← Derms on Drugs
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- [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 and provided at no cost to medical providers. Derms on Drugs is where cut against dur meets hit or miss comedy. I'm Matt Ziers, and each week I'm joined by my residency buddies, Dr. Laura Ferris from the University of North Carolina, Dr. Tim Patton from the University of Pittsburgh Medical center, and we use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of derm, and you'll actually have fun listening. New episodes drop every Friday on Scholars in Medicine, Apple Podcast, Spotify and other major podcast platforms. And there is a video component that has the key figures and tables from the articles that we talk about. So we've got another one of our patented six pack episodes. Dr. Farish just flew in from running, or I guess in a loose sense, running a half marathon in Florida just in time to. To get on for the show. So, Dr. Ferris, what do you got for us today?
- [01:08]
B
All right, Matt, thank you. So I have, you know, I'm gonna take a page out of the Matt Zyrus book, and when I'm supposed to do one paper, I'm gonna actually kind of make it two papers.
- [01:19]
C
Whoa.
- [01:21]
B
I know, I know. So first, one joint position statement from the National Board, the National Psoriasis Foundation Medical Board, and the International Psoriasis Council on routine testing for latent tuberculosis infection prior to and during treatment of psoriasis patients with Interleukin 17 or Interleukin 23 inhibitors. So this was recently published in JAD. Andy Blauvelt is the senior author. But it's, you know, a bunch of people who are on here. So the big question here is, can we finally get out of the toxic relationship that we have with TB testing annually for some of our biologics? So they really specifically just focused on those that hit aisle 17 and aisle 23, pathway. This was joint between the IPC, which is international, and the NPF, which is a U.S. based organization. And so basically what they're trying to do here is say, you know, all biologics are not the same. Why do we start testing for latent tb? Because of TNF inhibitors. And that makes sense. What does TNF alpha do? It breaks up granulomas. It is very important, protecting us from intracellular organisms like tb. So it would make sense that we would test for it, but then we just kind of lumped everything else in.
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A
So wait for a second.
- [02:43]
B
They're addressing. Do we have to do this?
- [02:45]
A
I gotta. I've never understood. And I've asked a bunch of people. Even with TNFs, like, I get testing at baseline. That's obvious. But once you've tested them at baseline, it never made sense to me to test them every year. Because if the TNF is suppressing your ability to fight off tuberculosis and you catch tuberculosis, then you shouldn't get. You should not be able to get latent tuberculosis while you're on a tnf. You should either get it or you're not. Like, you have a cough. And if the answer is no, okay, we don't need to test you. Like, I don't even understand that rationale.
- [03:19]
B
Okay, So I will say one thing. Over half of cases of active TB in patients who are on, you know, immunosuppressive medicines, particularly TNFs, are extra pulmonary. So, like, there's, like, there's so much myth busting around all of this that, you know, people will say, oh, should I be, you know, getting chest X rays in my patients who have had a positive test? And no, like, most of them. So, you know, a latent TB never has a normal chest X ray. There is no finding on a chest X ray. But that gets asked all the time. And then if you're really going to follow them, the only thing you see on a chest X ray is like, a cavitary active lesion of our miliary tb. But active tb, you don't see latent tb. And of course, you're not going to see, you know, TB reactivation. That's extrapulmonary.
- [04:07]
A
Okay, so see, far side learns. Thank you.
- [04:11]
B
Oh, Matt, it is my pleasure. The day I can teach you something is a happy day in my life.
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A
I know.
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C
It's rare.
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A
It's rare.
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B
It's rare. It's rare.
- [04:18]
A
Okay. All right.
- [04:19]
B
Okay. So basically we just kind of, like, lump them in and kind of. To your point, not even just on human. We'll talk a little bit about. There is some, you know, data on humans, but a lot of it's a little bit more, you know, theoretical. So what did they do? They got together. They looked at preclinical data on the aisle 17 and aisle 23 drugs. They looked at the clinical trials. I won't name all of them. We all know what drugs they are. And then they looked at sort of real, real world data and trial data, and they looked at structured searches of the Fairs database, which is Sort of the spontaneous FDA reporting of, of, you know, adverse events to drugs. And so what they focused on in fares, that was extrapulmonary tb. So they're, you know, using that as a proxy for who gets extra pulmonary TB, people who are immunosuppressed. And they looked across IL17 and 23s and across TNF inhibitors. Okay, so what did they do? First of all, they, they looked at mouse data, right? So they said blocking IL17, AF receptor and the IL17 receptor and IL22 in mice does not result in, you know, TB or susceptibility. However, blocking TNF does. Okay. Also they showed that IL12 is important, which is why they're then in preventing TB infection. So that's why they said, you know, Drugs like Stelara, IL1223 inhibitors, they're not putting in like that safe to move forward category that we put IL23 inhibitors in. Okay, so IL17 trials, there are actually hundreds of patients who had latent TB who went in these. Usually they had been treated and there were no cases of reactivation. They also said that there were a few cases in the ixacizumab studies where the patients converted from negative to positive, they were left on the drug, they didn't get prophylaxis and they didn't get active tb. They also looked at, you know, the kind of real world cohort of like the patients who aren't, you know, they're like the messy patients we don't put in studies. So people who got liver disease and who did not, you know, who had latent TB who didn't get treated, went on IL17 inhibitors. And they said at most there was maybe one single atypical, you know, case of a person con ser, you know, converting to active TB from latent TB. And then for IL23 inhibitors, after going through like thousands of data points, no cases, and then lots of case series. So basically they didn't find anything. Then the fares database part was that they looked at over 96,000 safety reports from IL17 and IL23 inhibitors in psoriasis. None of them were cases of extrapulmonary or disseminated TB. However, in the 140,000 ISH TNF inhibitors, there are actually 26 TB cases, including eight of which were disseminated TB. So they said, you know, this really shows. It's not that there's lack of reporting, there's do get reported, we're just not seeing it. The mouse data doesn't show it, the trial data doesn't show it. So, you know, they're, they're pretty clean for this. So then they had 112 experts vote, 87.5% of them endorse this statement, which is routine testing for latent TB infection is not required prior to or during treatment of psoriasis patients with IL17 or IL23 inhibitors, period. Now, they did say, well, there may be prudent inpatients in TB endemic regions or patients. And I think this is important on concomitant