SCC Scares, Lichen Planus Cancer Risks, CSU Breakthroughs, Psoriasis Wins, Chemo Hacks, and HS Itch Relief

[music] Welcome to Derms on Drugs. A video podcast brought to you by scholars and medicine, the best educational platform in dermatology, and totally free. Derms on Drugs is where cutting edge dirt meets hitter miscomedy. Matt Zyres in each week, I'm joined by my residency buddies, Dr. Laura Ferris and Dr. Tim Patton. We use our 60 years of combined experience to discuss, debate, and dissect the hottest topics in dermatology. It's everything you need to know to be on the cutting edge of Derm and it'll be the most fun you've ever had while actually learning something useful for work. New episodes drop every Friday on scholars and medicine, Apple podcasts, Spotify, and wherever else you might decide to get your podcasts from. So this week we've got one of our patented six pack episodes where it's kind of the equivalent of sitting on the back porch and cracking a six pack and talking about what's been the latest coolest stuff that you've seen in the literature. So we are going to go ahead and start this week with Dr. Ferris. Ferris, what do you got? So I'm going to start with a paper from JAMA Dermatology by Ran at All. Risk factor number and recurrence metastasis and disease related death in Coutaneous Scue Missile Carcinoma. Okay, so this talks about this is from the group really that came up with the Breggamon Women's Hospital or BWHT staging for Coutaneous Scue Missile Carcinoma. So really that is a staging system that uses the number of risk factors to stage. And so they have four different tumor risk factors that are used and however, it's not really precisely according to the authors, precisely associate the number of risk factors because Breggamon Women's Stage 2B includes Scue Missile Carcinoma is that of two or three risk factors. Do you remember offhand with the risk factors are in the breaking. As it turns out, Dr. Zaires, I do. They are number one, a diameter of two centimeters are larger. Number two, invasion beyond the subcutaneous fat. Wait, not into the fat beyond the fat. Into. Okay, all right. Because, yeah, that's okay. Yeah. Okay. Large caliber perinural invasion and poor histologic differentiation. Okay, so it makes sense. Okay. Yeah. So basically zero risk factors, your T1, one risk factor, your T2A, two or three, your T2B, and four, your T3. Okay. Okay. So that is, so that's what they looked at. So what they said was, or I would say, so site doesn't matter. Site does not matter. Embrysion and lip for any year and scalp. Okay. All right. That does not matter. What I've always thought was interesting also is, I mean, a suppressed status does not matter either. Right. So, so that's sort of interesting. So the outcomes that they looked at were five year cumulative incidents of local recurrence, nodal metastasis, distant metastasis, and disease specific depth. And so what you can find is that if you look at, you know, if you look at the number of risk factors, and you look at the cumulative incidence of these outcomes by risk factor, basically, it goes up with each one. So, you know, zero has fewer than one, which has fewer than two, which has fewer than three. So you can sort of break down that two, three, which has fewer than four. And that's pretty linearly, you know, that trend is seen by risk factor number for all of those outcomes that I mentioned. And so, you know, basically, squames with three risk factors had more, like 1.6 fold higher local recurrence, 1.9 fold higher, nodal metastases, and 4.3 fold more distant metastases than those with, you know, with two risk factors. So, it does suggest that we probably should be looking at the number of risk factors, not just within the T2B group. So that's kind of, you know, the take home point of this. So what do you do? It makes you wonder, why did, why did Brigham and women combine us? Have we talked to bring them or women? How called them both? We're talking to a woman right now, Pat. Yeah. So you really know to bring them. You know, like that this seemed so obvious. I, you know, I never thought about it when I, you know, would go through the Brigham and women staging. And then this, it's the same exact risk factors. It's like, well, of course, why why not separate two versus three? Right. No, it's a good point, but it did not. So, so why does this matter? I think is like, I was like, why are they doing this study now? Right. We probably could have intuitively said that. So, you know, much like we are, you know, sort of had our like this, you know, you know, all these studies of like, Ag event therapy and neo-ag event therapy for melanoma that we've talked about on our podcast before. You know, there's also been data for like, neo-ag event therapy for advanced, you know, squamous cell carcinomas, but, you've removed it. Now you're going to give immunotherapy. It's sort of going to be the next, I think, Renaissance entreatment of patients with high risk squamous. So, when we think about Ag event therapy for stage two melanoma, right? So, it's like, do you give this patient, a volume app or a pemberlism app for their, for their stage two B or two C melanoma? You know, there is a lot of debate over who is having a lot of, a lot of debate over who is high risk enough that their disease will return, that we want to actually give them Ag event therapy, right? So, I think that this is all about better stratifying that intermediate, that T2B group to say, okay, probably maybe the number of risk factors you have is going to be important. And maybe, you know, for