ACR 2025 PsA Topic Panel Save

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

Did you know that the subcutaneous formulation of Cosentyx, secukinumab, is included on most formularies for privately insured patients? We are committed to making sure your patients can start and stay on Cosentyx. Our dedicated team of experienced professionals is here to make onboarding seamless and efficient for you and your patients. We'll help your office navigate health plan coverage and reimbursement processes so that your patients can get started on Cosentyx quickly and successfully. Want to know what Cosentyx can do for your patients?

Visit cosentyxhcp.com to see the data. Cosentyx for subcutaneous use is present on formularies as either a first, second, third, fourth, or fifth line biologic. Novartis does not guarantee payment or coverage for any product or service. Actual coverage and reimbursement decisions are made by individual payers following the receipt of claims. Coverage information is subject to change by the relevant payer.

Hey, how are you doing there? This is Doctor. Arti Kavanaugh from San Diego. Just back from the ACR convergence here for RheumNow. Have a very esteemed panel of colleagues that are gonna talk about some of the topics on psoriatic arthritis that were either at the meeting or talked about at the meeting.

So let me ask my panelists to introduce themselves, starting with Doctor. Pope.

Hi everybody, Doctor. Janet Pope, rheumatologist from Western University London Canada. Another great meeting in Chicago and great weather.

Tony?

Hello, I'm Anthony Chen, rheumatologist from the Institute of Reading in UK.

Okay, Elaine?

Hi everyone, I'm Elaine Hussney, rheumatology from the Cleveland Clinic and boy it was really nice weather actually, It's really great. Hard to stay inside.

Alright. So let's, hit it right away. We'll ask Doctor. Pope to start us out. What what really got your attention?

Okay. So this was a good one because we're always asking for head to heads and hopefully it'll inform clinical practice and sometimes change it. So this was asking after a TNF inhibitor and psoriatic arthritis. So they might have been a primary non responder rare, an intolerant rare, usually a partial response or a secondary loss of response. These patients were randomized as secukinumab or used to kinumab.

So thinking an IL-17A inhibitor or a twelve twenty three inhibitor. So it was a large RCT. This was late breaking zero six poster. And what it showed was on both the PASI and the ACR fifty that secukinumab took home the trophy. Why is this important?

Because I think we've always thought that ustekinumab and secukinumab might be about equal on skin. In this case, they weren't in the psoriatic arthritis trial, but that secukinumab, we always kind of assume IL-17s are better than IL-1223s. Can I generalize this to other drugs such as IL-23s, risankizumab, gilsulcamab, etcetera? Maybe, but I don't know. They'd have to have their own head to head trial.

But what surprised me most was not the superiority on ACR fifty. I kind of would have guessed that, but that PASI also did better. Will it change our practice? Not so much because I'm already using IL-17s, A's and AF inhibitors and I don't use twelve twenty three too much. It's usually if derm prescribes it and they're doing okay on my end of things with PSA, I just keep it going.

Yeah. And as you said, loved head to head studies. This one was done with a purpose though, right? This was done because the German authorities wanted this because now, of course, there is generic or biosimilar ustekinumab. So they asked the secukinumab to say, showed us that you are better, and it did, come across as better.

Lane, Tony, what do you think?

Yeah. You know, like you said, we always want the head to head. And sometimes we really focus efficacy, but I think sometimes we have to think about safety, right? Because sometimes we differentiate on safety. So now in terms of joints, we never can get that ACR 100.

We're all kind of going in that middle ground where a third are not responding. So maybe based on safety issues, this would be interesting too. As we know IL-seventeen sometimes in our IBD patients and others, we tend to stay away from that. So that might be also helpful.

Yeah very interesting post. I mean the primary outcome was HAC, HAC DI rather than some of the other traditional outcomes that we measure. I suppose they just wanted to show a difference or improvement in the well-being of patients. Small number one hundred and nineteen patients probably not powered to show some of the changes if they had the other outcomes.

Yeah I think that was also from the authorities. I think they asked for that and of course the ACT is really relevant. So hard to argue with that. More arthritis driven, isn't it? Then other domains, particularly skin and nails.

