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- [00:02]
A
Welcome to season three of Terms on Drugs, a video podcast brought to you by Scholars in Medicine, the best educational platform in dermatology and provided at no cost. Medical providers Terms on Drugs is where cutting edge Durham meets hit or miss comedy. I'm Dr. Matt Ziers from Dr. Dermatology and each week I'm joining my residency buddies, Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. And we use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. There's everything you need to know to be in the cutting edge of dirt and you'll actually have some fun listening. New episodes drop every Friday and Scholars in Medicine, Apple Podcast, Spotify and other major podcast platforms. And I highly recommend that you download the Scholars of Medicine app to access the full podcast video archive and explore the best medical derm educational content out there. Real pharma independent coverage of all dermatology, supported by an amazing AI clinical consultant called Ask Science. Simon and I want to thank Johnson and Johnson for sponsoring this week's episode. And I am so excited. This week we've got another one of our patented deep dive episodes and we are going to get into psoriatic arthritis, but we're going to get into it in a much cooler way than you're used to getting into it. To help us do that, we've got with us a fantastic derm room double boarded position from Mount Sinai. Dr. Sakshi. Khatri Sakshi, tell us how you got into room derm and what your path is. The idea of being double boarded in room and derm. So you did internal medicine, then rheumatology, then dermatology. So you were a resident until you were 47. Is that, is that. You don't look 47 though.
- [01:45]
B
Well, that's all the Botox. That's all the Botox. Right, right. So I was a room fellow in Einstein and I just. Well, first of all, thanks for having me excited to be here. So I was a room fellow at Einstein up in the Bronx and there was just so much of skin that we would see in our patients and we knew nothing. Like, the most that I would do is like prescribe proberosol for everything and that was the extent. And even my room attendings didn't know anything about the skin. We just didn't get that much of exposure. So, so, and serendipitously at that time, there was a joint combined grand rounds between the derm department and rheumatology. The first of its kind. And there was a speaker who was both a rheumatologist and dermatologist. And that was it. It was like a light bulb moment for me and I decided that I wanted to pursue dermatology.
- [02:32]
A
And so you did an extra three years after finishing room or did you. Did some of the room count towards derm? Like, how did it work?
- [02:41]
B
I wish. No, so I did. I was in attending for a year as a rheumatologist. Then I had to do research in Durham for two years because Durham is extremely hard to match. And my room training was, was not giving any brownie points in my application. And then I did a three full year of Durham residency. Yep.
- [03:00]
A
See that's, that's the problem with New York City. If you had been like, in Columbus, Ohio. So our guest a couple weeks ago was one of my former residents at Ohio State. She was an OB GYN and like called me and was like, hey, I feel like we don't know any, like, stuff about the skin. You guys don't know anything. Stuff about the vulva. Can I come spend like six months and hanging out in clinic? And I was like, no, God damn it. You get a residency spot, you can't come to clinic. You've got to start residency. And she was like, okay, man, if a rheumatologist came and asked me, man, you know what?
- [03:30]
B
I did not get the memo. I'm going to tell my room colleagues if they're interested in dumb, to reach out to you.
- [03:35]
A
Oh, I will get him a spot. I will get him a spot. But all right, let's, let's go ahead and get into it. Dr. Farris, let's kick it off with our first paper. What do you guys.
- [03:45]
C
Okay, so I'm going to go over the APEX study. So the title, this was published in the Annals of Rheumatic Disease, a very rheumatology official journal. So this is inhibition of structural damage progression with the selective IL23 inhibitor selkimab. And participants with active PSA 24 week data. Phase 3b randomized double blind placebo controlled study. Okay, so you know what, why did they do this study? I think, like, for all these companies that make drugs, you know, first you get, you get your psoriasis indication or you get your psoriatic arthritis indication. Then you get your psoriasis one. But, you know, then it becomes like, well, you work in the skin, but how do you work in the joints? And then it's like, oh, it looks like it works in the joints. And then it's like, do you have, what about radiographic progression? You know, we get terrified in dermatology that if we don't refer to rooms that were going to miss radiographic destruction and everybody's going to basically be like disabled within a year because we didn't send them to room and that this is the holy grail. So actually one, I can't wait to ask Sakshi about this when we're done. But how did they do this study? So, you know, gel aisle. This is like up until this data came out, like There were no IL23 inhibitors while they were FDA approved for psoriatic arthritis. They did not have data showing that they prevented radiographic progression of disease. And there's even an earlier gelumab study discovered too that did not get them that indication. So apex multicenter phase 3b study. So patients had dead PSA for at least 6 months with active disease. And so, you know, one of the things I think is like important for us as dermatologists is what is active disease? It's like three or more swollen and three or more tender joints in an elevated crp. And then they had to have at least two erosive joints on baseline radiographs. So like this is not just the, oh, I maybe get some, you know, backaches in the morning. This is like people that pretty active PSA. Then they were randomized. They either got Selkimab 100 milligrams every four weeks, you know, or 100 milligrams after the loading dose every four weeks or every eight weeks or placebo and then they would cross over at week 24. So who were these people? They were biologic naive. They were jack naive. They had to either have like a 2cm or big plaque