example, we might want to think about giving Ag event treatment to the really high risk, the three risk factor, not the two risk factor. So, I think that's part of it. Are you, would you, at this point, what is your cutoff for sending somebody with a squame to see an oncologist? Or a surgical oncologist, or somebody who's more than a most surgeon? You know, I think if they have one, if they have at least two high risk features, I'm going to probably discuss it with the tumor board, if they have one. So, diameter of two centimeters are larger, maybe not, but, you know, invasion to fat, perinural invasion, poor histology. I mean, those are all things that are going to at least lead me to have a tumor board discussion and to consider, you know, potentially like, do we want to do Ag event radiation, right? So, those are all factors that would lead me in that direction. So, now-- 59.9% of dermatologists who do not have, not have, Durham providers who do not have access to a tumor board. So, it, so really our choice is why I can send them to a surgical oncologist, or a medical oncologist, and they're going to send them to a tumor board, essentially. So, you're, in fading into fat, big perinural invasion, and undifferentiated, any of those three you were at least going to think about it. Yes, I am going to think about it. And I would also put in there, particularly in the immunosuppressed transplant patient, right? So, that's where it's really going to matter. But, so, you know, what is coming down, I think the pike that is going to make this interesting is the idea of adjuvant therapy. So, you know, now we are like, should we do adjuvant radiation? We've treated them, we've removed their squamous cell, maybe they've had mose. Their squamous gone, do we want to do adjuvant radiation? It's a radiation after. But now there have been two studies looking at adjuvant PD1 inhibitors in this group. Interestingly, we do not have like, I cannot present that paper, which I would if I, if that were like my option. But, there's actually like press releases with information or top line results. So, first one is called C post. So, this was adjuvant submiplomab for the treatment of, you know, high risk, cutaneous squamous cell carcinoma's post surgery. And so, they show that they reduced the risk of recurrence or death by 68% versus placebo. So, patients, yes, a pretty big impact. So, this is really the first track. But if it was one person and a thousand died and now one person and 1500 died. No, this is high risk cutaneous squamous cell carcinoma. So, they're like dissect all the data. I mean, you would not do this in a patient with like, you know, the run of the middle squames that we see better ocementometer, not, you know, no perinural well differentiated. You would not be putting them in this study. In fact, they had to be, they criteria to go in more pretty high. So, like perinural was like a named nerve, for example. Then there's another study keynote, interestingly keynote 630, and it was basically kind of the same study, but with pemberlism app versus placebo. And that one was at the time at interim analysis. It didn't meet its primary end point of recurrence, free survival. And so, it was, you know, deemed unlikely to meet the secondary end point of overall survival. and so they actually stopped the trial early. So very interesting that one group, one had this like phenomenal result and then the other one got pulled early. They're both peding one inhibitors. So you know, there's some, like you could speculate, one people have speculated that potentially in C-post the semiplimab study, that those patients were a little bit higher risk and so there was a little bit more room for benefit than you saw in the inclusion for Pembalism app. - But 68% versus nothing is pretty hard to explain just on. Ah, they were a little higher risk. - Yeah. - So it may matter. So I think it's gonna become very important to think about like who should be getting adjuvant therapy and do we have criteria to predict who's gonna benefit or not? - Okay. - You were I thought was odd about this study is, when you look at NCCM guidelines for Cutani squamous cell carcinoma was they don't look at number, well they kind of do, but one of the things that stands out is pairing your own invasion of a large calibriner, what is that? 0.1 millimeter, right? - I see you've considered 0.1. - If you have that in that alone, it is like, yeah, you know what, discuss adjuvant radiation therapy with those. It's almost like some risk factors are worse than others as opposed to number. And so I thought that was kind of weird of like, yeah, okay, you have four risk factors, that's gonna be worse. But if you just have one risk factor and it happens to be pairing Dural where that jumps you up to, let's start discussing, should we advance their peer, you know, add some sort of adjuvant therapy in these people? - And I'll say intuitively that makes sense to me. I mean, it shouldn't. Why would we think that all risk factors are the same? Right? Like, you know, being a diabetic with a hemoglobin A1C of 14 is a worse risk factor for cardiovascular death than is, you know, having a blood pressure of 132 over 92. So like it, it intuitively it makes sense. Does it mean it's right, but intuitively it makes sense. - Yeah, so, you know, so staging is sort of a blunt instrument for risk stratification, right? So, you know, I think the thought is, are there ways that we can have more, you know, sort of fine risk stratification? So that's where gene expression profiling comes in. That's where looking at, you