there you go. Yeah,

thoughts from the rest of the group? Have any of you seen this or kind of thought how you might either use this in your own patients or had thoughts on these trials as they come forward?

Think they're really interesting. I think there are two points. One is that this will be for now the most severe end of the patients because we're using this kind of treatment. Clearly they have not responded to other treatments and we kind of have to take into account that the disease itself you know, psoriatic arthritis, psoriasis does predispose you to more infections. So, we might see an increased signal but whether that is just because we have pre selected these people because they're more severe.

What we need, I think the second point are registries to kind of collect a lot of data across many countries so that we can truly understand. With more treatment, more choices, this is the natural way we'll go and start combining treatments.

I like that the registries do this in a systematic fashion, absolutely, as opposed to I think Doctor. Meiss might be starting his own registry out of Seattle. He commented once in a meeting he had 150 patients on combination therapy and he said, Oh my gosh, tell us how that goes. Akhil, any thoughts on this before we move on?

Yeah, I think it's really exciting that the combination biologic therapy and even just combination therapy in general, Even for some of my patients in the clinic, there are some that are doing really well on one treatment, and then the considering of adding another is definitely one thing to consider, but then also looking at the risk versus the benefits as well. I think that the abstract 2,640 that looked at the risk of apramylast in combination with biologics, I think it's really interesting. But also, I agree is that we really need to look at the more details as which ones are more predisposed to risk of infection. Is it driven by the drug or is it the underlying disease itself? Because patients with psoriatic arthritis, some of these patients may have very active skin involvement and there's open skin lesions that may predispose them itself or maybe the drug.

And I think it's definitely a really interesting area and a really exciting area. I think definitely worth investigating. I would really consider it for some my patients if that opportunity is available, that combination, if that's a possibility. But definitely more, I'd agree with Anthony, the registries and more studies as well.

Yeah, I think we're all very, very comfortable with the Permalase combined with other therapies, but it's more of the question of the JAKs and the TNFs. Think the longer term safety data and getting some insight into the cancer risk there might help answer a few questions in the longer term. Yeah, think having a systematic way to look at it will answer most questions and give us evidence base to use it or at least discuss the approach, the idea with our patients.

Absolutely, and I have heard from people and I have seen this work myself and full disclosure that it is very difficult as a single prescriber to get combination therapy covered, but a workaround can be for dermatology to prescribe one and rheumatology to prescribe another. Again, totally off label, but in those patients in whom they just have persistent inflammatory disease, no matter what you have tried for your CSD MART or biologic targeted synthetic combination, this may be a potential option. Cleveland, tell us what you found fascinating at this meeting.

Yeah, so there's lots of hot topics in psoriatic arthritis this meeting, but I really enjoyed all the presentations on the sex differences in psoriatic arthritis and one highlight was Abstract five eighty eight presented by Doctor. Laura Coates. In that, her and her group looked at baseline characteristics at over fourteen hundred patients with psoriatic arthritis. This was pooled from three phase three RCTs. Amongst the fourteen 100 patients, there was about a fiftyfifty split between male and female.

And really, what they ascertained and what they highlighted for me to take forward into clinical practice is male versus female, how they present is different. Disease manifestations is different and clinical course can also be different, was something that was discussed in a talk given by Doctor. Potes and Doctor. Eder in a different session. But ultimately, you know, females typically present with less severe skin involvement, typically have longer duration of psoriatic arthritis by the time of presentation, typically will have higher BMI and did report a greater impact on their quality of life as compared to men.

So, I think they're all very important take homes in clinical practice. And as I mentioned, a lot of that information was presented, again, very eloquently by Doctor. Coates and Doctor. Eder in session 17.08. And it was really an excellent session.

I'm going to look back through it myself but would definitely recommend others to have a quick look through it as well. But again, just that how women present or females present is different to males. Their clinical presentation, their course, and their response to treatment is all quite different. So, it highlights just the need for us to have a sex kind of specification when we're assessing our patients with query psoriatic arthritis or disease response in people who are on treatment.

Fantastic. No, I remember thinking this was a fabulous session and I'm curious from the rest of the group, any thoughts on that sex differences in PSA?

I think it's interesting. Think we didn't pay attention to it before because PSA is fiftyfifty. So clearly in lupus, all the excitement around Xist and other differences genomically that can predispose to the disease makes sense because it's so much more involvement in women than in men and the opposite in ankylosing spondylitis. But because of fiftyfifty, I think we sort of said, oh, it doesn't matter, but clearly it does. And I think you gotta go back to, you have to stratify the studies now.

If you have an imbalance in the baseline in terms of sex, that can definitely affect the outcome. So the other, I mean, the interesting, I don't think we know the mechanism at all. Pain is more and maybe that's some of it, but so our immunologic responses are different in different sexes. So we just don't know what the difference is, but certainly we gotta pay attention.