or psoriatic nail changes. So this was not just like they had to have some skin disease. They could be on concomitant metrexate, hydroxychloroquine, leunamine, NSAIDs, even low dose prednisone at like 10 milligrams or less. And then there was an escape arm that they could have like their dmards, their con conventional systemic demards tweaked. And then everybody got radiographs of their hands and feet at baseline in week 24. And then they were scored centrally meaning like it wasn't the investigator doing it, but a central, you know, I guess radiologist looking at the, the modified Vandar Heidi Sharp score looking for erosions and joint Spain narrowing. Two readers. You know, so pretty like rigorous Primary endpoint was ACR 20 at week 24. Secondary endpoint was change in total PSA modified VanderHeidi Sharp score at week 24. Okay, so this was, you know, a multicenter study. Basically over a thousand participants, 370ish in the Gaselka. In each case, alkumab arm or placebo arm. Mean age was 53. Okay. Mean swollen joint count was 12. Tender joint 21. So that's actually, you know, pretty, again, significant PSA. And they had, you know, Vanderheiti sharp scores in the high 20s. Men, meaning that they did have erosive disease. And about 60% of them had a BSA of 3% or more. Meaning that's the reason that's going to be important is that, like, you could actually see, you know, skin changes as well. 40% had dactylitis or enthesitis. And most people were on some sort of demar, mostly methotrexate. So, you know, that's sort of the population that you're talking about. Okay, so how did the guselkumab do? If you look at ACR 20, which is I think maybe a low bar right now in PSA, 2/3 of them on consulkimab reached ACR 20, whereas about 47% on placebo. ACR 50 responses were in the 40% range versus 20% on placebo. ACR 70, 22% in case elcumab arms, 11% on placebo. Across these. I think one of the things I noticed is that it doesn't really seem like there was a better response to the Q4 versus Q8 week dosing. Okay. Radiographically, the sort of meat of why they did this, what did they see? Okay, so mean change in total Vanderheide Sharp score at week 25 was 0.55and 0.54 in the gelumab group versus it was 1.35 in the placebo group. So what does that mean? Lower means, like less progression, less joint damage. So there was more joint damage in the placebo group. You know, the group got placebo for six months versus the Geselki mab. So, you know, that was. That was a statistically significant result. Okay, how about the skin? You know, it was sort of what you would expect. Pazi 90 rates at week 24 were like 69% skin, 60% versus 22% on placebo. Pazi, 100 responses around the 40% mark. And then nails. They actually did see modified napsi improvement of about 40, 36 to 43% in the active arm. And it actually got worse in the placebo arm so did get improvement in nail disease. They did look at things like composite outcomes like minimal disease activity. And that was achieved by 30% in the. In roughly in the Gelumab arm versus versus 13%. So that was like, that's a, that's sort of a, you know, a combination of both skin and joint and lab changes that showed minimal activity safety. There's kind of nothing really to see. It was what you expect with an IL23 inhibitor. So I won't go into that. So I think, you know what's interesting, this is now the only selective IL23 inhibitor that has been shown to significantly inhibit structural progression of PSA. You know, that's only weaknesses. This is only at 24 weeks. Right. This is like a long term disease. This is also a biologic naive population. So what does this mean if this is somebody's like, you know, fourth biologic and then this wasn't a monotherapy study. So you know, I am super curious Sakshi to see, you know, I've got all these questions for you. So A, what do you think? B how important is inhibition of radiographic progression? Is that a marketing thing or is that like the real deal? Something that is clinically, clinically meaningful?
- [11:33]
B
Right. So I will say that, you know, IL23 blockers are excellent drugs. You know, they're excellent in the dumb space. So to have radiographic inhibition from a rheumatologist perspective is super important because we in the room space sort of think of can we minimize progress progression of joint damage that patients have accrued prior to starting systemic therapy. And having an IL23 that's used so much in the derm space now having that inhibition of radiographic progression is certainly helpful. That being said, we also have to understand that you're looking at patients who have radiographic damage from get go. The question about what if somebody does not have radiographic damage? Can this drug potentially prevent new damage from happening? You know, because in today's day and age, not often do I see patients walking into my practice. Whether I'm seeing them from a room perspective or a dumb room perspective. With 11 and 20 swollen joints, tender joints, you know, they tend to be oligarchicular. A lot of the last time.
- [12:33]
A
When was the last time you saw a telescoping joint? I saw one of those whenever, whenever I was in a resident at the va, a guy with a thumb. So for anybody who's not like done a lot of this. So a telescoping joint is when the finger is like so degraded that the finger becomes like a little nub. You can grab the end and pull it out like a telescope because the skin is all still there. When was the last time you saw one of those?
- [13:03]
B
So I do have a couple of patients that have telescoping joints. But mind you, these are patients who've had PSA before the advent of systemic biologic therapy. I have not seen that happen since, since having these biologics for PSA patients. So I think that telescoping fear is all pre biologic.
- [13:21]
A
Okay, all right, all right, all right, go ahead. Sorry. So these bs, these are people with bad disease.
- [13:26]
B
Exactly. So you're selecting a population with bad disease which perhaps does not represent the patients that we see in our tractors. I mean that being said, to have that inhibition of radiographic damage is super important, especially if a patient has radiographic damage to begin with. Because in that scenario I will reach for a systemic therapy that has that inhibition of radiographic progression as opposed to other MOAs which might not have that.
