The Episode You've Been Waiting For Your Whole Life

Welcome to season three of Derms on Drugs. A video podcast brought to you by scholars and medicine, the best educational platform in dermatology and provided no cost to medical providers. Derms on Drugs is where cutting edge dirt meets theater miscovy. I'm Dr. Matt Zyris, doc's dermatology. Neat tweak and join me in residency buddies with the law affairs on the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. And we use our 60 years of combined, firm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of dirt. And you'll actually have some fun listening. New episode of Drop Every Friday on Scholars and Medicine, Apple Podcasts, Bodify Another Major Podcasts, Platforms. And I highly recommend that you download the Scholars and Medicine app to access the full podcast video archive and explore the best Derm educational content on the planet. We're talking real, pharma independent coverage of all of dermatology, a robust core curriculum, a lot of analyses of the latest stuff going on in the field. It is supported by an amazing AI clinical consultant called Ask Simon. All right, so this week we've got one of our deep dive episodes and we are so excited to have Dr. Chris Syed from the University of North Carolina who is a deep, deep HS expert. Chris, great to have you on the show. Thanks so much for having me. Glad to be here. The first question that I think in any reasonable listener would wonder, why the heck did you choose to go into HS? Like that's a, you just, you like, like dealing with the most miserable people. You're not miserable because they're like miserable because that's an awful disease. It is an awful disease. So how did you get into HS? Yeah, I mean, that's part of what kind of drove me to it. When I was in residency, I think I saw a lot of patients come in and it's not that people weren't trying to get them better, right? But they were so little off of them, they were so miserable leaving. And when I was finishing up, I was like, okay, I'm going to be out in a few months and I've got to take care of people on my own. How do I do better than this? How do I fix this really challenging bunch of patients on my own and don't have some I had to back me up all the time? And so partly it was just a challenge to learn more how to try to do better for them at that point. That was 2013. So it was two years before how to live. That was approved. Nothing was approved. So everything was a fight if you wanted to get it approved at that point. And at that point, patients came in on a doxy cycle and they left on menaceically and like nobody in the room, me or the patient thought they were probably getting better at that point, right? So it just felt like we were throwing out random stuff and there wasn't really anything satisfying about it. So that's where I just took an opportunity to sort of research a whole bunch and try to learn it well. We had to give a senior talk and so I picked H.S. as a way to force myself to read more about it. And there it was picking up a few things like antibiotic combinations that we weren't really using all that much around, you know, kind of where I was training at least. And then things like surgery coming up a lot and something I had never had in the exposure to or never done before. But the idea that, you know, it had an important role and how to best use that, including the dermatology setting, which again, I never saw a case done in training or really talked about. We didn't release no steroids occasionally, 9D, but it was clear there was more to do and a bigger way to make an impact and it would be a challenge, you know, it'd be difficult many times. And like you said, like, miserable patients can make for miserable doctors very easily, right? You know, misery loves company and it's easy to sort of feel worn out right into the day, but it just felt like a good opportunity to do more. And I absolutely have people tell me when I was like, maybe I'll see H.S. patients, like, you know, like they sort of a pause and then like, why are you doing that again? Like what is it you think you're going to accomplish or you trying to drive yourself into the ground, but, you know, there was just this huge need and so few other people doing it, right? It just felt like, you know, partly just something where it was a gap that needed to feel like partly not opportunity to do things better and do, like, you know, sort of pioneer and try to do some different things procedure wise. You know, that was sort of the point of academic medicine was to offer something that others weren't, right? The patients didn't hit the end of the line and be told, sorry, nothing else I can do for you that somebody had to think creatively. And so it felt like again, a good opportunity. And where did you, where did you do residency? Yes, so I grew up in North Carolina and then went up to UNC for undergrad and never left. So I did like undergrad, med school, internship residency there and then joined the faculty. So I found a good place and didn't leave. So it's been fun to see you kind of all over the years. I got to, you know, work with people where my attendings, we still have some of them on faculty now. And so it's been a good place. Couldn't find a better place that pulled me away yet. Hopefully, you never will. That's a