Loading summary
Transcript200 lines
- [00:03]
A
Welcome to season two of Derms on Drugs, a video podcast brought to you by Scholars in Medicine, the best educational platform in dermatology, which was just recently revamped to make it even more user friendly and helpful. And it's provided at no cost to medical providers. Germs on Drugs is where cutting edge derm meets hit or miss comedy. I'm Matt Cyrus from Docs Dermatology and each week I'm joined by 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 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. There's everything you need to know to be on a cutting edge of derm, and you'll probably have some fun listening. New episodes drop every Friday on Scholars of Medicine, Apple Podcasts, Spotify, and anywhere else you might get your podcasts. And a reminder that this is a video component, a video podcast, and we do have some of the key figures and tables from the articles we talk about on the video component. This week we've got one of our patented six packs where we are going to talk about the coolest new stuff we've seen in the literature recently. Let's get started. Dr. Faris, what do you got?
- [01:07]
B
All right, so I have a paper that is hot off the pre release press from jad. Efficacy and safety of duroxolitinib and oral selective Janus kinase 1, 2 inhibitor in adults with alopecia areata. Results from the Thrive AA2 Phase 3 randomized double blind control trial. Some Greek S. Something at all. Okay, so what is this? This is a phase 3 RCT comparing placebo to two different doses of dib. So just a reminder, what does duroxalitinib do? It's a oral selective JAK1.2 inhibitor. It's claimed to differentiation. It's. It has a four hour half life. I don't know if that really matters. And it interrupts in interferon gamma signaling. And so mechanistically, what is this most similar to baricitinib, another JAK1.2 inhibitor. And then the other one that we have is ritlecitinib, which is on the market and that's a Jak3Tech Kinase family. So, you know, they would argue it's a little more lymphocyte focused. Okay.
- [02:14]
A
As somebody who did these trials, it's an interesting thing. You know, I don't know if they talk about this in the article. Probably not. Do you know what the difference is between it and ruxolitinib.
- [02:23]
B
Jack1 and something deuteration.
- [02:26]
A
That's exactly it. So they basically replaced one of the hydrogens on it with a deuterium. And in theory that changes the pharmacokinetics. And in theory. Well, not in theory, in practice now because it is on the market, most importantly, it makes it so that it's not covered under Ruxolitinib's patent. That's probably the biggest difference between this and Ruxolitinib is just that it got past the patent attorneys. But that's the, the deuterium in theory makes the half life different.
- [02:59]
C
Is the.
- [02:59]
B
Is the only difference, does it also Give it more Jack1 Selectivity? Did they tell you that?
- [03:04]
A
I don't. Anytime you start to ask the Farber people about Jack selectivity, they get very. We don't know because there apparently differences if you do a cell free assay versus if you do a cellular assay. And it depends on how you do the asset. So nobody will give you a straight answer on JAK selectivity from pharma.
- [03:26]
B
Okay. All right. That's kind of been my experience too. Okay, so back to our clinical trial. You know, typical adults 18, 6 to 65, salt greater than or equal to 50, meaning 50% or more of their hair is gone due to AA and you know, six months to 10 years of duration. So I think a lot of these trials have learned to exclude the people who've had, you know, alopecia universalis or Totalis for 20 years. So these guys were pretty severe mean salt around 88 and 60% of the group had, you know, they, they divided them into the group that was like salt 95 or greater. So 60% of the group fell into that. Like pretty severe hair loss, mostly females, mostly white. High rates of eyebrow, eyelash and nail and even nasal hair involvement. Okay, phase three study. Over 500 patients randomized 1 to 2 to 1 to D rocks, 12mg bid or 8mg bid or placebo 24 weeks and there they were stratified. Yeah.
- [04:39]
A
Just before I forget, did they talk in this article about why it only came out at 8 milligrams?
- [04:45]
B
I think it was based on the efficacy. But you tell me, Matt, because I'm assuming you got some insider.
- [04:52]
A
Yes. Well, as in the trials they were doing 8 and 12 and there were a few DVTs or PEs in the 12 milligram group. So they.
- [05:04]
B
In the long term extension.
- [05:05]
A
Yes. So they stopped that study and only went forward with the 8 milligram from that point forward.
- [05:12]
B
Okay, there we go. All right. Primary endpoint, salt.
- [05:15]
C
They do mention that.
- [05:16]
B
Sorry, they do mention that in paper. That was. But those were all in the long term.
- [05:21]
C
Open learn. Yeah, yeah.
- [05:23]
A
They're not in the set. They weren't part of the line.
- [05:25]
C
It didn't happen.
- [05:26]
B
Right. They did not say that's why we nixed the 12. But they did mention that that happened.
- [05:31]
A
Okay.
- [05:32]
B
Okay. Primary outcome. Primary endpoint, salt 20 or less at week 24. And that's kind of typical to what we see across these trials. Key secondary endpoint, salt 20 at earlier time points and then salt less than 10. So you get 90. You have 90% of the normal amount of hair. And then they had this very, you know, elegant patient reported outcome, which was, how satisfied are you with your hair today? And if you're satisfied or very satisfied, then that was a responder. Okay, so let's talk.
- [06:07]
A
I wonder what the results would be if you ask 50 random people on the street that how satisfied are you hair with your hair today?
- [06:14]
B
I know, I'm like, not quite satisfied with mine today, but it has nothing to do with alopecia areatis. Right?
- [06:20]
A
Yeah, exactly.
- [06:21]
B
I know. It's the fact that it keeps getting grayer, but that. I digress.
- [06:27]
C
All right, I still.