I don't know. I bet they do contribute some, but then I bet it's not a lot. Alright, Doctor. Chan, what was your, what struck you as the top?

Yeah, so there were a lot of presentations on GLP-one receptor agonists at the conference. The one that I was interested is 2687. This is from Lihee Ede's team from Toronto, and they looked at people who were treated with GLP-one receptor agonists in the PSA cohort. This retrospective analysis forty eight patients and there was a marked improvement in not only their weight but also their depths tender joint count LDL EQ5D and also systolic blood pressure. What was very interesting that 1% body weight loss accounted for marked improvement in some of these outcome measures so it's not a lot that you have to lose but every little helps.

Janet what do you think about that?

I think it's really interesting. I think we always have to try to untangle weight loss yes versus no, a lot versus a little, and then what happens to the joints? It's the same in the big OA study with the SGLT or sorry, with the GLP one. They said it could have been independent of weight loss, but most people lost weight. Even the control group lost a bit, but most people lost weight.

So it's hard for me to link it. And I think the bottom line is if our patients are high BMI, obesity, or overweight, I think recommending weight loss, however they can safely do it, might in fact impact positively on their PSA, probably PSO, possibly mental health, etcetera. So I think, you know, why not? And if you can get access and you meet criteria for getting access, why not try and see if you can approve the disease, but don't abandon your other drugs.

How is that working? We've got a relatively diverse group of us here. Access to these medications. I have to confess, I've not I've tried to write them a couple times. That has not been successful.

Of course, I think I, like we all

had a rough one.

Quite a number of patients who are on these medicines written by other providers. But it's I I I don't know. How is the access to it? Because it sure seems very compelling data that weights bad and if we can have something that really helps them lose it, that should be good.

So we have some private plans that will cover it. I have some patients paying out of pocket, but if it's an indefinite thing, it's pretty tough to pay indefinitely. There's compounding pharmacies for when there's a shortage, and soon some of these drugs, not all, but soon some will be off label, and that might lower the price, but it's not easy. Diabetes, no problem. Obesity is a very variable coverage for us.

Anthony, what about you?

Yeah. Mainly in in The UK for it to be prescribed is in the diabetes and BMI, high BMI greater than 30. But a lot of patients are taking a private prescription so those who don't have diabetes or may also just use it just for weight loss. And some of these patients have concurrent PSA and we've seen a very good improvement in their joint symptoms while they are on this treatment not prescribed by us but just concurrent treatment with GLP-one receptor agonists.

Doctor. Hastie, what do you bring up in Cleveland?

Yeah, I agree. There's probably not a clinic that goes by that someone asks me about it. That's number one. And do I prescribe it? Like you, Ardi, I don't prescribe it as much generally, but people do ask.

What I am struck with is the enthusiasm for people to pay out of pocket for this actually, compared to any of my other drugs that I give. So I think it's gonna just get more and more popular. And like Janet said, a lot of my patients are saying, is it okay, I'm going to this place that's doing micro dosing or I'm getting it online and all I have to do is video with a doctor and I'm getting it. So I think we're gonna be really charged with trying to understand, is that okay? It's a GLP-one, but in different forms, I don't know what micronizing actually means, but people are doing it.

So whether or not we approve or not, I think we have to really think about this. But I wanna be on one. I'll take it.

You're thin, you don't need that. Send it to me. I think the microdosing is fascinating because the I guess one of the downsides people say is you lose a lot of weight and then you stop and it comes right back. And so the maybe continuing it long term, maybe for very long term on the lower dose to maintain the benefits that you have. And I think that was a fascinating point.

People can't afford the copay for their biologic. Right. Copay for the VOP. That's a different story. Incredibly tangible results.

I know. I mean, for some people, boy, it has been I don't know if you you all think it's been it's been it's they're different people when they come back, and they've lost thirty, forty pounds. It's just that everything is better. Right, Doctor. Husni, what caught you here?

