Psoriatic Arthritis Panel Discussion Save

This is the RheumNow podcast, and you're listening to highlights from the ACR twenty twenty virtual meeting. Our faculty reporters have been doing videos and recordings so that you could stay up to date. Hope you enjoy these and our panel discussions. Hi.

Welcome to RheumNow. This is doctor Arty Kavanaugh, and I'm here with my colleagues, doctor Eric Ruderman, doctor Jack Cush, and Doctor. Alexis Ogden. And just got done with the ACR twenty twenty conversions and lots of stuff presented there, lots of abstracts, lots of posters, lots of oral presentations and summaries and stuff. So we're going to talk about psoriatic arthritis tonight and we're just going to ask our panelists kind of their takeaway from the meeting.

Now it's a lot as there always are a few intense days of looking at a lot of data. So what is it that you think of the most important takeaways from that? Eric, let's start out with you.

You know, we looked at the whole, mean, looked at whole meeting, it was a different meeting than usual because there a lot of new therapies, which we sometimes look to these meetings for. There's new stuff, there's new pathways, there's new things. There was one new treatment trial with drugravacitinib, which is the TYK2 inhibitor. Other than that, a couple of sort of phase four trials of some of the drugs we already have and a lot of stuff managing psoriatic arthritis and more sort of thinking about approaches than managing. I mean, other new therapy that was there was the upadacitinib, though that wasn't really new because it had been presented at EULAR previously, so it was represented at AACR.

And for a lot of people, obviously, that's going be the first time that they saw it, but it wasn't something new. We knew it was sort of out there and the data had been out there for a while. So that kind of made it a meeting where you had to sort of look around for something that was really, you know, game changing, basically.

Alexis, were you thinking abstract or presentation or something that really caught your eye from this

I think there were a couple of things. One was, so I think a general theme of kind of setting up for the idea of predictors of psoriatic arthritis, both in terms of couple of studies examining one, a prediction rule for psoriatic arthritis at one year or five years among patients with psoriasis, not fully baked yet, but really nice work that's hopefully gonna evolve into something more significant like a risk score. The other one was one that we presented which was kind of what's going on in the time period up to the diagnosis of psoriatic arthritis and how are different providers coding different things that has meaning in terms of if we're going to build algorithms within a medical record how we might code differently for different providers in terms of what people are putting into the EMR. And then smart devices. So thinking about using the cell phone or your Apple phone or Android in terms of accelerometer and goniometer just to understand how movements patterns might change over time on the way from psoriasis to PSA.

So that theme was there. The second theme that I thought was interesting and kind of discussed a lot at the very least was Kuselkumab presented their data for axial disease. Again, we saw that previously at EULAR, so nothing terribly new for us, but looking at BAZD changes among patients with radiographs done at their local institution, and how those BasDy and those people changed among with use of guselkumab versus placebo. There was a parallel abstract on the other hand that from our group that showed that FASD I really doesn't change any different patients with axial disease compared to those with peripheral disease alone. So really kind of questions whether or we can be using a FASD I as a marker of axial disease.

And like a back version of the rapid three, back rapid.

Yeah, it wasn't very specific. It actually picked up with disease activity in general, which was an interesting thread because there's this whole, you know, idea now to try to break psoriatic arthritis and psoriatic disease down into different domains and try to figure out treatments by domains, which makes a lot of sense. And except that if you can't, if you don't have outcomes that can figure out which domains are going to respond to which treatments, then you can't get very far with that. And so it was a bit of a challenge, this whole idea of separating out back it was interesting stuff, but separating out through axial psoriatic arthritis, it's hard to say it's really important to separate that out if you can't separate out outcomes and show that those people do worse in some way or another, and then you can't look at treatments if you can't hone in on that particular area.

Jack, would you take away from the mean?