Yeah, and to kind of to tag off that, there was the abstract presented by Stephen Dye in 1709 that did look at the proteomics and differential proteomics between men and women or males and females with psoriatic arthritis and that, you know, there was evidence of a sex related kind of biological difference or pathways in psoriatic arthritis between males and females. I think that's the start of some very exciting exciting frontier in terms of treating our patients with psoriatic arthritis.

I agree. Yeah, I think that abstract highlighted there was something like 20 fold greater number of deregulated proteins in men versus women, and it does call into question, Arty, like you're saying, what are the differences here between men and women? We know that hormones play a role in our pain perception, they also play a role in the immune system, and Doctor. Adar put up a slide that I thought was fascinating. I hadn't thought about the mechanism whereby genders have or the biologic sexes have different pain perception, but it showed that at the level of the spinal cord that women it's the T cell that actually has to do with pain perception, whereas microglia are more involved in biologic men.

And so there's really a lot more to the story here than we know. And Doctor. Adar also pointed out, so I think she did a 2023 analysis of all the RCTs looking at psoriatic arthritis response, to all these different agents, and only nine of the 54 reported sex de aggregated data, right? So how did women do versus men? So there's a paucity of information there.

And she points out, look, we're really also not collecting data on anything having to do with women's menstrual cycles, pregnancy, nursing, let alone even just if they're pre or post menopausal, right? So even in the rare instance that we have this data, we're not following a woman in response to therapy throughout all of the crazy hormone fluctuations that can occur between reproduction and then going post menopausal. So we really need to be collecting this data to know more about it.

And in that review of hers, only one study reported on safety by sex.

Clearly major work to be done there, right? Maybe call out to our registry colleagues and those in industry to hopefully give us more information. Akhil, what did you before or any other thoughts before we move on? And then I'd like to hear Akhil

from you.

Yeah, I think, I mean, I thought exactly the same findings were really interesting as well, but I think it warrants further investigation. And even looking at the underlying mechanisms, the exposures, I think that's definitely things that warrant further investigation. And for me, was looking at the abstracts at ACR24, I found that there were several abstracts looking at Epremilast and the potential benefits of Epremilast, which I thought were really interesting as well. So the first one I want to talk about was abstract 2,583, which looked at the effect of Epremelast on axial inflammation. It was a phase four open label trial, the MOSAIC trial, where they Wait, they had a group of patients with active psoriatic arthritis, and they evaluated the effect of Epremelast on axial inflammation at weeks twenty four and week forty eight.

And the outcome measured was axial inflammation. And they used the CANDIN score, which is a Canada Denmark MRI scoring system, where they looked at the total spine inflammation as well as different components of the spine, both structural and inflammatory lesions along the spine. And it was pretty interesting where they found that both at week twenty four and forty eight, after initiation of a premelast, they found that there was significant improvement in the axial inflammation with the total spine, as well as different components of the spine, including the posterolateral spine, as well as the vertebral body as well. And I think this is really interesting in that when considering the use of a premelast in which domains of psoriatic arthritis, this abstract highlights that maybe we should consider the use of a premilast in patients with axial involvement. There could be some potential benefits and this abstract would support that or advocate for that.

I think that's well, so I like how you phrased that, meaning this is a question mark, right? Because this is the first time that we have had an agent that categorically did not show benefit in AS and so the GRAPA treatment guidelines by domain then extrapolated a lot of their axial PSA recommendations by those in the absence of a dedicated axial PSA trial, which secukinumab had very early on, but otherwise if it worked for axSpA, it was considered very likely effective for axial PSA and got the green light for that, whereas apremolast gets a conditional recommendation against use in axial PSA specifically because it failed in AS. And so Mosaic brings to us now, I think we really do need to highlight that it is single arm open label. There is no double blind, randomized, placebo controlled, right? We're just sort of following these patients over time and okay, at twenty four and forty eight weeks it appears that their spinal inflammation is reduced.

But the other thing that we need to note is they also looked at the SPARC SI joint and SPARC spine score and did not show an improvement in that. So is the CANDON, which is more focused on the posterolateral elements, more sensitive for the changes in axial PSA? Is this the benchmark that we should be using? And if we're going to look forward for more RCTs, right, we're going to have like a double blind RCT, perhaps that is the modality that we should be looking for. And I think so there's another trial ongoing that you're all familiar with, probably the STAR trial looking at guselkumab in axial PSA, and they're only to my knowledge using the SPARC score.

So if it's a negative MRI, I would strongly encourage them in their hoc analysis to look at the Camden MRI score with this focus on the posterior lateral elements that we may see some reduction there that may be unique to axial PSA. But I'm curious, others in the RD, I see you nodding your head, you're having I thoughts on that

think it's funny. Permalast is like the drug that everybody likes to beat up on. If you look at the EULAR PSA guidelines, it got trashed. And I think that's the entirely the cost of it. And it's like Yogi Berra said, nobody goes nobody goes there anymore.