goal. Hopefully, yeah. Yeah. All right. So let's go ahead and get started. We've got three different articles we're going to cover this week. We're going to start with Dr. Patton kind of talking about how do we figure out who's got disease that's bad enough to really warn aggressive therapy. Dr. Patton, why don't you get us started? Yeah. So my deep dive paper March 2026 edition, American Journal of Clinical Dermatology titled defining moderate disease and progression and hydrodynamic subvertiva and expert framework to unlock the window of opportunity for prompt treatment by Mar-Tarell at Al Dr. Syed was also one of the authors on this paper. So if you're not familiar with the whole window of opportunity concept figure one has a nice little visual representation. You have an H.S. patient, they have disease onset and inflammatory nodule in the armpit. It becomes an abscess. That's mild disease. H.S. becomes moderate with multiple nodules and abscesses. And then a tunnel forms and then the disease progresses from there to severe. So the window of opportunity is between mild disease and severe disease. The thought being, hey, let's introduce biologic therapy in that window. I mean, I definitely got a, like, how can we get more patients on biologics vibe from the paper? And Novartis was involved in funding and hiring medical writers and two of the listed authors are Novartis employees. So it's kind of like a letter that says, dear doctors, put more of your H.S. patients on Cousentics, sincerely, Cousentics. Right. But I think the problem being addressed as a real one, like when do we start biologics in H.S. patient? Who's a candidate? A paper. It's like a sort of a consensus. They call it a framework, but 10 H.S. experts with defines moderate disease, table one, list criteria. And you know which patients have moderate disease? Every single H.S. patient you've ever seen. Table one. So moderate H.S. they define it as patients with an adequate control of H.S. symptoms or one active tunnel, draining or non-draining or at least four inflammatory lesions, inclusive of inflammatory nodules and abscesses involving at least two anatomic areas. Table two provides definitions of progressive disease in H.S. Pretty straightforward, you know, with defines progression. So my thoughts on the window of opportunity, well, it's never explicitly stated. It implicitly argues for initiation of biologics in all H.S. patients. And so that like the definition of moderate H.S. is such that there's no such patient with mild disease. That's kind of like the way I felt about it. So this is the only concern I have. So you have an H.S. patient with a few inflammatory nodules, post-inflammatory changes, no tunneling, no prior treatment. It's a reasonable candidate for like your topical therapy, clinical mice and hypochlands, bleach baths maybe. I put them on doxycycline, three month plan, spurnal actone if they're female, maybe. You do a three month follow up on the window of opportunity framework if that patient develops a tunnel and follow up. So I think that's really, I've missed the window and could be criticized for mismanaging in H.S. patient. Even though like stepwise care like that, initial sort of management plan seems appropriate. You throw in the fact that window of opportunity concept strongly promoted by industry, like is it putting providers in a tricky situation where we feel compelled to prescribe biologics to all H.S. patients from the very first visit, which again, like I lean towards aggressive therapy. But patients on IsoTreat, no one that I think other providers are like, why are you being so aggressive? Like, I'm an advocate for aggressive therapy. But having this window of opportunity and did we miss it, did we miss it? Aren't we kind of saying like if we're not using biologics and one tunnel forms, we're kind of in a bad situation because that window of opportunity is gone. Like who are we not considering biologic therapy on with this notion of like moderate disease being like not, you know, like two abscesses and you have moderate disease? Right. Now, good question. You bring up lots of points or you want to go first or I can give some initial comment. No, yeah, I'll take it. Yeah, so you know, the paper had a definition for moderate disease, which included patients who I think were a cousadrent to other therapies. And so like it's not that all people who have like just a few nodules would necessarily qualify as moderate disease. It doesn't always say like moderate disease has to equal you need to do biologic therapy. It's just the idea that if they have disease, it has to respond to other conventional therapies, they should qualify right? Like you've been through spirulac tone and abotic softened on, they're not tolerating those things. You know, at that point, you shouldn't have to wait for them to develop a tunnel if it's conducive with what they want to do. Right. And so that's the question. So if you look at the patient's patient provider discussion, like if you look at, you know, psoriasis appropriate use criteria, like any genital or scalp involvement is supposed to qualify for systemic therapy based on guidelines, right? There are a lot of patients who can do fine with topicals in that scenario. So it's not what we have to do every time. It's just that if that patient is not responding, you think they