- [13:51]
A
So do you first, do we have. So, all right, let me, let me start by telling you where I'm coming from. I'm like, look, I'm a dermatologist for God's sakes. If your joint hurts, I'm going to be like, okay, like here's a drug that I think is going to help. If your joints really hurt, I'm going to say go see somebody. Go go see the rheumatologist. But so from a. I don't follow. Psoriatic arthritis. Well, do, are there any head to head trials? Like do we know if they looked
- [14:20]
B
at inhibition of radiographic damage? The answer is no. I mean there are some head to head. Well, there are some head to head trials looking at different MOAs, but generally these are molecules that are produced by the same company and they look at non inferiority, not necessarily superiority. There is a head to head, but it looked at a composite score of skin and joints with superiority at the primary endpoint. But again we have to understand that besides of driven by skin. Right?
- [14:48]
A
Yes.
- [14:48]
B
So it does seem like perhaps for the most part our moas are non inferior to each other.
- [14:55]
A
So that's, so that's what I was kind of getting at. I hear, I still hear people say like, well if they've really got joint disease, I'm going to go to a tnf. Because I think they hear that I'm like, that sounds crazy. Like is like if you had to rank them not like particular drugs, but 23 17s and TNFs for people with meaningful.
- [15:20]
B
I mean, TNFs are like, like my lowest priority or go to. I do not use them unless, of course, they are patients who are just grandfathered in and are doing well, or if there's any other reason for me to consider an anti tnf, which again, from the top of my head, is not that many either, because we have JAK inhibitors that will treat multiple different, you know, immune diseases and so will an IL23 blocker. So really. So I mean, I was going to ask you, which rheumatologist are you talking to? Because I bet you probably the younger ones.
- [15:47]
A
This is germs, this is derm. So they don't know anything about it either. They don't know anything about it either. That's why I don't believe them. I'm like, I cannot possibly.
- [15:55]
B
And. And I DNFs own school.
- [15:57]
A
So do you think 23 or 17s are better?
- [16:02]
B
That's a hard question. I think, I think my answer would favor a 23. If I was looking at a patient with maybe early disease. And I know we'll be talking. I mean, there's a lot of chatter around 23 inhibiting the incidence to PSA in patients that have psoriasis. And then there's also data within the room space looking at retention of 23s and perhaps these patients don't switch to a different MOA that often or that frequently. So I do think 23s are excellent, certainly for a patient that has psoriasis and certainly for a patient that has psoriasis. And you're like, is this subclinical psa, early psa, you know, mild disease where, you know, the infrequent dosing and, you know, the safety, the skin clearance, the fact that it has an ACR 20, 50, 70 response, and now with the 23 having inhibition of radiographic damage, I think it's a, it's a win, win for 23.
- [16:56]
C
And do you think it's derms? You know, there was like this time in marketing where everyone's like, do the pest. And if they might have psoriatic arthritis, you must send them to rheumatology. Otherwise they'll all have telescoping joints in a. Right. And like, we all know that's kind
- [17:10]
B
of not gonna happen. Yes.
- [17:12]
C
Yeah. And I like my feeling. And you tell me if I'm wrong as a dermatologist, is if I get a history, I can get a history that is relatively consistent with psoriatic arthritis versus I know that's oa, right. I'm not going to be able to be like, there's no Vander Hardy Sharp scoring going on in my clinic. But there's like, oh, that's not even
- [17:32]
B
happening in a room clinic. Let me just tell you that I
- [17:35]
C
don't feel so bad. But, you know, so my feeling is if I suspect this is psa, I can give them something that will help their skin and their joint. And if they feel better, I don't.
- [17:47]
B
Yes.
- [17:48]
C
Okay. And like, and the other thing is, when you look at Those patients, like, 20 swollen joints, those are not the patients, you know, when they're like, whoa, send them to room. Like, that's not who comes to see us.
- [17:59]
B
Exactly.
- [18:00]
C
With like one or two, maybe, maybe
- [18:03]
B
three, four, max, five. Right. Beyond that, these patients are presenting to a rheumatologist just because they have, you know, impairment of their activities of daily living with their bajillion dozen swollen and tender joints. So I totally hear you and I agree with you and I completely second that thought as well. I think, again, you know, in every, like, depending on where you are, how soon can you even get your patients to see a rheumatologist?
- [18:24]
C
I can't. Like, I mean, they get like.
- [18:27]
B
Yeah, exactly. So if we have data that's published from, like, way back when saying that six months of diagnostic delay results in irreparable joint damage, then that patient can't potentially wait nine months to be getting an official diagnosis from a rheumatologist. So I think it should be more like, you know, start the systemic therapy. As long as it's covering psa, that's good. And then patients, if they improve, then that's great. If they don't improve, then see a rheumatologist.
