Dermatology Debates: The Derms on Drugs Try to Change Minds

(upbeat music) - All right, hello everybody. So I want everyone to know how fortunate you are to be present for the first ever live in person episode of The Derms on Drugs Podcast. So let me introduce my co-panelist, the two of my favorite people in the world, and the two best dermatologists that I know. So Dr. Tim Patton and Dr. Laura Ferris. So the three of us did residency together at the University of Pittsburgh 20 years ago. And we have stayed friends ever since. Dr. Patton is faculty at the University of Pittsburgh still has written a textbook about the skin signs of systemic disease and is just a phenomenal general medical dermatologist and really has a great take on the literature and dermatology in general. Dr. Laura Ferris was faculty at the University of Pittsburgh for a long time and then recently became the chair of dermatology at the University of North Carolina. She is a deep, deep expert in the world of psoriasis, melanoma, skin cancer, diagnosis, by computers. And if you have not listened to our podcast, you are missing out. So let's first, I'm going to have everybody-- and this is really to give you an idea of what the podcast is like. So first, everybody please scan the QR code because we're going to have this session is going to be really based around audience response. Really strongly based around audience response. I'm going to give you one more second to scan that because I really want to get some good feedback from everybody. All right, so let's go ahead onto our first one here. So first, do you watch or listen to podcasts? Yes or no? All right, let's see how many we get to give us a good idea of how many we expect. And I expect all of you to be answering every single time. So we're going to look like we're going to get up to around the 80 range. So we'll keep it there. And so we've got about 75%. So about 60 people who voted, listens to podcasts. All right, next question. Have you listened to Derms on Drugs? So this is our podcast that new episodes drop every Friday on Spotify, Apple Podcasts. And they live on the Scholars and Medicine platform. So if you listen regularly, you've listened a few times, but aren't tuned in every week or haven't listened at all. Not at all. Oh my god. So I first got to tell you, for the people who have listened to it, it honest to goodness is very different podcast. It's supposed to be set up like a sports talk show or like the view or something like that. But we're reviewing the hottest, coolest literature. The topics you really want to hear about. All right. So you got to tune in. You are absolutely missing out. You listen on your way back and forth to work. All right. And then third, for the small number of you who have been listening to it so far, have you engaged with the video portion? So it's a normal podcast, mostly us talking, but we do have slides as well where people-- we put up kind of the key tables or visuals from the articles that we are talking about. Yep. I've only gotten about 29 answers here because as far as I can tell, they're only about 20 of you who've listened to the podcast. So let's see here. So not at all. All right. So kind of as suspected, but it is made to be listened to. You don't need to watch the video. And if you haven't been watching it, you got to get in there. All right. So let's go ahead and get started. So controversies and dermatology. And we are going to cover three areas that we think are interesting. And what we're going to do-- so Dr. Patton's got some disclosures. Dr. Ferris got disclosures. I got a whole bunch of disclosures. I win by far. All right. So the rules here. Prior to each segment, we're going to have three different segments. We're going to ask you to vote for one of three different positions that you think is correct. Then we are going to each give our little speed. Each of us will be supporting one of those potential takes. And then we're going to ask you to vote again afterwards to see which of us is most convincing. And we're going to get some real live feedback on this. So whoever gets the most people to switch is the winner. All right. So even if you've got the least popular one, if you get a few people to switch, maybe you're the winner. All right. So let's go ahead and get started here. Do you think that gene expression profiling for melanoma is useful/should-be-done for any invasive melanoma? Literally every melanoma that you get, no matter how deep or how thin you should do it? Number two, in some situations, it's reasonable. Use it occasionally. Or number three, you really don't use it. Like, you know what's out there, being or really use it much. Go ahead and let's get your totals up there. All right. So we got the 80 plus perfect. And we didn't know that we were going right after a Castle product theater, by the way. That was like a total random event. So let's see what our votes were here. So we got a good spread. OK. So it is a good controversial topic. So we got people all over the place. So let's go ahead, Dr. Ferris. You want to give us the quick explanation of gene expression profiling. I think everybody probably already knows. Well, you guys are all