- [06:29]
B
At week 24, salt 20 was achieved by 30. About a third 33% of patients on the 8 bid, 38.3 on the 12, and 0.8 on the placebo. Now, if you look at just those people who had the salt score of 95% or 95 or greater, so they've lost 95% or more at baseline. So their response, their salt 20, was 20.9, 26%, and 0% in the 8:12 placebo group. So not quite as good of a, you know, making it to a salt 20, but still, you know, statistically significant salt 10. So 90% of your hair comes back by like 25 and 26.7 in the 8 and 12 versus none in the placebo. So, you know, if you take that, you know, super meaningful endpoint, like, you know, you got 90% of your hair back, there really wasn't a significant difference between 8 and 12.
- [07:28]
C
Okay.
- [07:29]
B
So I thought that was interesting. And then that satisfied, or very satisfied, was basically like half of each group versus 1.7 in the placebo. And they did see responses as early as week 12, and they saw that they kept going up at week 24. And we've had lots of discussions on this podcast about JAK inhibitors. When do you give up? And I think we've all agreed that like six months is not your maximum response. If you're getting growth at six months, we know you're going to. Most people will continue to get it. We've even talked about that. Sometimes, you know, patients will have hair regrowth at six months and then, or will not have it at six months, but they really do start to get it in that 6 to 12 month range. So 6 months is an early end point and they were probably going, you know, to get better. Okay, our favorite jack topic, safety over that 20. Yep.
- [08:22]
A
That I was laughing about that being our favorite jack topic.
- [08:27]
B
Well, okay, maybe it's not our favorite one. I think our favorite one is do you switch jacks and when do you give up on them? So our second favorite topic.
- [08:34]
A
Yes, that's, that's better.
- [08:36]
B
Our second favorite topic. So treatment emergent adverse events. 81% on the D rocks group. 70% and the placebo. Most of them were mild to moderate. It was like Covid nasal pharyngitis, headache. There was acne, CPK elevations. There were, you know, 1 to 2% on active drug had serious AES, none on the placebo. And those were like influenza, pneumonia. No mace events or thromboembolic in that 24 week, you know, period. Labs, increased platelets, amylase, cholesterol, decreased hemoglobin, alk fast, some neutropenia and anemia. You know, the, and then the, the five potential drug related thromboembolic events, mostly in the 12 milligram bid dose, were in that longer open label extension. They do qualify that with, they were all in patients who had other, you know, predisposing risk factors. Okay. So, you know, this was, I thought a pretty standard, pretty good, you know, clinical trial. The early efficacy, you know, they did see some early efficacy at week 12. So you know, what are the, the faults? I mean like we talked about you need some more long, you know, ongoing. Like we need more long term data on all of these both in terms of how much hair do you really regrow, how long do you keep it, etc. Etc. You know, this was also, they did have pretty good like hair regrowth, like eyebrow, eyelash regrowth as well too. So, you know, it's another tool in, in the toolbox. Now I will say, and I'm not going to go over the whole, I'm not going to go over the whole paper, but there was a, we do love a good meta analysis here on, on derms. On drugs. And so there was a meta analysis published in the jdd, Babel et al, and they did an NMA and they compared the three approved jacks at their label dose. So berry 2 and 4 once a day, ritle sitinib 50 milligrams once a day and duroxolitinib 8 milligrams twice a day. And so they pulled data from all of the clinical trials and they did say on this NMA that all three drugs were superior to placebo, but that Durock's 8 bid consistently ranks highest for both salt 20 and salt 10 at 24 weeks. So I'll throw that out there.
- [11:27]
A
So, you know, one of the things that's fascinating to me is they got more different results between their two trials than you normally see. So. Meaning? Well, I went back and looked at Thrive AA1 and in that one the difference between the 8 and 12 was bigger. So it was like 41.5% versus 29.6%. So like 12 point difference. Whereas in this one there was only a 5 point difference between the two. So just that that was interesting. It's it like.
- [12:07]
B
Yeah, and I think the inclusion criteria, I mean those are two like parallel studies. So the inclusion criteria were similar. You know, all it takes is a couple people who, you know, grow or don't regrow hair. I mean I, you know, it's not a huge difference, but yeah, so, so.
- [12:24]
A
Do, you know, obviously none of us have enough clinical experience to be able to be like, oh yeah, they get this one is better than the blah, blah. The other thing that is interesting about it is I believe in their approval. Before you can prescribe this, you have to check people's cytochrome P450 like 2C9 activity or something. So it is a little like azathioprine where you gotta check a thiopurine methyltransferase. And I don't think they were expecting that during the trials because there was like a protocol amendment near the end of the trial where that's when we suddenly had to test everybody and genotype them for their cytochrome P450 status. But I think that is in the label now.
- [13:16]
B
It is. And people have complained about that, that you have to order that, right? So like, yeah, I think that's probably a little bit of a barrier. So it's almost like in, you know, we all have the experience of you decide you're going to, you know, prescribe drug A for this condition and then the insurance is like, nope, you got to do this other one. And, you know, so it's almost like you have to prospectively think about it and now test everybody with aa because what if you're like, I'll just do bar sitting up? Well, they may come back and be like, no, you got to start with, you know, durock. So.
- [13:50]
C
Yep. Is that. Do you think that is because the higher dose had, like, three pulmonary embolisms. And so if you're not metabolizing it and you build up, like, that's. That's a real risk. I. I think the. The PE stuff that's a little bit scary. I mean, I remember that in the news, like, they. They halted the trial, and they're like, we got to look at this. And. Yeah. I mean, I don't know. I. I think that's a. That's going to be a huge knock on the drug. Yeah.
- [14:19]
B
But they were mostly in that higher.
- [14:21]
C
Yeah.