- [18:53]
D
A lot of times insurers just say, like, we're not giving you a 17 or 23. We have these very inexpensive adalimumab biosimilars. And my sense is, like, most of the head to heads, like you said. Yes. When you combine skin and joints, there are, you know, superiority. But for the most part, when they look at specifically like, acr50 scores, the tnfs actually still do. Okay, so if that's what my patient gets, because that's what the insurance says, is there an obligation on our part if we think psoriasis is going on to say, no, no, no, look, we need to get this person on a 17, we need to get this person on to 23. Or like, TNFs are actually okay in the, in that situation. Like, I, I, I don't see myself fighting with an insurance company over arthritis? Because I'm not a rheumatologist, and I think that's what a lot of derms are like. Do we need to put that. Put up that fight? Like, if they have joint pain, we're going to say, okay, maybe it's psoriatic arthritis. The adalimumab biosimilars are what I can get you or you stick in umab biosimilars or what I can get you. That's actually. Okay, so.
- [20:02]
B
So that's an interesting point that you raised because I think coverage for systemic therapy is a lot different in the DOM only space where you just, you know, coding for psoriasis as opposed to in rheumatology, where you might even be forced to giving them methotrexate as first step before they agree to giving a biologic. So I kind of like. My cheat sheet is I tell patients that I'm going to just try to get everything approved for your psoriasis diagnosis because that opens my ability to get you a lot of different moas and. Or perhaps go with my shared. Sorry, let's call it shared decision making. Our shared decision making with regards to a particular moa. And I don't get arm twisted that often into giving methotrexate or an anti TNF as possible.
- [20:43]
A
So you get a more sort of leeway in prescribing to some extent from psoriasis than from psoriatic arthritis.
- [20:52]
B
Yes, yes, yes. Because if I just use PSA often, I'm told I'm supposed to give them methotrexate. And that's the reason why, if you have rheumatologists in the community that you're sort of sharing patients with, you'll hear this sort of, oh, they started me on methotrexate. It's always starting them on a conventional synthetic demon.
- [21:10]
A
Yeah, that answers a lot. Because I always wonder, like, what the hell are those rheumatologists doing?
- [21:15]
B
Thinking. Exactly. Exactly. Methotrexate is not book. It's not even a proof for psa. Like, why.
- [21:22]
A
Yeah. What. So you did mention JAK inhibitors. And so I. I'm curious here. The first time we've had a room on the show I think of. So I. I talk pretty regularly that I. I look at the Zel Jans oral surveillance trial and say, zeljans didn't cause any events. Adalimumab just made the events go down. Is. Is that the general take in the room world? Like, do you guys. What do you guys think of Jax?
- [21:49]
B
Are you guys like, so we, we like our jacks. It's just that we cannot use them first line and we have to use them after using an anti tnf and
- [22:01]
A
that's insurance me like if you could use them first line.
- [22:05]
B
No you can't. So the fda, the FDA approval for say PSA says you have to have tried an anti TNF before you can give them jack. So it's never going to get approved without them having tried an anti TNF first. So we don't have any issues with jacks in the room space. But then I think as a rheumatologist who then forces me to then do the whole methotrexate anti TNF and then a jack pathway or cycle which I, Yeah, when I put my room dom head I'm not very comfortable with because why should I do that?
- [22:35]
A
I always wondered like the, I wish there was a way to like, I feel like it's not unreasonable to try somebody on like adalimumab plus 10 milligrams of methotrexate. That's going to cost like nine grand a year. And if they're the 50% of people that like that happens to work, great, okay, we just saved society like 50 grand. But if it doesn't work. But then I'm like, I wouldn't want to try it. Exactly.
- [23:05]
B
Oh my God. I was, I was going to ask you that. Would you do it, would you do it for yourself? Yes.
- [23:10]
A
For 30 grand to go on the cheap stuff. I'd be like, I'll take the 30 grand and I'll try the cheap stuff. Like we should pay people to take the cheap drug.
- [23:19]
D
No, but put yourself in the, in the, on the insurance company's shoes.
- [23:25]
B
I would never want to do that. They're making millions. Their CEOs make millions in profit. So no, thank you. Absolutely.
- [23:31]
D
But it's not. If you were to say to me, no, no, no, this has to be 17, I'd say show me the study where 17s or 23s went up against Adalimumab and showed superiority in arthritis. Right. And they're, they're. And it's not like those head to heads haven't been done. They've been done.
- [23:51]
A
It's the same as an insurance.
- [23:53]
B
It's always, oh, that's right, exactly. Are you working for an insurance?
- [23:58]
D
I'm, I'm not. And I hate it. Like I, I hate, I hate the insurance, like having to fight them. But when you sit back and think about it, I'd be like, you know What? I would deny this. I would deny this and I'd make them do the biosimilar.
- [24:13]
B
Right.
- [24:17]
A
Next time he's fighting a prior auth, they're going to be like, hit play. He's like, I would deny this.
- [24:23]
C
Exactly. So never get released now.
- [24:27]
B
Yeah, but, but, but the thing is that I don't think that's the same issue in dermatology. So if you're using a psoriasis diagnosis, I am pretty certain that you can get a 17 or a 23 before an anti TNF. So just use the path of these resistance, which is psoriasis.
- [24:43]
D
I think that that depends where you are and who your coverages are. In western Pennsylvania, the coverage is horrible. And they're like, no way. Like, if I try to go to 17 or 23 first, they're like, no, here's what we'll do. It'll be amjavita. There you go.
- [25:03]
C
Okay.
- [25:04]
A
In western Pennsylvania, they. They only have like two insurance products and they're both like super pain in the butt.