It's too crowded. Nobody uses a prem last except everybody does. Everybody uses a lot of it. And this would be fascinating if it was held up. Years ago, Peter Taylor had a imaging study which suggested it worked.

Then the clinical studies failed, so it sort of fell by the wayside. But this, maybe there is something to it. And as we saw, as we talked about combinations, we think of it as being so safe and it's still used a lot by our dermatology colleagues because of the lack of need for monitoring. Fascinating, fascinating how we consider it and that there's still new data with it every meeting.

Fantastic. Yeah, Akhilen, you had actually a couple more abstracts on a PRIMELIST. I don't know if you want to run through those quickly or

Yeah, there was also, it was kind of more along the lines of the effect of PSA and metabolic syndrome, just to more understand that relationship. There were some tie and overlap with the Primalast and other medications as well. So Abstract 2639 looked at the effect of therapies on weight change in patients with psoriatic arthritis. This was out of the University of Toronto with their psoriatic arthritis cohort. They had around 1,800 patients on different combinations, including NSAIDs only, conventional synthetic DMARTs, as well as biologics, as well as apremelast only.

And they found that when looking at the impact of initiation of drug and weight change, they found different effects of these different treatments. They found that with TNF use, after initiation of the TNF, it was associated with weight gain but not statistically significant. But they found that IL-seventeen and IL-twenty three, following the initiation, were associated with weight loss, and that was statistically significant. And they also found that a prem was associated with weight loss as well after the initiation. And when they looked at a separate model looking at the predictors of weight loss in patients with psoriatic arthritis, they did find that a prem last was associated with weight loss in this cohort as well.

So it was pretty interesting that maybe there is some metabolic benefits. And there's another abstract, five ninety eight, that looked specifically at the impact of a premelast on metabolic changes. They had a cohort of patients, of 40 patients with PSA, and

they

found that after the initiation of a premelast, they found after one year, there was a significant reduction in abdominal fat that was measured on a DEXA scan. But I do want to point out that it was a really small cohort, and there also was a relatively high dropout rate. It started at 40 but went down to 20 participants that completed the study. But I think it's really interesting that it sheds light. There may be some both these abstracts shed light.

There may be some metabolic benefit, whether with the medication itself or these other biologic therapies as well that do warrant further investigation.

Fantastic. Yeah, I already, you said it well. So Euler, I think, put a premilast. They said, In patients with mild PSA who have failed conventional DMARDs, who are not candidates for biologic or targeted synthetic DMARDs, you can think about a premilast. So, it was this terrible thing that they were near.

So, clearly, here's some abstracts that are supporting a potential greater benefit for this agent, and especially as we talk about combination therapy. But yeah, any other thoughts from the group on that before we move on?

I think, you know, weight loss is a great added benefit for any and all of our patients nearly. And I wonder with the Eperma last, if some of that was driven by, you know, the side effect profile, particularly in the first fourteen days when people start therapy, it's often the biggest burden to people continuing or some of the GI side effects. Yeah, I think, you know, Permalast is great and I think we love it because of the safety profile and we're so comfortable with prescribing it. At least in Ireland, we don't have issues getting access to it, which is wonderful in combination with therapy, but if there was an added like metabolic effect beyond just weight loss, then that would be very positive.

Yeah, think it controls the disease very well. Although they say not to use it, we still use a lot of it. So because of the safety profile and also the lack of need for monitoring and these are also very young patients who don't necessarily want to be having lots of tests or having injections. So we find it quite a convenient way. First line on also is add on.

And if it can control the disease fairly well, they might result in the improvement in the metabolic status. I think every drug has its day. It's not over yet. We'll have to study this a bit more.

Touching on weight loss has also been a hot topic, not covered extensively at this ACR, but looking at GLP-one agonists in PSA patients, more data coming on that, right, as trials are starting to enroll. But fascinating topic, can we influence disease outcomes just by improving BMI? So yeah, Anthony, tell us more about what you found.

Yeah, I'm gonna move to imaging. We talked a lot about therapies and one of the highlights was on the Saturday of the meeting and this was the preliminary ACR guidance on the use of musculoskeletal ultrasound in both rheumatoid and PSA. Quite useful because it's been over ten years since the last guidance. It was quite a lot of work listening to the the presenters. They had four domains, 26 picos and 20 statements and kind of whittled down to a single document.

And and this looked at structural causes, a progression, disease remission, disease states. And, Catherine, you were actually one of the lead presenters, so maybe you could give us a few highlights of that session.