know, - There is. - Different, you know, the different risk factors. So, you know, like a lot of times even in melanoma, like we have nomograms that will predict risk probably better than staging alone. So I think that's where we're moving sort of as a field and oncology or ketenis oncology is more, you know, sort of granular risk stratification. - And speaking of that, in one of our early episodes, our first or second one. So if anybody doesn't know on the scholars and medicine website for each of our episodes, we have links to all of the articles. We have, I think it was in the second episode, we have a link to a online risk calculator with melanoma, the Dr. Patton, right? Do you remember what it's called? - Nope. - Yeah, but so you type in like, what's their age, where on their body, the whole, it has like 10 different factors. - There's an 8-PC-C1, I think, and there's like an MIA1, the melanoma institute of Australia. - I think it was the MIA1. That's on the front. - That's on the front. - Yes. All right, let's move on to our second article here, Dr. Patton, what do you got? - All right. My first six pack paper was, "Impact of oral precancerous lesions on oral cancer development in patients with oral Lycan planus." A retro-spective cohort study of 318, oral Lycan planus patients by Chewitt All in the March 2025 edition of Frontiers in oral health. I think oral LPs challenging to treat, and I remember learning in residency risk of oral SCC is higher in patients. Wasn't that high? I always use the 1% number when I counsel patients about SCC risk when they have oral LPs. So it was funny, I was asked to give a lecture to a bunch of maxillofacial pathologists. So I started looking into the OLP thing. Maxillofacial pathologist, there's actually this controversy where if you have run in the middle, oral Lycan planus, that is not precancerous. And so why are you calling it that? It's the patients that have OLP with other atypia. And it's kind of funny to read about. They get all, they kind of get bitchy towards one another. - Yeah. - Yeah, personally, that's a bunch of garbage. It was kind of funny. But anyway, that's kind of an aside. This was a retrospective review of 318 patients with a histopathologic diagnosis of OLP, a single institution in Taiwan between 95 and 2018. They didn't divide those patients into those with and without oral precancerous lesions. So that's OPLs, not OLP. It's very confusing. So in this study, Veruca's hyperplasia, mild to any worked from mild to severe atypia, that was what it was considered an oral precancerous lesion. 207 OLP patients without pre-milligment lesions and 111 with pre-milligment lesions were more common in patients younger than 50 males. People that drank ethanol chewed betel nuts, smoked head candidises, had oral cancer. The overall rate of SEC was high overall, like in all of the 318 patients, oral squains developed in 10% of patients, but that's way higher than, I mean, 10 times what I would tell people. It was higher in patients with pre-milligment lesions. So 20% of that group compared to 4% of patients without pre-milligment lesions, but even 4% is kind of high just for normal outpean. Now this is an Asian population and there may be risk factors in it. - I have a vague recollection that it was in particular, ulcerative oral like in planis. Like normal, like wikumstria, stahada, haid, was normal. - Yeah, because you've obviously that, you're probably not going to see much in the way of atypia or the other things that, you know, these very strict pathologists are like, that's the high risk patients, not wikumstria, where you're just going to see, you know, the like annoyed infiltrate without significant atypia. You start getting erosions, you start getting like the atrophic form, you know, there's all these other pre-canceres changes, lucoplegia, or rithroid lucoplegia, things like that. Right, you're going to see that more and probably the luc, like in planis that is clinically more severe. I think that's probably true. The second table showed what was associated with the development of oral cancer and LLP patients, and yet statistically significant higher hazard ratios for cancer were seen in patients with pre-malignant lesions. That makes sense. Patients over 50, ethanol drinkers, patients with kidney disease, that was kind of weird. The one thing that they had never been reported that they thought was interesting was, cutaneous LLP was more common in patients without pre-malignant lesions. So like cutaneous and mouth, less likely to have the pre-malignant lesions, which that had never been reported before. Ten, there was a figure that showed 10-year chymalytic incidence rate of oral cancer, and it was higher in patients with pre-malignant lesions, and one would anticipate. So just a little bit more info on like in planis and cancer risk, but I thought was kind of interesting. - So what is your threshold for, hey, maybe you better go see somebody, like, 'cause you tend to their dentist or do you have to find an oral pathologist. I think you're best off finding like either like a. - O-M-F, oral, extra, great. - Yeah, like an oral or maxifofacial surgeon. I think they're much better with kind of the medical stuff. I think ENTs are very, very good at cancer, but when you start getting into, well, I think this could be like in planis or MNP, I have found that the oral or maxifofacial or like the dentists that also have a medical degree, they understand the medical side of mouth stuff, a little bit better. So we happen to have a dental school at Pitt. It's very, very helpful. A lot of