immunosuppressives. So if you've got patients, particularly who are in like systemic steroids and another, and One of the IL17, 23 is probably still reasonable. So it's not never to test. It's just stop the reflexive testing of every single low risk IL 17 or 23 inhibitor patient who, who you're starting or considering a biologic. So why does that matter? Like, you know, we all just put in order sets like biologic start. We don't, we don't need, we probably don't need to do it. Now, is it still sort of in the, in the package insert? And are you still going to get insurance companies asking you, yes, you are, but they're, you know, sort of nudging like, we need to change this. We need to, you know, advocate for not checking this in everybody. They also said, hey, ibd, community room committee, HS or community, like, you guys should be doing the same thing. You should be trying to push for these drugs, that we do not need to be doing this. So. And then they're like, why? So why does that matter? You know, why? Why, who cares? It's just like in the grand scheme of cost, it's a cheap test. The reason is like, there are false positives, right? So there's, it's not a harmless thing. So when you have a false positive, what do you do? You do go get a chest X ray, that's radiation. You send the patient to id, they're likely going to be treated. And these are not, you know, benign drugs that they are being treated with. You know, they decrease the efficacy of birth control. If you have women on OCPs who are on them and patients who have, you know, liver disease, they are hepatotoxic drugs. So that's why we don't want to do this. And of course, now you've like committed to somebody to this diagnosis of latent tb. So that was kind of the paper that I thought was interesting. The other one is, was also recently, it was in JAD and it was. Steve Felman is Group. And one of the other offers was Willie Wong, professor of Dermatology at unc.
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A
Great name.
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B
It is a great name. That is a great doctor.
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A
Fantastic name. We once, we used to have an NP at OSU when I was faculty there, whose honest to goodness, real name was Ying Yang.
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B
That's awesome.
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A
That was a great name. Right?
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B
I would marry a guy named Yang just for the ability to have named my kid that.
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A
So that's good.
- [10:40]
B
Okay, so Feldman's group actually said, like, took a look at all of the data and said, you know, what do we need to really be like, should we. What about all of our biologic panel? So here's like, key things that they said. They also said they looked at TB testing or screening and they said, yes, it is like they gave it a level of evidence grade B for. For TNF inhibitors. For TNF inhibitors. However, they said that Hep B testing and monitoring carries a small net benefit. They gave it a grade C, but they said, you know, that benefit's really just in TNFs for IL17 and IL23 inhibitors. What did they say? They said, no need to do routine testing for Hep B or TB screening or sort of the broad lab panels. And they said, you know, what we should actually be doing is screening by history for IBD type bowel changes and for mucocutaneous candidiasis. So really we should be doing more. More getting a history, less getting a bunch of labs. They also recommended against like hep C testing, HIV testing, cbc, cmp. You know, they gave those all a grade D. So I thought that was, you know, interesting. So this is really rethinking. How much should we be. Can we, like, really de escalate all of the monitoring and retesting and testing that we're doing with these drugs? So two good papers to take a look at.
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A
That's really good stuff. And what I wanna know is, why are the insurance companies so miserably awful? Like, they won't let us prescribe drugs, but they will make us get unnecessary
- [12:32]
B
blood tests because I think it simply delays the prescription. Right. Two weeks of not paying for talts saves them, you know, thousands of dollars.
- [12:46]
C
So I had a CSU patient, omalizumab. I mean, not a reason in the world why this woman should not have been given olizumab. And it was four months back and forth with the insurance company. She just got her first inject injection, I think last week. And this was somebody I saw back in October. I mean, huh. It's just right. If they can Put it off. I, I had them say, hey, you ordered Eustachinumab, you said every 30 days insurance, we need that to be every 28 and that, like that, like delayed treatment for three months for this poor guy with his horrible sorry ass form. I mean, it's just right.
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A
You ordered Stelara once a month.
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C
Well, no. So it was something along those lines.
- [13:36]
B
Second dose. You said the second dose.
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A
Okay, okay.
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C
Yeah, yeah, yeah, yeah.
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A
All right. Yeah. Okay.
- [13:41]
B
Yeah. Maybe you were actually the problem here.
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C
Yeah. You know what? That one was probably on me.
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A
Yeah.
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B
And I, I will say, and not to like out Matt Zyrus. Matt Zyrus, but there is actually like a third review article that was recently in jeadv, which was looking at sort of the European consensus statement on TB testing. And while they don't say don't do it, they have said for IL23 and IL17 inhibitors, you know, fine to screen, but if they're positive and they are at high risk of being treated, just use an IL17. And Aisle 23 or Premalass, they threw in there too, and they said, don't treat for the latent tb. So, and then they said, do not do. If you're in like a, a low risk situation, don't keep testing for patients who are on IL17, IL23 inhibitors or a premolast. So that is sort of the European guidelines really also backing this up. So I'm hoping in a year we're not doing all this testing for everybody on biologics, particularly IL17 and 23S, but
- [14:47]
C
the insurance landscape would have to change dramatically. Not that they would be requiring it, but I cannot get patients on 17s and 23s first line. I mean, I cannot do it. And the adalimumab biosimilars are really, really cheap. There's a USTEC IMAB biosimilar, and so that's going to drop the price of that one. Insurances like, to this day still make me do TNF alpha inhibitors. And that's fine. I think they're good drugs. But every psoriasis patient that I'm like, systemic therapy is probably going to be somewhere along the line. They're still going to be getting all this testing. And I don't really feel that bad about it from a cost standpoint. I think your point about saving them from possibly being treated for something they don't need to be treated for, that is when you could say, go back to the insurance company and say, this is a positive TB test patient, we really should get these patients on 17s and 23s instead of putting them through the TB treatment. So I'm still probably like, I don't see myself changing the testing part of it for like the next six months, maybe even longer, but it may help me get to 17s and 23s quicker.