qualify at that point, they should be able to be on one if they've been recalsterned enough and had enough quality of life impact that you think is necessary for that patient. But it's not saying you have to use it in that scenario because the other definition was at least full, like, you know, four or more inflammatory modules or any draining tunnels at all, which is the idea that if they make tunnels once they're going to do it again, they've got surgical burden, irreversible damage at that point. Like, that's a pretty straightforward, like if they feel like they would want to be on a biologic with where their disease is, I think if they have a tunnel they should absolutely be allowed at that point. Four nodules is, you know, you're not going to catch them on a day when they're that active, but that's the idea that look, are we really going to waste time? Force them to do an antibiotic for three months. When you can just kind of tell already they're advancing quickly, they've got pretty active disease, a pretty big impact on quality of life. So I don't think there's ever a situation where we'd say, like it is inappropriate, like you, you know, you must treat this or you're doing something inappropriate in that modern disease category. You should absolutely be able to do antibiotics, be in a lactone, laser hair removal, lots of other things in that context. And even a patient with one draining tunnel, it's context dependent, right? Like if I have a young female, like there's a subset of patients three or four percent, they get like one area that flares over and over again. They're really not developing widespread disease. It has been three or four years every month and abscess on the labia. And if you take care of that one spot surgically, they might do great and really not need any medicine at all. So it's more about, you know, if they hit these criteria, you should be thinking about biologic therapy. This is the chance to act if there's no meant to move in the wrong way. But it's not that you have to do it. It's tough when there's bias. Like you said, that study, you know, Novara's tough to organize it, you know, the experts get together and they sort of get to say their message and have veto power, like it's not to wear, you know, but it has an uneasy feeling to it for sure. And there is like a whole other effort very similar to finding modern disease, you know, which is maybe gonna come out different and make it even more confusing, but that's the problem is you have, you know, groups that aren't talking to each other, developing different guidelines. And we'll really probably just need as appropriate use criteria. Like when should you consider it as opposed to saying, this is modern disease and therefore, you know, maybe we should consider it for those patients. But if you had a patient come in and say like, you know, let's say they got one nodule in each axilla, one in each groin. So four nodules, wait, the person has. - And they said to you like, hey, you're saying the patient has two groins? - Yeah, a right one and a left one. So they, and they said, hey, I have a chest, I've seen the commercials. I mean, like if they wanted to start at a limb amount or any of the biologics, like I think it's totally appropriate, right? I mean, do you, do you start people on biologics where other people are like, what are you doing? Like this isn't that bad of a disease. - I mean, I don't think we get that much pushback. I think most people feel like, like, and that's a personal I'd say, like sure. It would be reasonable for you to do it if you're motivated. You feel comfortable with escalating. It's having a big impact on you, and especially if you're young and it's advancing and the momentum is in the wrong direction. And if it's somebody where things are like relatively stable, they've never tried anything else, I would absolutely layout options at least and let them pick, right, whether that again be things I mentioned earlier, legs or hair, movable things like that. Like sometimes you do just fine with those things. You don't have to escalate over time. But yeah, that person was highly motivated again, just like somebody with congenital psoriasis or sort of other things where we consider treating them. We're gonna like acne like you mentioned. Like you got a low threshold to treat nodular acne because you know it can form scarring. Once it starts, you should get ahead of it. So maybe some people would say that it's overly aggressive. I also think, I'm skewed towards patients with really bad disease. Like I have a lot of patients who come in there, it's for the feral center. They often have bad disease. I don't have 100% of people on biologics, right? So I have plenty that we're doing other things for. But I think it gets to the point where it is very reasonable to offer it. Like if that's conducive to the patients sort of risk benefit profile, these are pretty low or strokes for the most part. I think it's a reasonable thing to try to get ahead of it if you can. Do you find that, I mean, this, I probably know the answer to this. It seems to me like papers like this are trying to encourage earlier use of biologics. Do you think that's a huge problem? Like patients come to you and they've never even been offered a biologic. Is that sort of picture changing because of the fact that it was