those patients actually, I'm sorry, a lot of those physicians actually will do the procedures and they do histopathology, so they really understand the diseases, I think a lot better. - All right, so if you have the, so just thinking about right, we have listeners in big cities and listeners in the middle of nowhere. Top choice would be an oral pathologist, second choice would be an OMF guy or those would be the same. Or OMF. - I know that's true, I mean the same, yeah, right. - Okay, and then an ENT and then sort of after that, like if you're in the middle and nowhere, nowhere and the only thing around is a dentist, a dentist is still better than us. - They do in the biopsies, yeah, I think so. - Yeah, okay. Well, okay, fair. - Much comfortable doing, which I am not, but if you were comfortable doing the biopsy, then it's fine and derm path, your derm path, because I've totally read that. - I know what I'll do is like oral Lycan Plannis patients come in. I see this sometimes with the PEPIGAS patients too, and it's just like a bunch of the things get better, but they still have this one erosion, or they start to develop like a macerated, hyper-caertonic whitish, that's when I start thinking, all right, this may be like progressing or getting to one of those pre-malignant lesions, where maybe they're gonna see the dental person on a regular basis and then they're just coming to see me. - Right, the Arithro-Lucoplegia, where the ones that are like the strawberry, red, and white are worse than if it's just white and worse than if it's just red. All right, let's move on to our next one, which was mine. This is the first big publication of a new drug that we're gonna be hearing a lot about over the next couple of years. So Remi Brutinib and Chronic Spontaneous Articaria in the New England Journal of Medicine. First off, was Dr. Hyde. And so essentially the takeaway here, Remy Brutonib, extremely effective and very fast. So the big takeaway here, Remy is a Bruton Terosene kinase inhibitor. And for anybody who's in allergy or oncology, that is a little bit scary of a thing because Bruton Terosene kinases are actually used for treating real cancer. And they can have real adverse events. And so there's some element of like, oh my gosh, a BTK inhibitor for something like or to carry. That just seems like too much. But Remy is a extremely selective BTK. And the way that you want to think about this, the drugs that we've had up till now, anti-histamines block histamine after a mast cell releases it. Right? Omalizumab, you think of that as trying to prevent the mast cell from degrading by either blocking the IgE or blocking kind of the Ig from getting to the Ig receptor. And it's pretty effective. So about two-thirds of people will do really well with Omalizumab. But it usually takes a month or two to really start working. BTK is downstream from that. So BTK is after the IgE binds to the mast cell, the Bruton Terosene kinase that Remy is inhibiting is part of the pathway from that cell service activation to degranulation. So you can almost think of this. And I don't want to give anybody the sense is like a jack inhibitor and you know the adverse events and immunosuppression. And whatever it's not. But it's kind of the same idea that it's an intruscellular blocking the signal from the surface to cause the degranulation unlike Omalizumab, which is trying to block the signal on the surface. So this should have broad applications. So Remy, it's the first thing we've ever had that really effectively prevents degranulation. It should work in regular allergy. It should work in CSU, which we now know it does. There's even some belief now that it's going to work in a topic dermatitis. There are studies going on for Hidrad Nitis. For anybody who hasn't listened to our episode with Dr. Dan Kaplan, we get into a little bit about turns out the mast cells have a much bigger role in container inflammation and immune responses than we used to know. And Remy is the first drug we're going to have come to market that might really have a broader spectrum effect on mast cells than trying to prevent IgE from activating them or trying to prevent the histamine from doing something afterwards. But the big takeaway is how I guess that was the third thing that I just said the big takeaway for. So the other medium takeaway, just how fast the drug works. So within the first days you're typically seeing people start to get relief and then very consistent and durable relief as well. The other thing that's going to be interesting though is it's a BID drug and it has such or anything that has a really rapid onset of action. It has a really rapid loss of onset of action. So we we may see people literally like if they forget a dose before they get a bed at night they may wake up with with itching. Like is is a real possibility. So it'll be interesting to see how that part plays out as well. But but that's kind of what I got for for Remy. Thoughts comments. Yeah, I thought it was I mean it looks promising right. And I forgot one thing the only adverse event. Three percent of people get petikeye. But none no cases of like you know it being like acting like basculitis or something like that. It's just petikeye with no clinical relevance. Yeah, no I think it's interesting we definitely need more CSU treatments. I believe that they're going to say what's going to be interesting is when we start to have head to head studies right. So I believe we're going to have head to head with this and to pill you mav at some point. And I mean I would imagine this was Zolaire as well because Zolaire