Well, to your point, obviously, rapid three works in all of these including axial spondylitis and psoriatic arthritis. Finding a better version of that, don't know. One of the things that I cover a lot of RA, I looked at the PSA stuff, I found it interesting that machine learning found its way into PSA as well. Really in the one area that I thought was maybe the greatest need and that's reading images. I saw that your group looked at that information, I found that really compelling because really think we're not very good really looking at images or certainly quantifying them.

But using machine learning to score images for the spine, I think that's really compelling. And I think that could be that's one of the machine learning things I'd like to see actually translate to practice.

Yeah, I think the radiologists are, they're definitely being, it's like Terminator, they're being replaced by the machines. And in this case, think it's good because if you don't have a radiologist who cares about the spine, you're never gonna get good information from it. And there's such wobble. Mean, many studies have we seen in the spine where the local read was that if they had the spinal development, then the central read is no. I mean, come on, that's not data.

I mean, a lot of places that help. So that's great for studies, right? Because then you can standardize what's going on in the studies. You can read them centrally, but it saves a lot of time and money by having it read sort of a standard commuter way. But it's totally all, it's potentially very helpful in practice, right?

So if you've got a if an algorithm that's developed, there's a machine learning algorithm and once this is set up, it should be sort of generalizable. You can export it to you know and it end up being sort of part of the software locally And then you get an image and then as a rheumatologist, you don't have to feel obligated to sort of figure out how to read the MRI because you don't trust your radiologist. You don't have to have a radiologist who knows what they're doing. You can get a report then. I mean, it's like getting a lab test basically.

Or remember that abstract that Jose had last year with the MRE. If our GI colleagues get an MRE and the radiologist doesn't have to go, oh geez I don't I hate looking at bone. They can just, you know, push a button and it'll give a good bone reading to see if there's any axial involvement. Then you get double the value out of every MRE then. And they're doing more and more of those it seems.

I mean, you remember a million years ago when you had to have a good pathologist who could look at your ANA plates and figure out the pattern figure

out how old are you?

No, but that's not that far back. I mean, it is and I remember that when I was, you know, I mean, that's not that far back and now it seems like crazy old antiquated and and I think in five years, we're going to say the same thing about having a radiologist try to score a sacroiliac joint on an MRI. It probably doesn't make sense

microscope is right next to your VHS machine.

I think the other thing we saw that this is should be extended to tendons too. Mean we saw with the Achilles study, was a they looked at baseline, people had to come into this randomized controlled trial using secukinumab to treat emphasize that the Achilles tendon, they had to have emphasize demonstrated on imaging locally. And what they found after central reading was only half or so of those actually had real emphesitis in the way that should be read. So I think that we have the same problem in the spine that we have peripherally as well. So maybe we'll see more standardization of NPCL readings on MRI as well.

The problem though, potentially is you kind of a lot of times you want the image to show what you want it to show. And if the computer says it doesn't, then you're stuck with that, right, then you have to live with that. And people may say, well, I don't know that I believe that anymore. So it's going to be a work in progress.

And radiologists will continue to have jobs for that reason.

Yeah, that's true. I mean, but they're doing this in other fields too. They're already doing this kind of stuff looking for lung nodules on routine tests, x rays and things like that. Mean I this is the future in imaging for sure.

So let me ask you guys, I thought it was an interesting sub analysis, as you said, it wasn't new necessarily, the ACCEED study, the sub analysis by sex. Because generally when you go into a clinical study, avoid some of the influence like methotrexate and psoriatic arthritis studies generally doesn't do anything because you have to get in the study with disease activity. It doesn't matter if you're on it or not. But here there was pretty sizable differences in outcomes based on sex. Seems like that must be a real thing.

Yeah, mean, people have been talking about this for a long time. There's plenty of studies that show that even baseline women start higher on their patient reported outcomes than men. What was fascinating in this study is that, A, the change is also different. And this is showing this in a very controlled environment as opposed to maybe a different time points in an observational study. So at least we have that kind of internal consistency there.

But what's interesting is it also played out within the skin which was fascinating to me because it's, we think of maybe this is more of a subjective outcome difference but it wasn't, it was actually across more objective outcomes like the PASI, for example.