Sure. I wanted to talk about abstract five twenty nine. This is with Anna Marie Orbi with a abstract titled anti PAD2 autoantibodies in psoriatic arthritis. Why I like this is traditionally we don't think of psoriatic arthritis as having any autoantibody and we don't order rheumatoid factor, we don't order CCP. And so this now is kind of challenging that notion, I think.

There's recent studies that show that B and T cell auto reactivity, For this one, it's specifically to LL37 where they undergo a PTM, a post translational modification, which is responsible for the citrullation and the carbamylation, which we all know about in RA, but now we're looking at PSA. So they took an ELISA assay, they looked at about two hundred patients with psoriatic arthritis and seventy five controls, and they found a difference in this anti PAD, autoantibody. They found twenty nine percent in the PSA group versus nine or nine point three percent in the control. So they saw that in addition to the presence of this PAD antibody, they also correlated that that group had more joint specific active disease compared to skin disease. So now we're like, can we use this to stratify a certain type of PSA phenotype?

So I thought this was really interesting because it really raises this question about whether this can serve as a biomarker of joint dominant PSA subtype.

Yeah, we don't think of it. It's funny, isn't it? I mean, it's an autoimmune disease, but without the autoantibodies, we sort of kind of put it to one side and throw it in with the type one notopathies because of the lack of autoantibodies, but maybe we haven't just found them as of yet. Doctor. Chan, Doctor.

Pope, what do you think?

Yeah, really interesting. I mean, if the literature is similar to the rheumatoid, this should predate the onset of the arthritis by many years. And if we can find this in the, our PSO patients much earlier, then there could be that, there could be where this prevention type work could be done because at the moment it's these people already have arthralgia so maybe they're not really prevention they already had PSA. Right

and it's only one third of patients so I'd like to see it reproduce somewhere else. Number one. Number two, it makes sense. Glycosylation of proteins will give antibodies. This happens in RA pad four.

So the whole pad two idea makes sense, but I wanna see it another group and I wanna know if the rates really are twenty nine percent versus eight percent because we'd still be mostly seronegative, but it's kind of a cool idea.

Yeah, that's why it caught me. So, you know, hopefully more to come, you know, maybe other auto antigens that we can find, the antibodies that we can find. So thanks.

Alright. Well, I'm gonna go off piste a little bit and talk about something that was not presented at the meeting, but it was certainly talked a lot about at the meeting. That was the AFFINITY study. So the AFFINITY study, remember that kind of follow on to Vega. Vega in ulcerative colitis was the twenty three inhibitor gazelco mab, the TNF inhibitor glemmab, or the combination.

And these results are a couple of years old, spectacular results in that it kind of really single handedly resurrected the idea that combination biologic therapy may be something that we can think about. The AFFINITY study, was an offshoot of that in psoriatic arthritis. They had two of the three groups. So it was gazelkumab monotherapy, and they're relatively small, thirty two patients or combination therapy, gazelkumab and galimumab. Primary outcome is kind of interesting, was the, MDA, at week 24.

The results have been publicized, so we've been able to talk about it. Although I said it wasn't presented as an abstract at this meeting, but I think we're going to be seeing the data, and we want to see it in more granular detail. It didn't meet the primary outcome. It was 22 versus twenty nine twenty nine versus twenty two percent achieved MDA, so it, was not statistically significant. But, there's some information that looks like, as we saw in Vega, maybe if you look at the higher levels, so here if you looked at people who entered the study with a little bit of elevation of the CRP, they actually did better.

They had significantly improved chances of getting the MDA. And that's what we saw also in the VEGO, is that it was really the higher levels of response. So the MDA is a really good and high outcome. And then the safety, there's small numbers, but the safety looked really good. So I think combination therapy, we talk about it, and I think it's something we're going to see.

We got to see more data with this, but now I think it's back open. We can really entertain the idea of combination therapy in psoriatic arthritis and in other conditions. What do y'all think? Janet, what do you think?

I think it's really cool. And I think that it was the old studies of TNF and IL-one and Avatacept with our old drugs like TNF that really kind of said there was no added value with increased infection. I think we gotta get beyond that now with different MOAs combining them makes sense, and let's go for it. Let's design trials, and let's follow what they do in GI with Crohn's.