- [16:01]
B
Yeah, I think it's a good point to say, like if you have a patient with latent TB, it is more responsible to put them on an IL17 or 23 than it is to, you know, get them treated and then put them on a tnf. I do felt that way. And I will say, you know, I coacher Kenra in their phase three studies, they actually allowed people with latent TB to be enrolled without being, without like to have it untreated. And people got a coacher Kenra with untreated latent tb, no cases of tb. So that's the other place where, you know, that may actually be our first cytokine inhibitor where the label will actually say you don't need to test, but time will tell.
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A
That's cool.
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B
Yeah, that's what I got.
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A
Okay, Ferris, that was good stuff this week.
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B
Thank you.
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A
Good.
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B
I'm glad.
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C
You're sounds so surprised.
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B
Yeah, I know. So glad to impress you for once.
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A
All right, let's go, Patton, what do you got?
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C
All right, I. I will not impress you. All right. My first six pack article from the January 2026 edition of the American Journal of Clinical Derm titled Nicotinamide for Skin Cancer Chemo Prevention. The jury was out and still is. Is that a, that is a attention grabbing headline, is it not? I'll say it was by Tan et al. On a prior episode, we reviewed a paper suggesting maybe hydrochlorothiazide isn't really contributing to non melanoma skin cancer in a significant, significant way. And now we have another paper casting some doubt on what I think lots of dermatologists believe to be true. Nicotinamide prevents skin cancer. So I am an iconoclast. I find iconos.
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B
Dude, now you're trying to kill everybody with skin cancer. That's the other.
- [17:46]
C
I've just always been skeptical. Right. I mean nicotinamide prevents skin cancer. Like seems too good to be true. It's cheap. It's all right. So previous article in 2018, Australian Journal of Dermatology, similarly titled. I think this is kind of because this was another. There was one Australian guy and one guy out of England that did the current paper. This paper in 2018, nicotinamide and skin Cancer Chemo Prevention. The jury is still out. That was an Australian author. So the skepticism about the effectiveness in the cite isn't really new. So why the new paper casting doubt? Because of some other paper that we covered published in Jama Derm, I think, stating that nicotinamide works. That was the VA study. So the authors of my six pack paper looked specifically at that jamaderm paper and they point out problems that they had with the study. So what did the recent study show? Nicotinamide, 500mg bid, decreased non melanoma skin cancer by 14%, squamous cell carcinopolis by 22% and if started early, decreased skin cancers by 50%. And again, I just don't understand.
- [18:53]
A
That was purely observational though. That was just like willy nilly, you, anybody you wanted to could put them on or whatever. And then after a long time there was no, it was, there was nothing prospective about it. Correct, correct.
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C
Purely observational. And so like I don't understand statistics and studies well enough to be able to identify these problems, which I think isn't a problem like in and of itself. I mean, as dermatologists, you know, you, you see like the abstract, you see the headline, you hear other people talk
- [19:21]
B
about it, you listen to some fools on a podcast.
- [19:24]
C
I like, I don't, like, I couldn't go through that paper and be like, here's the problem. This, that and the other. So they talk about things like, I mean, there's no charts or anything. They just kind of go through and point out the problems. Unmeasured confounders, possible misclassification of interventions, possible deviation from intended interventions, issues with measurement of outcomes. You know, like they went with CPT codes and ICD9 codes and ICD10 codes. They didn't do it based on histology. So they kind of really just point it out and all they really want to say is, you know, and they have like a 56 page supplement that you can go through that kind of goes into gory detail about all of the things that they went through the study and pointed out. Like this is why it's not the most reliable thing. So their takeaway point is, should taking nicotinamide to prevent skin cancer be made part of our clinical guidelines? And according to these authors, the answer is not yet. So I think that's interesting because you hear people talking and they're like, look, you have your skin cancer patients, you talk to them about sunscreen, you talk to them about wearing clothes and avoiding, you know, sun. You talking about self exam. We're just going to have to throw in the NIC tinamide into that conversation. It's going to be standard of care because it shows. And like for me, I think I'm more along the lines of I'll mention it. And there was a study and it's not definitive and if they feel like doing it and it's like they can afford it and they can tolerate it, maybe it will help. Like that'll be my counseling. But I'm just not going full into. Oh my gosh, this study absolutely proved it and so everyone needs to be on this. I just don't think I'm there yet.
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A
I like supplements in general. Today I almost bought 130 bottle that makes hydrogen water because there was a small randomized study showing that it helped with keloid. So I'm all about supplements.
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B
All water has hydrogen in it. I just want to tell you that there was that.
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A
It's, I didn't buy it, but I sent myself an email to see if I still want it in a week.
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C
Okay.
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A
But like I, it's, it's easy. Like it's, it, it's just so easy to be like, here you go.
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C
I know, take this. I know.
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A
And I, I don't know. I think there's so much stuff that we tell people to do that I don't think has that great of an evidence. Like I'm never, I'm not convinced that counseling people about sun, like obviously we should, we got to document it so we gotta get our asses sued off. But I don't, I don't know. Have I seen a randomized double blind placebo controlled trial that counseling people about sun exp reduces mortality from skin cancer? I don't think I have.