approved, Adalimav was approved as long as it was? It's better than it used to be, but there are still a lot of dermisol, so we've been practicing a long time in the community that are just minimally comfortable with biologics in general, like minimally comfortable with HS. Don't really know where that threshold is. They're waiting to pull out the big guns the last minute. Right? They have this idea that I'm really only going to save it for if you get bad enough because I'm not wasting it too early, which I think is the wrong way to think about it. Earlier, you treat somebody at the better their response tends to be. So I do think sending that message is important for a lot of folks out there who don't maybe see as HS is off and are thinking about it as often. And part of it's also, you're partly speaking to payers with this kind of thing. And the idea that you can't put barrier after barrier and fraud enough access for some patients who do need it. Because they're not checking whatever boxy thing is required that you just kind of made up when you don't really know the disease very well. So I think the more precedent there is in literature when we think it is appropriate, the easier it should be to access it over time. Do we have good data that certain therapies will actually prevent progression, let's say from her at least, stage one to two or two to three. And so the window of opportunity, I think a surri-- I do a lot of surrises. I don't think a surrises is having a window of opportunity. I can start somebody when they're pretty bad. And that's-- I mean, arthritis, that's another story. That's just playing like this again. - Just a wee window. - It's a really big window. - It's a bigger window. - Yeah, it's a bigger window. It's like a picture window. But no, it is not-- Yeah, so I guess that's-- But my gut feeling is that with HS, it is a little different, right? So once somebody has her at least, stage three disease, I can never make them, IgA. I can never make them feel as though they are clear. Whereas with surrises, I can take you from 80% BSA to 0% BSA. - It's a lot more surrientic arthritis. - I was like, what's that? - It's a lot more surrientic arthritis, right? I mean, if you get arthritis mutalands, you've missed your window of opportunity. - Yes. - No, absolutely. - Yeah. - And do we know, do you actually, there are markers of fibrosis and things like that? Like do the biologics change that? - So there isn't-- it's going to be really hard to do that study. Because you'd have to look at patients with early disease. You'd have to put them on a, you know, biologic or placebo for six months and see, like at least six months, maybe a year to really get a sense of who's going to progress and who's not, and do you truly slow it down? I mean, there are some evidence that, like, you know, patients who have shorter disease duration before you start treating tend to have better outcomes. You know, those that have sort of less severe numbers of tongue, like, you know, fewer numbers of draining tunnels. That kind of thing, they probably do respond a little bit better overall. So the idea is that, like, the ceiling of how much improvement you can get declines, the further you wait, and the worse you let things get, right? So the percentage to get, you know, 90 and 100%, you know, high score, you know, like high score, 90 and 100, like, you know, that really sort of dramatic reduction disease. Those responses are better for patients who aren't as bad at their baseline. So the worse you let them get, the lower your ceiling becomes. And the other big thing is that they have higher surgical burden at that point, like, to get them that much better, that means they have to have a lot more surgery done, which is also a burden on its own. You know, it's not a magical thing. You get the way the one that happens. That's recovery and downtime and more time to get the same level of improvement overall. See, I agree with you. It's different than psoriasis or exmo. Like, we can put a patient on a drug who has terrible, terrible disease for a long time. Six months later, their skin can look normal, right? Like, they have no, they might have some disfigmentation as possible that you can get scarring with those things. But, you know, and what's different with joints even is like, say even you can recover like the skin itself, you know, that like, there's not inflammation around, you know, there are marks left behind forever, right? And it is for a, you know, a teenager, somebody in their 20s who is trying to get romantically involved to have to explain away, you know, what it is that has permanently changed them. Like, you cannot take that back once it's happened. Even if you get the, even if you get high school 100, zero nodules, zero abscesses, no drainage anymore, right? Like, it is still something that that burden with forever if you don't jump in and really induce something about it. So, in the moment, there's tunneling, the moment they're scarring just like an acne patient, like, yeah, we have, I think necessarily a low-wirt threshold to treat. Like, there are more psoriasis patients out there in the world. But I think we have a greater number of HS patients, ultimately, that might need biologics. Because even if it's a quarter of many people with HS compared to psoriasis, like, what the disease does is