- [25:13]
D
You want to go like one even further. So this geselchumab, so the joint progression on the. Probably the biggest cover or the insurance person in western Pennsylvania took geselcumab off the formulary. It's not an option.
- [25:31]
C
It's crazy.
- [25:33]
B
I think, Tim, you should definitely move to the Upper east side.
- [25:36]
C
Yeah, I'm doing it on the Upper east side.
- [25:39]
D
My Internet connection may be better.
- [25:41]
B
Yeah, you certainly will be. And you'll be able to prescribe an IL17 or a 23 first line for your patients without pushing back.
- [25:49]
C
I'm trying to. It is, it is remarkable. But because I used to work at that place. It is absolutely true that they just said we're just not going to let you give gab at all. You're like, oh, you mean like it's not preferred? No, you cannot give it at all. You mean after they failed two things I could give it. No, you may not. We will pay for it under no circumstances. Isn't that just absolutely crazy?
- [26:16]
B
Okay, I'm going to remind myself not to look for a job opening in western Pennsylvania.
- [26:20]
C
No, no, come to North Carolina. It's much better.
- [26:24]
A
All right, so wait, let's. Let's. Let's move on here. So we, I think we've established that there aren't really head to head trials, but we would not want to be if, if I suddenly got psoriatic arthritis, I would not want to be on a tnf.
- [26:41]
C
And we've also established dermatologists can on suspicion of psa treat it with a drug that we know works for the
- [26:49]
B
skin and the joints.
- [26:50]
C
We don't have to send everybody to
- [26:51]
B
room because you don't have to. And if the patients are doing well, then that's about it. If they are not doing well, or if they start stop doing well, then send them to room. But I do think making them wait for nine months makes no sense.
- [27:03]
D
I would still send them. I would still send them to room, though. Even if they got better, I would know, like, okay, nine months, I'm not going to worry about that. But look, there may be subtle changes in the joint exam that as a dermatologist, I'm not going to pick up that a rheumatologist would. And so with arthritis at the outset, even though you're better, I think a rheumatologist should be seeing you somewhere in your care.
- [27:30]
A
See, that's why. That's why Pittsburgh has to keep care so cheap, because Patton is doing all of these unnecessary referrals and running up the cost of care.
- [27:39]
D
That's.
- [27:40]
A
Yes.
- [27:41]
B
So you can either get humida. So basically it's like you can either get humid and see a rheumatologist, or you can get an anti, you know, I 23 or a 17 and just stay with me.
- [27:53]
A
Yeah. No, but either way.
- [27:55]
D
Either way, it'd be like you had arthritis. I just want to make sure that it's being followed up. It doesn't have to be right away because you feel much better, but.
- [28:03]
B
And then you know what happens? The rheumatologist does an ANA and it comes back positive because that's what.
- [28:09]
C
Because that's what they always do.
- [28:12]
D
I check ANAs on all my psoriatic arthritis patients. You don't do that?
- [28:16]
B
No.
- [28:17]
D
Is that a mistake? I'll see.
- [28:19]
C
He's being sarcastic. I hope he does not do that.
- [28:23]
A
All right, let's. Let's move. Patton, let's move on to your. What do you. What do you got, Pat? You know what?
- [28:27]
D
Because we started late because of me, we can skip mine. I mean, it was an interesting paper, but there's so many overlaps. The one that you had, basically it was, you know, interception of disease. When patients have psoriasis, how can we design trials to detect what's the best drug that's going to prevent the development of psoriatic arthritis? And, you know, the, the conclusions were, we don't really know. Here are the factors that we need to take into account. But it was more of just a descriptive. We don't really know what's going on. Here's some great ideas and that's kind of how they ended it. So there's my paper.
- [29:06]
B
Okay.
- [29:06]
C
Yeah. All right.
- [29:08]
B
It was a pretty data dense paper and I will say that perhaps the only thing from the paper is, you know, just a shout out to PAMPA trial. Hopefully we know if early treatment with biologic changes outcome. So.
- [29:20]
D
Yeah, so PAMPA trial. Yeah. Real quick. Geselkumab again versus placebo patients with psoriasis and they have to have ultrasound findings of inflammation and that's the inclusion criteria. And then they're going to do caselcumab versus placebo and are they going to prevent the onset of psoriatic arthritis? So inflammation is not necessarily psoriatic arthritis. Inflammation is inflammation. Psoriatic arthritis is like synovitis. And so is gselkumab going to prevent that versus placebo? And kind of an interesting arm where the, you know, because the placebo group is going to cross over I think at week 24. But there's also this, this observation arm. Those patients aren't going to go on any biologics whatsoever. Topicals and narrowband uvb. And so we'll have a nice comparison of like at one year, two year, probably like what percentage of patients were we able to prevent the development of psoriatic arthritis?
- [30:18]
A
Are they going to enroll like 157,000 people into this trial?
- [30:22]
D
Like, that was one of the points, that was one of the points brought up in the paper. Like, look, if we want to show a 30% reduction, we're going to have to enroll 1,000 people in each arm. I mean, yeah, it's, it's, that's a challenge. It'll be interesting to see what, what that study shows.