Was this an issue of the way differences between men and women, the way they seek medical attention and how often and quickly and whatnot? Or is this really pathogenic like it is seems to be in spondylitis where women just present with a different disease and later and stranger manifestations that make it more delayed in diagnosis?

That's the big question, Jack. Unless you start to break up studies or stratify studies by text, you can't get to that, right? There are certain differences. Women tend to have more pain. So that sort of changes things.

Women have more radiographic change, and that for sure is there. There are differences, and they showed differences in outcomes by gender in terms of rate of change that was subtle. But especially if you're going to compare two studies head to head with small differences, which is what this was about, right? The ACCEED study was adalimumab and secukinumab, where they both work very well. So, you're looking for small differences.

And so, If gender can change things and you have a gender imbalance in the two arms, that's going to change your outcomes if you don't account for that. It could be something to be focused on, particularly if we do more head to head

Yeah, the register, if this is a register you're talking about Jack then yeah, it said, well maybe patient characteristics are different and how they present to you as a physician is different. But this is a clinical trial you had to have this much activity to get in the study and it's not like they were looking for men or women,

they were just looking

for eligible patients. So to me, this seems really that it's very clear that there's a difference in the disease, then maybe we have to stratify more.

Yeah, I agree. And I think more studies to really understand biologically what could be driving some of those differences. I think we have this preconceived notion that there's more fibromyalgia nests in women. And I don't think that's necessarily always the explanation. And I think this study kind of further emphasizes that by showing some of these objective measure differences.

So more biology studies to better understand this would be important.

Eric, else got your floated your boat on this meeting here from the, just looking at the psoriatic arthritis.

Well, did mention the one and the one new drug which was sort of interesting because we've kind of waiting for it is ducravacitinib. I know you have a different way of pronouncing it, but that's okay. It's a TYK2 inhibitor, so we've gone down the path of JAK inhibitors. The JAK family has four different major molecules in a JAK123 and then TYK2, and don't ask me to explain how that happened, but it did. The kind of claim to fame here is that interleukin-twenty three seems to signal preferentially through TIC-two, as opposed to the other JAKs, and we know that there's a lot of intermixing with JAKs and cytokine signaling, and it's a mistake to assume that a JAK target is going to stop one cytokine.

But you know that IL-twenty three has turned out to be a really effective treatment inhibiting IL-twenty three for psoriasis, and so it poses the possibility that an oral agent that blocks IL-twenty three signaling could be particularly good in this space. The psoriasis data was good, it wasn't kind of the same kind of level that we're used to seeing with the you know IL-twenty three antibodies which are approved, and this was the first data with psoriatic arthritis, a phase two study, and the drug clearly worked, but again the skin response was good, but it didn't look like the kind of skin response that you would see if you had an IL-twenty three antibody, which doesn't mean it's a bad drug, it just may be not getting to the place that one might have hoped thinking about the mechanism. That was kind of the hope for this agent. But it was effective, it worked, worked on skin, it worked on joints, very well tolerated, seems to have a very good safety profile. So, more to come, but we'll see.

One of the interesting safety things to me was the acne. We talked about this a bit you know is this just because it's dermatologists picking up acne you know why is that different we don't see that with other IL-23s we don't really see that as much with the JAKs so it's kind of interesting and it will be interesting to play out in the phase three studies.

Yeah, there was acne in the psoriasis study and it was it was definitely skewed towards the treatment arm and not the placebo arm. And I went back and looked at the paper and they postulated, you know, that maybe it had some effect on the skin bacteria that sort of evolved with acne and did that, but it's all speculation. I don't think anybody truly knows. There's no good mechanism.

And you say acne, but boy, I'm surprised. I'm not surprised, it really bothers people. Know, you've got a little bit of steroid and they get some acne and that's all they want to talk about, you know, is the acne. So it's like, I'd rather have the psoriasis.