experts now. But basically, gene expression profiling is looking at if you have a tumor that's benign, and one that's malignant, if one gene is highly expressed in the benign one, but not in the malignant one, versus another one that is high in the malignant, but not the benign, that can help us to give information about that tumor. So it's using the gene expression to tell us more about a tumor. And there, as you know, there's a few available. But the one that we're going to focus on is actually decision DX, which you just heard about, because really there's the most clinical data and the most use. All right. So first, I am going to take the first position, which is-- we should use it in every single melanoma. All right. So my basic position is that if I had a melanoma, I don't care if it was 0.1 millimeter thick. I would want GEP done on it. And I don't care if it was 17 millimeters thick. And I already had lymph nodes coming out of my neck. I would want GEP profiling done on it. Would that give me any actionable information, probably not? But I want-- if I can get a little extra prognostic information, I want a little more prognostic information. It's-- I am purely thinking about it from what I would want. Now, there are counterarguments to this, of course. So I'm not saying I would do anything different based on the results. If I had a 0.1 melanoma and got a high risk result, I still wouldn't get a lymph node biopsy or taking immunotherapy. But I'd be like a little more nervous, right? Now, maybe I wouldn't be happy that I was a little more nervous, right? But I would want to look harder to pay more attention for anything that was concerning. And if my insurance wouldn't pay for them, I'd probably pay for it out of pocket to get my full body MRI every year. And if I had a thick melanoma and got a low result, I would still get the sentinel lymph node biopsy. I wouldn't be like, well, but my chiseled test was fine. I would still get the sentinel lymph node biopsy, but I would be a little less anxious, right? So now, the downside of this, of course, is it could lead to some difficult conversations with patients, right? So if you've got a 0.1 millimeter melanoma and then you get a chiseled, it's high risk. Now, that's a painful conversation. Like, Boots should have been like, oh, you're going to be fine. But now you've got to talk about it. You've got the high risk, right? So I get the other side of it, but I think of it as I would want to know, right? So downside, right? The painful conversation. And so I don't follow a whole lot of high risk melanoma patients. So maybe I'm not really thinking about how much it could make those conversations painful. All right, but that's my take on that we should pretty much be ordering it in every single person with a melanoma. Because Matt wants to know. I wouldn't know, damn it. So I'm going to go with the argument of in some situations for guiding clinical decision making. OK. So the one clinical decision that I think is really important is should this patient get a sentinel lymph node biopsy, yes or no? Why? Sentinel node is something we use regularly. It's a good predictor of survival. But as we can see from the graph on the right, it does not improve melanoma specific survival. So the only reason you undergo a surgery is to get some prognostic information. I'd rather get that from a slide from something that's already been removed. Also, while you can see on the left that sentinel node negative patients are less likely to die of melanoma in MSLT1, most of the melanoma deaths actually occurred in patients who are sentinel node negative. So it's really not like this guarantee good. I've got the information. And overall, 84% of patients had a negative sentinel node. So could we maybe spare those patients? And so there are several studies looking at different cohorts using decision DX. Looking at their risk status and then correlating that with their sentinel node positivity. Now, to Matt's point, T1A, the thin melanomas. Look, in this study, it's a small sample, but there's many other cohorts that look very similar. Pretty much none of them had a positive sentinel note. So don't do the test. Even if it came back positive, I would argue the whole reason that we removed thin melanomas surgically is because we think we have a window to catch them, even if they might be bad. So I don't need to know that it might be bad, but I'm going to remove it anyway. So I don't think it's helpful in T1A. T1B, T2A, maybe those tumors are ones where the sentinel note positivity rate is lower. And as we can see here, looking at a risk threshold of 10% or higher, really did pull out those. So I think that we could reduce the use of sentinel note by doing castle testing first. So you would only do it in people who have like a melanoma that is like 0.5? High risk T1A, which would be like a positive deep note, positive deep margin, or T1B, maybe with depending on the surgical candidate, a T2A. And does it add any additional info to the sentinel note? So in other words, the-- Is it additive? Yes. So having a high risk tumor and a positive note is worse than having a class 1A and a positive note. So there's a little bit of additional