The Derms on Drugs Bust Myths and Make Life Easier for Derms This Week

Welcome to season two of Derms on drugs, a video podcast brought to you by scholars in medicine, the best educational platform of dermatology and provided in no cost to medical providers. Derms on drugs is where cutting edge dermis here in this comedy. I'm Matt Zyres in 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 dermis 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 Podcasts, Spotify and other major podcast platforms. And there is a video con ponet that has the key figures and tables from the articles that we talk about. So we've got another one of our patented six-peck episodes. Dr. Ferris just flew in from running or I guess in a loose sense running a half marathon in Florida just in time to get on for the show. So Dr. Ferris, what do you got for us today? All right, Matt. Thank you. So I have, you know, I'm going to take a page out of the Matt Zyres book and when I'm supposed to do one paper, I'm going to actually kind of make it two papers. Whoa. I know. I know. So first one. Yep. Joint position statement from the National Board, the National Suriases Foundation Medical Board and the International Suriases Council on routine testing for latent tuberculosis infection prior to enduring treatment of psoriasis patients with interleukin 17 or interleukin 23 inhibitors. So this was recently published in JAD Andy Blowveld 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 US-based organization. And so basically what they're trying to do here is say, you know, all biologics are not the same. Why did 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. So, wait for a second. It's, do we have to do this? 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 and 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, so you have a cough and if the answer is no, okay, we don't need to test you. I don't even understand that rationale. Okay, so I will say one thing, over half of cases of active TB in patients who are on, but immunosuppressive medicines, particularly TNFs, are extra pulmonary. So, there's so much manifesting around all of this that people will say, oh, should I be getting chest X rays in my patients who have had a positive test? No. Most of them, so 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 a cavitary active lesion of TR-military TB, but active TB. You don't see latent TB and of course you're not going to see TB reactivation that's extra pulmonary. Okay, see at first I learned, thank you. Oh, Matt, it is my pleasure. The day I can teach you something is a happy day in my life. I know it's rare. It's rare. It's rare. Okay, all right. Basically, we just kind of like lump them in and kind of to your point, not even just on the human. We'll talk a little bit about there is some 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 IL-17 and IL-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, you know, adverse events to drugs. And so what they focused on in FAIRs that was extra pulmonary 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 IL-17 and 23s and across TNF inhibitors. Okay. So what did they do? First of all, they looked at mouse data, right? So they said blocking IL-17, AF receptor and the IL-17 receptor and IL-22 in mice does not result in, you know, TB or susceptibility. However, blocking TNF does. Okay. Also, they showed that IL-12 is important, which is why they are then in preventing TB infection. So that's why they said, you know, drugs like Stilara, IL-12, 23 inhibitors, they're not putting in like that safe to move forward category that we put IL-23 inhibitors in. Okay. So IL-17 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 are a few cases in the exochysmab 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 got liver disease and who did not, you know, who had latent TB, who didn't get treated went on IL-17 inhibitors. And they said, at most there was maybe one single atypical, you know, case of a person converting to active TB from latent TB. And then for IL-23 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 fairs database part was that they looked at over 96,000 safety reports from IL-17 and IL-23 inhibitors in psoriasis. None of them were cases of extra pulmonary or disseminated TB. However, in the 140,000 isht and F inhibitors, there are actually 26 TB cases, including eight of which were disseminated TB. So they said, you know, it's really shows it's not that there's lack of reporting. They 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 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 IL-17 or IL-23 inhibitors period. Now, they did say, well, there may be prudent in patients in TB and themic regions or patients. And I think this is important on concomitant immunosuppressive. So if you've got patients, particularly you are in like systemic steroids and another and one of the IL-17, 23s, probably still reasonable. So it's not never test. It's just stopped the reflexive testing of every single low risk IL-17 or 23 inhibitor patient 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 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 sort of nudging like we need to change this. We need to 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, 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, right? That's radiation. You send the patient to ID. They are 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. Their other one was also recently, it was in JAD, and it was Steve Feldman, his group, and one of the other offers was Willy Wong, Professor of Dermatology at UNC. - That's a great name. - It is a