- [30:38]
A
Yeah, yeah. All right, let's, let's move on to the one that I had because, and I, I picked this one because it, I think gets at a really difficult question that we've kind of been alluding to here. So it was looking at a claims database and saying how many people. So first, how many people who show up with psoriasis have musculoskeletal complaints like period, not like psoriatic arthritis, like have back pain or arthroges or fatigue or whatever. And does that predict who's going to get a formal diagnosis of psoriatic arthritis? Going, going down the road? Now first, for people who haven't been, I assume the vast majority of our listeners have not done health outcomes based research with claims databases. The first thing is like, you have to take this with a huge Grain of salt. Because it's like how, how rigorously did people make the diagnosis of psoriatic arthritis versus not make it right so much.
- [31:44]
C
How rigorously do you document and code things like back pain or.
- [31:48]
A
Yes, you know, yeah, so it's, it's so much so you got to take it all with a grain of salts. But the big pictures here, number one, half of people who, who got diagnosed, showed up and got diagnosed with psoriasis had musculoskeletal complaints. So things like back pain, blah, blah, blah, which, Right. Okay, so is the back pain axial arthritis? Is that early psoriatic arthritis? Are they more likely to get diagnosed subsequently? The answer there was interesting. No, back PA pain was not a predictor. A formal diagnosis of enthesitis was not a predictor. Now that's though probably one that who the hell's diagnosing people with enthesitis other than if you're like, I think you maybe have psoriatic arthritis. Like, so it's, that one's a little iffy. The back pain one was kind of surprising. But in general, the people who showed up with musculoskeletal complaints or througes arthritis, that kind of stuff had an increased rate of getting eventually diagnosed with psoriatic arthritis. And so I think it gets back to what we're talking about earlier that like if your psoriasis patient shows up and you're like, oh, you got psoriasis, blah blah, blah, oh, you got some back pain, oh, your ankles hurt. Whenever you wake up in the morning, just put them on a 17 or a 23. And if they get better, it was psoriatic arthritis. And if they don't get better, then it was probably osteoarthritis. That's like, is that a reasonable takeaway of the like, it's if they get better, then unless you're seeing a wuss like Dr. Patton, they don't need to go see rheumatologist.
- [33:22]
D
But if they don't, conservative medical care, it's you say wuss. I, I object to that characterization. Thank you very much.
- [33:33]
A
So do you. Is that that general approach seems very warranted to me. And that's again, so.
- [33:43]
B
Absolutely. And I do think that I would probably add another layer of like age because like, if it's a patient that's skewing younger and then they're talking about arthralgias and sort of just non specific joint pains, my index of suspicion for these patients is possibly having PSA is a lot higher because, you know, you don't have like that osteoarthritis mechanical component. You know, anybody who's like 70 who gets sent to me for like ruling out PSA and they've had psoriasis for years, and they might even be on systemic therapy for their psoriasis. I'm like, the odds of you having OA are a lot higher than, you know, active PSA at this point. So I do think as like that age should sort of be also used as a form of stratification in some ways.
- [34:22]
A
All right, so do the tick two drugs or PDE four drugs, do they work for psoriatic arthritis at all?
- [34:31]
B
Well, they are approved for PSA. We do have one TICTU and we've had a PDE4 for the longest time approved for PSA. Again, if you're asking my opinion as a rheumatologist, I do think it depends on where in the PSA disease paradigm you're starting that medication. If it's super early, yes. If it is more established, I don't think them by themselves potentially take care of everything.
- [34:58]
A
Do you think they're as good as the 17s and 23s?
- [35:01]
B
Oh, my God. Well, there's no head to head, so. But, but like in clinical experience, I would say probably not. But then again, if it's a, if it's a patient that has like, you know, some morning stiffness, you know, like big joint pain, and they are, they don't have a swollen joint, tender joint, then they could potentially respond to a tick to and a PDE4 just because they probably had a really mild. I mean, I don't use the word mild, but perhaps they do have MIL disease. But I'm not going to consider it for a 20 swollen tender joint, irrespective of what their inclusion criteria might have stated, because I don't think that they by themselves will be helpful.
- [35:38]
A
So really whittling this down to the fundamental question for me, does joint pain ever really play a role in your therapeutic decision? Like, is there ever a time where you're like, okay, I'm gonna be, I'm
- [35:56]
B
gonna, I'm gonna sound like an ageist when I say that. Younger patients perhaps, yes. Older patients, perhaps no. Just because there's just so much of mechanical OA that comes into play and pain is pain, the body does not cannot differentiate between pain from inflammatory arthritis. And for osteoarthritis, certainly we can ask about morning stiffness to help distinguish between the two. But sometimes patients have both and pain is just a catch. All that being Said we probably should not start to go and discuss fibromyalgia because fibromyalgia can be a thing that can be contributory to pain. And our PSA patients certainly have fibromyalgia. So it's not a very linear. Yes, no. But younger patients, I'll still give pain sort of that importance because I do think it's probably inflammatory. Unless, of course, they were a Division 1 football player or they've had some good, you know, trauma to their joints and. Or they've, like, physically exerted themselves, they're less likely to have oa.
- [36:50]
A
So that means in a younger patient who's got some joint pain, you're more likely to go 17 or 23 and not go tick two PDE four. Is that. Is that.