information, yes. But we don't really know quite what to do with all of that. But other things. So this is out of the Memorial Sloan Academy Group who is actually generally not a huge proponent of GEP. But they did this analysis of one of these studies. And what they found was if your usual is to say every T1B patient gets a sentinel note biopsy, if you use the guidance of the GEP testing, they modeled-- and their model, you would have a 23% decrease in sentinel note biopsies with no increase in the number of patients with the sentinel note metastasis left untreated. So I think there's real potential here. So here's an example of a patient I had. An 85-year-old, he came in for something else. I found this big, let it go malignant behind his ear. Biopsy, it was a 0.7 millimeters at least, say, you'd call that a high risk T1A. And all of the margins are positive. It's also-- there's a basal cell in here somewhere. And so I went back and did scouting biopsies, and they're all positive. So this is a hard lesion to clear clinically. But you're like, ah, should this guy get a sentinel note? And plus, I'd like to get rid of that basal cell. Most would be a great option for this patient. So we got GEP testing. And it told us that his melanoma specific survival was incredibly high, like 99%. But also that the likelihood that that sentinel note would be positive was only 2.9%. So we just didn't do the sentinel note. He got treated with mose, I think, his bigger issue was clearing that primary. And he's done well. So this is a-- this sort of algorithm would suggest that if you've got a T1, maybe an early T2, or T1T2 melanoma, get a GEP result if they've got a class 1A or a less than 5% probability of a positive note to skip it in those patients and just follow them clinically. The other place where this could be helpful, we know that adjuvant therapy, which is immunotherapy, given after clearance of all tumor and patients with stage 2B or 2C melanoma, so negative sentinel note, we know that that does improve melanoma specific survival. But you know, it's not like the greatest separation of those curves. It's maybe not like this huge clinical benefit. What is a big difference are the adverse events rates. Having the immunotherapy can give you things like permanent hypothyroidism, colitis, that can be big problems. So, you know, how do you weigh the risks and the benefits? Well, I can't show you something that says we have that data in melanoma, but there's a GEP test for squamous cell carcinoma. What we have traditionally done with high risk squamous cell carcinomas is offered adjuvant radiation therapy. And this retrospective study showed that the only patients who really benefited were the ones who had class 2B, a really high risk squamous cell carcinoma. So, maybe that'll work for melanoma too. We still need the data. So, in summary, I think it can help guide patient care to reduce sentinel note biopsies and maybe to guide adjuvant therapy. I always get in trouble for making this run long because I ask questions. So, Ferris, why wouldn't you? So, you didn't -- so, I've start with my argument. Just get it and everybody. So, mainly your takeaway was in the super thin ones, like it's never positive. You don't like it's -- there's just no point. It's a waste of money. Or it could be positive. And then you go get a surgery that you didn't need because you're nervous. And, you know, and it's not -- it's not going to be predictive of their -- sort of their long-term outcome. And again, we're not trying to make sure everybody gets a sentinel note. We're trying to make sure we pick out the truly high risk patients. And you -- So, it's surgery and it's cost. Yeah, the yearly MRIs, too, more additive costs. And you probably are increasing harm. The number of positive MRIs that are actually going to turn out to be not negative. But you're going to have to go after and chase whatever shows up on that MRI. That could be a fine needle aspiration. Something shows up in the liver. You need a liver biopsy. I probably need one anyways. That's a probably a good idea, yeah, based on last night. We also don't do screening MRIs. Just going to take that off the table, too. But go ahead. Yeah, exactly. Yeah, PETCT would be the way to go. Right. And then you're, you know, increasing -- Yeah, I'm getting out. All right. All right. So, I do not use GEP testing for melanoma. And I want to make it clear, I'm not saying it shouldn't be done. It's just I don't do it as the dermatology provider. Why don't I do it? I pulled some cases. Just three typical things that we see in clinic. 0.8, 0.7, 1.8. So, to me, we know what to do because of NCC and guidelines. These are very clear. Stage 1A. Cut it out. Stage 1B. Discuss. Consider Sentinel-Node. Stage 1B. That's a T2A lesion. Discuss. Offer Sentinel-Node. None of that's going to change. So, for me, from the dermatology health care provider, how am I going to manage this patient? Will GEP testing change that? No. Melanamon site 2. I like oxygen. Stage 1A. Wide local oxygen. Stage 1B. And above, I think the most appropriate thing to do is refer to medical surgical oncology. Discuss Sentinel-Node. I think the GEP testing has utility in those instances, as Dr. Ferris was saying, because he could pick out who should get a note and who shouldn't. But they need to make that decision, talk to the patient about the test, what the results of the test would be. I don't think it's appropriate for the dermatologist to be ordering it at the time. Because if you have a 0.9 millimeter melanoma and it's Casal-Node, do you not send them to oncology? I think it has to be done when it's going to be part of the conversation. If they're saying I'm going to get Sentinel-Node, absolutely no matter what, then that's different. What happens, I think, is the dermatologist orders the test, say 0.9. It's a stage where I'm sorry, it's a Casal-Node. They go to see oncology. oncology says you're a candidate. They say, yeah, that sounds good. I want a Sentinel-Node. You just wasted $7,000 in the management of that patient. And that $7,000 could go to Matt's monthly MRI. $7,000 to do a Casal test. Roughly. Holy cow. Right. Wow, it's a lot of money. So, right, I mean, I think everyone in the room would agree that spending money for you personally is worth it. You were a national treasure, but for the rest of us, you know, I think it needs to be cost effective and it needs to avoid harm. And so that's why I don't do it. We know that T1 tumors by Casal-Zone data, you know, if you look at this one paper, 281 patients, T1, there were 14 patients that developed distant mats. Three of the 14 were 2B. The rest were 1. So, more often than not, the bad things are going to happen. Similar to the deaths in the Sentinel-Node negative patients are going to happen in those 1 patients with the thin lesions. NCCN guidelines are not alone. You know, NCCN does not equivocate. Panel does not recommend incorporation of commercially available GE tests and the melanoma care. The only thing that's going to happen is the genetic disease. The genetic disease is going to happen in those 2D patients. See what we got? I don't remember the initial numbers, but-- All right, all I know is I went up. You went up from 53 to 66. Son of a gun. And I was sitting here listening to Ferris being like, I don't even-- it's too smart for me. I can't figure it out. Man, OK. All right. Damn it. All right, next topic. If you could only keep one of the advanced topicals, if you-- if they said you're only allowed to ever prescribe, either to pin her off, reflumalast, or ruxilittinib, ever again, which one would you keep? All right, so this is not a like, which one's best for an atopic Durham patient? Which one's best for-- which one would you keep? All right, if you could only keep one of them. That's it. That's nice. Sweet dreams, the Erasmus. All right, let's go on. Click next. Oh, look at that. Reflumalast comes in at 10.50.40. I'll try and commit that to memory. I got it. All right, next-- Right it down. Next click. Right it down. Next click. OK, well, I got a lot of work to do to pin her off cream. Here's why I would have it. All three drugs, by the way, I think are great non-staroid options. So I'm happy to have all three. But if I had to pick one, I would pick to pin her off. We're not going to go into how it works. I'm sure you've seen talks about this. So looking at it in a topic that I've tied us, I think Ruxoletinib is probably the most effective medication. You know treatment success. You look at the percentages. I know reflumalast that's lower numbers, but it's kind of cheating because that's four weeks versus eight weeks. But the difference from vehicle just for reflumalast is not that good. So I would argue Ruxoletinib fine. Efficacy to pin her off is not going to win. But I think it's equally effective in itching. It may not be as rapid. There are no restrictions on use. Approval down to two years of age, there's no black box warning. I think Ruxoletinib, while being more effective, is just a more difficult medication to kind of counsel patients on because of all those negative things. It's approved for short term non-continuous use. I don't know what short term-- That's called PRN. Right. PRN. It's on 10% of the body. If it's Vidalago and 20%. So now you have to do math with your patients. You're going to do that? It's very tough. I think the black box warning, you just tell the patients just ignore that. Which I think the black box warning should be ignored. But patients have to look at that. And it's just a harder discussion. Can I use it on my little kid? No. I mean, technically, you said you're later. You're worried about them licking it. So even you have worries about, Ruxoletinib. You weren't supposed to. That was between us. We all went through the slides. That was one of the things that to pin her off stands out. The other medications-- I'm not saying they won't work, but it's not been proven. Whereas with to pin her off, it is proven. And that is a remit of effects. And that's for both atopic dermatitis and psoriasis. I think the remit of effect for psoriasis median effect for months and for atopic dermatitis about 2.5 months. And that's proven remit of effects, which the other medications don't have. So that's why for those reasons I go with VTAM, I think it's a more effective medication than Ruflumalast. And I think there's just fewer negative things that you have to deal with compared to Ruxoletinib point in case. This is your Ruxoletinib. Look at that. It's a mess. It's the black box. It's dosage and not for 20%, 10%, warnings, precautions. Contrindications didn't have any. Contrindications-- Ruflumalast has one. Moderna to severe liver impairment. This is a little bit cleaner. The Ruflumalast prescribing information. And I just think the VTAM-- or I'm sorry-- the Tepinner Off has the cleanest sort of package insert. And that's why I want Tepinner Off more than the other two. All right. Well, I am going to make the case for Ruflumalast cream and foam. So why? It's a PDE4 inhibitor. But it's 25 to 300 times more potent in vitro than the ones that we know-- a premalast in chrysaboral. It comes as a cream and a foam. And so we know how it works. We know it's effective. We know it's safe. It's really versatile. And it's really easy. OK. So this is the data that Dr. Patton talked about. So yes, you may say, well, that's not that impressive. But that's four week data. It's also the lower strength of Ruflumalast. But I think that Dr. Cyrus is going to talk to you about its reduction. But you can see statistically significant early its reduction is earliest 24 hours with Ruflumalast. And again, this is just a four week study. And if we look out at their more long term data, here's easy 75. And here's that IGA success and IGA of 0 or 1. So how does that compare to pinner off 1% at week 8? It's about 45%. Ruflumalatinib is about 53%. This is about 42%. And you get at week 28 to 55%. So I think the efficacy is pretty good. It's just, do you look early or not? This is looking at psoriasis data. And so you can see here Ruflumalast, IGA success at week 8, 42, and 37%. And if you look at the to pinner off data on top of that, you reach those numbers, but more like at week 12. And at week 8, they're a little bit lower, although I will give you that the vehicle rate is a little bit lower, too. And then there's also intertrigidous data. So intertrigidous psoriasis is a big deal. And then you can use this in a foam. And it now is approved for psoriasis about the scalp and the body. And I think what's amazing is actually the IGA success in the scalp. Scalp psoriasis is a real pain. And over 60% of patients had an IGA of 0 or 1 with the foam. And the foam can be used scalp and body. And then also, of course, lots of our patients have subderm. There's a lot of overlap. And we've got good data and indication for the use of a refluent last foam with inpatients with subderm as well. So this is-- I won't quote it sort of harp on this too much. But the safety concerns, headache and diarrhea, low rates, I can live with that versus I think that the folliculitis and the dermatitis that patients get with tipineroff can actually generate a lot of foam calls and discussion. And then, of course, the black box morning. So why do I like it? I know how it works. We trust that mechanism of action. It's got a good safety history with oral use, much less topical. It works and the versatility and the once a day, any location. And none of the other two can be used in the scalp easily. All right. So first, I'm going to give you-- here's the summary. All right. It just is-- well, here, I'll do mine first. I want topical ruxilin and ib. All right. I'd be super bummed to give up for flume molasses. This is an incredibly good drug. I'd be super bummed to give up tipineroff because it's a totally new mechanism of action. We're the only people in the entire world of medicine that have an aero hydrocarbon receptor that we get to use. That is cool as heck. So they are great drugs. But rux is a freaking miracle. So here's what I get. It gets the itch better in 15 minutes. Think about that for a second. Imagine if you had a topical for acne. If Dr. Baldwin and Harper were up here, and we're like, oh, there's a new cream for acne. And it clears their acne in 15 minutes. You would be like, oh, my God, I'm never going to prescribe anything else ever again for acne. The kid comes in from school over the break. And oh, here, here's a sample put it on by the time you get back to school, your acne will be gone. And then, oh, just whenever you have a pimple put it, just whenever you get a pimple put it on in 80% of the time you want to have any acne. Now, it's-- You could get that with ILTAC. Was ILTAC better than IsoTrat knowing? No, it is not. You're going for the quick reward. I think you have to look at longer terms sort of success. OK, so Pat, stop criticizing my life choices. That literally is my problem with my life choices. Yeah, that's a huge life problem. Although there's a reason to discover the Plaquino works for Vidal Igo was kind of crazy. So I don't know if I've ever heard anybody else talk about that here at the conference, but we now have dated the Plaquino as highly effective for Vidal Igo very low dose. That's really cool. And I don't care about psoriasis. I suspect that if you used it for psoriasis, it would work. But we've got other great drugs for psoriasis, right? We can get rid of them and forget psoriasis, drugs who cares. All right, so type of thing. That's just how I'm trying pretty good. Systemics are getting really cheap. It's miracle, right? And I already talked about all the acne stuff, right? It's the worst part of the acne is the way it looks. It's the worst part of ADS. And by the way, Pat, now that I'm thinking about there, was just an article about somebody came out with a self-administered little thing that you put on, it's like an interleesian attack. Yeah. That people can do it home by themselves and it's highly concerning because I would never-- people would kill themselves. But-- Maybe not kill themselves, yeah. But they would hurt themselves badly. But we had a drug like Rucks Frack, and you already went through all of that. So I'm meant. The box warning sucks. And I probably want to have one of the other drugs for the little kids, right? Because it does occur to me like I can hear the parents now. But what if they lick it? And being like-- because my usual spiel has always been like, oh, it's got these warnings. They're not real warnings anyways. But just don't eat the cream and you'll be fine. And the boy, what if they do eat it? What if they lick the crate now? I don't-- go see somebody else, all right? But I get the downside to it, right? So I-- the cream will help with the rich of it's even if this is a miracle, right? I've looked at all the data, and I think it's totally safe. But this cream comes with some warnings. Just don't-- don't eat it, right? And I would-- I might as well as that be a little like hesitant to put it on the hand of a one year old. One last thing about Roflum last two. I like Roflum last, but isn't it weird that Roflum last systemically? I mean, it's okay, drug, right? I mean, we like it because it's really cheap. It's available cheaply, but it's not like this blockbuster, huge, great drug. And yet, topically, we think it's really, really good. You get it right to the scene of the inflammation. But what other-- and it gets concentrated, and it actually has a long half-life of several days in the skin. So it gets trapped and it stays in the skin. What other systemic medication is way better given topically? So I would bet that if you had one small plaque of atopic dermatitis, and you could either give somebody, or you pat a sit in the ab, or just rub, I would bet that topical rucks for small BSA disease would be better. Okay. I don't know-- I'm totally making that up to try and win the argument. Like, that's-- That's a good strategy with it. It worked on the first one. No, you didn't win the first one. All right, those-- let's get your votes. All right, which would you keep? To pin her off, Roflum last, or Ruxl-Leddinib, if you had to pick one of the three. [MUSIC] All right, let's see here. Let's get up to the 80. Come on. Come on. Come on. It was 1050/40 whenever we started. I grew flimeless on the hardest lift, because you saw an ounce of mine. Ten, old patent got a few-- 61. Son of a bitch, I was the worst by far. Yeah. I thought I was going to kill you guys. Yeah, I don't care about psoriasis. That's a good-- That's a good-- That's a good-- That's a strong thing to say to a group of people. That treat a lot of psoriasis. And you're going to win a lot of hearts over with that one. All right, we're going to go very quickly for our last one here. We're kind of using it for our time. I think you're using it for our time. Shut up. Shut up. What's going to make our dermatology practice most effective over the next five years? Introduction of BTK inhibitors, AI, or affordable jacks. Right, affordable systemic jacks, right? So jacks going generic, orally. Okay. [MUSIC] What do you think? BTK inhibitors, AI replacing us. Carpacamia. Trying to make it sound bad. Culture club hits. Or, tofacinative going generic. All right, let's see it, Patton. Is good? Yeah, 95. All right, let's go, Patton. Is there some work? Good, all right, let's go, Patton. I think starting low is actually good. My strategy is last thing. All right, let's see. Pay it off. All right, so I'm taking introduction of BTK inhibitors into the field of dermatology. These are BTK inhibitors. I don't want to get too much into it. But I think the history of it is very similar to what we see with jacks. Another kinase inhibitor. Jacks, I think we can all agree, have kind of revolutionized dermatology treatment in the last five years. Alpish, Ariata, Vidaligo. The things that we can now treat because of the availability of these kinase inhibitors. And I think BTK has a similar sort of history. And I'm in presentable multiple cell types involved in inflammation, mass cells, B cells. Maybe not neutrophils. I may have made that up. But it's in the picture. I go by pictures. It looks like it's in the picture. Neutral fill is based on the photo, right? It could be in. And look. That's how I work. We're seeing this come to fruition already. MeritMe, Brutonib, and Chronic Spontaneous Urticaria, the rapid improvement. I think we're going to start using this more and more. What other disease states are being studied? Reels of Brutonib and Tyrbrutonib for Pemphagus. CSU talked about Remy already. They're also looking at Pemphagus. HS, there's Remy being studied for the treatment of HS, SLE, A-topic, or Matitis. So I think that very similar to the Janice kinase inhibitors, the other kinase inhibitors, BTKs, are going to sort of revolutionize how we manage these patients in the future. I think they're going to make a big difference. Okay, so Patent's general argument, these are going to be like the jacks, open up us, being able to treat a whole bunch of new things, but without any of the safety concerns of jacks. That's what they, he didn't quite touch it. I didn't talk about it. BTKs are like water in terms of safety, unbelievably safe. All right, I'm going to try to convince you. It's AI. That's going to change the next five years. So right now, we have these, these are three different deidentified melanoma diagnostic tools to be very CME friendly here, but you maybe can guess what they each are. And so, you know, what is the problem with looking at just single lesions or sort of what we have now? This is from the FDA, because the ones that are FDA approved are devices. So you can see super high sensitivities for melanoma, 97, 98%, but specificities that are kind of low, like 10 to 30%, and if you look at the PLA, which uses gene expression profiling, much better specificity, but a little bit of a lower sensitivity. So the low specificity means that they tell you a lot of stuff is melanoma that is not melanoma? That is benign, correct. Okay. Now, what's happening across the pond? This is derm, this is actually a device. It's just basically a program with a dermatoscope on an iPhone, and GPs use this for patients who have a lesion of concern, and it says is it melanoma? No. Okay. What about squamous cell? What about basal cell? And it's really used to just triage referrals, and it's actually approved by the sort of FDA equivalent in the UK. And they published their data recently looking at this, you know, using this tool at multiple different centers. And you can see the sensitivity, like, is this melanoma? Yes or no? It was really high, like 100%. And the negative predictive value, meaning if I say it's fine, is it really fine? Is like 100% to 99%. So what I thought was cool was when they actually said, how did this work? In two different centers, they had the tool, and they looked at the patients where the tool was used, and the patients where it wasn't. And when it was used, the machine basically let them discharge, like 40% and 25% of lesions that it evaluated. Dermatologists reviewed them all. None of them actually did turn out to be skin cancer. Of those that were sent for review, the positive predictive value was higher. Like of those that were biopsy, 17% of those were skin cancer, 5% were melanoma. And the ones where it wasn't used, a much lower rate of those biopsies were positive for skin cancer. So I think, you know, this could be great for not finding things, but for saying, what do we not need to look at? But, you know, why are we focused on single lesions? You know, we know that what the patients worried about that sub-K on their arm is not, you know, they don't even know about the melanoma on their back. Full body skin exams take lots of time. And if you look at what is cancer, it's a growing or changing lesions. So if it's not changing or growing, it's actually not cancer. So there's lots of ways that we can use AI to identify new or changing lesions we have that now. And so one of the things that, you know, these tools can do, if you look in that lower left corner, all those blue, these are two different tools. They're ones better than the other, picking up, but both of them are great at figuring out what we don't even need to look at. And this was a study in Germany where they looked at, you know, patients who were they used one of these imaging devices versus just tip that it's the image consultation versus outpatient care. And what you can see here is that when patients have this imaging available, they had more of those visits were associated with the biopsy of melanoma. There were fewer Nevi biopsy, and the ratio of melanomas to Nevi that were biopsy was like, there was like a tenfold difference. So finding more melanomas biopsy in fewer Nevi. And what I think is really cool, this was in the chat. This is a machine that scans, and it gets not just your clinical images, but also dermatoscopic images. And when dermatologists evaluated these, compared to taking a manual dermoscopy photo, you know, totally as good and readable. So I think there's great help here. I'm excited. I think that AI is going to be helpful for identifying the lesions that we can ignore, and then we can focus on the ones we really need to look at. The big question for me with all of that though is what is the financial model going to be? Like that machine did not look cheap. And it really becomes like if we're going to have to buy the machine, is insurance going to reimburse enough to make it worth buying and using the machine? So it's like another 40 minute conversation, but you know, there are models where patients pay for this. Right now most patients do get mole mapping, pay for it out of pocket. Okay, okay. All right. So mine is that an availability of an affordable oral jack inhibitor. So tofacidinib is coming off of patent. So within the next one to two years, it should be the case that Zell Jans, right, the original jack inhibitor, you will be able to prescribe it willy nilly. Right. So literally somebody comes in with poison ivy and you can instead of giving them prednisone, you give them tofacidinib. Right. So the suming is cheap and easy to get. Right. We should never have to prescribe prednisone again. So every single patient who comes in and who's got something where you're like, I don't know what to do and they're miserable and we don't have a good FDA approved option. Now you can give them tofacidinib. Now you'll have to talk about the boxed warning and the fact that there is a study that says it increases, there was a high, doesn't increase the risk. I wouldn't be really clear about that. So because we say everybody makes with jack inhibitors, there is no warning, nowhere anywhere. Does it say that jack inhibitors increase the risk of macer VTE, right? That nowhere on earth does it say that. What it says is there is a higher rate of macer VTE compared to people using a TNF and the analogy I would give for the jack inhibitors for the macer VTE. that study is if you took a bunch of people with rheumatoid arthritis and you gave one group of them anything, methotrexate and you gave the other and they all had high cholesterol and you gave the other group statins and then after five years you came back and said okay who had more heart attacks? The people who got methotrexate or the people who got statins? It would be the people who got methotrexate. Nobody would think that the methotrexate made people get them that what happened was the statin made them not get it and that's the real way that the oral zelgians trial it it wasn't that zelgians increased it it was that the TNFs decreased it right that is the big difference so but but that regardless of anything is about to say I'm 100% soton tofacidinib is always safer than prednisone right it always safer than prednisone and jack inhibitors we know this work for everything so you will always in your back pocket you will always have something no matter what is happening with a patient where you could be like I've got something that will work right there might be some risk associated with it I don't know if you want to take that risk I don't think there's any risk but I can't guarantee you but it will work it will get you better right anyway like in planister madameisitis LPP CCCA Pempagos Pempagoid CSU AA Sarcoyd Morpheus everything right you will always have in your back pocket that you can just prescribe and go to the pharmacy and pick it up right and be fair and balanced right if there is a meant risk of mason vte's it truly is the way you can know if you should be concerned about using a jack if a disease is responsive to TNF inhibition or isle 17 inhibition then there might be some risk with using a jack if a disease does not respond to TNF or isle 17 then there is no risk of using a jack mechanistically epidemiologically clinically every bit of data in the history of the world shows there is no risk with using a jack in a disease that is not responsive to IL-17 or to TNF right mechanistically we now know that pretty well right so based on the data mechanism tof will have no pro-therombatic risk in diseases that are not TNF or IL-17 dominant right so I would expect that it could in psoriasis it could in H.S. but all the other diseases we've got there is absolutely no reason to think there'd be any risk right so as he like this if we got FDA projects we should use those we can get them but what if we want to use a jack and can't get it right when all those other diseases now we've got something that is super effective and all of the evidence again clinical epidemiologic basic science says there is no risk but we will still have to talk no risk of major VTE there will be a risk of immunosuppression but right for willing to talk about those risks we can now treat every single disease easily and cheaply right I think you're trying to run out the timer so nobody can vote all right so let's hit it again introduction of BTK inhibitors to the field of dermatology I thought patents arguments were very we I'm trying really hard to win this one I thought patents arguments were really weak artificial intelligence I think fair is convinced me that that it works and it's going to be better than us but I think it's gonna cost all of us money so no way so it's obviously the oral jack inhibitor you're going way over your time you know I went through really quickly because I knew we were short on time and now you're saying that's a weak heart that's very very very all right let's see what we got that's all yes I found I won that one right yeah yeah so no patent done by patent went from 12 to 24 that's a 100% I'm going relative increase all right so thank you guys so much we we will be out in the back after this rise this session we've got a nice if you want to get a backdrop picture with us but since none of you've watched the podcast why that would you care you don't know that we're celebrities but that's interesting state if you haven't you haven't watched the podcast watch that like it or listen to it listen to it it is so much fun and you were really learned to from it thank you