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B
No, yeah, no, I hear you. I hear you. Yeah, I, I do feel like there's, there's enough data that suggests that it might help. And again, it's risk, benefit, trade off. The risk is pretty low, the cost is low. There's really not, you know, I know there's been things like, oh, might there be some risk of, you know, cardiovascular disease that really hasn't panned out.
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C
There was a study that said it was cardio protective.
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B
Yeah, cardio. So, yeah, you know, those are the things that people, you know, bring up. So I, I'm hard pressed to find a bad, a reason to recommend against it.
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C
I probably would not say like, absolutely don't do this. It's a waste of time. There is a study done by these two statisticians and they went through all the data like I'm not going to like, adamantly discourage, but it's nicotinamide. But, but I'm going to be like, it may help, it may not. If, if you feel like doing it, go for it. If it's just one more thing that you, you know, it would be added to your regimen that, that's going to be a pain in the ass. Probably not that big of a deal. Don't worry about it.
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A
It's reasonable to go either way.
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B
Let's.
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A
We'll put it, we'll put it that way. Okay. All right.
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B
All right.
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A
Moving on to my first study. This one was actually. Could be a little bit of a game changer. Could be. So it was association between topical corticosteroids and risk of upper gastrointestinal complications. And essentially they use. It was done in Taiwan. They have national, like healthcare systems. So they have, they're able to do really good, like studies looking at associations between different stuff because they've got like millions and millions of people in complete health records on all of them. And basically what they showed was that topical steroids meaningfully increase your risk of stomach ulcers, of like duodenal ulcers and gastric ulcers. So the adjusted odds ratio, if you just went on topical steroids, your adjusted odds ratio was 1.785, which is like, you know, a 70% increase. Now whenever I really went and did the math and. Because then the question becomes like, well, okay, but like, if it's super, like I, I have double the risk.
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B
Absolute risk versus relative risk.
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A
Yeah. So, right. I've double the risk of winning the Powerball if I buy two tickets. But like, is that a absolute. No, but. So it's, it's not an unreasonable. So that the absolute risk is about one in a thousand at just normal people every year will get an ulcer, at least in Taiwan. And so this takes it to 1 in 600. Which isn't that, you know, it's meaningful. But then if you add it together. So if you're taking, if you're regularly taking NSAIDs and a topical steroid, your risk of a stomach ulcer, duodenal ulcer is. Adjusted odds ratio is 4. If you're taking a systemic corticosteroid and NSAID and aspirin and TCs, your risk is eight times the norm. Like it. So it is additive with other stuff. Now is this gonna make me go out and stop? Oh, my God. We shouldn't be prescribing topical steroids. I mean, I'm only gonna say that, because the other topical companies pay me a lot to say that. But like from a real medical perspective, I don't know that this is really gonna change, but it's, it like there is. We, you know, we now have data that topical steroid use is good data is associated with osteoporosis, that long term use is associated with increased risk of type 2 diabetes. Now we've got pretty good data that it's associated with increased risk of stomach ulcers.
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C
The osteoporosis group, I think was the same group that did the stomach ulcer, wasn't it?
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A
Wait, I think the osteoporosis and diabetes people were the same people.
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C
Okay.
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A
Because those were all done out of like Denmark, I think because they have the same thing. They've got the national healthcare thing.
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C
Oh, okay. Well, I think this group, because in like the second or third reference, it's like the same guys and it's like osteoporosis. So same.
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A
Ah, okay.
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C
So they, they probably all work for like Insight or something.
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A
No more topical steroids.
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B
They're talking about how derms. We don't, we're not good at statistics. It showed an association. It didn't show that it causes.
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A
That's true. That is true.
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C
It was actually very similar to the nicotinamide. Right. This was observational. It was based on ICD9 codes. It wasn't based on actual endoscopy. Diagnosed stomach, you know, peptic ulcer disease. What's odd is, you know, systemic corticosteroids, if you look at, if you go through some of those studies, just because I give a ton of systemic corticosteroids to my immunobullis patients and the GI stuff I'm always a little bit confused about. I mean there are GI studies that have the like a similar number, like a odds, adjusted odds ratio of 1.7 or 1.8 for systemic corticosteroids. Like there's just no way that topical corticosteroids have that same adjusted odds ratio. And even with systemic corticosteroids, if you're not on like an nsaid, if you're like a non smoker, if you're less than 65 years old, they don't recommend like PPI, they don't recommend peptic ulcer disease prophylaxis. So if systemic corticosteroids without any risk factors, we don't worry about peptic ulcer disease. I, there's just no, like, I'm not worried about topical corticosteroids at all it
- [27:55]
B
seems like putting my patients at a higher risk too. Right. Like, I mean, if you look at that paper, the people who really were at risk were like, they were on systemic steroids and NSAIDs and aspirin and topical steroids. Steroids, yes. Like, that was where the real risk was. But. And maybe I'm missing it, but I feel like they didn't have a group that was because like that was what they. They, they had the peptic ulcer disease group and then the no peptic ulcer disease group. But I don't see. And maybe I just didn't read the paper carefully enough that they looked at like, what about like, did they compare it to systemic steroids but not topical or NSAIDs, but not. You know what I mean? Or aspirin? Like, I don't feel like you got all that data. So I don't know.
- [28:42]
A
I agree. My main takeaway with this, my main takeaway was that it, like, it does seem like there is some effect of like covering your body in topical steroids internally.
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C
I think that the overuse of topical corticosteroids would be more concerning of like, we do not have your skin disease under control. If you. This is how many steroids and things that you're going through.