Thank you for highlighting. All so I was going to say I do know this presentation well, and I think what we were trying to do is develop some guidance for the clinician in everyday practice for the application of musculoskeletal ultrasound. For me, the three statements that I think are going to be the most impactful is number one, in patients with psoriasis and musculoskeletal symptoms that ultrasound can aid in the diagnosis of early PSA. And there's a lot of different ways to look at this. One is in enhancing the number patients that are eligible for the application of the CASPAR classification criteria, aka who has confirmed inflammatory articular disease, either in the joints or in theses, and or can we use this to funnel more of the appropriate patients to the rheumatology offices?

We're already backed up. We know that the sooner we get our patients diagnosed and on treatment, the better that they do. And if we can not just have every patient who screens positive on the pest screening questionnaire from dermatology practices, but if we could also put them through an ultrasound, then there was one study that showed that the specificity of that referral for the presence of psoriatic arthritis went from nine up to seventy seven percent. So we went from seeing nine patients that don't have PSA to all of a sudden it's only one out of four that doesn't have PSA, right? So three out of four do.

So it's really potentially helpful and there's even some thought, and this is not something that was presented in this session, but I'll just mention it because it's fun. There is work with AI being done to say, can AI diagnose ultrasonographic synovitis? So could we someday have it be like an ECG machine where we just put the probe on the patient? The dermatologist has this little pocket handheld transducer and they put the probe at a couple spots where the patient hurts. And if the light turns red, then you go to rheumatology.

So to be continued, right? It's just fun to do the thought experiment. But the other two that I wanna highlight quickly, the definition of a positive joint for aiding in diagnosis of psoriatic arthritis is either a grayscale of two or at least a grayscale of one with a power Doppler of one. And this is different from statements about treatment escalation, require power Doppler in the synovium, TINA synovium, right, so that indicating current disease activity. We wanted to differentiate because you can have cool, sort of hypertrophied fibrotic synovium that can indicate prior disease but not current active disease.

So we wanted that to count for diagnosis but not necessarily for the treatment escalation portion. So thank you for highlighting that. I hope it is something that people will find useful in day to day practice, especially as we tease apart the quagmire of clinical versus ultrasonographic enthesitis and who has true inflammatory disease and so on.

So Catherine, let me ask you, you're an expert in performing ultrasound. I don't know if you had a chance to go to the late breaker session, but they had the, it was a Danish company that has a machine called Arthur and it's an automatic ultrasound. The patient just shows up and they put their hand where they're told to put their hand. The patient squeezes gel on it and the robot arm comes over and does the ultrasound. And that's been, they've had this, they published this like a year and a half ago, but now they have Diana, they're like British names or something, they, to the AI to read it.

And it does as good, pretty much as good as the expert reader. They had an actual reader, then they had the expert who adjudicated and the machine did pretty well. So as you were saying, do you wanna go to the rheumatologist or not? Do you need to go to the rheumatologist or not? Maybe you go by and you put your hand down and if you have something, you go and if you don't, then you don't have to go.

I love that. Arthur and Diana, no, that's fabulous. I think if they could so what's nice about sticking your hand in the machine is that it is taking away how much pressure do you hold on the transducer and do you have the right angle, right? So something that you can just put your extremity into. In a perfect world, we could have something that could also incorporate elbows and knees and other joints that are larger, right?

But I love I think we're going to see more to come on that. Fabulous. Wylan, any other abstracts you found helpful?

Oh, there are so many to choose from, but I really enjoyed Abstract 600 by Anna Maria Orbi looking at kind of the durability of response of bimekizumab in patients with psoriatic arthritis. And, you know, I think it's partly because there's so many new therapies available to us now, but, you know, questions patients often ask are, you know, is this going to last? How long is this going to be good for? But in this study, they looked at patients who were enrolled in both B optimal and B complete trials. And they found that, you know, amongst responders at the fifty two and forty week mark, that the responses were sustained at the one hundred and four and eighty eight week mark respectively.

That's, you know, the two time points in the two trials. So, I think it's, you know, positive data for bimekizumab. I know Anthony wrote a lovely article on all the other abstracts which were covered that new therapy, but I think it's just nice data to have for patients when discussing the durability of the treatment.

Yeah, absolutely. I think they they looked at many other outcomes. So, I think it's nice to know at least we could tell our patients that we have data at least to two years of how they might be and obviously we need to take this longer to five years and see how the long term outcome is.

That's right. This was our first ACR after the approval of bimekizumab for PSA and AS and NRxBA, and I think they just got HS as well, and so this is really good timing. Because of the holdup in the FDA, we already have some long term data to show right after launch, We've got some two year data to show our patients about efficacy in their diseases. So, very exciting to be able to share that, I completely agree. Any other thoughts before we round up for today?

Well, want to say thank you. You guys all just worked so hard. We're everywhere all at once covering ACR twenty twenty four. So I thank you for the discussion and the articles and videos and everything that you've already done. And thank you to our audience for tuning in for this year's episode of PSA at ACR twenty twenty four.