I think biosimilars are just coming out for Zolaire. So if they want to be you know considered as first line therapy by insurance companies they're probably going to need to generate data saying we are better than them. If they want any chance of getting one formula area ahead of a cheap biosimilar. Yeah, not that you can compare cross trials but I did go back and look at the omelizavab trials like omelizavab numbers you know using the same sort of mean reduction or whatever in the USA 7. A little bit better I mean I know it's two different trials but USA 7 seems like that's probably an UAS 70. Yeah, ErdiKerry USA. USA, USA, USA. The biggest benefit of this drug over omelizavab is how fast it is. It is just like almost instant. First dose people start to notice a benefit from the people I've talked to did the trials. And you know just how much easier to have an oral medication than like omelizavab is a pain to given the office. And this with how rapid it works. CSU is another one of the conditions where once people are doing well on Zolaire they're often like can I stop it? And you're like oh it's going to be such a pain and then cover it again and the whatever. This they can much more be like hey I haven't had anything in a month I'm just going to stop it my hives come back I'll start it back up I've got you know my bottle sitting there. The only advantage I thought to omelizavab would be with potential monitoring it seems like these these you know used to be used in cancers ear monitoring them all the time you're just kind of freaked out about. Yeah like if we use this in cancers like we're going to have to check CBC and LFT. I don't think there's any it is it's selective for a different BTK I don't think there's going to be any monitoring. Well see yeah I mean the lab data looked fine right like I didn't know. Was that Petiki but the platelets I didn't. Yeah the single down it was fine. I and R was fine so yeah I think it's going to be interesting and the wrong concomitant and histamines too right? Yeah so with the early carrier trials they it's always that people are on a stable dose of anti histamine coming into the trial and they're allowed to stay on it. Throughout the trial it's a much better way to do the trials is how we had to do a D trials where you're on a stable topical regimen rather than you have a wash out and it actually makes a lot more sense but it's harder to show that your drug works in that situation. Okay all right let's move on to our next article here Dr. Fares where you got. So I have the study on systemic therapies for psoriatic disease and serious infection and older adults. Drucker it all from JAMA dermatology. Who wait Dr. Dr. Dr. Dr. Dr. Dr. Ron in a month or so to explain to us how meta-analyses get abused in the world of dermatology. Okay. A drug companies manipulate them in order to make their drugs look better. Great well this was not a meta-analysis this was a cohort study. Okay. Well this was but it was in Canada our sworn enemies so we're not keep that in mind. Let's not talk about this paper. Let's talk about USA scores in early class. Exactly. So this was health administrative data from Ontario Canada. So it was over 11,600 people 66 and older with psoriatic disease who were given their first systemic medication basically between April 1, 2002 and December 31st 2020. And so data analysis was like 21 November 21 through August of 24. So this was not like a case control or like you know they didn't have a control group who didn't get them. What they did was they looked at sort of people began accruing person time in a medication category on the day that they started a new medication. So you may have like your methotrexate era and then you may have your chumira era. And then you can you would you know have you would accrue data as long as you were on that. And then once you stopped it they sort of that rules as to when you were considered off of it. So they looked at basically five different categories. So you know who were these people psoriatic disease 73% of them were just skin only. Cutaneous psoriasis not PSA. So they looked at five categories. People are five sort of exposure categories methotrexate older systemics your acetretin cyclosporin TNF biologics other biologics. So these were basically your IL-12/23 and IL-17 inhibitors and then tofacitinib. So what they looked at was time to serious infection. So that was hospitalization but your main reason that your hospitalize was because you had an infection or it could be death from infection. And so a lot of these patients like about half of them were in the methotrexate cohort and about 12% overall were hospitalized for infection. So we in the Methatrexate cohort or overall. - And overall. - Okay. - Okay. So most common infections, pneumonia was number one. UTI, sepsis, cellulitis, and then COVID, there were 36 hospitalizations for COVID-19. So if you look at the hospitalization rates per 100 person years, right? So person year is one person exposed for a year or two people exposed for half a year each. So rates per 100 person years, 2.7 for Methatrexate, 2.5 for older systemics, 2.2 for TNFs, 1.4 for other biologics, and then 8.9 for Tophicinib. So I mean, I thought that was really kind of, that to me was the most interesting. What's that? - What was the reference group? - No, it is. - Each group is sort of, there is no reference group. So it is, it, well, no, that's not true. I have to see a has of a reference group. The reference group is, for is time not using that medication class. So compared to everybody, you know, on a drug that's