And we don't know how much acne they really had. As Alexis said, they were dermatology studies, dermatologists, no acne, right? And so a little bit they would have picked up and said, Yeah, there's some acne here, but I don't know how significant clinically that was, we don't know.

So we'll take to parallel the development of all the IL-twenty three, tildeckizumab, the mirikizumab that they're in skin trials that have just been reported or approved. Is that why tick is going to pave the way? It means phase two, it gave a 64,020 response that's all well and good. But I think that they need to go to the next level one go look at this particular side effect, but also to can show that they really are going to have the staying power, either with the skin or with the joints.

I mean, it's not going to be any better for joints and anything we have already. Mean, because it you know, looks a phase two trial that 64,020, you know that the phase three trial isn't going to be better than that, and it may likely be not as good. So it's going to be good for joints. The question is, what's the hook? Is it better for skin?

Is it safer overall?

I think they're hoping for a filgotinib like sort of angle that they can make the claim, yeah, we work, but look at our safety data. Our safety data looks really, really good. I'm just speculating right now. I'm sure you do too, plenty of people that are taking the approved JAK inhibitor and doing great with their skin and their joints with really problematic disease. That's what you're looking for.

I

have a feeling the target here is going be a premilast. In fact, in the psoriasis skin trial they did they compared to a premelast that was they haven't published yet but just had a press release for. So I think that that might be the market they're going to target to for this. I don't know. Mean this is all speculation as well but I think that may be where it lands.

So Jack I was gonna have to follow-up on that. You've been on the FDA panels. How much evidence will they need to say well you don't need to check lab tests? I mean that's a premilast big niche. That's a big seller for that drug is you don't have to check blood tests, but this is a JAK inhibitor and JAK inhibitor you have to take blood.

So what's the threshold?

I think they go into this, Arti, it's just like when you were on the FDA session at the ACR meeting, along with Nikolay and others and I asked them how's the tick to going to be treated as far as VTE risk and he went like this. But I really what he was saying was, it's going be treated the same until we learn otherwise. They're expecting that this is going to be a lab monitoring drug. Of course, they have to do the labs, but they're going to have to show a premilast like safety in labs where nothing budgets. The CBC doesn't change, the chem profiles don't change, there's no lymphopenia risk, there's no CK, EMEIA that people are worried about, the lipids are not an issue.

They got to prove a lot and I think that's a betting man, I'm not betting on that.

Well, and let me ask Alexis and Eric, a difficulty is in PSA, I think you see less problems lab wise than you do in RA with the jacking ups. Everything is a little bit better, right? I think the CK signal is less and so I think you're proving it by disease because there's no, I mean, do cravastatin may go into lupus and other diseases but I think it's not gonna go into RA that I'm aware of. So where are gonna get the compare?

Yeah, I think the LFTs are always an issue in psoriasis and PSA because they're fatty liver disease, so we'll see if this has an impact.

Yeah, but I sort of agree with Jack. I mean I think that know, Apremelast got a pass because they didn't see any issues and it had nothing else that was sort of comparable, they could say it's a different drug. So the only way even if they don't see any lab abnormalities, and even with the VTEs, the only way they can get that past the FDA is to say, No, no, no, no, it's a TYK2 inhibitor. It's not a JAK. We don't really consider it a JAK inhibitor, because look at upadacitinib.

No VTEs in the clinical trials at all, no signal whatsoever, but the label carries that risk that is pulled over from the other drugs. It's really going to come down to whether the FDA decides this is the fourth JAK inhibitor that we're inhibiting, or they're willing to say it's a different molecule.

They'll say no, we're not a JAK inhibitor, we're a tickinib.

That's exactly right. We're presenting two doses for you for your consideration, like all the other jacks that didn't get two doses.

I don't know, we'll see.

Right. Well, waiting on filgotinib, they got two doses in Europe. I'm betting they will not get it whenever they get approved twenty twenty one-twenty twenty two. They got a few things, few hurdles to jump over before they can go over consideration again.

So Jack, think we're about at the time that we're looking at you want to anything final or you want to run the panel, the final thing or I think we're almost at the time.