- [37:06]
B
I am more likely to say that maybe this play pain is indeed psoriatic arthritis, as opposed to an older patient who has longstanding psoriasis and just like. And they have like, some knee pain and their dermatologist happens to ask them now about arthritis symptoms just because that is in vogue. And now because they complain of knee pain going up and down the stairs, they get referred to me for ruling out psa. That patient is perhaps less likely to actually have PSA than the younger one.
- [37:34]
A
Okay, fair.
- [37:37]
D
We've done some stuff with psoriasis and inner class switching versus intraclass switching. Is. Is there similar studies in the room world with psoriatic arthritis? And. And when do you make the determination? What's a good, like, three months, two months, six weeks?
- [37:55]
C
Right.
- [37:55]
B
So in the room world, you know, a lot of data has been taken from rheumatoid arthritis where treat to target is a big thing. And unfortunately, you know, the RA data also talks about triple therapy with DMARDs being comparable to an anti TNF. Right. This was like when I was a room fellow, this was all triple therapy. Oh, my God, it's going to blow your mind. Methotrexate, sulfasalazine plaque.
- [38:21]
C
Now,
- [38:24]
D
I thought lucillinamide was in there.
- [38:26]
B
Well, either of these three, but, you know, it's a combination of these three.
- [38:31]
A
You guys tried to kill people.
- [38:32]
B
Exactly, Exactly. We're trying to give them sjs from sulfasalazine. Yeah, Gas. Right.
- [38:37]
A
They didn't. They didn't come back. They must be better. No, they're dead.
- [38:40]
B
Exactly. Now they need an actual doctor who's a dermatologist. I'm kidding. So in the psorias PSA space. It's a little hard.
- [38:49]
C
It's.
- [38:49]
B
It. It's not clear because historically everything that they did for RA they sort of co opted to psa. And that's why, you know, everybody would get DMAR therapy. I sometimes even see patients in 2026 on sulfur salazine for PSA and I'm like, what are you talking about? This is crazy. But you know, I think rooms tend to be more change averse. So they do like, you know, let's do a DMAR, let's do a combination DMART, then they'll go to an anti TNF, then they'll cycle between anti TNFs before they even think of a different MOA. That's just because they're habituated for doing that from RA. And then the EULAR did come up with some guidelines a few years ago where they did say that, you know what you could consider a switch within the same class. You know, like you could go from one anti TNF to another anti tnf,
- [39:33]
C
but that is there are more switch in class before you move on to the next one. I think we're a lot more like,
- [39:41]
B
let's just move to a different mo. Yeah. Yep, yep, yep, yep, yep.
- [39:45]
A
And the data is bad. I mean there's, I haven't seen that.
- [39:47]
B
Like I. Yeah, there isn't a, there isn't great data now. Yeah, I mean whatever data that's there is, it's sort of. We have data in the PSA space which says because IL23s for the most part, patients retain on them in the real world in registries and sort of claims databases a lot longer or they have the least amount of switch. Now again, you take that information with a grain of salt. Is it because these patients prefer the infrequent injection safety and their skin is doing well and they're willing to be fine with a little bit of arthritis that's left behind? Who knows. But it does show that IL23s tend to have the most retention and the least amount of out of switch. So I guess that means something.
- [40:26]
A
All right, to change subjects a little bit here, since we've got a rheumatologist,
- [40:30]
C
we got to move on to, we got to get, we got to do trivia.
- [40:33]
A
We're going to, I'm saving time. We've got, we've got like three more minutes here. So rapid fire for, for a rheumatologist, which drug are you most excited about in the connective tissue space? Breau or Lift? Lift.
- [40:53]
B
I mean, I'm a little excited about L. Fuller Map just because of the MOA being so different and you know, it's kind of like to spice things up. So I would say I'm kind of excited about that, so. Because, you know, the lupus. The lupus space is heating up and that's, you know, it's about time.
- [41:06]
A
And do we. Do you think that they will work for each other? So right now. Right. It's Bre is coming for DTO and little is coming for Lupus.
- [41:14]
B
Yes.
- [41:15]
A
Do you think repo will also work for Lupus and lift Little work for Dramato?
- [41:20]
B
Of course, there are always overlaps between the two diseases, so I would say yes.
- [41:25]
A
Okay. And then last thing before we get to. To trivia. Fibromyalgia. I. I think it's a real thing. That it's neural hyp. That it's the equivalent of neuropathic itch.
- [41:35]
B
Yeah.
- [41:36]
A
But it's neuropathic pain.
- [41:38]
B
Maybe we should. Maybe we should try giving them nemalizumab and seeing if that helps you.
- [41:43]
A
Right. Just try something.
- [41:45]
B
Is.
- [41:45]
A
Do rubes think it's a real disease at this point? Like, because when I was in med school, it was like, fibromyalgia just might be whiny people, people. And I'm like, I pretty sure that we don't think that anymore now. We're. We're pretty sure that it's like a real, A real thing.
- [41:58]
B
So it, I, I think it comes down to who you're talking to. If they have sort of personal research, academic interest in fibromyalgia. But I do think for the most part, we are still like, oh, it's kind of like this catch all for. You just have pain.
- [42:10]
D
You just.
- [42:11]
A
You have pain. You have.