not Tophicinib, the, that's sort of your reference group. When, and that's really more, so the person years thing, the numbers I just gave you, those weren't relative risks. That was just, you know, number of hospitalizations per 100 person years. - Okay, okay. - Like when you look this, the multi variable adjusted, you know, model. So what, where like the reference group is important is when you're looking at relative rates or relative risks. So what you really saw was that the group that actually had the lowest infection rate. So a relative rate of 0.65 was the IL-1723 group. So they were really let, you were less likely to have a serious infection on an IL-1723. The group that kind of crossed one in that relative risk group were the TNFs, the older systemics, and then the MAP, the trixate. And then the group that really favored a higher risk with the relative rate of 2.89 was Tophicinib. - Yeah, that all makes sense. Did they break out the IL-17s and the IL-23s at all? - They did. Yes. So the IL-17s relative risk was 0.59 For the 1223s, it was 0.68, but they had confidence intervals that were pretty overlapping. So there really wasn't a big difference. There was not a big difference between classes when you looked at different drugs. So things to consider, this is Canada, and people would have been manned. I mean, not to not Canada, I like the Canadians. But realize that if you look at like step therapy, everybody probably would have had to have been using method trixate or an older systemic medication at some point prior to getting on a biologic. So just keep that in mind. And there's been changes in practice over time. This also didn't, you know, account, this is non-randomized. So, you know, it may be that like maybe your sickest, elderly, most frail people don't end up going on like an IL-17 or IL-23. So there's like this healthy patient bias for newer biologic. So, it's an interesting-- Yeah. I was surprised that the IL-17 and IL-23, that the 17 that they overlapped. I guess I had always thought of the 23s as being the least impressive if at all. But this makes this kind of says, ah, they're about the same. But serious infection, right? So like, I think if you looked at Canada, you're going to see a difference between those two. But these are things that land you in the hospital or kill you. OK. So, you know, why does this matter? Like, if you look at a lot of clinical trials, inclusion criteria, particularly for things like a Jack inhibitor, but a lot of times patients who are older than 65 are excluded. Or there's an upper, you know, limit on age and maybe at 75. But so this was helpful to look and think about, you know, what about elderly patients. This would argue that, you know, their risk of infection is going to be lower if they have an IL-17 or an IL-23 versus other medications. And it really kind of drove home a pretty significant difference for a tophysinum. Patent, any, is this going to change anything? Or, you know, like we think those are safer. And we still do. Yep. And I would, you know, with atopic Durham, when people hear me say, Jack inhibitors don't cause-- they don't increase your risk of Mesa VTE, which is controversial statement, but I'm comfortable making it. People often hear me saying that that means that jacks are safe. And no, jacks are immunosuppressive. I mean, that happens to be a side effect we're comfortable with. But jacks are immunosuppressive, whether they cause Mesa VTE or not. All right, let's jump onto our next paper. Dr. Patent, what do you got? My second six pack was titled "Safety and Efficacy of Prophylactic Topical Stereoid Administration for N4DAMAB VETO-10 Related Cutaneous Toxicity by KETA. The senior author was Kobayashi, who was-- that was Kaiser Soze's assistant in the usual suspects. And I wondered what he'd been up to. But it was published in the European Erology Open Signs in December of 2024. And Fordamab VETO-10 is an antibody drug conjugate used in the treatment of advanced aerothelial cancers. And Fordamab is an antibody that binds to a protein called Nectin-4 that is highly expressed by aerothelial cancer cells. Then it delivers some chemotherapy I didn't write down the agent. It has a long name. So I didn't want to remember it. So does it connect to particular cell? So it's kind of like that old one we used to use in CTCL, where the-- So I know-- --divitox. Yeah, where there-- So it's an antibody is a wind fear. I don't know. But it's got a-- Yeah. --so an antibody that delivers the drug so that in theory, you prevent toxicity because the drug only gets into cells that are targeted by the antibody. No, right. So I read something. Like antibody drug conjugates. Like this is going to be the big thing. I don't know. Yes. I think when you look at oncology, I mean, it's an antibody drug conjugates as like that's the new wave. Hot hot hot. Yes. OK. So this antibody binds to Nectin-4. You know who else expresses Nectin-4? Paratinocytes. Oh. Oh. So these patients often develop Cutaneous side effects. Up to 50% in some studies, you combine that with Pembro, percentage of patients with Cutaneous side effects to be as high as 70%. That's like three exclamation points. So this study enrolled five patients, three males, two females, which you're looking at a drug side effect. You're in a row of five people. You're not going to see it. Well, they saw it. They saw it in three patients. So they applied Petrolotum on one side of the body in Clobatusol on the other side of the body. And Fortabab rash occurs predominantly in inter-trijeanous areas. So the patients only applied the