just that much worse and that much more long lasting. - Now, that's, I would agree. And then my other question is laser hair removal. So, I know that's something that you do. We do a lot here at UNC. And so, my question is, do you think that you can prevent people from going from, really, curly stage one to two, and how about two to three? And where do you think laser hair removal is helpful? Is that an early intervention thing? Is that more of a, you've got a bigger window? - Yeah, I mean, earlier is probably better. Once somebody has an armpit full of scars and tunnels, like you can't fix that by removing the hair follicles on the surface and half the time the hair follicles are mostly gone from all the scar. So, earlier is probably better. And I do think it can have a relatively lasting impact for some patients. The idea is that fewer follicles around, I mean, fewer inflammatory, two-ernotals that pop up and each nodule, maybe has a chance of spiraling, leading some scar and some tunneling behind. And so, yeah, like earlier is probably better, like, early one and two patients. There are some early three patients that, you know, you clear certain areas with surgery and you treat the rest of the surrounding area with laser and it probably helps to stabilize that disease a little bit better. But it's hard to predict, you know, just like with any medicine, you know, some people go into the laser and still just plow right through and get worse regardless. But I do think, I think we do a better job stabilizing patients when we add that to the mix, especially in kind of that earlier moderate disease. You're gonna have some patients who, again, are inflammatory disasters and it's just, it's not enough. - For early stage, an early stage patient, Like we were just talking about with Patten if if they came in and you Had no barriers you could either put them on whatever biological you wanted or do laser hair removal with like which one would if it was your your child You know who's 23 and started to get HS would you want the hair removal the biological? I know both are you don't read you can't do both but Which one would like can it be curative? You know for these patients if you get it early with the laser hair removal Yeah, I mean I think it can be stabilized into the point that you get them through Their most active years of disease with much less activity and you maybe spare them in many cases the need for escalating to a biologic like I think it's really foolish to these companies sometimes to not be like really gone How about covering things like lazy hair removal and paying docs if you under bucks without question because If you just delay the start of a biologic by a month or two like that that pays for your year of laser right? If you skip if you get rid of one dose of a biologic is the same thing with psoriasis it should be That the day you get your first psoriasis, you know systemic before you Every single patient gets a home never been to be be box Just right here at end of story right if it if it prevents one dose it has no pain for Yeah, I totally agree. I mean I think it is Yes, yeah, if I had a kid it was a teenager, you know early 20s You know if all they were getting were you know a few lesions, you know every month or two like along the bikini area Yeah, probably I would encourage something like laser before committing them to you know a couple years or a decade of being on a biologic So I would start there and then escalate over time rather than going straight to a biologic But again the moment it's you know they've had a few sessions. They're not improving. They're not stabilizing I have a low threshold to do something Sooner rather than later. Okay, all right, but Fair sense go ahead. Let's talk about your paper All right, so we're gonna move on to a biologic so we're gonna talk about bimicism ab so this is the two year Two year data for patients with moderate to severe Hs pooled results from two phase three randomized control trials and Their open label extension doctor siet is the senior author here So this is pulling data from be heard one and we heard two so these are two phase three Study so bimicism ab is this you know a monoclonal antibody and have its aisle 17 a and f which are both important drivers And so the these are two identical 48 week randomized placebo control phase three trials and then once they finish the 48 weeks They could roll into the open label extension Which is you know planning to go for 188 weeks, right? So that's some Strange number. That's a little over three years So in total they had 868 patients on bimicism ab 146 On placebo in the parent trial and then they had 657 that went into the extension so pretty good size trial So you know what they looked for was safety data and then efficacy data So the dosing is kind of interesting when you rolled over You were you were stratified on whether or not you had achieved the high score 90 so that's a 90% reduction in abscesses and inflammatory nodule count With no increase in abscesses and kind of appropriate or you know reflecting back on what we were just talking about No increase in draining tunnels Okay, and so the people who were who did not have a high score 90 went on 320 milligrams every two weeks and the high score 90 Responders got to pull back a little bit to every four weeks and then you know They could go back up to every two weeks if they were you know not responding well basically with you know with criteria that I won't go into Okay safety they did not see treatment emerging adverse events go up From year one to two And they did not see you know that they saw like stable or decreased numerically the number of serious Adverse events - most common ones were covid probably due to one they were doing the studies oral Candidiasis which I think is saying that's really I'm always amazed by how common that is with bimicism lab in particular So 12.5 per 100 patient years So that is you know pretty frequent mostly mild to moderate rare You know sister rare Serious infections and there were like low events of IBD mace Malignancies suicide et cetera, and there were no new safety signals Okay, moving on to the efficacy by year to 85 percent of patients has achieved high score 50 77 Percent achieved high score 75 and 57 percent hit high score 90 and then 44 percent achieved complete Clarence or high score 100 Mean abscess and inflammatory nodule counts dropped from about 17 at baseline down to four and then down to a bet year one and Bound to 2.3 by year - for the patients who had draining tunnels at baseline Which was about three quarters of that cohort the mean count dropped from 4.9 to 1.8 at year one and then 1.4 at year two So you know that was pretty I thought pretty interesting so it actually looked like the draining so I would imagine they still scarring there But their tunnels are no longer draining and then for the people who had none they Basically very few of them developed they went from on average From 0 to 0.2 tunnels by year two so you know about one and five I guess would develop a one draining tunnel if you want to look at it that way Quality of life measures, you know, we're kind of as expected. They went along with they they tracked with lesion response um and A roughly a third of patients had a dlqi of 0 or 1 so that means essentially no impact of their disease on their quality of life by Year two and so you know, I think that's pretty significant because of the you know profound impact on quality of life that HS has So what are the strengths? This is a pretty large cohort size. It's two years. It's going to go on You know even longer so you know, what what could we say that's like criticism critical pat and really starters off on the Snarky criticism side so how can I add to this? You know, there's actually not a ton. I mean, I guess what you would say is you know with an open label extension There's no control arm after week 48. I also think it's hard to enroll and probably not ethical to put people in placebo controlled studies for two to three years um also I think that you know the other important thing anytime you got an open label Studies to realize that people do there is a trition People do drop out so there is some attrition bias that the sickest or at least response of patients tend to be more likely to drop out which means that if you're looking at the results and the people who are left They're going to generally be the people who are responding Better so you know, they're you can look and compare this to other data But we don't have had to had data again. This was like a single drug study. It's not you know Compared to like seki kin you maver compared to adalimimab So, you know, I think that this was good evidence that you know patients one This is a long-term disease and it can be a progressive disease if you look at the curves patients did tend to do better Over time, I think that the tunnel reduction is probably more important than the um The like inflammatory nodural reduction because that's very much a snapshot in time and what they have at that study visit I think that tunnels are harder to um resolve so So that that was my take on that paper chris anything else any other data from there they think are important that I didn't talk about I'm jumping in hold on here. I'm sorry. I know much you like dinner around me. Go ahead Well, that's your finish I'm technically I interrupted Chris Uh, so Chris here so Laura touched on this, but it is a soap boxy Bing for me attrition so that like because in in some of the ad literature there's like oh 98% of people will do great at three years and it's like no you started with 600 people you finished with 82 You don't know what the hell happened with and it's so I may And when I did a really deep dive on was the idea that You can assume that it is not Data missing it random it is it is non-random and Exactly as Laura said the people who are not doing as well tend to be the ones who drop out and in that setting There is absolutely no way to correct for it like people like to be oh we did Monte Carlo mixed my model bootstrap analysis and so we accounted for the maybe didn't you didn't kind it's impossible it is literally impossible So I'm a believer that they should all be L.O.C.F that that L.O.C.F Is the best because if you're not doing great and you drop out then we'll see that because your last observation will like and I but Everybody pushes back on me in far more and and and Just like I've had since she made You numbers I know what you're saying just to give you numbers at week 48 the number of subjects that were in was 556 and then at week 96, it was 446. So you're losing about 110. So it's about 20% attrition from week 48 to week 96. So if you said it's 20% attrition, and if you look at it, the numbers go up a little bit, like for your high score, 100 goes up by about 14%. So it's not just the people, the non-responders, but that's just to put it into context. It's not that 90% of people drop out. It's about 20% at least in the study. - Yes, and that's, yeah, I mean, to me, whenever you look at the high score, 75, for example, there were fewer people, although it went from 64% to 77%, there were fewer people, right? So meaning there were 36 people who got high score 75 at 48 weeks, and there were only 344 people who got it at 96 weeks. So for all of these, so like high score 90 did actually go up a little bit, and high score 100 did actually go up a little bit in terms of the absolute number of people. But that's what I always look at to try and give me a sense of. - Yeah, that's a good point. So the lower response rates, the high score 55, 75, you would imagine those patients are more likely to be on that cusp of wanting to drop out, and that number does go down the high response rates. It's a lower percentage, but the absolute number, the numerator goes up and the denominator goes down. - All right, so Dr. Pave, what do you think about all this? - Yes, so I'll give you both sides of it. I have some beef out of support, even though again, I'm one of the folks on there, like OC data is the rosiest way of looking at it. And so every farmer company that publishes a paper is going to want OC data to make it the number of it's inflated as they could. I agree the last observation carry forward is usually my preference, and I think there's a supplemental figure that I had pushed for for either last observation carry forward or at least even like a non-responder invitation. If you really want to be stringent, you do non-responder invitation, so that anybody leaving is considered a non-responder. - Just not always fear in a long term study. - For people who lie about this all the time, they'll call it a modified NRI, and then when they modify it, then it's not an NRI, like a pure NRI. - Why? - Not always, like a, 'cause some non-responder modified are actually worse. Like in the sort of initial study for this one was if you got an antibiotic, like a rescue antibiotic, you were also considered a non-responder. So it's like worse than a standard non-responder invitation. But you're right, people fiddle with it, they're trying to like, you know, juice their numbers a little bit. But since I'll tell you why, like I think it's overall a very positive story, like, and again, this is the context of the only people who included in this analysis or those who entered the open label extension, they had to stay for a year, which automatically gives you a more favorable look, right? People who dropped out in the first year would have been less likely to respond to in three years later. So you're already filtering, you know, through that lens, and then you get to the end and you say, "Okay, about, if you really want to look at the number I care the most about, it's high score 9,100." Like those are the folks who are super happy. High score 50s, they're better, they're probably not super satisfied. But if you want to look at who is really responding, really, really well consistently, who's the patient who comes to you and is super happy with the drug, it's their high score 9,100s. This study started with about 800 people that were getting drug from day one, and then over the course of time, like you said, they got to about 400 by year too. So even if you assume that everybody who left was a non-responder, and you cut your numbers like in half almost, you know, you say a 20% high score 100 response rate, 20%, 25%, with that, you know, if you just looked at everybody who entered on drug on day one and went to year two, that is still like pretty darn good. Like 25% of people with no active disease after two years, you know, I think is better than what Adalim Mab did. I think it's a little bit better than what Cosintix does, and that'd be sort of the harshest way looking. And reality, I think a lot of people who leave the studies, they do it because it's, you know, a big time burden, it's a big travel commitment. I had people driving three hours during my involvement in the study for every single visit. And over time, some of them were actually really good and said, you know what, like, I just can't keep doing this. You know, I'm glad I did it. I'm way better than what I was. I just can't keep it up. Or they moved across the country because they had a new job over the course of two years. I had to be close to family. So I have people who were very sad to leave the study because they were doing much better when they did leave. So it's a bit of a mixed bag, especially if you filter for people who have been there for a year. Like they were probably pretty happy at a year. Like they didn't all leave because they suddenly became unhappy at week 52 as opposed to week 48. So I don't think a lot of the attrition in this type of follow-up is purely because people aren't doing well most of the time. It's just you lose, like to only lose 100 folks out of 550 over the course of the, from week 48 to 96, isn't that bad, actually? And those numbers do treat upward with some extent. And that's the reality is that I think people, if they do well with IL-17s, TNFs tend to weigh in over time. That's one of the biggest problems that a limb have. The responses between Demzelix, Cosintix, and Humira, like all look pretty similar at week 612 and 16. But when you get out further as when you see things improved, whereas I think Adalim, Mab levels off early and then starts to wane. Cosintix holds up pretty well. Demzelix, I think, is the best of them in terms of its ability to maintain response and probably have continued to improve responses more time passes. So I do think this is an overall positive story. But yeah, there are ways where things could be reported more fairly. It's not a story of, if you start a person on the drug, 45% have high score 100 years later. Like that's too rosy of the picture. And I think you could get that impression looking that slide to start with. But yeah, it's somewhere in the middle of those two things. - So, Chris, I'm kind of ready. I'm gonna go on to the next paper, but the paper was really just a, first of all, our readers to know, where our listeners to know about it, 'cause it is such a useful article. So, Rich Seb was a author on this one as well. It's in the American Journal of Clinical Dermotology 2025. - Can I give you two more from that study? Is it okay if I give you two more quick things? Like what was about the rush? 'Cause you mentioned throsh, but that is a nuisance side effect for sure. And I tell people one in eight folks are gonna develop thrush through the study. If you notice it, I get people flukonazole 300 milligrams, take once weekly as needed, give them 10 tablets, they have control over it. If they notice symptoms coming back, they can use it and stay on top of it. Most people are willing to put up with that. The other side effect that comes up in about 12 or 15% of patients after that first year, or sort of if you look out at the one year data and two year data, it's about 15% get dermatitis, which is a broad spectrum. And so that's one of the more important things to look out for, 'cause it's probably more of a barrier that gets in the way of treatment. Some people you treat through and it's fine. It clears after three to six months, and their HS does great, and they're really happy. There are some words as like rip-roar and like awful, you may be in like two percent, and it can be it's most often an inverse pattern. So they might come in and say my armpits are hurting, like it's really raw and sore, and their HS looks pretty good, it's just the dermatitis. And so if you can get them through it, sometimes they still do great in the long run, but that's maybe the more important thing to watch out for. - So I gotta say that is such a fun. - How do you treat that? You just do a tropical like chrysancyleone and top them through it, or what do you do when that happens? - Yeah, it depends on how severe, you know, you're dealing with intertrogenous sites a lot of time, so it is difficult to have them do topical steroids for a long period of time, but that's how I would start. You know, I don't think there's that much yeast growth that complicates things, all sometimes do like a, you know, it's heresy, some people think it's terrible to give somebody like a topical steroid, and an antifungal, but I'll give them low to some, because it's easy and like they're worried about yeast, 'cause we talked about it at some point. I know, but it's my theory of this, it's my theory of like, you know, I'm covering all the bases, I don't wanna have to keep changing it over time. And so, you know, it's, you can start with something like that, you can try to do a non-stairway, but it's often sort of macerated and sore or so pro-topic and things like that don't do great a lot of the times, just too much sting to it. And then you can try to just call it a topic dermatitis or inverse psoriasis and get whatever other topical you like, and sometimes that's where I'll transition to things like a Jack inhibitor, a Jack inhibitor, saying we're managing that. So, yeah, sometimes you can manage through other times, you gotta switch something else. - It's a fascinating topic, this whole slide of kind of shift phenomenon, 'cause we see it in right and dupe, get about five to seven percent of people will get either nuance acceptor, nuance at psoriasis, nuance at psoriatic arthritis. And it's fascinating to me that with the I/O 17s, it goes along with efficacy. So, it happens the least, the least with cosentics, then taltz, you get a little bit more dermatitis and then bimselic, you get the most. And that, that cytokine shift is just, it's pretty cool and it's pretty fascinating to me. That goes both ways. Down. - Dirt first, do you know, do you get as much of that in psoriasis as you do in HS? I feel like the number that I've seen psoriasis is more like in the 5% range, I think is the kind of what I've seen in the literature. But that's kind of a random question. I mean, - I want to see that very much. I think in part, it's also because most of our psoriasis, patients we do have on topical steroids as well. I think that they just sort of end up treating through it. That's my impression. - Okay, all right. So, all right, let's go on to that last article. So, American Journal of Clinical Dermotology, 2025, comprehensive and updated algorithm of hidrodinitis, subproteva management from the experts. