What Actually Changes Practice (and What Doesn’t)

Welcome to season three of Terms on Drugs and Video Podcasts brought to my scholars in medicine the best educational platform in dermatology and provided no cost to medical providers. Terms on Drugs is where cutting edge dirt meets the interview's comedy. I'm Dr. Matt Zeyers from Dr. Dermatology in each week. I'm joined by residency buddies, Dr. Laura Ferris from the University of North Carolina and Dr. Tim Batten from the University of Pittsburgh. And we use our 60 years of combined derming experience to discuss, debate and dissect the topics in dermatology. It is everything you need to know to be on the cutting edge of the term and you'll actually have some fun listening. New episodes drive every Friday on Spotify, Apple Podcasts, Scholars and Medicine and all the other major podcast platforms. And I highly recommend that you download the Scholars and Medicine app to access the full podcast video archive and explore the best term educational content out there. We're talking real content, not far from a driven, you know, oh, what's a great way to think about, but no, like real stuff, right? So check it out and it is supported by an amazing AI clinical consultant called Ask Simon. So this week we've got another one of our patented six pack episodes before we get started. I am going to tell everybody I took the plunge this week and started an ex account Matt Zeyers M-E-T-T-Z-I-R-W-A-S. We're going to be talking about medicine, AI and other weird stuff. So check me out, but now that I've done, I'm always feel slimy after I do anything remotely self-promoting. All right, Ferris, let's kick it over to you. Okay. For the get rid of the slime. Okay. So my paper is, I don't think I understood what you said and I don't think I want to. I have integrated 31 gene expression profile test identifies low risk patients with cutaneous melanoma who can forgo the sentinel lymph node biopsy procedure results from a prospective multi center trial, beard, et al and future oncology just published online about a couple weeks ago. Okay. So this is the desize. Hey, Ferris, I'm sorry. I'm sorry. I want to get this before you get started. Yeah. Do you have an opinion? Just publish somewhere that sentinel node biopsies make people live longer. Now, let's cover it on a separate podcast. Okay. Okay. It's too complex for me to give an off the cuff answer. Yeah, I couldn't figure it out. I couldn't figure it out. Couldn't figure it out. Okay. All right. Okay. So this is the decide study sentinel lymph node biopsy. The test is decision DX melanoma the 31 GP test from castle biosciences. Okay. So this is a prospective study 912 patients, stage one and two melanoma 30 US centers. And it's basically sort of trying to be prospective and sort of trying to be real world. And so who got enrolled in this people who had cutaneous melanoma who were being considered for a sentinel node biopsy and who happened to have had the 31 GP test ordered. And then they were they were then, you know, offered to be in this study. So it's a prospective study, but these are patients for which the test was already ordered. So unlike other studies where you say we're going to randomize you or we're going to enroll you then, you know, order a test and blind you and compare the outcomes. Like you've got the test you're being sent to somebody for a to be evaluated for sentinel node biopsy. Okay. So what they did was they wanted to use the outcome. So the GP test gives us I 31, which is basically how likely is it that if you got a sentinel node biopsy, it would be positive. Is it less than 5% 5 to 10% greater than 10% kind of in the NCCN framework of when we recommend discussing consider or don't recommend? Okay. So who are these people? They mostly had thin melanomas, median brazlow, thickness of 0.8 millimeters. About a third of them actually had T1 a lesions, about a third of them had T1 B lesions. 18% of them were T2A. There's a smattering of thicker lesions. So, you know, T1 a lesions, we would normally say those aren't people for whom we would consider sentinel node, but they will say, well, they were high risk, meaning maybe they were transsected at the base. Maybe they were less than 42 years old, high mitotic rate, et cetera. About half of the, so the way that this study worked was you had your result, your GEP result, and then you met with the surgeon and you said, well, here's your, you know, percent likelihood. And then together, you made a decision based on, you know, did you want to do a sentinel node? Yes or no? They, if you did, they followed what was the result. And everybody, they looked at like recurrence free survival, three year recurrence free survival. So, about half of the patients in this study ended up getting a sentinel node. And in this study, of those people who got it, 89.8% of those had a negative sentinel node. So you would say as a group, they sort of fell in that like 10% positivity rate. Okay, 474, which is roughly half of those patients were predicted to have a less than 5% probability of a positive node. And of those 114 still decided to get the sentinel lymph node biopsy. Okay. So this is, so again, they did not all get sentinel nodes. So if you just looked at those group who did get sentinel node, remember, they're not randomized. So we don't know if we can say, you know, they are, you know, the unique thing is just that they got the node. Maybe for some reason they were higher risk. But if you look at it among the 430 patients who actually underwent sentinel node, those the test peg did a less than 5% rate had a 2.6% positivity. So they looked at actually T1 to T4 lesions across the entire study. So 2.6% of those had a positive sentinel node and 1.8% of those if you just limited it to T1 to T2A had a positive node. Okay, so that's in the group who we called low risk. So with the risk was predicted to be less than 5% and we saw that it was 1.8 or 2.6%. In the group where they were predict up greater than 10%, so the high risk group positivity was 21.4 overall or if you broke it down 16.7% positivity rate in the T1 to T2A. And so if you look at like how did that differ? So having a high risk test made you 8 to 9 times more likely to have a positive sentinel node biopsy. If we look and then, you know, trying to like do some backwards math because what they did not do here was like break everything down by T stage. Here's the percent that were considered to be low risk, medium risk, high risk. Here's the number who got sentinel node. Here's their rate. But if we look at the numbers, you know, you could say that in that group that composed the entire T1 to T4 group, there basically were three patients who had T2B or thicker tumors who actually were predicted to have a less than 5% risk of a positive note. So most of those T2B and thicker patients, their risk was greater than 5%. And so, but of those ones who did have a less than 5% risk and then had a sentinel node done, one out of the three was positive. So really, although it's not like a statistically high powered thing, you could say a third of those patients still did of those predictive less than 33% had a positive note. Does that make sense? I think so. Okay. I mean, if you do have a thicker melanoma and you have a low probability on castle, you are kind of taking your, the small number we have said it's not very predictive. Yeah. So, yeah. So tumor thickness, I guess like my take on message on that is tumor thickness does still matter and I would not have the comfort level to say, you know, hey, no worries, you know, you, it says less than 5% even though you got a T4 melanoma, you're good, right? So that group, a third of them still had a positive sentinel node. Again, it was only out of three people. And then if you took that, that thicker group T2B to T4 with the, with the, who had a greater than 10% risk, 27% of them had a positive note. So really kind of the same number, right? So again, to break that down your T2B to T4 group in the less than 5% group who got sentinel nodes, 33% of those were positive in the greater than 10% risk group who got sentinel nodes, 27% of those were positive. I would argue those are two very similar numbers. So back of the envelope math, but it didn't seem like this did a good job of stratifying for those thicker tumors. I'd love to get all the data and numbers and look at it. As you can guess, back of the envelope math is really the only kind that I do. Yes, I know. There was no. You're a big fan of this. Yes, no. So basically, if you again, a little more back of the envelope or not even, this is, this is in the paper map. So the, the I31 test identified 65.1% of patients. with T1 tumors as having a less than 5% predicted risk, and about 4.7% of patients with T1 tumors as having a 10% or greater risk. So, you know, most patients are going to fall in that lower number. Among those patients with T2 tumors, 21.5% had were predicted to be low risk. So, you know, what do we do with all of this? It's good because it's a bigger, it is like prospectively followed patients. It is a bigger subset of patients, but, you know, they are still primarily patients who have thin melanomas. So, they did also have this table where they compare, you know, their accuracy to CPGEP, but it's kind of apples and oranges. They're two different study designs. And overall, the Merlin 001 study, which is the other test, they had 1761 tumors. Their Sentinel node positivity rate was 17.6% versus like around 10-ish percent in the castle study, so that's sort of a higher risk group. Only 1.5% of patients in the Merlin study had T1A tumors, and 27.3% had T1Bs versus like a third and a third, and about half of those, half of the patients in the Merlin study had T2 tumors. So, you know, strength is size, you know, size matters. I set you up for that one. I've already distinct out my territory that I no longer can figure out how I think castles should be used. And I'm relying on the two of you, does this change anything for like, okay, if it's one where you're really not sure, you okay, it's reason for the order, and Pat, I know for you, it's that we should never order at the oncologist's order if they want it. Right, if you have a T1A, that's high risk, if you have a T1B, or you have a T2A, and obviously above, those patients should have a discussion with a surgical and medical oncologist about whether or not they want to do the sentinel node. If they're himming and hawing, and they're like, is there anything else I can do, like that would help me, I think castles not unreasonable, right, if you have a low castle. But, I think that's a tricky situation to put those physicians in, because that's outside of guidelines. Now, you can do stuff outside of guidelines. It's not like you're going to be arrested or hauled away by ice and deported. I mean, maybe I, you know, just don't go to the airport. Just right. It's not an unreasonable discussion. Yeah, so that's fine. But I think when you, my experience has been, when sentinel node is in play, patients just really like that idea of, yes, let's do that test. We can see if my cancer is spread, and if I'm going to die from melanoma, it's a misconception that they have. But they often will go for the node. And at that point, what there's no point in doing the castles test. So, you know, I think castle is way, way overordered. I think something like this is kind of encouraging. Like, yeah, there's a specific scenario where it would be kind of helpful. But, is anyone going to do that? I just don't know that they're going to go outside of NCC and guidelines, which has offered them this node. And I like, I think I have one patient who didn't even want to talk to the oncologist. It was a 0.9 millimeter melanoma. She was like, I'm not doing that sentinel node thing. Like, I understand it. I don't really like if this is going to metastasize, I'm going to learn about it one way or another. I wouldn't accept the chemotherapy if they offered it to me. But that was like N of one. Every other patient that's a candidate for sentinel node wants to know. All right. Let me explain the recurrence-free survival better because I did not do a very good job of it. So, I pulled up the figure in front of me. So, what they say is that the patients who have a low risk, a low risk, the less than 5% group versus the greater than 5% group, they looked at recurrence-free survival. And it was 97.8% in the less than 5% group. And it was 91.1% in the greater than 5% risk group. Okay. So, those are different numbers. The group is the greater than 5% group does have a higher risk of recurrence. However, what I was trying to say, and I didn't say it very clearly, was that there are far more T1 tumors in the less than 5% group than there are in the greater than 5% group. So, you would expect that there'd be a difference that you would have a higher recurrence rate in a group that has like 91% T1s versus- or 50% T1s versus a group that has 91% T1s. Does that make more sense? I think so. Okay. So, basically, what you need to do is use it and stratify it by T stage and look at the data that way, I think, to decide where you're going to, where you're going to use this test. So, what's your boil it down into one sentence for me, Ferris? Did this study change anything for you? No, not yet, because I don't, I want to see it by what I really, really want to see is the data for the group who I think the hardest decision is for sending, making a decision about Sentinel-Node biopsy, which is T1b melanomas. So, what I want to know is can I take just T1b's, because I really don't want to do this with T1a's, can I take T1b's and can you tell me just among T1b's with a less than 5% risk, am I truly less than 5% and can I safely not send those patients for Sentinel-Node biopsy? But, unfortunately, we keep getting them all lumped in and that's what's making it hard for me to know how to use this. You know what that's like? It's like the research, did you know how much research there is about a bad screen time is for people and it makes you dumb and the brain rot and all that kind of stuff? You know, in all of that research, they never separate out, like the sub-stack or like smart people stuff versus like cat videos on TikTok. All they just, they lump it all together. I don't know if I agree anymore. All right, let's just, Cassel's just doing the same thing. No, I just think, I would say if you look at the Merlin paper, they actually just break it down by every T-stage, show you the numbers and then you can think about it. Now their study was a somewhat negative study, meaning that they did not, their low risk group had a 7.1% positive Sentinel-Node, which makes it hard to say how you would use it and their T1b group, their low risk was 5.2% or positive. So that again, I would, I want to see them beat, I want to see Cassel compared it for T1b's compared to Merlin and that would be to me really helpful. These are the most challenging times when I'm like, do we really want to be doing a Sentinel-Node? That's where I stand. Okay. All right, Pat, and what do you got? My first six pack is a jab, the proof, proof article from March 2026 titled US expert opinions on the treatment of Bulls Pemphagoid based on guidelines from the European Academy of Dermatology and Veneriology by Michael Kasperkowitz at all. I'm probably pronouncing that wrong. Donna Colton was a senior author, Ferris, you give your faculty like a $10,000 bonus when they get published? 25th Allison. Yeah. Yeah. Donna's buying drinks at the age of eight. We're not cutting that out, Ferris. Cut it out. I think that's, yeah, that's a standard, anyway. So European published guidelines of ANGBP in the Journal of the EADB in 2022. It's a good paper. It's very thorough. It goes through how to diagnose it, what to look for. There is a table that goes over management recommendations for different levels of disease. Like if you have mild and moderate, or if you have severe, of course, of course, cordico steroid dependent, I don't really agree with the recommendations, but they're all like smart European dermatologists. So I wouldn't tell anyone that I disagree with them. So I was interested to see like, how do other human dermatologists practice when what they thought about the European guidelines? So surveys were sent out to 75 germs that specialize in immunobulose disease, 46 responded. So for mild and moderate disease, 70% of US immunobulose specialists would use systemic cordico steroids over topical. I mean, that should be 100% but whatever. I mean, nobody should be using topical steroids to treat like widespread BP that European study, New England Journal of Medicine article was like, those patients got hospitalized. They had nurses come in and apply clavitas all over the body. But that just cannot be done realistically for an outpatient sort of setting. I mean, they couldn't even pick up the amount of clavitas all that they would need, right? The pharmacy and the insurance would be like, you're not getting like 1000 grams of clavitas all for the month. So don't nobody use topical cordico steroids. That's a European thing. We're Americans are smarter. We don't do that. 90% would use Doxie over Dapsone as a second line treatment. So that's fine. I mean, I see this is a disagreement. So like just put everyone on Doxie. It's cheap and it might work and it does work in a patient here and there. And then like why not consider Dupy early on? I don't think Dupy works really really great for severe disease or what I would say is severe disease like that should be a candidate where you would give her a Tuxumab and when you have her Tuxumab, you