Petrolotum or Clobatusol to the to the axilla and the groin. They did this for four weeks while receiving and Fortabab. Two patients did develop the rash at all. The other three, they didn't have any rashes on the Clobatusol side, but they did develop a rash on the Petrolotum side. Retro-represented photos are shown. We'll put that up in the slideshow. So Clobatusol prevents and Fortabab rash. And with such a high percentage, it seems like a crazy thing. Doesn't seem like a crazy thing to recommend to everyone on the drug, right? - Did they do the Clobatusol first? Yes. Did they do the Clobatusol like just every single day or was it five days a week? Or you may have said that I missed it. Or what they do. - It was, I mean, double check me on this. It was twice a day. - For four weeks from the start of the year. - For four weeks, maybe because the dosing of the M4Mab is week one, eight, and maybe 21 or 15. And then if you give it with Pembro, you only get the one and the eight dose. I think don't quote me on any of the dose. - So it was for the first four weeks. It's for the four weeks after each dose. - Yeah, it's just the four weeks while you're on cycle, so to speak. - Yeah, so you get four weeks on, four weeks off, kind of a deal. - Yeah. So that's just too risky. People are gonna get stretch marks. - I mean, it could be. - Right, maybe. I mean, you know, what Yacquitheson was like, Clobatusol will kill you. - I mean, it killed you. I think the takeaway I got from him, maybe you go attack or bait a methazone, maybe you don't go full Clobatusol. - Oh, come on. - You go Clobatusol. Go bigger, go home, Pat. - Yeah, I know. It was interesting. I've seen this. I've seen the M4Mabrash pretty interesting. It was in the Buk area. And I thought it was like BP. There were these erosive, you know, the pictures of the one patient. It's these erosive lesions, pretty painful. Yeah, so if we're using more and more of this, we may be seeing this more and more frequently. - So then the other question becomes, does the Clobatusol still help if you once the lesions start, but not, it's not gonna hurt. It's still reasonable to, you know, and then you would do it with future cycles, obviously. - Yeah, well, I mean, honestly, like everyone using the Clobatusol side did not break out in the rash. I think in the, the petriot side were developed, they stopped the medication, they gave the patients, the patients' systemic steroids. I don't know if they like, it was a crossover where they started Clobatusol. I mean, obviously it's a small study. Short, short period of time, but yeah. - Okay, okay. Useful for if we're seeing these people. Whenever you put this in as what you were gonna do, my main response was like, what the hell is, and Forty-Mab, Vadoeton. Now I know, and that's actually kind of pretty-- - Everybody's gonna learn something on the episode. - ADCs, and I body drug complexes, okay. - Conjugates, yeah. - Conjugates, okay. For last article here, I've got one efficacy of strontium cream in alleviating paritis and hydrodynamicoperaetiva by Walker Brooks and D'Avalui. And Steve D'Avalui, and I have no idea how to say his name, really good guy at Wayne State who does a lot of H.S. And the first question that came to mind for me is like, "Are H.S. people itchy?" Like, and so, like, why were they doing this study? And so I went back, there was an article in 2017, American Journal of Clinical Dermatology, assessing paritis and hydrodynamicoperaetiva across sectional study, and the big takeaways were this, about 57% of people who had H.S. had an itch score of at least three. Three, so when you think of it, you think zero one is pretty much know itch, two, three, four, probably two and three is myoditch, four, five, and six is moderate itch, and seven, eight, nine, ten is severe itch. So, almost two thirds of people with 7% had an itch score of at least three. The mean itch score was 6.1, which was actually pretty high. And whenever you really look at this, there were two big predictors, Hurley Stage 3 in the growing. Those people, so Hurley Stage 3 was like an odds ratio of seven or eight for having an itch score of at least three. Hurley 2 was an odds ratio of almost two, about 1.69 to 1.8, and the vast majority of the itching was growing and exilla and buttocks, but growing was like by far the top one. And then again, by far, Hurley Stage 3, and that makes sense, so we know that scars can itch, especially scars that are inflamed. Makes lots of sense, so okay fine, I'm now reasonably convinced that at least for people with scarring from HS, they've got significant itching. And so then the efficacy of strontium cream. So strontium cream, this is dermal leave, right? Hopefully most people at this point have heard of dermal leave. We've had data since the 90s that strontium topically is actually quite effective for itch. It seems to be it's a calcium mimetic, so meaning it affects calcium channels and calcium dependent receptors. And those happen to be very important in itch processing. The data that we have historically for strontium is that it's very effective in itch in about two thirds to three quarters of patients. And so they decided to do a study of it in HS. They enrolled these people from a support site called connect HS. And that's a useful thing just to know that that exists to send you if your HS patients are looking for a support group at all. But so they use it to recruit people. Like they had a substantial number of people that ended up including 50 in the study. And the big takeaway, so it definitely helped. So they only looked at one week follow up. And this is an over the counter, so it's cheap. Right. There's not going to be any funding for like a big or a long term study. And the dermal leave is actually really cheap. You can get it on Amazon or you can sell it out of your office. But the thing that I thought was most useful, so they did survey questions. And in the survey questions, did you experience an overall reduction in itch? 76% said yes. 24% said no. Did you experience a stinging sensation when you applied the cream? And that's important because dermal leave stings like crazy. If you put it on broken skin. And so 60% of people said yes, they got stinging. 