great name, it is a great doctor. - 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. That's awesome, that's a great name. I would marry a guy named Ying just for the ability to have named my kid that. So that's good. (laughing) Okay, so Velman's group actually said, like took a look at all of the data and said, "What do we need to really be?" Like, "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 TNF inhibitors." For TNF inhibitors, however, they said that HEPB testing and monitoring carries a small net benefit. They gave it a great C. But they said, you know, that benefit's really just in TNFs. For IL-17 and IL-23 inhibitors, what did they say? They said, "No need to do routine testing for HEPB, 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 getting a history less getting a bunch of labs. They also recommended against HEPC testing, HIV testing, CBC, CMP. They gave those all a grade D. So I thought that was interesting. So this was really rethinking how much should we be, can we really deescalate all of the monitoring and retesting and testing that we're doing with these drugs? So two good papers to take a look at. That's really good stuff. And what I want to 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 blood tests. Like it's-- - Because I think it simply delays the prescription, right? - Yeah. - Two weeks of not paying for taltz saves them, you know, thousands of dollars. So. - I need to see a CUP patient, Omalizumab. I mean, not a reason in the world why this woman should not have been given Omalizumab. And it was four months back and forth with the insurance company. She just got her first injection, I think, last week. And this was somebody I saw back in October. I mean, it's just, right. If they can put it off, I had them say, hey, you ordered you stuck in, you ma'am. You said every 30 days insurance, we need that to be every 28. And that delayed treatment for three months for this poor guy with this horrible, sorry, ask for. - Oh, you ordered Stellara at once a month? - Well, no. It was something Omalizumab. - Probably the second dose. - The second dose, yeah. - Okay, yeah, yeah, yeah. - All right, yeah. - So-- - Making people were actually the problem here. (laughing) - That one was probably on me. - Yeah, well, and I will say, and not to like out Matt Zyris, Matt Zyris, but there is actually like a third review article that was recently in JEDV, 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 IL-23 and IL-17 inhibitors, you know, fine to screen, but if they're positive and they are at high risk of being treated, just use an IL-17 and IL-23 or a premalass they threw in there too. And they said, don't treat for the latent TB. So-- - Yes. - And then they said, do not do, if you're in like a low risk situation, don't keep testing for patients who are on IL-17, IL-23 inhibitors are a premalass. 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 IL-17 and IL-23s. - But 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 Adelimimab biosimilars are really, really cheap. There's a U-stack Indimab biosimilar. And so that's gonna drop the price of that one. Insurance is 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 gonna be somewhere along the line. They're still gonna 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. And so I'm still probably, I don't see myself changing the testing part of it for the next six months, maybe even longer, but it may help me get to 17s and 23s quicker. - Yeah, I think it's a good point to say, if you have a patient with latent TB, it is more responsible to put them on an IL-17, or 23 than it is to get them treated and then put them on a TNF. I do felt that way. And I will say, I coach Akhenra 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 Akhenra with untreated latent TB, no cases of TB. So that's the other place where that may actually be our first cytokine inhibitor where the label will actually say you don't need to test, but time will tell. - That's cool. - Yeah. - Huh? - That's what I got. - Okay. Ferris, that was good stuff this week. - Thank you. - Good, I'm glad you're honest. - Sounds surprised. - Yeah. - Yeah, I know. So glad to impress you for once. - All right, let's go patent, what do you got? - All right, 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, "Kemo 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 hydrochlorothyazide isn't really contributing to non-millanoma skin cancer in a 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. - Yeah, that is how you're trying to kill everybody with skin cancer, that's the other. - I've just always been skeptical, right? I mean, nicotinamide prevent skin cancer like seems too good to be true. It's cheap, it's well, all right. So, previous article in 2018, Australian Journal of Dermatology, similarly titled, I think this is kind of, 'cause 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 nicotinamide 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 JAMA Derm paper. And they point out problems that they had with the study. So what did the recent study show? Nicotinamide 500 milligrams BID decreased, non-millanoma skin cancer by 14% at squamous cell carcinoma by 22%. And if started early, decreased skin cancers by 50%. - And again, I just don't understand. - That was purely observational though. That was just like Willie Nilly, anybody who wanted to could put them on or whatever, and then after a long time, there was nothing prospective about it, correct? - Correct. - All right. - Purely observational. - But I don't understand statistics and studies well enough to be able to identify these problems, which