- [14:22]
B
Dose. And it's not gonna, you know, it's not gonna be approved. It's not approved at the higher dose, so.
- [14:27]
C
But has anyone said, like, that's why we have to check that?
- [14:31]
B
Because I have not seen the reasoning why. No, Matt, you were in the trial, so you would have gotten the protocol amendment. You don't know.
- [14:38]
A
I do not remember seeing what the reasoning was, other than I assumed that it was. Yes. That. That they. That the 12 milligram, in theory, having a higher risk. That they were more concerned about drug levels than they are with other, you know, Jacks. That's the only thing I could. I could think of, but I don't know for sure.
- [14:59]
B
Yeah. Or was it, like, the cytopenias? Right. Like, was it the other side? I don't know.
- [15:03]
A
Yeah, it'll be interesting. If they're smart, they will cut that data to see because it's a low frequency. So in Caucasians, it's like 3% of people or something. It's a small frequency of how many people have that genotype. But if they get enough people in the study who had it, it would be interesting to see if it affects efficacy as well.
- [15:24]
C
Right.
- [15:24]
A
Like, it works better, but you're more likely to get a blood clot in your lungs, like.
- [15:29]
B
Right.
- [15:31]
A
But I. There is some new data out about the relative thrombogenic propensity of different Jacks, which I will be covering later in the episode.
- [15:43]
B
Okay. Yeah. So it is CYP2C9. And they are actually. I was just looking this up, and I think it. They actually did say that they were at higher risk of the thromboembolic Events. So there you go. So test CYP2C9.
- [16:02]
A
Okay. All right, let's. Let's move along. Patton, what do you got?
- [16:06]
C
All right, first six pack paper. October 2025 edition of Journal of Clinical Practice and Research titled Subclinical Spondyloarthritis features in patients with Hydride 90 Supper Tiva. A real world cross sectional analysis by Baquet and baquet. So in 2022, JAD published screening recommendations in HS patients. And if I read it, I can't say it stuck with me. And I think the reason why is because the authors recommend that we screen for. Are you ready to write this all down? Acne dissecting cellulitis of the scalp, pilonidal disease, pyoderma gangrenosum, depression, generalized anxiety disorder, suicide, smoking, substance use disorder, pcos, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction. And I think I looked at all that and said, well, I'm not doing that. They also recommend that all patients with down syndrome be screened for hs. And I think it'd be funny if you read that wrong and tested all your HS patients for down. Like we're going to do some blood tests, including one to make sure you don't have down syndrome. I don't do all that screening. I have a skincare routines to go over. I don't have time for all that nonsense. Nonsense. Anyhow, this article focused on one of those comorbidities, spondyloarthropathy. They took 120 patients, systematically evaluated them for spondyloarthropathies. They consisted of some different scoring system, a sacroiliac MRI that was only in some patients, that wasn't in everybody. Some blood work, ESR, CRP, and HLA B27. What did they find? Table 2 lists percentages of different diagnoses in these HS patients. 13% of patients had MRI detected saccharitis, 12.5 were HLA B27 positive, 10% were diagnosed with peripheral spondyloarthropathy, 12.5% met the New York criteria for ankylosing spondylitis, and 18.3% were diagnosed with enthesitis. So almost 20%. That's kind of high. There is not a strong correlation between HS severity and any of the rheumatology diagnoses. So you could have very, very mild HS and still have one of these rheumatologic diagnoses. So my takeaway is That I will try and be better at screening my HS patients for spa and maybe start referring more of my patients to room. But the other takeaway is that, you know, with a diagnosis of spa in our HS patients, you could use on label spa meds like Oopa and Tofa and exekizumab, which could help treat the HS as well. So maybe we start raising the possibility of our HS patients having to get those, you know, to get those meds covered. Like back when we diagnosed everybody with psoriatic arthritis, because Embryo was approved for that, but not for psoriasis. So just. That's all something that I thought about. I mean, when I have really, really bad HS patients, I know, kind of I think, okay, maybe this is Sappho or pash or papa. And so you start asking about joint pains and things like that. But I can't say that it's on my radar the way that it is in psoriasis with psoriatic arthritis.
- [19:02]
A
So when you say you're going to start screen, like, are you basically just going to start asking people about, do you have any back pain? Do you have any joints that hurt? And then if they say yes, you're going to send them to room.
- [19:12]
C
I don't know. What I'm going to say is if they have any of those symptoms. And you kind of think like, okay, well, this doesn't sound like it's anything bad. Probably not. I'm probably not going to send them to.
- [19:23]
A
Unless you want to. Unless you want to try and get them on a drug.
- [19:28]
C
Yeah, but in that case, I'll just say like, you know what, you could have spondylo. Like, are the insurance company going to be, say, like, well, was that rheumatology diagnosed? Actually, these days they probably will.
- [19:38]
B
Yeah.
- [19:38]
A
Yeah. That's why you would say you're not going to be able to put them on a jack for spondyloarthropathy. That's part of the. A lot of the prior auth criteria nowadays, like, only derms can prescribe germs, and allergists are the only ones who can prescribe doopie.
- [19:51]
C
Yeah, then I would. Especially if I run into trouble with getting those meds. Like, if, if my HS treatments don't work, I'll be like, you know what? Here's a way that we could possibly go about getting that. You know, I thought about that actually, because there was a, this, this diagnosis of metastatic Crohn's disease. You know, there was a Jamaderm paper published early this year. It was Like a Delphi panel on diagnosing metastatic crohn's. Three major criteria, five minor. And because the diagnosis of IBD or, like, a skin bio. See, we're in the minor. You actually don't need either one of those things to make the diagnosis. And I had a guy with just really bad groin HS and massive lymphedema of, like, the genital. Like, the scrotal skin.