Okay. Doctor. Husni, what do you think?

Yeah, I definitely have patient groups that I'm struggling with right now where I'm really looking to do combination therapy, but maybe just a little squeamish. So needing the affinity data to help me challenge myself to get there because these patients are probably using too much steroids, not having the quality of life that they deserve. Can you remind me if there was any safety signals in Affinity?

They you know, they they and that's why I really wish it was an abstract because it was it's really just a press release that was actually released in Europe more than here. So kinda everybody heard about it. They didn't they they said there was there was not a lot that no serious and no opportunistic infections, no TB, and they said no new safety signals, but they didn't I have at least I haven't seen the actual data yet, but absolutely wanna really, really hit that first and see if it's truly good safety profile that we saw in Vega.

Yeah, it'll be interesting to take note, so thanks for bringing that up.

Doctor. Chan, what do you think?

Yeah, really interesting. We've had a few posters last year and this year on combination, mainly in IL-twenty three and Pramilous groups. But I think there's this cohort of difficult to treat or treatment resistant or truly treatment resistant where they still have objective signs of inflammation despite one biologic. I think that's you know this is where the opportunity comes. It'd be also interesting to see what the impact is on these complex to manage people when we use this in the longer term.

Although at the moment we're probably just focusing on the treatment resistant.

Yeah it shows that we do need to think about what is treatment refractory? What is complex demand? Maybe we do have approaches for them. All right, go back to Doctor. Pope.

What else?

So Other I have some really fast honorable mentions. So LB09, the poster, another head to head. So it was post TNF and they were randomized the TNF or IL-seventeen and there was no difference. So that's important because if the patient has say IBD as a concomitant problem, you'd probably go TNF to TNF. It's important if say a woman is contemplating pregnancy TNF to TNF.

I suspect it's a failed trial because I think it was actually planned as superiority to IL-seventeen, but this is very different than our NRA where TNF to TNF is never as good in RCTs. I don't know at an individual level, but in RCTs and RA TNF to TNF, you're better to go TNF to other MOA. So I think it's kind of telling.

Yeah, that's, you know, I think in, in those studies to me highlight the difficulty in primary failure, secondary failure. I think we all know what that means, but it's really hard to write it down and it's even harder to mandate and put that in the study. And I think in general, if somebody really, I don't know, but to see what you all do, if somebody gets on a mechanism, TNF has absolutely no response, which isn't common, I'd be less likely to go. But how do

I And they they did say, Arty, that the primary nonresponder is very rare. It's always less than ten percent in any study. They didn't do well. You they should go out of class in the study, but that wasn't a primary. It was an observation that makes sense to me.

Wasn't a primary outcome or anything. Doctor

Chan, what do you do over there?

Yeah, now that we've got more choice, I think we would switch to a different mode of action if you hadn't responded to the first TNF. The only ones are those who are secondary failures where they have a long periods where they were responding to a TNF. May consider another TNF but in general changing mode of action.

Okay they're not mandates to try or where you go with your second choice?

That we will go by mainly the grappa sort of pathway where we go down and say which extramuscular skeletal manifestation you have or which type of domain you have.

Doctor. Husney switcher or God, these

are the pros and cons, right? We want more therapies. Now we have it, now we're like, okay, how do we use it, right? It's like a problem we created, right? Because we now know so much more about the pathophysiology of psoriatic arthritis.

So I think in general, I do believe in shared decision making. I think patients have a voice in this. Some people understand this is a long term disease and they might not wanna be switching, switching, switching. At the beginning, they might wanna stay with one class, really exercise, maybe one other switch before switching MOAs. But like Antony, I'm probably someone, if there's really primary no response, I mean, I gotta switch mechanism of action.

And sometimes I see a lot of women patients too, that are doing family planning and sometimes we go back to a particular TNF as we all know. So I think it's really nuanced, but I found that adherence has been really helpful when I really give them the lay of the land. Hey, I really don't have the specific head to head to know what the next switch is. These are our options, and I think I do get a lot of more buy in kind of explaining my thought process with them.