40% of people said no, they didn't. So the majority did. Next question was if you experience stinging. Was it worth the itch relief provided by the cream? And so whenever you look at this, about 20 people said yes, 10 people said no. And the other 20 people didn't have any stinging. So of the people who got stinging, two thirds of them said that the, I'm sorry, not to hear, two thirds of them said that the stinging was worth the itch relief. But then the most important question to me is, would you recommend dermal leave to other HS patients? And 42 people out of 50 so 84% said yes. And 16% said no. So the you know, take away here. If you've got somebody who's early stage three, especially in the groin, it's worth, you know, basically saying, hey, reichi, might want to try this cream. And it's cheap. You get it on Amazon. It's extremely safe. I primarily use it for break your radio parietist, the Tauja paresthetic and scalp itch. They've got a scalp serum that is really useful for, you know, the little old lady, or little old man who no redness, no flaking. Maybe a tri-clubate is all first and it doesn't work. Dermal leave is is a second line there. Had good success with it for scalp. But the strontium is an interesting thing. And we had like, so we have data going back to the 90s. It just took this long for somebody to really commercialize it. So really useful for your any kind of a neuropathic itch, genital itch, a genital itch, like an amyloidosis, break your radio parietist, scalp itch, that kind of stuff. Yeah. Good for itch. Good for itch. Good for itch. Not for an inflammatory itch. Not for a inflammatory itch. We can break it down like a topic dermatitis or to carry it. That's inflammatory itch. Other things are like more neuropathic itch. Yes, if you I do there are some people who use it for a topic. Derm if you are going to use it for a topic. Derm have you steroid for a few days first. Just to prevent the stinging. But it is it is a really useful drug in that sense. And also your sort of elderly itchy people and your diabetic itchy people. I do really like this company. I haven't really made any money from them from drug talks or anything. But I just really. Get on that. They're too small. They can't afford me. But I do really like this because this came out about five years ago. And the first company that brought it out when bankrupt because they spend all their money. Getting it into CVS on the shelf. And these guys have done a much better job of like sort of shepherding it through. Derm keeping their costs way down. Because the key thing is just keeping it on the market because it really does help. So how much does it cost? It looks like it's twenty five dollars on on on Amazon. For for for which size tube? Gosh, let's see. It looks like this is like 60 grams. So not bad. Yeah, pretty, you know, six. Yeah, it's expensive moisturizer, but cheaper than most co-pays. Yes. And it truly, I mean, the active ingredient, the strontium, we've got good data going back. 20 years. Like I said, they don't have the money to do like big studies at this point in this. This when I talk to Steve, he didn't. He's not like he got any funding from from the company to do this. They just don't have the money to pay for the stuff. But we've got data from Howard Maybach, like, say, going back to the 90s. Yeah. So the study, the thing I would say is like we have validated it scores, which are, you know, we are to 10, why'd you go zero to five? Like that's, you know, if you have a validated score, just use it. Yeah. And then it's really hard with non-randomized studies. I mean, I think it's, I like it. This looks like it was probably like a med student trial. And I like applaud students who try to take off things like the clinical child. So I like it. But yeah, use the validated score when you got it. And one week and non-randomized can be tough. But hey, you know, it's it's preliminary data. And that's where you start to figure out how to do things. And we need more research in HS. So good. And this stuff in its shape, right? So like 25 bucks for 60 gram, too. You know, it really last people a long time. It's not like this is a, you know, $80 for a tube of the stuff or something. Right. It's not like that vitamin C serum I use on my face. Looks amazing, Ferris. Thank you. Amazing. Amazing. Amazing. Right. We got to get Ted Lane back on here. His skin was perfect. Of a face off with him. Give me like another month of my theorem. I'll be good. All right. Well, we're, we're going to wrap up this week's episode there. I want to thank everybody for joining us. If you got questions, comments or ideas for topics we should cover on the show, shoot us an email at questionsanddermsandrugs.com. You know, hope you learned a few things. I hope you laughed once or twice. And mostly I'm open. You're planning to join us next week. Until then, I'm Matt Cyrus. I'm Tim Patten. And I'm Laura Ferris and we are Derms on drugs. (upbeat music)