- [20:33]
A
Yeah.
- [20:34]
C
And it kind of made me. And he said he had a family history of Crohn's because I told him if he. I asked him if he had any GI stuff, because. Right. We were running into issues with kind of running out of options. And, like, you could give that patient a patacitinib, 45 milligrams a day to treat metastatic crohn's. Just kind of a strategy of maybe getting some other drugs to your HS patients. That's two things to think of. Spondyloarthropathy and metastatic crohn's. Okay.
- [21:02]
B
You would think. I mean, you know, you would also consider, like, starting with the TNF inhibitor for those patients first.
- [21:08]
C
Yeah. In fact, you know, with this guy, we went back to infliximab, and that was kind of another interesting thing, because he had not tried Bimi, and he wanted to do infliximab. I don't know why, but he was just, like, focused on that.
- [21:22]
A
Had he been on it for years.
- [21:24]
C
Insurance company denied the infliximab, saying it's not FDA approved. And when I called them up and said bimakizumab is FDA approved, they were like, you know what? We'll pay for the infliximab.
- [21:36]
B
Yeah. Thank you.
- [21:37]
C
And if, like, tofacitinib goes generic.
- [21:41]
B
Yeah.
- [21:41]
C
You know, there may be that there's maybe a way to get them on these other medications. Just something I thought about. What do you have, you guys, Is that on your radar with your HS patients? Spondyloarthropathy?
- [21:53]
B
No. Yeah. I mean, yeah. I feel like these people are, like, chronically inflamed. They are miserable. They've got pain everywhere. It's not shocking. You know, we look at their labs, like, doing trials, like, their CRPs are off the charts. Like, I feel like these people are like, you know, I feel like sometimes we're like, oh, it's inflammation. But now I'm beginning to, like, believe that, like, they have horrible systemic inflammation.
- [22:19]
C
Yeah.
- [22:19]
B
Damn it.
- [22:20]
A
First, whatever. I'm like, no, I'm not. And you're like, yeah, actually, I feel like, we're like, playing good doctor, bad doctor.
- [22:26]
B
I know. Obviously, I'm glad I. Today I'll be playing the role of good doctor.
- [22:30]
C
Thank you. I think that's always your role.
- [22:33]
B
That is. I try. Yeah.
- [22:34]
A
Mine is generally bad.
- [22:35]
C
Let's say bad doctor, better doctor.
- [22:40]
B
Bad doctor, not as bad doctor.
- [22:42]
C
Yeah, exactly.
- [22:44]
A
All right, so let's. Let's move on to my two here. So, first, there was an article. We talked about it a couple of months ago about the mechanism through which jaks might increase thrombosis risk. And basically the idea is, in diseases that have too much IL17a and TNF, those two molecules increase thrombosis risk in diseases like psoriasis, HS, rheumatoid arthritis. And JAK inhibitors don't reverse that. So they. It's essentially that other drugs, IL17s, TNFs, reverse it. Jak inhibitors can get the inflammation better, but they don't reverse that specific effect. So they. It's not so much that they raise the risk as that they don't reduce it like other drugs should. But then the next question becomes, okay, if there is this effect, which JAK inhibitors are better or worse? And so these. The same group that came up, I think that came out with that original one, published this article, understanding cardiovascular events with JAK inhibitor similarities and differences between the vascular effects between different JAK inhibitors on endothelial cells exposed to inflammatory cytokines. So basically, they took endothelial cells, put them in with inflammatory cytokines, and saw what happened to them. And then, you know, they. They gave them the same similar micromolar concentrations. They tested each of the drugs at 1 micromolar and 10 micromolars. They did tofa berry. So, right. So tofa, I E, Zeljans berry, I. E. Allumient, UPA, I E. Rinvo. Two cancer drugs that are a cancer drug and an inflammation, one that I've never heard of, perficitinib, and then they did ruxolitinib, which is Jakify. And so basically the takeaway was Barry showed the least risk, the least effect on endothelial cells that would, like, potentially, you know, make it least likely to cause thrombosis or to be associated with it. Rinvoak was second best. Rucks was in the middle. And then Tofa, I E. Zeljan's, was the worst out of the drugs that we've got. And then the two that I'd never heard of, pefecitinib and fedratinib, were worse than all the other ones. So the. This is. At this point, I'm comfortable saying AD and alopecia areata, since they are diseases that don't have overexpression of TNF and and or IL17A. There shouldn't be any risk of thrombosis from JAK inhibitors in those diseases. Mechanistically. And then the data. That's what the data has all shown as well. However, when jaks come out for hs, it absolutely is possible to me that. That cardiovascular risk improvement with TNFs or IO seventeens could be a real reason to use them instead of JAK inhibitors nhs. And that this data might become very relevant. So that. But that's. We'll see if and when they get approved for HS. But basically, I'll take you way, way.
- [26:02]
B
Back to 15 minutes ago when we just discussed the five thrombotic events with duroxalytin alopecia areata.
- [26:11]
A
Blah.
- [26:11]
B
And alopecia areata.
- [26:13]
A
No risk. No risk.
- [26:16]
B
Okay.
- [26:17]
C
You should call them and see if these assays are easy to do. Which they sounded really, really easy to me. Like, I could do this in my kitchen. If they could do this with duxolitinib. Like, what. What does that do to the endothelial cells? Like, is it the worst?
- [26:32]
A
Yeah, that's a good. Because it could be different from the rocks. That'd be an interesting thing. Mechanistically, does it make it different than the rooks?
- [26:38]
B
Yeah, there you go.