- [42:12]
D
Stuff hurts.
- [42:12]
B
Yes.
- [42:13]
D
Yeah.
- [42:13]
B
Life is hard, you know.
- [42:14]
C
You don't like it any more than we do.
- [42:16]
B
Oh, I, I sort of joke and say that fibromyalgia is like, like talking about hair loss. I mean, thankfully now we do have options for, like inflammatory hair loss, but, like just hair loss in general.
- [42:24]
A
Yeah. Hair. The hair loss of room.
- [42:28]
B
Yeah, it's the head loss of room. Yes.
- [42:30]
A
I like it. Okay. All right, let's move on to trivia. So actually the. So the rules just.
- [42:35]
D
You gotta let Pat finish this week. You don't have to let me finish because it's these longer questions, and as soon as you know the answer, you shout it. But once you give your answer, you're out now.
- [42:47]
A
Okay.
- [42:48]
D
Sound good?
- [42:48]
A
All right.
- [42:49]
C
Oh, wait.
- [42:49]
B
It's a competition between the three of us.
- [42:52]
D
We don't keep track. I'll give you your name. I'll give you your $9 back that you gave me to buy that paper.
- [42:58]
B
I did not grow up in America. We don't believe in trivia in India, so I'm definitely going to fail this. But.
- [43:03]
D
Okay, you'll get these. All right, so these are the category room derm eponyms. Got it.
- [43:10]
C
Okay.
- [43:10]
D
All right, first one. This French medical student described his eponymous condition in 1862 as part of his doctoral thesis. The title of that thesis, and this is obviously translated, because I'm not going to massacre French for everybody. Local asphyxia and symmetrical gangrene of the extremities. The white, red, and blue of the different phases of the conditioning.
- [43:33]
C
Right now.
- [43:36]
B
Yes, yes.
- [43:38]
A
Thought of it, but I couldn't.
- [43:40]
B
I mean, I. I heard asphyxia, and I'm like, what are we talking about? And he's friends, and he's talking about asphyxiation.
- [43:47]
A
It must have been weird stuff.
- [43:48]
D
Yeah, it must have been, like, the worst Ray Nod's patients in the world. I mean, gangrene of the extremities. That is not Ray Nods.
- [43:55]
A
But, hey, I don't know, it was kind of neat.
- [43:58]
D
It was his doctoral thesis, so that was always an impressive thing that he. That's where he described it and is named after him. All right, ready?
- [44:04]
A
Second, when you said asphyxia, I immediately went to thinking you were going to now talk about auto asphyxia.
- [44:10]
B
I mean, that's what Auto was thinking.
- [44:12]
C
And then mine's in the gutter. You people.
- [44:15]
D
That's weird that that's where both of you went. But that's.
- [44:19]
B
That's French. He's also French. Like, what do you expect from them?
- [44:23]
D
Yeah, right. Oh, man. The letters. The letters. After this episode.
- [44:29]
B
All right, they don't speak English, so we are fine. They only speak English.
- [44:33]
D
Fibromyalgia doesn't exist. French people auto asphyxiate. We're. We're doing real well.
- [44:38]
A
Good. We're good.
- [44:40]
D
This physician's description of his eponymous disease in 1937 was initially met with skepticism. Medical professionals at the time felt he was merely describing a constellation of findings seen in patients with syphilis.
- [44:52]
A
Reuter syndrome.
- [44:54]
D
No, you're out. The Greek physician Adamantiades had described the disease six years earlier, leading some to suggest that his name should be added to the name of this. This disease. That being said, most of us know this disease only by the name of the Turkish physician who described. What's that?
- [45:12]
B
Bachette.
- [45:12]
D
It's bachettes. Okay.
- [45:17]
A
You knew because of the little thing that hangs down off of the.
- [45:19]
C
That's right. The only Turkish thing.
- [45:24]
D
All right. Number three. This physician completed much of his foundational research in Sweden in the early 20th century in an area era before autoimmune disease was a well understood concept. His 1933 thesis was largely ignored at the time but is now considered a landmark document in room. The condition he described is now one of the most common autoimmune conditions in the world and consists of the classic triad of keratoconjunctivitis, Sika xerostomia.
- [45:52]
B
Sh. Sh.
- [45:55]
A
Knew it was sh. I was like their mouth dry. Their mouth dry.
- [45:59]
D
Matt knows all the answers. It just doesn't get to his mouth. Which from Matt's mind to his mouth, usually that's a split second.
- [46:09]
A
Yeah.
- [46:10]
D
Somehow with trivia didn't work.
- [46:13]
C
It's really his frontal lobe to his mouth.
- [46:15]
D
That's okay.
- [46:17]
A
Yeah.
- [46:18]
D
Different, different part of the brain that makes total sense. Total sense.
- [46:23]
A
All right. Well, Sakshi, it has been so much fun having you on today. This was really, really a fun episode and I want to thank, I would thank you for joining us. I want to thank all of our listeners for joining us. Hope you laughed a few times. Hope you learned a thing or two. But mostly hope you're planning to join us again next week. Until then, I'm Matt Zyrus.
- [46:41]
D
I'm Tim Patton.
- [46:42]
C
And I'm Laura Farris. And we are derms on drugs.