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A
Oh yeah.
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C
And that's the bigger issue. Not like, ah, you're gonna get peptic ulcer disease. Stop using all these steroids.
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B
But it's just how much you are using or you were not like a.
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C
They did like an equivalent based on potency and amount.
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B
I think they did.
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A
Yes, they did.
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B
They did.
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A
Higher cumulative long term, increased it a little bit more, but not a ton more more. It was like 1.6 to 1.8.
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B
So that's the low and high. That's the low and high. Okay.
- [29:39]
C
You earned your money from all the topical non steroid companies. Okay, okay, we can move on.
- [29:45]
A
We can move on now. Now let, now let me get myself in trouble. We'll make this one quick because it didn't tell us anything useful. Switching from dupilumab to upadacitinib in adults and adolescents with moderate severe atopic dermatitis after an adequate response to dupilumab efficacy and safety. Results from period two of phase B4 study level up. Basically, people got doopy or Rinvo for 16 weeks. If you were on the dupy and you didn't get to easy 75, you got switched over to Rinvo and then you know what happened. So the results were almost identical to somebody who's never been on dupy. So about 80% of people got to easy 75 by week 32. So basically what it says is Dupy not working does not in any way predict whether Rinvoak is going to work. And that's, that's kind of the takeaway. The thing that was just drives me nuts is like the question that Abbvie needed to answer that they didn't answer. And it's just like I wanted these drug companies, what the hell are they doing? Because it's just stupid. The question every patient I've ever been is like, they're doing good on Doopie but not great. And I'm like, well we could switch over to this pill. It's, there's a good chance it's going to work better, but we don't know for sure. And then say, well, what are the chances it's going to like, what are the chances I'm going to get worse? And was like, I don't know, probably like 5, 10%. And they're like, I don't want to take the chance. If, if Abbvie had just given the number of how many people did at least as well on Rinvoak as they did on Dupy, my bet is that number is like 98%. And then people would be way more like, patients would be way more interested in switching. If I could tell them, hey, there's a 98% chance you're going to do at least as well rather than now I'm just making a number up. And I told ABBVIE this and multiple times to their like top people. And the publication comes out. Nothing, not, not in the supplements. Nothing. Bastards.
- [31:42]
B
All right, that's what you want to know.
- [31:43]
A
All right, okay, let's, let's, let's move on. Ferris, what do you got?
- [31:51]
B
Okay, so I have Remy Brutinib in chronic spontane urticaria 52 week results from two phase three studies gas are now at all. Okay, so this was, this was the, this is the basically 52 week data of remix one and remix two. So what is. I think we, we've talked about Remy Brutinib again, but just a quick refresher. It is an oral BTK inhibitor that is currently FDA approved for the treatment of chronic spontaneous urticaria 52 or 25mg bid. So CSU, why do we need more treatments? Half of patients remain symptomatic despite antihistamines. And even with those who are on four times approved dosing, they say in the introduction 75% of them still have itching and have urticaria. And that omalizumab still leaves around a third of patients uncontrolled. They also say that CSU often lasts two to five years. So we need durable treatment. Okay. Remi Brutinib, BTK inhibitor. BTK is sits downstream of the FC epsilon receptor and mast cells and basophils and that it blocks Both the type 1 auto allergic which is IgE, to auto antigens or to auto allergens and the type 2B which is the autoimmune. But the autoimmune type, which is where you've got IgG, IgM or IgA that binds to the IgE that's already bound to your own FC Epsilon. So they're like it cut. It works on both types. I don't know how important the two types of CSU are, but there's been a lot made of it recently. So remix one, remix two two phase three studies, 470 patients and remix one, 455 and remix two. So this is a lot of patients randomized two to one remi brutinib, 25 milligrams, bid or placebo for 24 weeks. Then they went into an over open label extension, which is what we're talking about, which went through week 52. All patients were on like stable locally approved dose of their second generation antihistamine. So they did have an, and they did have antihistamine and then they could get rescued which was generally to go up to second generation antihistamine. And 30% of them had prior basically omalizumab or some sort of anti IgE. So not biologic naive. And in both studies 60% of patients had what would be called severe CSU at baseline, meaning their UAS score was around 30 or was, was higher and the mean score was around 30. So that's pretty bad disease. Okay, so for patients who were randomized to remibrutinib they did see improvements. So they looked at like mean improvement in UAS 7. It occurred as early as week one and that at week 52 the main, the mean change in their UAS, which is urticaria activity score over seven days was a decrease of 23 basically in both studies. And this is a score of 0 to 42. So if you're starting at about 30 and you're going down by about 23, that's a pretty significant drop. And 63% of them had, were well controlled, which was a UAS of 6 or less. And about 45% of them had a UAS 7 of 0, meaning no itches, no itch, no hives. You know, basically when people rolled over, they did about as well as the people who went in new. So had improvement by, you know, by like one week in. They also did these like swimmer plots where they showed patients. So they, they put them into disease bands. So severe was 28 to 42. And then, you know, there was like another band that was like 0 to 6 and then like over 6 to something like 14 or whatever. So they looked and they could show that patients move from more severe to L to less severe and that they could jump bands as early as one week. So that's kind of an interesting way to look at it. By 50 over half. By week 52, over half of the Remy Brutinib patients needed no rescue meds at all. So safety really, like there was no new safety signal. So rates of AES and SAEs and discontinuations declined with continued use. So from the 24 to 52 week analysis, so no signal of like longer exposure made you at higher risk for any AES. There were no deaths. They saw, you know, the usual suspects of like nasopharyngitis headache that you see in every clinical trial of any drug. Petechi. That is the one known side effect. I think, Matt, you're going to talk about that in another paper today. But that occurred in about 4% of patients. It was mild, mostly in the first three months. And there was really, there was like a cosmetic finding, not a, you know, not a bleeding risk. The one like AE that they talked a little bit about was that there was one patient who had late asymptomatic bump of his transaminases, but three to five times upper limit, normal. Interestingly, they associate, they attributed that to excess antihistamine use. And there were really no other. And that patient, you know, continued in the study. So that was interesting. So, you know, kind of bottom line, same stuff that we saw, 24 weeks fast onset. And this was really more to say, you know, a, you don't lose efficacy, people can stay on this out to a year, and B, it stayed safe. So another drug for us, for csu. Any thoughts on that paper from my friends?