- [26:40]
A
I will email the authority and ask them. I email authors pretty regularly and most of the time they respond because they're like, holy shit, somebody read my paper. Yeah, all right, I've got it.
- [26:53]
B
I've got it. It's kind of a trivia question. What's the other drug that we use in dermatology that is. Has the hallmark of deuteration?
- [27:02]
A
I have no idea.
- [27:04]
C
Do testeride.
- [27:05]
B
Nope.
- [27:08]
C
I didn't really think that was the answer.
- [27:13]
A
Nib. It's got the deu.
- [27:16]
B
All right.
- [27:16]
C
I've seen that lecture.
- [27:17]
A
So is there just kravicit nib. Is that a thing?
- [27:20]
B
No, you're a kravicitinib. Sometimes, but, yeah. No, it is.
- [27:25]
A
All right. The other one that I did was an HS1. That's just an example of. The journals are terrible. This was from JAMA Dermatology. I couldn't believe that they let this get published. It was ridiculous. Hidradenitis supper. Tiva. Remission and progression in a community setting. And the takeaway here. So they basically. This was from Denmark. They looked at like a hundred and some 107 HS patients followed them for like 10 years. And we're just see how many go into full remission. And their takeaway was 2/3 of HS patients will go into full remission and only 1 out of 6 will have their disease progress. And even if you have severe HS, there's a 50% chance you'll go into full remission. Ridiculous. Like just stu. Like dumb. Right? Dumb. That's the most ridiculous thing I've ever heard. Is it really? Half of your HS patients who have severe disease will go to full re. No. So this was done in Denmark. So a completely racially homogenous group. Number two, these were skinny people. So their BMIs, all of the groups the mean was below 30. They were very wealthy comparatively. They actually showed their income bans and they all have universal health care.
- [28:45]
B
So.
- [28:46]
A
And all of that is okay that like okay, this patient population is totally irrelevant to everyone in the entire rest of the world. Except they never mention it. They, they attribute the difference to. Well this is community based compared to most are hospital based. So it's that you know, those hospital based studies are overestimating the severity.
- [29:08]
B
It's good.
- [29:08]
A
No, it has nothing to do with community base. It had to do with race and socioeconomic stuff. And like it drives me nuts because these journals like Hammer, Hammer, Hammer on, you know, socioeconomic and Skin of Color and you got to include that and you got in the one study where it like is a huge factor. They didn't mention it. Like journals are just put like even the good journals suck nowadays. Like it's just, it's crazy what they will let through. And I'm now never going to get another article approved anywhere. Never submit one.
- [29:41]
B
I love JAMA Dermatology Listening. Next time I submit something. No, it's like yeah, that like Denmark is the, is the antithesis of North Carolina because nobody gets better here.
- [29:55]
A
Yes.
- [29:55]
B
Nobody meets any of the criteria that you spoke of either. But yes.
- [29:59]
C
Right.
- [29:59]
A
It's. And it's like insurance companies someday. Like well Dr. Farris, that all of the patients you've had with HS for 10 years, 2/3 of them should be in remission and they're not. You're a bad doctor. Like that's why they shouldn't like drives me nuts. Okay, that's it. That was a little bit of a soapboxy one. Sorry. Let's, let's, let's move on to our next. Dr. Ferris, what's your next article?
- [30:22]
B
Well, I have efficacy and safety of sequential treatment with cryotherapy followed by 1% topical turbinebulin for actinic keratosis and organ transplant recipients. A randomized clinical trial. Okay, so this, it was, I mean, it was like not a big study, but it was sort of interesting. So, you know, so a couple interesting things out of the intro that I guess are important, but I hadn't really thought about. They said in solid organ transplant recipients, the spontaneous regression rate for of a specific actinic keratosis has been reported to be 0%, versus in the immunocompetent general population, it's 28%. And transplant recipients, their AKs are 32 times more likely to develop into SCCs. So kind of interesting. So why. This is sort of the. Why treat? Like, why do we worry about a case? Sometimes you're like, do we need to worry about aks? Probably the answer is yes in trans solid organ transplant patients. So 40 transplant patients, 37 completed the study. They were who you would think they are, who get a case. They are older Caucasian men, mostly mean age 71. And they were heavily pretreated. So they'd had PDT 5 fu, amiquimod, diclofenac, lots of cryo. They had to be at least one year post transplant and they had to have four to eight AKs on a 25 square centimeter area. Two of them on their face or scalp, like one on each side, like left cheek, right cheek, left scalp, right scalp. So this was a split field design. They could not be on like nicotinamide, oral retinoids, blah, blah, blah. So most of these patients were fits 2 and 3. They were all Caucasian. They were mostly kidney transplant. Second biggest group was liver transplant. So, okay, so what they did was basically like everybody got cryotherapy and then one half of the face got turbinebulin and then the other half of the face didn't. What is.
- [32:40]
A
I got. I gotta ask you something.
- [32:42]
B
Are.
- [32:42]
A
I've never. I. I pronounce it turbanabulin.
- [32:47]
B
Are.
- [32:47]
A
Is. Is the way you're like. Are you pronouncing it the way the drug company pronounces it or you may. I made. I made up how I pronounce it. I don't know if I'm.
- [32:56]
B
No, I think I am. I have been on an advisory board with them.
- [32:59]
A
Okay, so. So I have been saying, not because.
- [33:02]
B
I'm a huge prescriber, but okay, because they needed another female on their advisory board. That was me.
- [33:09]
A
It was right, because I'm so much.
- [33:10]
B
Fun to hang out with.
- [33:11]
A
It is not because you're a woman. It's because you're brilliant. Now, how do you say it again?
- [33:16]
B
Turbinebulin.