Yeah. I I think it perfectly well stated, it's complicated, which I guess is good because chat GPT won't replace us in prescribing what medication for which patient. It's just there are too many moving parts, like you said. This is really complex, and of course, has to absolutely positively involve the patient in the driver's seat of that. Doctor.

Chi what about your second abstract?

Yeah the second one is a late breaking abstract LB20. This is the ducrevacitinib. This is in the BioNaive PSA patients. This is the fifty two week results. Essentially it works.

The ACR twenty, fifty and seventy follows the sixty, forty, 20 rule. At fifty two weeks they had people from both the poetic PSA1 and some from PSA2 because some in the PSA2 study were also naive. Essentially at sixteen weeks when they crossed over the placebo group caught up at 52 and no new safety signals. So reassuring data and the primary outcome is ACR20.

Okay so what do you think, you know there's a couple of, there's the TYK2, there's another TYK2, we of course have a couple of JAKs and I think in other parts of the world, there are more JAKs than we have available to us here. Do we group these? Do we differentiate them? How is that going to and these data, just tell us, hey, this is another option? Doesn't tell us that much more than that?

Yeah, at the moment we don't have head to head studies. This is one of the issues with these. But I think it's another option really for us to have in our treatment.

I just think that oral option, I don't know, you guys think that convenience and adherence with an oral option, some of the younger patients that just don't want to do injectables, So that's that oral niche that this may fill, I think, always thinking And about whether or not this safety, just going back to safety issues, if this one may differ from the other JAK, know, his ears are little more specific, you know, is it gonna like have more tissue penetrance? Is it gonna have less of the black box warning that we're afraid of with the other class? So, so much to think about.

Right. So I fully agree safety. You don't have to follow labs. They don't have the warning, but FDA had mandated in PSO that the tick to do crevastatinib has to do a a big outcome trial. I think it's all enrolled.

It's in psoriasis. And we have to remember that really the tick to seemingly by my guess and looking at data, not head to head and JAKs and TNFs all are about the same on joints. Maybe some JAKs are a little bit better on joints depending on how you do your outcome. And they're about the same in the doses we use on skin, but they're not as good on skin as say an IL-seventeen or a twenty three, etcetera. So I think it's a great option.

Someone asked at the presentation, what about MDA being slow? I think it takes a long time to go from a high disease activity to minimal disease activity in, like, however many you need, three out of five or five out of seven, whatever. Of So it takes a long time. So I didn't think it was slow at all, but I was I was chairing so I wasn't going to butt in and make my own opinion. So I will now.

Okay, Doctor. Husky, what about your other abstract?

Yeah, well, I wanted to switch gears if that's okay. I also wanted to highlight before I go quickly into the abstracts, there was a great session, I'm gonna talk about sort of beyond skin and joints, and I'm kind of, it's one of my passions, I'm really interested in looking at non traditional sort of fatigue, brain fog, pain, the other symptoms of psoriatic arthritis that we see a lot in our office. But there was a session on Sunday, before I get into my abstracts, 01:00 that was called Physical Activity Stress Management and Nutrition to Improve Outcomes in Bringing the Science to the Clinic. So I just wanted to give a shout out, that was Brian and Sarah and Neha giving little tidbits on movement, stress and nutrition. So that's Sunday, hopefully you guys can go back and on demand to see that.

So along those lines, I just wanted to do a quick round robin on abstract fourteen twenty one and abstract twelve forty one. So the first one is to deal with brain fog. So, a lot of us, we hear the symptom and you're sitting there like, Oh boy, what are we gonna do with this? So they complained about this, but in this particular abstract, it just showed that about ten percent of patients are reporting brain fog and it increased to about sixteen percent in patients that were not fulfilling MDA. So these symptoms of brain fog correlated with higher rates of fibro, fatigue, anxiety, and depression.