- [38:12]
A
Mainly that like, why is it that the only drugs that like stop working or work less overtime are like the fun ones? Like, why is it that like the same amount of whatever, I don't know, opioid, like works less and less over time, but that doesn't happen for other drugs that just always strikes me as weird.
- [38:35]
B
I think it's that you build up a tolerance and there's something about the signaling. But why don't you not see that?
- [38:41]
C
Yeah, why don't you build up a tolerance to.
- [38:43]
A
To. To all of these.
- [38:45]
B
To all of these. I don't know, like Jack inhibitor, Antibiotics. Like antibiotics, you don't build up a
- [38:51]
A
tolerance, but, you know, it's why it's. It's an interesting, like, maybe it's because you're act. You're blocking something rather than activating something. Maybe that's it.
- [39:01]
B
Maybe it's what you're act. Yes, I think it could be that. And it's intracellular versus where do opioid receptors. How do they signal? Are they intracellular?
- [39:10]
A
I have no idea. I have no idea.
- [39:13]
B
I mean, they're transcription factors, right? We are giving you no information on how opioids work. Not helpful. It's all things speculation, but I, I've.
- [39:25]
A
I've no personal knowledge for the most part. But like all of, like marijuana opioids, all of it. Like, the more you use, the more you need.
- [39:36]
B
Yeah, but it's metabolism for alcohol. It's the. You know, it's true. I don't know.
- [39:44]
A
All right, all right.
- [39:45]
C
It's a mystery move.
- [39:46]
A
All right, let's move on. Patton, what do you got?
- [39:49]
C
All right, really quick on second six pack. January edition Journal of Dermatology titled A Premolast Associated Clinical improvement in Bulls Pemphigoid with Plaque Psoriasis by Shohei Kitayama. So, as we all know, some evidence. BP occurs more frequently in patients with psoriasis because compared to patients without psoriasis, overlap.
- [40:08]
A
Don't say we. As we all know. I didn't know that.
- [40:11]
B
He meant. As all the smart people know, as
- [40:14]
C
all smart people know, that BP occurs more frequently in patients with psoriasis compared to patients without psoriasis. So overlap of the two conditions is not a super rare event. And treatment can be a little tricky. Systemic corticosteroids are standard of care in many BP patients, but that can make the psoriasis flare when it comes time to taper. Dupy, which was approved by the FDA to treat bp, could pose problems with managing psoriasis. Like, would you say, like, what percentage of. If you. If you were just like, sadistic and you were like, I have 10 psoriasis patients and I'm going to give them all doopy. Do you have any idea what percentage are going to get worse? Do you think it would be all
- [40:56]
A
of them or Like, I think it would be most.
- [40:58]
B
We get worse.
- [40:59]
A
I think It'd be like 90% would get worse.
- [41:01]
B
Okay.
- [41:02]
C
No, I was thinking about that and. Right. That was kind of my take too. Methotrexate's a good option in these patients and I've done that with decent results. But with all these newer drugs, is there another option to manage these overlap patients? That is the question. The authors present a case report of a 65 year old gentleman, 8 year history plaque psoriasis managed with topical corticosteroids, who developed BP and kind of significant bp. Like did he die? Which does.
- [41:26]
A
Did he get any stomach ulcers?
- [41:30]
C
Yeah, like 20 stomach ulcers that complicated everything. So his BP die, which nobody ever does, but it was 36, which kind of puts him in like moderate. He was prescribed, as far as I could tell, only a premolast, 30mg bid. I kind of assumed he continued the topical corticosteroids, but the, the paper did not explicitly say that. And by week eight, both his BP and psoriasis were under control. Control was maintained at week 36. Some pretty nice before and after pictures. I have treated two patients with BP psoriasis overlap with SOTIC two with very good results. Interestingly, both of those patients were treated with IL23 inhibitors because their psoriasis was so significant and they actually developed BP after that. And so maybe there was a push towards the th2 axis, blah, blah, blah. Who knows? Very interesting. It was interesting enough that I, I had a resident present those two cases at fall clinical and she wound up getting like invited and they paid for everything. And what did I get? The senior author? I didn't get shit. That's garbage. So anyways, we, we presented those two cases. It was just like an oral presentation, wasn't even a poster.
- [42:47]
A
So I think first I do want to chime in, that's interesting because IL17s clearly cause a Th2 deviation, but it's not reported with IL23s. So IL17. The more potent the IL17 inhibition is, the higher the rates of new onset spongiotic dermatitis, IL 23 inhibitors. It's not so like it's higher with BIMI than it is with Cosentix and Tulsa's in the middle io23s. It's really very rarely reported.
- [43:17]
C
Yeah, I was a little bit surprised, but it was both. It was Geselcumab and it was risen kizumab.
- [43:22]
A
Okay.
- [43:22]
C
After starting those biologics, I mean this, the Skyrizi patient, not to bad mouth. Skyrizi. We love Skyrizi. Great drug. I don't get paid by them. I don't get paid by suit. I don't get paid by any of these drug companies.
- [43:33]
A
Pat, you need to, you need to
- [43:34]
C
work on that Dupilumab. Dupilium. I do stuff with Regeneron. But I mean one dose of her Skyrizi and her, her like psoriatic plaques developed all these bullet. It was, it was really, really.
- [43:48]
B
This is where we could use trinetics, right? We could say, you know, what is the incidence of BP in patients on, you know, being treated with or with psoriasis? And look and see if it's associated with it. We cannot air this until I've run that analysis and submitted the.
- [44:07]
A
And you got to compare that.
- [44:09]
B
What's that?
- [44:09]
A
You got to compare 17s and 23s and O Tesla because that, that'd be actually a really interesting analysis. And then we could come on and say how it's a trinetic study, so you shouldn't believe it, but it'd be interesting.
- [44:21]
B
You could make fun of it and talk about it.
- [44:23]
C
So I think so. Tic tuna, Tesla are good options for the overlap patients, but the question is, could they just be an option if the patient only has BP insurance? Probably wouldn't cover them. But if there were a way, like if there was a medication similar to a premolast that was very, very cheap, if that only existed, like that is a reasonable thing to think of with like your BP patients. I mean, and just adding it to anyone because like, right. Reflumelast Oral. We're of course talking about the podcast's favorite drugs. Rflum Elast Oral.
- [45:01]
B
Why is our favorite drug of company is a drug that will never ever sponsor our podcast. We're glad it makes for punishment, makes it pure. It does make it pure. It's pure unadulterated love that we have.
- [45:13]
A
And you know what? They reduced the price even further on Mark Cuban's Cost Plus Pharmacy. It's now $5 a month for the 500 microgram pills. What's weird is the 250 microgram pills are like 50 bucks a month.
- [45:28]
C
It's weird.
- [45:28]
A
Yeah, it's weird. But yeah.
- [45:30]
C
Yeah. So like, I just want to say with my next BP patient, I'm just doing it. I want to be like, whatever we're doing, we're also going to start this oral medication. Having 80 year old patients figure out Mark Cuban, that I think is a legitimate challenge. But, but man, like, why not?
- [45:52]
A
Yeah, I don't think it's too good RX in normal pharmacies. I think it's like 15 bucks a month. It's still not that bad.
- [45:57]
B
It's not that much.
- [45:58]
C
It's a little higher than 20.
- [45:59]
A
Yeah, yeah, yeah, but it's not that
- [46:01]
B
interestingly, I had a pharmacist, I did give it to a patient who I thought could not handle Mark Cuban. And I said, just use this good Rx. I gave it to him. The pharmacist refused to take it and said, I am putting it through your insurance and I'm going to ask for a prior auth. And he said, my doctor said, they won't do it. I'll just pay for it. And she said, no, not interesting.
- [46:24]
A
Because the pharmacist probably makes more on revenue by running it through insurance.
- [46:29]
B
Yes, exactly.
- [46:32]
C
Price markups.
- [46:33]
A
Yep.
- [46:33]
B
Yeah, they lose their markups. So.
- [46:35]
C
Yeah. All right, but.
- [46:36]
A
So yet yet another use for reflumelast. And Patton, you could. Any BP patient you have, no matter what they're on, you could add reflumelast.
- [46:47]
C
I know, that's what I'm saying. Like, yeah, yeah, yeah.
- [46:50]
A
Okay. All right, let's. All right, let's go to my last two. So first one so far's talked about Remy Brutnib. So this was a fascinating article. I love this kind of mechanistic stuff whenever it explains something interesting. So what I have kind of been told by the company about. So first with Remy, people like just in case. And Ferris talked about this already.
- [47:14]
C
Right.
- [47:14]
A
8% of people had a bleeding event. The bleeding events were all petechiae. All right, so no real bleeding events. All right, the. But so why. And so the answer that I had gotten from the company was that so BTK the general pathway, because there's a lot of Bruton's tyrosine kinases. The general pathway is involved in collagen driven platelet activation and the integrin related thrombo stabilization. So this study, or this was called mechanistic insights into petechiae observed with rembrutinib therapy and chronic spontaneous urticaria. And so REMI in theory could cause petechiae via that pathway. And you would expect it to be a pretty minimal effect because it's so much more selective than the other BTKs. But the student never explained to me, well, why would it just be capillaries? Like if it affects bleeding at all, like, then if it's something about the coagulation pathway, then it should not be just petechiae. And so this paper Maybe gives us an answer. And so possibility number two, they had no particular data. This was just like somebody like, hey, this is interesting, right? So mast cells.
- [48:24]
B
What's that? This is your kind of paper.
- [48:26]
A
This is my kind of paper, yeah. Just making it up.
- [48:30]
B
Speculation, I know.
- [48:32]
A
Yes, speculation. So. So mast cells reside perivascularly right alongside the capillaries, and they help maintain endothelial stability via precisely timed release of vasoactive mediators. An abrupt silencing of mast cell activity could transiently disrupt this process until it, you know, everything gets back into balance. And I love that explanation because it would fully explain why it's only capillaries. Right. Why we don't see any other bleeding effects. So just. That was interesting. Not terribly. The only relevance is, like, don't worry about bleeding with. With Remy Brutinib, which I always have to say the name anyways. Rhapsodo. Right. Love it. All right, so my last, and then my very last one. Safety and efficacy of ICP332 for moderate severe atopic dermatitis. A phase 2 randomized clinical trial. So this is a tick 2 inhibitor, and it was spectacularly effective. So people got, like, average easy improvement of about 80% at week four. So it was, like, up there with a JAK inhibitor in terms of how fast and how effective it was. And so that's kind of exciting. There's literally no reports in the literature of anybody using so tick 2 for atopic dermatitis. So you would assume. So tic 2 would do the same thing. But it's a great example of, like, don't ever listen to the basic scientists. So back in the day, whenever. So Tick two was like, still in phase three trials. I was like, you got to study this free topic term. They're like, oh, no, no. Our scientists looked into it and they talked to blah and blah and blah who were like, the three top basic scientists in the world. And they assured us that it would not have efficacy in atopic dermatology. So they never studied it, and now they're going out of business. Well, not they're going out of business, but they're getting out of Durham. Just like, don't listen to the basic science.