- [33:17]
A
Turbinebulin. Okay.
- [33:18]
B
Turbine is the drug because we're allowed to say that. Yeah. Okay, so it is not. So this is an anti. It's a microtubule disruptor. Right. So it's not like inducing an immune response. It inhibits tubulin polymera polymerization. It disrupts kinase activity and rapidly dividing cells. So it is. You know, BAS basically causes apoptosis. I'm sure you say that. Apoptosis or something like that, but I say apoptosis. Cell cycle arrest, blah, blah, blah.
- [33:55]
C
I don't think you're supposed to pronounce the second P because it's a combination of apo and then ptosis.
- [34:02]
B
Okay, I know, but I say apoptosis.
- [34:05]
A
I say apoptosis.
- [34:07]
C
It's so wrong. It hurts my ears to hear people say that.
- [34:10]
A
From the guy who for years called it pruritus.
- [34:13]
B
That's right.
- [34:14]
C
Right. It's ironic.
- [34:17]
B
Okay, so everyone's. They. Everyone got the double freeze draw, 5 to 10 second. And then. And then after 30 days, then one side got the clay. Siri. We'll just call it to stop the discussion. Once daily for five consecutive days. And the other one didn't get vehicle. They got no additional treatment. The first application was supervised in clinic, but then the rest, the other four days, they were done at home. And then blinded. Dermatologists did the efficacy, and they did all that. I've done like one. A case study. It's kind of painful. Like, you got to take these transparencies, you map them, you know, blah, blah, blah. And then they looked at. And there's this Olson scale, which is like the pazzy of AKs to classify them. They did it at day 30 and then again at four months. So basically, three months after starting the turbine, nibul or clary. And then primary endpoint percent change in AK count from baseline to month four in each area. Okay, and then secondary endpoints were like 100% clearance and partial. And then partial response was 75 to, but less than 100% clearance. Okay, so what happened at four months? Both sides got better, but the sequential side did better. So the mean reduction in AKs was 81% on the cryoclisceri side versus 53% and the cryo alone, and that was statistically significant. The total lesion count across all the patients went from 197 down to 38 in the sequential therapy group and 195 down to 91 in the cryo alone. And so then if you're like, what percent of patients had no visible, like total clearance? 51% in the sequential, 10% in the cryo only. That partial response of that 75 to less than 100 was like 2 thirds of. Now, hang on, what was it? Oh, about a quarter of the patients. I may have that number wrong. Forget that. Just go with the full one. Okay, so they, so they basically, they're saying like, oh. Then they also looked at like, who got more AKs. So like, so they actually did see a rise in the total AK count in the cryotherapy only group, about a 34% rise. Whereas in the sequential side they saw a 36.7 decrease. And this is in new AKs because you're marking and counting every single one. So there you go.
- [37:05]
A
Like, I won't do any more vitiligo trials because they make you like count all the spots of vitiligo and it's a night. Now that's worse than a case because you got to do their whole body, but it's terrible. So.
- [37:19]
B
So yeah, so and then like, you know, all the safety stuff with fine, it was like what you would expect with any sort of topical AK thing. You know, pain scores were low. There was two, one SC. So there were two SCCs that arose in treatment sites, one SEC in situ on the turbinebulin side, one invasive SCC on the cryo side. And the AK quality of life was, was low at baseline and remained low. Let's see, any of.
- [37:54]
A
What do we really care about by quality of life? You mean the aks were not affecting their quality of life much or.
- [38:01]
B
They were, yeah. So, yes, relatively small. Yes, it was a small impact on quality of life.
- [38:09]
A
So.
- [38:11]
B
So, yeah, I mean, so I like the split face because at transplant patients are so vastly different that I don't think you can take like 40 of them and say 20 and 20 and think that you're gonna get something. Now, I assume that they did stuff like flipped out. Like it wasn't always. The left was the, the clyceri, the right was the, you know, cryo alone. I, you know, they did like seem to do some pretty good, you know, counting and everything. It's small. You know, I, I thought this was interesting. I mean, this was actually like, it's. Very few people study the, the transplant patient population. They did the study in the way that we're going to actually use drugs like this, which is we're going to freeze a bunch of stuff and then we're going to put on a topical. They had the patients do it at home. You know, I, I have used Clyceri in patients who are like, I hated 5 fu. I never want to do that again. And so I'm like, all right, well, will you try something else? And so it's sort of like it's a something else for them to try.
- [39:17]
A
So if we take insurance coverage out of it and we're just talking efficacy and tolerability, like what's your go to? If you, if it wasn't. But if you didn't care about cost, what do you, what do you, what do you do in a transplant patient?
- [39:36]
B
5 fu. Calcibetrine.
- [39:38]
A
Okay.
- [39:39]
B
Compounded. That is my go to. And the reason is we've got good data that prevents future SCCs. I don't have that data for anything else that there's like, you know, that is my go to. But there are patients who, they do it and then they refuse to ever do it again. So I like to have another option.
- [39:56]
C
Indeed, that is also the NCCN guidelines.
- [40:00]
A
Yeah, I'll pat you in your guidelines. Okay, Mr. Good Doctor.
- [40:04]
C
It helps, but it does. It helps to know what the guidelines are. Yeah. And I thought, I thought it was interesting that they specifically said 5 fu and they actually, actually mention if you can get the calcipatrine in there. Because I thought that was relatively new data, but it's already made its way to the nccn.
- [40:21]
B
But NCCN guidelines are updated like twice a year with skin cancer, I feel like. So.
- [40:26]
C
Yeah, yeah, I didn't know there was that much overwhelming data where they're like, oh my gosh, we gotta make that part of the guidelines.