And this kind of thinks about the concept of whether neuroinflammation could be part

of

our psoriatic arthritis patients, and maybe highlight that need for that holistic management. How do we get into true remission? Should we be screening more for this? And then I'll quickly go into the second abstract, which is twelve forty one, which is looking at pain catastrophizing. So another symptom that we see, patients that come in and the sky is falling.

So in this particular abstract, they showed that it was about five point five percent of all patients. And those people tend to have lower odds of reaching DAPSA, so reaching that low disease activity, they all have worse quality of life. And this persisted even after controlling for pain intensity and depression. So catastrophizing seems to be an independent determinant of disease burden is what I saw in these two. So I just wanted to highlight some of these nontraditional.

Love to hear from the group how you may be dealing with this and maybe screening for this in your office.

That's a chance. I actually think brain fog is contagious because when the patient uses those words, I sort of glaze over a little bit, and I think they lose me for a little bit. But it is important to the patients. If it's a neuroimmunomodulatory pathway, maybe we can do something specific for it. You know, doctor Chan, doctor Pope, what do you think?

Yeah. He said

brain fog from the just discussing it. Give them both brain fog. I can tell.

I think for a long time we used to put lump all of this as non inflammatory pain or non inflammatory pathways but in fact there might be an immunological you know system behind all of this that maybe it's not all non inflammatory we just don't know this is the whole idea that you can have an inflamed brain in maybe down the metabolic pathway in PSA one of these pathways and I think it's great to discover these things and then hopefully find a treatment.

I think as well in some other diseases such as lupus brain fog and Sjogren's that brain fog is a big complaint and you kind of think okay traditionally we can think if you have chronic pain you don't sleep right Even when your pain improves, your sleep cycle is so disrupted that it's kind of like this feedback loop. However, some people have said, and again, I don't know any data like this in PSA, but if they've been say very successful CAR T and say an early lupus patient who was quite sick, that the brain fog goes away or that if we get a highly effective treatment, not everyone, but some of them, and it takes time, it's slower than the other, you know, tender, swollen joints, skin, etcetera, but that the brain fog can improve. So there is obviously something to it, and I do believe it's more than chronic pain, and I think it could be neuroinflammatory pathways, or it could be a whole different hardwiring of your brain because you have pain, you can't sleep, you might be at risk of job loss, etcetera, etcetera. I think it's really kind of difficult to know.

Yeah, and ties it in maybe some of the things we were talking about before. IL-seventeen certainly has a central role, besides just the role in the synovium and the gut, etcetera. And I you know, now that you mentioned that, I'd be really interested to see now that we're gonna look at studies, go back to the GLP ones and weight. What if you treat people and they get better in all these domains? Does this get better, and what does that tell us about it?

Wow. What do all bet? Interesting. Mhmm.

Right. People do feel better, though, when they lose weight. I've I've seen patients come in and because they got motivated and felt better, then they started going to the gym. They started eating healthier. They started going out more with their friends because I think sometimes when you don't feel good about yourself and you have no energy and you're fog ventilated.

You basically kind of become insular and their world expands. I'll tell you, they look better and they feel better. Look better not just by BMI, but they they look happier, they look healthier, and feel better.

Yeah, think these sort of, non weight benefits of GLP-one that we're all describing, I think is just gonna explode and really excited to learn more about that. The one sort of overall take home point I wanted to make with highlighting these abstracts is we are so good at, someone comes in with psoriatic arthritis or RA, we have that pharmacologic DMR that we know what to do. Would it be reasonable to think that every time you do a pharmacologic DMAR that you think about a psychosocial intervention as well, as part of that holistic care? It doesn't mean we have to take care of every pain, fatigue, brain fog that happens at each visit, but maybe perhaps every time we think about handing that DMARR prescription that we do so well, what is one lifestyle pillar or factor that you could also give with that patient in that visit.

Great. Thank you all. Important stuff. This is the room now and it's ACR twenty five topic panel on psoriatic arthritis. I'd to thank my colleagues, Doctor.

Chan, Doctor. Pope, Doctor. Husney, Arty Kavanaugh, and we will see you next time on RheumNow. Take care.