know, are you really going to go with Dupy on board? I think that'd be really, really hard to get insurances. I don't think we'd cover that. So all sorts of like in full disclosure, Regenerant pays me, they get me money for stuff. So I could be just totally biased there. Sure. For sure. Severe BP, 83% of American dermatologist preferred systemic corticosteroids. If you're treating severe BP with topical corticosteroids, don't be treating severe BP. Refer to those patients. If severe BP doesn't respond to systemic, 91% of respondents would increase the dose of steroids versus adding topical steroids. So two people actually said, well, okay, if they're on steroids and it gets worse, I would just add topicals. Donish should kick them out of that group. I'm going to run that by her. So yeah, and this is where I disagree. So European guidelines, when they say severe BP, they're like, okay, use a higher dose of corticosteroids. And if they don't respond, bump up the dose, there's no mention of retuximap. Like that's where you introduce retuximap for those patients. Like you have them on a pretty good dose of corticosteroids and they're not responding. So I don't know. Maybe it's harder to get retuximap in Europe than it is in the US. So whatever. Stereoid, but dependent patients, micaphenolium offethyl is the preferred steroids bearing agent over methotrexate and esothiaprin. I think that's probably true. I mean, that's consensus of talking to with immunobulose people. Again, I would use retuximap. I wouldn't go to micaphenolate esothiaprin or methotrexate if retuximap is an option. I mean, again, this is steroid dependent patient. You can't get them off a reasonable dose of steroids. Use a drug that's going to let you get them off that medication that the corticosteroids retuximap does it better than any thing. Rekalcitrant BP, micaphenolate still preferred. Rekalcitrant BP in the US, 60% of dermatologist preferred Dupy and 17% said use retuximap. Like I just totally disagree with that. I think retuximaps has a longer track record. I think it's a more effective steroid sparing medication. So I don't I would be in that 17% saying retuximap is probably the preferred agent over Dupy. Do you think you be hanging out with the topical steroid people in your 17% or? Yeah, I'm naming. I don't know. Guys, can I'll go get a drink together at AAD. Omalizimap, IVIG, amino absorption. That got no votes in the treatment of her calcitrant disease. I do agree with that. I don't think those are very useful medications. Moving on to Dupy specifically, more than half of respondents said they would initiate to pilling them for all degrees of BP patients, first line for mild disease treatment, refractory patients, etc. So when looking at the European guidelines, more US practitioners found the European guidelines to be applicable versus in applicable. So it was like not applicable at all, moderately applicable mildly than then the other way with in applicable. So 67% applicable. They said these guidelines are applicable to how I practice and 33% said in applicable. And I'm pretty sure I was in the in applicable group. I just have a lot of disagreements with what the Europeans recommend. Topical steroids are pointless, right? I mean, don't even have them in the treatment algorithm. Retuximap should be considered way earlier, right? I mean, they have retuximap way down at the bottom like corticosteroid refract. How do they classify it? They say treatment, recalcitrant BP resistant to 0.75. That's where you start to consider retuximap completely disagree. You have severe disease that you know, so severe BP. That's like the second line. That's where you start bringing retuximap into the discussion. What else? Yeah, there's other tables bar graph summarizing responses. And the only number I want to call out that was one of the respondents said that they see 120 BP patients a month like no, you can do not get out of here with that. That was the only thing I wanted to bring up about the, you know, the bit the characteristics of the people answering the survey. But yeah, I don't know. I mean, do you guys treat BP? I only treat like 119 a month, so I don't know that I could be helpful here. That was you. I have one that I'm treating right now. One, and we're being very careful to just to taper the prednisone slowly the same way that it got tapered in the duplum have trials because I think that's the biggest mistake that people make is they're like, okay, I got them on Dupy. I can taper them in three weeks. No, you can't. You got to do it slow. Yeah, I don't treat that many mostly like somebody else is out of town and somebody needs to get in. They're like, we can put you in with this person. I think that's my nation treating immunobullus disease. But yeah, I think like with the thing I've learned most from Tim over the years is that it has to be the slowest prednisone taper ever and that that's the way to get people better. And I feel like I saw maybe more of these people earlier in my career when we didn't have Dupy and we didn't really have like retoximab and that was the like the take home lesson is do some doxy but like taper them really slowly like five milligrams a week. I don't know is that five milligrams every two weeks. What would you define really slowly patent? I would put them on like max of 60. A lot of these patients are elderly. So sometimes the max is 40. And it that shuts down the disease and it's two week minimum. I mean for like Matt, you've written a good point like regeneron that that protocol of how to taper cortical steroids. I mean just really really good right. I mean it's like a 16 week you know six weeks they had them on the high dose. I mean that's actually way higher than what I usually do. 60 or 40 milligrams and then every two weeks you kind of reassess. I'll usually go down 10 milligrams every two weeks. Maybe 20 milligrams it like completely melts away in that first two weeks but it's two weeks and that's when you decide okay am I going to taper or not. So just based on my no experience in doing this six I go by 20 from 60 to 40 and then from 40 to 20 and then once it gets to 20 I go to 10. So it goes to 20 to 10 and then I go 10 to five and then five to zero. Now I have no idea if that's but that's that's that's that's that's beautiful. I mean trust me it's it's a hundred times better than 60, 40, 20, 10, five days of each. Yeah. Which is done all the time. Okay. All right. All right. Moving on to to my two. So we we've had a lot of serious stuff so far. So first I'm going to throw something out there that is primarily for our listeners who have their own children and are struggling with diaper rash because that comes up all the time on the board certified dermatology group like I'm a dermatologist. If I can't have diaper rash and I can't get them better. Something came out that was pretty interesting green beans. So this was a study out of a a medical center where they were have a lot of problems with diaper rash in their little kid in the neonates. So they figured this out as some university in Minnesota. So you put some group pure rate green beans into the formula. So you start with 30 ml of green bean into eight ounces of formula and then you slowly ramp up how much green bean you're put in the formula and that is some fiber. And so it makes their poop a little bit less runny and it probably slightly acidifies their poop because whenever you metabolize the fiber it makes some short chain fatty acids. And when the poop is a little more acidic it reduces the activity of the proteases in the poop. And they've been doing this for 12 years at this institution they think it really works. She's never heard such a thing. So that one just that was a nice easy one to put out there. I might neither of my kids ever had any diaper rash. You guys ever have any diaper rash problems with your with your kids. Do you remember back that part? I remember. Definitely. And no. Did you happen? Yeah, yeah. My kid had sensitive butts. Okay. Here's my theory is that I like I always any paper where Matt can say the word poop like seven to ten times that really brings the discourse to a level that I think people expect from this podcast. So Bravo. Bravo Matt. Thanks, man. Thanks. Okay. My theory is that having a working mom is associated with lower rates of diaper rash because we send our kids to daycare and my kids at daycare like there was like a chart and And they got a diaper change every two hours, whether they needed it or not. And I would have never done that at home. At home, they get them once every eight hours, whether they needed it or not. It's a totally different type of whether they needed it or not. Yeah. There's just competing priorities if you're at home at, you know, a date there. They're just, they're doing it. I like that. All right. So, now that everybody's gotten, you know, approvals for chronic or de-carrier, now people are going after inducible or de-carrier, send-do, term we use chronic C, I.N.D. inducible or de-carrier, send-do. And so, duplomab released their results and it does not work at all. I literally nothing. So 82 people randomized is exactly the same response rate in the people who got the duplie versus the people who got the placebo. On the other hand, Remi Brutanibe and bars of live-a-mab, the barzo was something both seemed to work very, very well for send-do. Specifically in this study, they did cold inducible or de-carrier, but that's usually the marker for send-do. And it mechanistically makes sense because, you know, we think duplie is somehow working through reducing TH2 activity. So the mast cells have the I/O4 receptor on them, so duplie binds directly to that. And duplie reduces the IgE level. And in this study, it did reduce the IgE levels, but it had no impact on the send-do. And that makes sense because we think that, you know, the way that I think about all of the physical or the carriers is not that you're, it's not autoimmune or allergic. It is literally your mast cells being too sensitive. So that like in demographicism, it's the scratching causes them to pop and it's cold, makes it whatever. So it just made sense that duplie doesn't work for send-do and it does not. And that does make me wonder, and there's no data on this, if a reasonable way to try and predict who's going to do well on duplie versus who's not, would be like, do they have any physical or a carrier type stuff? Like do they have CSU plus some demographicism? Do they have CSU plus some colder to carrier? And if they do, maybe that makes it less likely that duplie is going to work. That was the takeaway. But that's just interesting. That's all. Yes. And just for the listeners, it bars all volumab. I don't know what you, what you call them. I don't think it was that. It's the mechanism. Okay, yes. So barzo, really cool drug. So it binds to the sea kit receptor on your, so it just literally kills all your mast cells. But it's phenomenally effective for urinary carrier. The thing that's fascinating about it though is it makes your hair turn white and it makes some people get spots on their skin. So at least they're not fully depigmented, but they are very noticeably hypopigmented. They've just drugged their melanocytes, come back. What I've always wondered is why don't we see people get an in meninjial size because we always learn about you've got those meninjial melanocytes or retinal stuff like wired people going blind if it's getting all your other melanocytes. I'm going with it has to, but it doesn't penetrate the blood brain barrier because it's an antibody. Fair. That's the, and I guess the eye, the retina is also a immunoprolegic site. What was I going to ask? I had a really great question to ask you, oh, why don't we use it for mastocytosis? I bet we will. But they'd be out of their mind to go after mastocytosis is their first indication. I think it will work great for mastocytosis. I think it's going to work great for a lot of stuff. I think we're going to find out that mastocytosis are involved in a lot more than we realized. That's my guess. I want to say like the abstracts I read when they're looking at SINDU with bars of volume lab like colder to carry, it worked. Oh, it worked. Yes. But they had a comment of it was also studied in dermatographia. And I don't, it, from the way they phrased like this little abstract report, it almost looked like maybe it only worked for colder to carry on noctomatographism. I could be totally wrong. Whereas Remi, they specifically, I think, said cold, dermatographic and colonurgic and Remi showed benefits in all. Interesting. Don't know the. They, they, they, they, they, they, they, they, they, they, they, they, they, they, they, they, I, I, just had their meeting. And so there was a lot of abstracts like coming out of that meeting about the CSU stuff. It's very, very exciting. It's, I will say dermatophysism is hard to study. So we did a dermatophysist study and you get this little dermatophimeter that is like a little, looks like a credit card that has different length, little pegs sticking down. So then you run that across their skin and you see which, like how long do the pegs have to be forward to matter. Yes. All right. Let's move on. Ferris, what do you got? All right. I'm continuing on the Urtecaryatrain. So my next paper was recently published online in JAMA dermatology in February of 2026 to Epileumab in patients with CSU phase three Liberty CSU cupid randomized clinical trials because Sal at all. Okay. So they say interestingly in the intro that even with up to fourfold second generation anaestamines about half a patients are still, you know, symptomatic miserable. Omalizamab gets about 70 to 75% of those H1 refractory patients to complete control, but there's still this unmet need. So that's why do Pileumab. And so this is basically like a replication of the Liberty CSU cupid A study, which I know you all remember because we covered it in the in the past. So this is a phase three Omalizamab naive H1 anaestamine refractory patients. And so so cupid C was basically designed to be similar. So 24 week multi center randomized double blind placebo controlled phase three in patients who had never had an IG anti IGE and who are still symptomatic on fourfold H1 anaestamines. These patients could be down, they looked as low as six years old, six to 80 years of age. They had to have a UAS seven of 16 or higher and a itch severity score seven of eight or higher. So that's like the standard stuff that they're itchy and they do have active hypes. And they basically background H1 anaestamine could be continued. They were randomized to do peer placebo for 20 weeks. It was that you know the weight based regimen we know which when I heard Mac give a talk, he's just like just look it up. So look it up. I also have to look it up by age and et cetera. Thank God I mostly treat adults. So it's not that hard. Primary endpoint ISS seven or UAS seven depending on the regulatory region and they were looking at change in baseline. And then they also looked at some things like you know, were you a good responder which meant a UAS less than seven or a ISS reduction of five or more. So 151 patients randomized, 60% of them had a UAS seven a greater than 28. So that's like considered severe disease. And they were at 24 weeks the placebo at do people beat placebo for itch and urticaria. So the ISS seven least you know the change was basically nine minus 8.6 in the doopy group minus 6.1 in the placebo group. So not this huge spread but there were different UAS seven went down by 15.9 in the doopy group 11.2 in the placebo group. So then the other thing that they did was then they also like did a combined analysis where they included the cupid A and the cupid C. So what did they see similar things basically that they it was a greater reduction in UAS seven and ISS seven in the doopy group versus the placebo group. And if they looked at the percentage of patients who got to well controlled it is roughly like 43% of patients on doopy versus about 23% of patients on placebo. So that's a UAS seven less than six complete control which is basically no hives was about 30% of patients on doopy and about 15% of patients on placebo. Another interesting thing that was in here was that they looked at IGE total serum IGE and they found that it dropped by about 50% in the doopy group. Well what really didn't drop in the placebo group but they also said that the clinical benefit was seen, like it didn't matter, your IgE threshold baseline target or baseline IgE didn't really matter. Whereas with Omalizamab, it really works better in patients who have a higher IgE. So I thought that that was interesting. So that's kind of all that I had. It was sort of, you know, continuing getting more data. It wasn't anything that was super new, but you know, sort of doubled the numbers that were out there. Again, a reminder, if you look back at the other study where they looked at, if they looked at Omalizamab failures, Dupy did not meet its end point. So, you know, I don't think this is a good place to go for patients who are Omalizamab failures, but it does seem to be, you know, an option for patients, you know, maybe it's a more first line, something that's easier to give and more familiar to us as dermatologist. I agree. I think I still, I think at this point, it's hard for me to rationalize not using reps, you know, as our first line in the world of dermatology is just such a safe, easy drug. And it's so much faster, you know, you give it two weeks, and if they're not better, then, okay, that's not the drug for you. We'll move you over to Dupy, whereas if you put on Dupy, you gotta give it probably three months before you were gonna say, eh, didn't work. Like that, the rapidity of Horsano makes it an easy catch for me. All right, Pat, what do you got? - I think Barzo actually did okay in dermatographism too. I wanna take that back. I don't want Barzo reps harassing me. I just, I don't need-- - We're gonna start getting Barzo, male. - Yeah, yeah. - Just add it to the pile. All right, my second six pack, a brief report from December 2025, Chad. You guys are gonna kill me for this paper, 'cause it's so dumb. I went back a few months for this one, 'cause I think it's an interesting side effect that maybe we'll shine some light on hydrodynamic as pathophysiology. Are you guys intrigued with that little lead in? - Intrigued. - All right, the title of the report is Dermatologic Adverse Events Associated with Gamma, Secretase, and Hibiter, Neroge, the Sestats, probably not pronounced right. A retrospective multi-center cohort study by Rue at Al, Neroge, Sestats, brand name, OXIVIO, is FDA-proof for the treatment of progressing Desboy tumors, we've all had 'em. The study evaluated 28 patients at Mass Gen and Dana Farber that were treated with that medication. Most common Dermatologic Adverse Event, more Billeform drug, no surprise there. But the second most common adverse event was follicular-based adverse events, including things like H.S., in Flamede, I.C., KP. So I remember, I thought this was interesting, 'cause there was a report about genetic defects and Gamma, Secretase, complex genes being affected and familial cases of H.S., and so I thought H.S.? - What is Gamma, what is, are you gonna tell us where the Gamma, Secretase is? - I am going to try, based on my five minute review of what the hell is a Gamma, Secretase, and Hibiter. So from what I could tell. - All right, good, okay. I gave a Secretase as like by notched protein, right? So the notched protein is involved in characterization, follicular type things, maybe some immune things. And for notched to work, something binds to it. And then the Gamma, Secretase comes by and like clips an internal portion of notched, therefore activating it and letting it do what notched does. And so when you block that notched can't do what it does, including things like follicular differentiation, characterization. So the fact that you have this drug that blocks that in H.S. as a side effect, that's not a lot of patients, but like that's a weird side effect, right? And then there's also this familial form of H.S. wherein the patients have a defect in the Gamma, Secretase gene. I thought maybe a drug that could stimulate that would be a good target. But then I like read some more about Gamma, Secretase back being actually elevated in some H.S. legions. And I don't know, I thought it was worth mentioning. I thought it was an interesting thing and I kind of put the Gamma, Secretase. Like maybe something with notched is the root cause of H.S. and maybe someday that'll be, and people would be like, I remember the Derms on Drugs, people talking about that. They're visionaries. - Is it not somehow, I wanna, when you say notched, I always wanna put Wint WNT together with it. Was that, - I thought, ASE, yeah, I have no idea. - For, for this case. - I was getting confused with notched and patch. Like patch, I'm like notched, isn't that the basal cell in the Evis, but no, that's patch. - Oh, that's it. - Is it, is it, with patch? - Maybe. - Don't learn your basic science from here, dermatology residents. - Yeah. - So, is it a, is it a, like a protease basically? - It's a secretease, it's right in the name. - It's a secretease. - Okay, okay. It seems like it cleaves things. Isn't that what protease is? - Yeah, it's a cleaver. - Okay, that's the official Derms on Drug term for proteases for now on. - Got it. - Revers. - All right, that was my paper, move along. - Okay, you wanted to know. - We don't have to discuss this anymore. - I pulled up with Dr. Syedon, also another great UNC physician in the Department of Dermatology to did identify Locyte associated with H.S. susceptibility. One of them is SOX9. SOX9 triggers the activation of matrix, metalloprintase 1 and 2, which is what made me think, is that it does it all sort of fit together in that pathway. So. - Yeah, and it's, so the Gamma secretease, it was like an Asian study, and I think Dr. Syed did his on Chapel Hill people. He probably expanded it to samples outside of that, but he had two totally different genes. Like the Gamma secretease didn't even come up in the study that he did. There was one on chromosome 13 and one on 17, I think in Dr. Syed study, and I think that Gamma secretease is on chromosome one. - It is, okay. - Kind of different. That's why I was all excited and as I was reading more and more about this, but at that point, I couldn't change my paper. I don't do that. Once I start working on something, I'm committed. - You're committed to it. - I should be committed. - Okay. - I mean, you have been married forever. See, that's a good, like, I'm like, I forget that paper. I moved to this paper, I'm like, that's some divorced twice. It just plays. - Right at it all comes full circle. - Yeah, this is full circle. - Makes a lot of sense. - Yeah, right Matt, what are your last words? - All right, my last two. First one, just a nice study that's a follow-up from something that came out a few years ago. This was melatonin supplementation and adult patients with a topic dermatitis, a randomized clinical trial. This was in the journal of penial research. And most importantly, it came out of Iran. My favorite country for coming out of. (laughing) So, this was a randomized double-blind with a typical controlled trial with 80 patients. Melatonin versus no melatonin and people who were otherwise getting standard of care. So very applicable to real world, like they were given them whatever, you know, topical steroids, whatever they didn't want to give them. And it was actually pretty darn good. So, score add dropped from 31 to 11 in the melatonin group and it dropped from 31 to 22 in the placebo group. So it was like substantially, there was like a 60, some percent reduction versus a 30 percent reduction. BSA went from 6% to 1.5% in the melatonin group. It went from 6.5% to almost 4% in the placebo group. Paritis scores, same, like everything that they looked at, the melatonin made a big difference. This now makes three randomized double-blant placebo controlled trials that we have that are showing that melatonin makes a difference in a topic dermatitis beyond just that they're sleeping better. The other thing that I dove into a little bit for this is people who often ask me, oh, but I'm worried about taking melatonin. Is it gonna suppress my endogenous melatonin production? And no, it does not. So your endogenous melatonin production is not on a feedback loop. So it is purely driven by light dark. So light dark cycles are what drives melatonin expression. The one thing that they can't rule out though is when you're taking super-physiology doses, which they did 10 milligrams in this QHS, it might downregulate your receptors. So even though you're still making enough melatonin, you might not be as responsive to it so you might get hooked on the melatonin. But that they were like, when I looked this up, my main takeaway was, no, that doesn't happen. It was like, we can't, like we don't have absolute proof that it doesn't happen, but people have looked and it doesn't seem to happen. So that was number one, melatonin seems to work well. - So we know like the mechanism, what the mechanism, the question. - I know we don't know a mechanism, but I know-- - Wait, there is, there is actually. In your mind, have a mechanism, and I'd like to hear what it is. - So there was a study earlier this year that showed, that taking melatonin affected your intestinal microbiome in a way that increased properionic acid and that somehow improved your cataneous microbiome. Uh, let's, it's a stretch, but there was that study came out this year because I have been like why was melatonin work in those two pediatric studies. There is apparently melatonin receptor is in your skin, so it could be a direct skin effect as well. Why don't we just give people properionic acid? Uh, that's a good, I don't know. Maybe we need to do that trial. That's, we'll see if we can get my, see if I can get my hands on some properionic acid. Okay. No, I know. See if the auto effects my poop. Uh, there you go. There you go. Wait, wait, real, real quick with the melatonin. I mean, isn't it just related to sleep and maybe you said this and I, it could be, it is theoretically possible that it's just that, oh, they're sleeping better. But that's hard, that's hard for me to believe that like, okay, like it could be though. It could be, because it's like, randomized them to melatonin versus ambion. Ambion will make you sleep better. Uh, yeah. That's the trial. There we go. We get addicted, but we probably, yeah, we find. All right. My last one, uh, this is just kind of a warning one for dermatologist. There's some data that Taiwan, uh, the association between GABA, PEN or pre-Gablin use in the risk of dementia analysis and the national health insurance research database in Taiwan, basically 35, 34,000 ish users matched one to five to 172,000 nonusers, uh, kind of, you know, propensity score matching, whatever hazard ratio overall was about 1.5 if you were on a GABA peninoid. So you were 50% more likely to be diagnosed with dementia. Uh, and there was a very clear dose response that the more GABA pen you got, the more likely you were to have to get dementia and younger patients were the main people at significantly increased risk. So if you were under 50, your hazard ratio was 3.16. If you were over 50, your hazard ratio was 1.3. Big problem with this study. It didn't control for other drugs. So like if you're on GABA peninoid because you're have pain, you might also be on an opioid or you might also be on, you know, other stuff that also, uh, affects cognitive function. But it's at least for all the times patients are like, oh, GABA made me feel like a zombie. Like we have this sense in Durham, the GABA pen is a safe drug and is not a safe drug. Uh, yeah. Couple things relative risk versus absolute risk. The absolute risk of dementia in somebody under 50 is very low. So even if you triple it, who cares? Dammit fairs. Stop being the smart one. Well, all right. I'm sorry. But if you're going to be the word story, I'm going to have a class this up a bit. Um, so there's a judge rules on class. Anybody who says they're classy that it absolutely means you're not classy. Okay. Well, there you go. Um, okay. So that's the one thing. So the other interesting thing is, did you all see the study that Schingrich's vaccine was associated with lower risk of dementia? So I wonder if part of that is that when older people get shingles, what do we do? We throw them on some GABA pen. It's a, it's a, it's a, it's a, it's a busy problem, not a GABA pen problem. Yeah. Yeah. So for anybody out there, uh, Schingrich's reduces your risk of, uh, dementia by like 30%. The other thing that's been shown to see differently reduced the risk of dementia, being on Tadala Phil, uh, as a daily dose, which is the Alice, right? That's the Alice. Yes. All right. I knew you were seeming so bright. Now I'm number. Why? Wonder why you've been doing research. Perky as we say. Chief, that camera pointed out. I might make you edit that out. We'll see. You can keep it. Thanks for joining us this week. We hope to learn a few things. We hope to last. Watch it twice. And mostly we're hoping you're planning to join us next week. Until then, I'm Mads Iris. I'm Tim Patton. And I'm Laura Ferris and we are Derms on drugs.