- [40:32]
A
Well, and again, it is super cool that they've actually shown that it decreases the risk of squams. Because that's always been my thing of like, without data that something decreases the risk of squames, treating AKs is basically cosmetic because it's, it's totally plausible that like the 5 fu only gets rid of the ones that weren't going to turn into cancer anyways. Right. So it, it like just because something gets rid of AKs doesn't mean it's going to reduce the risk of squames. So the fact that 5FU and CUSP TRI has data that it does that, that. Because other things don't. So that's, that's a big deal.
- [41:13]
B
Yeah. So I, I like the fact that they did this study. I thought it was interesting. It is a tough patient population to do it in. So good and It. The fact that it prevented new ones was kind of interesting to me. Not just that it like decreased. It improved clearance. So it made me feel warmer and fuzzier about clay. Scary. And transplant my patients.
- [41:37]
A
All right, Pat, what do you got? What's your next one?
- [41:40]
C
All right, second six pack from December 2025 edition of Annals of Dermatology. Impact of hydrochlorothiazide on non melanoma skin cancer. A distributed Network analysis of 100, 100 of 11 real world databases. Lead author was Park. In 2020, FDA approved a label change to hydrochlorothiazide to include skin cancer risk. And I have to admit, I'm not great about cancel counsel non melanoma skin cancer patients about stopping hydrochlorothiazide if they happen to be taking it. I think if you ask most derms, does hydrochlorothiazide hctz? I'm not going to keep saying that HCTZ increases skin cancer risk. They would say that it does. But to be honest, the data is not like slam dunk. There are some studies that show increased risk, some studies that don't. Some studies say there's an increase in secs, but not basic BCCs, and there's studies showing the opposite.
- [42:35]
B
It.
- [42:35]
C
And I always thought that maybe that's why I'm not terribly diligent. It just seems like the data is not dispositive. There's your word of the day.
- [42:45]
B
Anyway, not as good of a doctor. I think I'm gonna. I'm gonna go with the bad doctor on that one, but.
- [42:50]
C
Yeah, hold on, hold on. So anyway, this study looked at data from 11 healthcare organizations in Korea. I think that population being Korean is important. Something like 14 million records overall. They fed the records into this OMOP CDM thingy. It seemed like something similar to trinetics. An epidemiologist could explain this better. I mean, anyone could be explaining this better right now. But the authors compared patients with hypertension prescribed HCTZ to patients with hypertension who were prescribed something else for their hypertension. And after propensity score matching a little over 8,800 patients in each cohort. Big takeaway. There was not an increased risk of non melanoma skin cancer in patients taking hydrochlorothiazide compared to patients not taking that. Subgroup analysis of patients taking HCT Z for less than one year versus more than one year. Subgroup analysis based on age. Subgroup analysis based on sex. All analyses did not show an increased risk. Are we over counseling patients or did I just cherry pick A study that justifies what some people may say is my negligent patient care. What do you guys think?
- [43:54]
B
The biggest thing about that paper, they're all Korean. It's a totally different group.
- [43:59]
C
But it doesn't matter because there's a European study that went back, they did not show an increased risk for hydrochlorothiazide. There was a transplant patient population. They're like, yes, it does for BCCs, but not SECs. Like, it's for having data that this study showed this. This study showed this. And then FDA changed the label like I did. They.
- [44:23]
B
I believe. I totally believe the hydrochlorothiazide thing. I believe it. I feel like I see it all the time. I don't know. I mean, but like, Koreans are, you know, a different Fitzpatrick skin type, B, totally different sun behavior.
- [44:37]
C
If hydrochlorothiazide increases your risk for skin cancer and you have a population of patients, no matter what their skin type and pop, like, you're gonna see more secs in that patient. Theoretically, like that. That's what the study should show. If hydrochlorothiazide increases skin cancer risk, I'm.
- [44:55]
B
Gonna say it's among people who are irresponsibly, ridiculously out in the sun. That's who I see. It's like those people who are just so.
- [45:04]
C
It's not gonna help you if you like, yeah, I got some sun exposure, but I'm not crazy about it. Versus, like a farmer. There's like a threshold where hydrochlorothiazide is going to push you over the edge.
- [45:15]
B
I believe that is the case.
- [45:18]
C
I guess I'm trying to find a way of, like, why am I not great about this? And I guess the answer comes down to me just being dumb.
- [45:26]
B
No, I mean, just lazy.
- [45:29]
A
Do we basically agree that the mechanism is photosensitivity, that it makes you more. Basically magnifies the effect of sun?
- [45:38]
C
Yeah. Right. I think that's the theory behind it. Yeah.
- [45:41]
A
So I don't even tell people. I tell people, don't use. I specifically tell you, do not use sunscreen unless you're going to get a sunburn. And you guys have heard me talk about this ad nauseam. There's as. There's good data that the more sun you get, the less likely you are to die from a heart attack or a stroke or get autoimmune disease or whatever. So maybe the reason we don't see it in all populations is because sun isn't that big of a deal.
- [46:04]
B
No, there. But sun Is a big deal for some patients.
- [46:07]
C
Right?
- [46:08]
B
Like, I mean, I look at, like, you know, the. The older, fair, you know, Irish skin type guys who spent all this time outside, either about the shore or working outside, and they are, like, covered in a case. It does make a difference for those people. If you're Korean. And maybe, like, in a culture where you don't sit outside in the sun all day, it probably doesn't matter and you have a different skin type. I. I still think it matters.
- [46:40]
C
There is. There is a European study. Like, I think it was Danish. No, the Danish study showed the increased risk. But there was another Danish. Yeah, there was another European study that didn't show the risk. I guess you should see it every time if it's like a definite risk. And even the FDA warning to the label, it's pretty wimpy. They're like, it may increase it a little bit. And I think they actually give this number of like, like, you will stop one skin cancer in 16, 000 patients.
- [47:10]
B
Right?
- [47:10]
C
Like, that's what the FDA. That was like the FDA page.
- [47:14]
A
So do they actually have the. In there?
- [47:18]
C
Yeah, they do.
- [47:19]
A
That's in the label.
- [47:20]
B
Maybe we could pull that label and put it as a link like for. For the show of, like, what the FDA label actually says.
- [47:28]
A
And see, just look at fairs. Being a chair and assigning work, that's not gonna be my job.
- [47:33]
B
Job, Cyrus, that's going to be your job. Please.
- [47:35]
C
I'll do it. I brought it up. I'll do it.
- [47:37]
B
All right.
- [47:37]
A
Okay, good.
- [47:38]
B
Thank you. Maybe I'll make you a better dermatologist, too.
- [47:40]
A
All right, let's jump, viewers. So to my last two. So the first one was combination of oral minoxidil and baricitinib for alopecia areata. Retrospective study of 77 patients. I did this one because the results kind of shocked me. So I've. I have been in the camp of like, ah, that Brett King guy, He doesn't know much about alopecia areata, and he keeps talking about this minoxidil. I thought. I thought he was smart. And turns out the minoxidil looks like it actually does do something. So this. This was not a prospective study. This was a retrospective of 77 patients. But here was the big takeaway. That with combination starting baricitinib 4 milligrams plus minoxidil with a median dose of 2 milligrams, 50% of alopecia totalis patients. Alopecia, Dallas universalis. Got to salt 20. And in the. The. You know, original studies, only 20% of those people got to salt 20. Now they did go longer here. This was a 12 month study as opposed to the 24 weeks and whatever. But it, it did actually. I'm probably going to start recommending to people that okay, if we're going to put you on a JAK inhibitor, we're going to also start you on minoxidil, 2.5 milligrams. I'm now like this has been the best data I've seen to support that. Is is more where I would put it. You know, it's interesting, there were a couple of other things recently about minoxidil just that were also kind of interesting that basically 100% of men who go on minoxidil will get forearm hypertrichosis, but they don't care. That was, that was kind of just an interesting takeaway. There was another one just out that you, they monitored labs and blood pressure and all that prospectively and a whole bunch of people. And the takeaway was, it's now in the literature. It literally says there is no need to monitor, routinely monitor blood pressure, pulse, labs, anything in low dose or minoxidil. But so this, this convinced me somewhat that it's worthwhile in alopecia areata because it's so safe and so cheap. Then the other thing, well, first before I go to my other one. Any, any comments? Do you guys do this already? Do you think you'll start doing it?
- [50:00]
B
I do. I do it.
- [50:01]
A
Okay. Pat.
- [50:03]
C
I don't know if I do. I, I use minoxidil in so many other hair loss things. I, I would be surprised if I haven't also recommended it to a. It just seems like it grows hair. Like how's it gonna ever.
- [50:15]
B
Yeah.
- [50:16]
C
Hurt anything?
- [50:17]
A
Okay, fair.
- [50:18]
C
All right.
- [50:18]
A
This is my other one. Kind of some, some biggish new data. So this is from rokatinlimab, the OX40 receptor blocker. So this is efficacy and safety of Rokatinlimab for the treatment of moderate severe diabetermatitis in Rocket Ignite and Rocket Horizon 2 global double blind placebo controlled randomized phase 3 trials. Main takeaway for me here. So efficacy. So the, you know, the. When I say, what do I mean? So if we look at everybody who got the drug, whether they got rescued or not. And so rescued was just means if they use topical steroids, and usually if somebody uses topical steroids, you call them a failure. They reported the data both calling them failures and leaving them in. If you leave them in. So best Case scenario of the data, about 50% of people get to easy 75 and about 25% of people get to IGA 0 or 1. And those just aren't very good numbers. Right. So for the drugs that we're used to, it's about 2/3 to 70% of people get to easy 75 and about 40% of people get to IG01. So the numbers weren't great. The other things that are just interesting about the drug, small number of people will get fevers and fevers and chills whenever they take their first dose. Don't know if that is indicative of efficacy. Small number of people will also get oral ulcers. So, you know, regular aphosis. I've seen that in some of the patients we've had in the trials. Again, unknown if that's correlated with the efficacy or not. But so that's, that's, it's gonna be. The OX40 drugs are gonna be interesting. Totally different mechanism of action. Could be very broadly usable. Just gonna be interesting to see. We don't have enough data to really know anything yet, but it was interesting that this data just came out. So.
- [52:26]
B
Yeah, And I think the idea with OX40, OX40 ligand pathway is that it increases. Decreases the activated T effector cells. Like it rebalances T effector, T regulatory. So it's like you get more T regulatory cells and fewer T effectors. Yes, Right.
- [52:44]
A
And so there's a hope that it basically retrains your immune system, gets rid of the effector memory T cells or they, you know, they just go away over time and that. So people might be able to go on these drugs and get better and then go off them and have it be very long term durable improvement in their disease state. That's, that's kind of the holy grail of what. But that data is still a ways out because. Right. We've got. They have to do the withdrawal and then, you know, give it a year before they can even start to look at that data. All right, well, I want to thank everybody for joining us today. Hope you laughed a few times. I hope you learned a thing or two. But mostly hoping that you're planning to join us next week. And until then, I'm Matt Zyrus.
- [53:30]
C
I'm Tim Patton.
- [53:31]
B
And I'm Laura Ferris. And we are derms on drug.