I think is a problem in and of itself. I mean, as dermatologist, you see the abstract, you see the headline, you hear other people talk about it. - You listen to some fools on a podcast. - I don't, 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 ICD-9 codes and ICD-10 codes. They didn't do it based on histology. So they kind of really just pointed out and all they really want to say is, you know, 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 talk about self-exam, we're just going to have to throw in the nicotinamide 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't 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. I'd like supplements in general. Today, I was bought a hundred and thirty dollar bottle that makes hydrogen water because there was a small randomized study showing that it helped with the keloid. So I'm all about supplements. But water has hydrogen in it. I just want to tell you that. There was a, it's, I didn't buy it, but I sent myself an email to see if I still want it in a week. Okay. But like it's easy. Like it's, it's just so easy to be like, here you go. I know. Take this. I don't know. I think there's so much stuff that we tell people to do that. I don't think that's that great of an evidence. Like I'm never, I'm not convinced that counseling people about sun. Like obviously we should have got a document. It's where you're going to ask us to do it off. But I don't know. I've seen a randomized double blind placebo controlled trial that counseling people about sun exposure reduces mortality from skin cancer. I don't think I have. No. Yeah. No, I hear you. I hear you. Yeah. 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 cardiovascular disease that really hasn't panned out. There was, there was a study that said it was cardio protective. Yeah, cardio protective. So, you know, those are the things that people, you know, bring up. So I'm, I'm hard pressed to find a bad reason to recommend against it. I probably would not say like absolutely don't do this. 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, yeah, it's in a mind, but it's, but I'm going to be like, eh, it may help. It may not. 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, it's probably not that big of a deal. Don't worry about it. The reason we're going to go either way. Let's, we'll put it, we'll put it that way. Okay. All right. Move it out of my first study. This one was actually could be a little bit of a game changer. Could be. So it was a association between topical corticosteroids and risk of upper gastrointestinal complications. And essentially they, it was done in Taiwan. They have national like healthcare system. 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 do I know ulcers and gastric ulcers. So the, the, just an odds ratio. If you just went on topical steroids, your just an odds ratio was 1.785, which is like, you know, a 70% increase now, whatever I really went, did the math. And because then the question becomes like, well, okay. But like if it's super like I have double the risk. Absolutely risk versus relative. Yeah. So right, I've double the risk of winning the power ball if I buy two tickets. But like is that a absolutely no. But so it's, it's not an unreasonable so that the absolute risk is about one in a thousand. And just normal people every year will get an ulcer, at least in Taiwan. And so this takes it to one 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, do I know ulcer is just an odds ratio is four. 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 going to make me go out and stop? Oh my god, we shouldn't be prescribing topical steroids. I mean, I'm only going to 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 going to change. But it's it like there is we, you know, we now have data that topical steroid uses good data associated with osteoporosis that at long term uses associated with increased risk to type two diabetes. Now we've got pretty good data that it's associated with increased risk of stomach ulcers. The osteoporosis group, I think, was the same group that did the stomach ulcer, wasn't it? I wait, I think the osteoporosis and diabetes people were the same people. Okay. And were they because those were all done out of like Denmark, I think because they have the same thing. They've got the national health care thing. 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 saying, they probably all work for like insight or something. No more topic of steroids. So they're talking about how germs we don't, we're not going to statistics. It showed an association. It didn't show that it causes. That's true. That is true. It was actually very similar to the nicotinamide, right? This was observational. It was based on ICD-9 codes. It wasn't based on like actual endoscopy, diagnosed stomach, you know, peptic ulcer disease. Right. 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 immunobulose 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 adjusted odds ratio of 1.7 to 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 end said, if you're like a non-smoker, if you're less than 65 years old, they don't recommend, like, peptic ulcer disease prophylaxis. So if systemic corticosteroids without any risk factors, we don't worry about peptic ulcer disease. I'm not worried about topical corticosteroids at all. It's like a higher risk. It's like a certain kind of higher risk. I mean, if you look at that paper, the people who really were at risk were like, they were on systemic steroids and end-sets and aspirin and topical 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 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, like, do they compare it to systemic steroids, but not topical or end-sets, 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. I agree. My main takeaway with this, I mean, takeaway was that it, like, it does seem like there is some effect of like covering your body in topical steroids internally. I think that the overuse of topical corticosteroids would be more concerning of like, we do not have your skin disease under control. If he, this is how many steroids and things that you're going to do. Oh, yeah. And that's the bigger issue, not like, ah, you're going to get peptic ulcer disease, stop using all these steroids. Yes. But they didn't notice how much you were using. They did. They did. They did, right? Like, they did like an equivalent based on potency and amount, I think. They did. They did higher cumulative long term increased it a little bit more, but not a ton more. Okay. It was like 1.6 to 1.8. So that was the low and high. That's really high. You earned your money from all the topical non-steroid companies. Okay. Okay. We can move on. Now, now, now, let me get myself in trouble. We'll make this one quick because it didn't tell us anything useful. Ah, switching from do Pilimab to you, Pat, a sit in there, but he and Adolescent adolescents from the mother. It's a very topic. But tight is after an adequate response to do Pilimab, efficacy and safety results from period two with phase three B slash four study level up. Basically, people got Dupy or Rinvoke for 16 weeks. If you were on the Dupy and you didn't get to easy 75, you got switched over to Rinvoke 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 Rinvoke is going to work. And that's kind of the takeaway. The thing that just drives me nuts is like the question that Abby 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 going to do people not great. And I'm like, well, we could switch over to this pill. 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 I was like, I don't know, probably like 5, 10% and they're like, I don't want to take the chance. If Abby had just given the number of how many people did at least as well on Rinvoke 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 Abby this multiple times to their like top people and the publication comes out nothing, not in the supplements, nothing bastards. All right. That's what you want to know. All right. Okay. Let's move on. Ferris, where do you got? Okay. So I have Remi Brutanib in chronic spontaneous urticaria, 52-week results from two phase three studies. G-menus are now at all. Okay. So this was the, this is the basically 52-week data of Remix 1 and Remix 2. So what is, I think we talked about Remi Brutanib 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 25 milligrams BID. So CSU, why do we need more treatments? Half of patients remains symptomatic despite an histamines 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 Omalizamab 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 Brutanib, BTK inhibitor, BTK is, sits downstream of the FC Epsilon receptor and mast cells and BASIFILs 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 type, which is where you've got IgG, IgMR, IgA that binds to the IgE that's already bound to your own FC Epsilon. So they're like, 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, Remy Brutanib, 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, Anna-Histamine. So they did have an Anna-Histamine and then they could get rescued, which was generally to go up to second generation, Anna-Histamine. And 30% of them had prior, basically, Omalizamab 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. Our R was higher and the mean score was around 30. So that's pretty bad disease. Okay, so for patients who were randomized to Remy Brutanib, they did see improvements. So they looked at mean improvement in UAS 7. It occurred as early as week one. And that at week 52, the main 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 well-controlled, which was a UAS of 6 or less. And about 45% of them had a UAS 7 of 0, meaning no itch, no itch, no hives. You know, basically, when people rolled over, they did about as well as the people who went in news, so it had improvement by, you know, by like one week in. They also did these like swimmer plots where they showed patients. So 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 moved from more severe 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 52 over half, by week 52 over half of the Remy Brutonib 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 nasopharyngeitis headache that you see in every clinical trial of any drug. Partique I, 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, they 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 laid a symptomatic bump of his trans aminases, but three to five times upper limit normal. Interestingly, they associated they attributed that to excess anti histamine 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 on set. 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 be. It stayed safe. So another drug for us for CSU. Any thoughts on that paper from my friends mainly that like why is it that the only drugs that like stop working or work less over time or 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. Like they just always strikes me as weird. I think it's that you build up a tolerance and there's something about the signaling the letters you're not seeing that. Yeah, why don't you build up a tolerance to to all of these to all of these? I don't know. Like Jack and I know antibiotics like antibiotics, you don't build up a tolerance. But you know, it's why it's it's an interest. Like maybe it's because you're act you're blocking something rather than activating something. Maybe that's it. Maybe it's what your act. Yes, I think it could be that and it's intracellular versus where do opioid receptors? How do they signal? Are they intracellular? I have no idea. I have no idea. I mean they're transcription factors, right? I don't know. I don't know. We are giving you no information on how opioids work. Not helpful. It's all speculation. But I have 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. Yeah, start like that. But it's metabolism for alcohol. It's the, you know, it's true. I don't know. All right. So Mr. Move. All right. Let's move on. Pat, and what do you got? All right. Really quick on second six pack. January edition, journal, the dermatology, title, a premalized associated clinical improvement and Bulls Pemphagoid with Plexarise by the Yamar. So as we all know, some evidence BP occurs more frequently in patients with psoriasis compared to patients without psoriasis. I did. I did. Don't say we as we all know, I didn't know that. He was all the smart people know. As all smart people know, the 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. Intreatment can be a little tricky. Systemic corticosteroids are standard to care 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 Dupy? Do you have any idea what percentage are going to get worse? Do you think it would be all of this? I think it would be, I think it would be, I think it would be like 90% would get worse. Okay. No, I was thinking about that. And right, that was kind of my take to met the trexate. It'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, eight year history, psoriasis, managed with top corticosteroids, who developed BP and kind of significant BP like, did he die, which did he get him or does? Did he get any stomach ulcers? Yeah, like 20 stomach ulcers that complicated everything. So his BP die, which nobody ever done, but it was 36, which kind of puts them in like moderate. He was prescribed as far as I could tell, only a premise, 30 milligrams BID, kind of assumed he continued the top of corticosteroids, but 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 so tick two, with very good results. Interestingly, both of those patients were treated with IL 23 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. Who knows? Very interesting. It was interesting enough that 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 ain't get shit. That's garbage. So anyways, we presented those two cases. It was just like an oral presentation. Wasn't even a poster. So I think first, I do want to chime in. That's interesting because the IL 17s clearly cause a TH2 deviation there, but it's not reported with IL 23s. So IL 17, the more potent the IL 17 inhibition is the higher the rates of new onset spungiotic dermatitis, IL 23 inhibitors. It's not so like it's higher with bimmy than it is with cosentics and pulses in the middle. IL 23s, it's really very, very rarely reported. Yeah, I was a little bit surprised, but it was both it was Giselle Kima and it was risen kizumia after starting those biologics. I mean, the skyrizzy patient, not the bad mouse guy, Rizzy. We love skyrizzy. 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. Pat, you need to work on that to pill you map to pill you map. I do stuff with Regina. But I mean, one dose of her skyrizzy and her, her like psoriatic plaques developed all these bullets. It was really, really, really rare. This is where we could use trinetics, right? We could say, you know, what is the incidence of BP and patients on, you know, being treated with, are 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 paper. And you got to compare the idea. What's that? It's got to compare 17s and 23s and Otesla. As that. That'd be actually a really interesting analysis and then we could come on and say how to try netics studies. So you shouldn't believe it, but it'd be interesting. You could make fun of it. So I think so tick to know 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 premise 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, just adding it to anyone because like, right, reformal last oral, we're of course talking about the podcasts favorite drugs over a Fumalast oral. Why is our favorite drug of company is a drug that will never ever sponsor our podcast? We're glad it makes our pun. It makes it pure. It makes it pure. It's pure on adulterated love that we have. And you know what they think they reduced the price even further on Mark Cuban's Cosplus pharmacy. It's now $5 a month from the 500 microgam pills. What's weird is the 250 micrograms or like 50 bucks a month. That's weird. It's weird, but yeah. 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, uh, but may it like why not? Yeah. I don't think it's too good. Our ex in normal pharmacies. I think it's like 15 bucks a month. It's still not that bad. It's not that much. It's a little higher than 20. Yeah. But interestingly, I had a pharmacy. 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 off. And he said, my doctor said they won't do it. I'll just pay for it. And she said, no, not interesting. Because the pharmacist probably makes more on revenue by running it through and shirt. Those. Yes. Exactly. Ice Markups. Yep. Yeah, they lose their markups. So. Yeah. All right. But so you had it yet another use for reflumalist and patent. You could any BP patient you have no matter what they're on. You could add reflumalist. I know. That's what I'm saying. Like, yeah. Yeah. Okay. All right. Let's all right. Let's go to my last two. So first one. So Ferris talked about Remi Brutonib. 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 Remi people like just in case Ferris talked about this already, right? 8% of people had a bleeding of the bleeding events were all particularly. I alright. 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 tier seen kinases. The general pathways involved in collagen driven platelet activation and the integrity related thrombostabilization. So this study or this was called mechanistic insights into patique I observed with the Brutonib therapy and chronic spontaneous ricaria. And so Remi in theory could cause patique IV of 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 it if it's something about the coagulation pathway, then it should like not be just patique I. And so this paper may be because it's an answer. And so possibly number two, they had no particular data. This was just like somebody like, hey, interesting. Right. So Matt sells. What's that? This is your kind of paper. This is my kind of paper. Yeah. Speculation. I know. Yes. Okay. So so mass cells reside perivascularly right alongside the capillaries and they help maintain endothelial stability via precisely timed release of vasoactive mediators and abrupt silencing of mass selectivity 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 Remi Brutonib, which I always have to say the name. Anyways, rapido. Right. Love it. All right. So my last and then my very last one, safety and efficacy of ICP 332 for Montage Veritabia Dermatitis, a phase two randomized clinical trial. So this is a tick two 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 jack 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 two free topic dermatitis. So you would assume so tick two would do the same thing. But it's a great. great example of like don't ever listen to the basic scientists. So back in the day, whenever so tick-to was like still in pastry trials, I was like, you got to study this free topic, Derb. And they're like, oh no, 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 road of dirt. And they assured us that it would not have efficacy in a topic, Derb. So they never studied it and now they're going out of business. We're not they're going out of business, but they're getting out of Durham. Just like don't listen to the basic science. They're not marketing it. You can write it on marketing it. You don't know if a drug works in a disease until you have a, or a pathway is relevant until you have a drug that affects that pathway. You just you never know. So you, 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 the same thing, you just like the IEL 17s for a topic, Derb, right? Chronic A topic, dermatitis transitions to TH 17. No, it doesn't because IEL 17 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, I don't know, it could be totally wrong, but I'm going to pretend like I'm for sure. But I'll just, okay, but the takeaway is take two inhibition works great in a topic, dermatitis. So if you've got a bunch of, have you tried it off label? Like have you tried so tick two in any of your atopic patients? 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 yet approved. And I don't like begging for samples forever because 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. That's this trail. So you write, if you're going to do that verbally talk to somebody, don't like put it in 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. So then I have a question. So it seems like this is a pet peeve you have against your basic scientists. Yes. So what future thing are you going to be like, I told them that. Do you have one? Oh, I'm, you know what next episode I will have my I told them so. Okay. And then what I like is that you just presented a paper with a basic science theory with no data that you thought was awesome. Yeah. Hey, it's that's because there's no data. So nobody can prove them wrong. Right. That's the you got to you got to 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. All right. 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. Matt and you pro anti what do you think? No, I liked Tomlin. I understand 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. So I like it as a coach as well. You made a good point whenever I was like they've lost seven play of games in a row. Like that's like a record. How could 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 your conversation. So the counter argument is that's not like that's not your job as a head coach. You you get teams to the playoffs and then you advance in the playoffs. Right. They were. I mean, you see McDermott got fired this morning. Yeah. Yeah. Yeah. I mean, his teams have done really well in the playoffs. They just don't make it to the Super Bowl. Yeah. So he's gone. Yeah. Ferris. What do you think about Tom and being canned? 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. Patents, ensure the only one of us still in Pittsburgh. What's the feeling in town about if they should keep airing rogers or not? People hoping he comes back or not? I don't think there's a strong consensus either way. Okay. Fair. Fair. I've enjoyed watching your and rogers. 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. That's right. That's old guys. We've got something going for us. Right. Yeah. Yeah. All right. Well, I want to thank everybody for joining us this week. We hope you learned a few things. We have to laugh once or twice and mostly we're open your plan to join us next week. And until then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Ferris and we are Derms on drugs.