I think that this was really an interesting discussion. And I think that the one thing that this panel of experts on psoriatic disease could tell us is what's the best way to treat anthocytis? Let's go around the horn. Alexa, you want to take a stab at that? Alexa, I'm sorry.

I think in addition to treating the whole disease with a biologic or whatever you're treating with, I do think that actually physical therapy rests as needed and sometimes for the Achilles in particular a boot is sometimes needed especially when it's really robust and NSAIDs. So I think that treating just with a DMARDs, CS DMARDs, whatever you choose is not enough, think you have to do the conservative route as well.

If you're asking for treatment, Jack, I mean all the biologics work well on anthocytis and I don't see a distinguishing feature there.

Alexis stole mine. I was going to say non steroidals.

Other thing that wasn't at this meeting, but it's sort of trickling in the background '20 is '21 is the year of JAK inhibitors for spondyloarthritis in general, that we're going to get upadacitinib now all of a sudden for psoriatic arthritis, we're going to get, upadacitinib for ankylosing spondylitis, we're going get tofacitinib. First six months of next year is going to be JAK inhibitors and spondyloarthritis like it was an RA a few years back. The use in RA has kind of set the stage for that. So I think it's going to take over even faster.

So I have one more question I have to get in from because you guys are the experts. What do think of the TYKOSPA study? I mean, tight control and spondyloarthritis and usual care was as good as tight control in the primary endpoint. What's the deal with that?

I think the primary endpoint is the deal with that. So I think that if you're targeting disease activity along the way, but your outcome is something different, I mean, I understand why they chose that because that you ultimately want to improve how the patient feels. However how the patient feels in terms of their quality of life is impacted by many other things. It's a multifactorial outcome and so now you've kind of gotten one piece into a big piece so I'm not sure that's the best way to look at it. Clearly they did better overall but it just didn't meet statistical significance.

I'm skeptical about tight control and axial SpA altogether one of the goals for tight control in rheumatoid arthritis has always been better long term outcomes, less structural damage, better function in the long run, and when we're working with drugs that we just don't know truly change those outcomes, I mean the the structural benefit from biologic therapy and axial spondyloarthritis is, if anything, very tiny, and I'm not even convinced it's really that in a lot of people, and so it's all about symptoms. When you treat somebody, you know, then the Brooklyn hack is good enough. If you're doing symptoms and the patient says I'm good, then you've treated their symptoms. They're in tight control, and doing a measure that puts a number on that may not get you any further.

I think that the most notable thing to me about the presentation of that was it was incredibly cost effective. Although insanely cost effective. It was like a couple of thousand dollars for a quality.

Know. If you don't count the biologics nor the visit costs, you get extremely cost effective.

Wait, the biologics that cost how much do you get? I mean you have to count that. They don't,

I mean, that's the problem. And there's just no way to believe that it's cost effective in The US with the cost of the biologics. Study you

have, that's a really good point.

I have more people on biology, you know, you go to a tight control approach, and it's set up to drive more people to biologic use, it's going to be more expensive. The problem is a tight control there in Europe and in countries in Europe is the cost analysis is different, because they can roll in societal costs, are they at work and in The US, that's a separate issue that the cost, you know, the cost savings by keeping people at work and not out on disability or not out on short term leave, that doesn't get accounted for in your insurance costs and the cost of treating somebody. And so there's just no way to put all that together. And given that if you don't account for that, there's no way that tight control with more aggressive use of biologic could possibly be cheaper.

Yeah, it's not.

Right, well Jack, you want to wrap us up?

Yeah, I want to thank this panel of psoriatic experts and contributing greatly to the RheumNow audience. And by the way, you all look wonderful having just survived a four day virtual meeting. It's just sort of amazing. So congratulations on all your hard work.

Fun meeting. Thank you, Jack, by the way, RheumNow has done a great job during this meeting and the coverage was phenomenal.

Right, enjoy.

All right, bye.

All right folks.

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