- [50:28]
B
They're not marketing it.
- [50:29]
A
You Right, they're not marketing it. You don't know if a drug works in a disease until you. You have. Or a pathway is relevant. Until you have a drug that affects that pathway.
- [50:41]
C
You just.
- [50:41]
A
You never know. So you can say it really, that pathway we know for sure is involved, but you can never say we know for sure it's not involved. Right. Until you try it. And same thing. Just like the IL17s for atopic derm. Right. Chronic atopic dermatitis transitions to TH17. No, it doesn't. Because IL17 never works. Right. It's just the basic scientists just, they need to caveat it a little bit more. Like, I say a lot of stuff that I don't know is true or not, but I'm always willing to be. I don't know, it could be totally wrong, but I'm going to pretend like I'm for sure, but just. Okay. But the takeaway is tick 2 inhibition works great in atopic dermatitis. So if you've got a bunch.
- [51:30]
B
Have you tried it off label? Like, have you tried so tic2 in any of your atopic patients?
- [51:34]
A
No, I have not. Just because I'm not a big believer in doing that because I'm going to be really unlikely to go through the effort to actually get it approved. And I don't like begging for samples forever. And here's one tip for our listeners. In theory, if you say to a drug company, hey, I would like some samples of X to treat this disease off label, the drug company by law cannot give them to you.
- [52:07]
B
This is true.
- [52:08]
A
So you. Right. If you're going to do that verbally talk to somebody, don't, like, put it in an email. Because if you put it in an email, then they have to respond with a like, no, we can't do that and we're never going to give you a sample again. If you use them off label, they legally have to do that.
- [52:27]
C
So then I have a question. So it seems like this is a pet peeve you have against your basic scientists.
- [52:34]
A
Yes.
- [52:34]
C
What. So what future thing are you going to be like? I told them that. Do you have one?
- [52:42]
A
Oh, I'm. Huh. You know what? Next episode, I will have my I Told Them so.
- [52:51]
B
Okay, What I like is that you just presented a paper with a basic science theory with no data that you thought was awesome.
- [53:05]
C
Yeah.
- [53:05]
A
Hey, that's because there's no data, so nobody can prove them wrong.
- [53:09]
C
Right?
- [53:09]
B
That's the.
- [53:10]
A
You gotta. You gotta stick in the nebulous areas. Why do you think I went into dermatitis in the first place? Because nobody knows what the heck's going on.
- [53:17]
C
Right?
- [53:18]
A
That's the beauty of it. All right, well, before we sign off tonight, I do have to say with all of us being Pittsburghers, it's. How do you guys feel about Mike Tomlin? The longest tenured coach in any sport at this point being Let go. Patton, you pro anti. What do you think?
- [53:43]
C
No, I, I liked Tomlin. I, I unders. I, I understand the arguments against it, and it's not like they're completely wrong, but I think that the. Some of the fans just dislike of Tomlin was over the top. It never made a lot of sense to me.
- [54:02]
B
So.
- [54:02]
A
Okay, I, I liked him as a coach as well.
- [54:04]
C
I.
- [54:05]
A
You made a good point. Whenever I was like, they've lost seven playoff games in a row. Like, that's, that's like a record. How could. In. In. Your point was like, well, maybe he's a good enough coach to get teams into the playoffs who otherwise wouldn't get into the playoffs. So that was a good. You know, I could see where you're coming from.
- [54:21]
C
And so the counterargument is that's not like, that's not your job as a head coach. You, you, you get teams to the playoffs and then you advance in the playoffs.
- [54:28]
A
Right. Let me win.
- [54:29]
C
You see, McDermott got fired this morning. Yeah, he's.
- [54:33]
A
Yeah.
- [54:34]
C
I mean, his teams have done really well in the playoffs. They just don't make it to the Super Bowl. So he's gone. Yeah.
- [54:39]
A
Fairs, what do you think about Tomlin being canned?
- [54:43]
B
I thought he was. I thought he did a good job. I thought he represented Pittsburgh well, you know, but sometimes it's time for a change, and maybe a change will be a good thing for Pittsburgh, but, you know, I hate to see him go. And it's hard to be. It's hard to be a. You know, you can only be as good as the material you were given to work with. Right. So maybe, hopefully they'll get some better players as well.
- [55:10]
A
Patton, since you're the only one of us still in Pittsburgh, what's the feeling in town about if they should keep Aaron Rodgers or not? People hoping he comes back or not.
- [55:19]
C
I don't think there's a strong consensus either way at this point.
- [55:24]
B
I've enjoyed watching Aaron Rodgers. I thought that has been like something that was a nice, a nice thing. As a spectator who doesn't know a ton about football, it warmed my heart to see the old guy back on the field.
- [55:37]
A
That's right. Us old guys have got something going for us.
- [55:41]
B
That's right.
- [55:42]
C
Yeah. Yeah.
- [55:43]
A
All right. Well, I want to thank everybody for joining us this week. We hope you learned a few things. We hope you laughed once or twice, and mostly we're hoping you're planning to join us next week. Until then. I'm Matt Zyrus.
- [55:55]
C
I'm Tim Patton.
- [55:56]
B
And I'm Laura Faris. And we are Derms on Drugs.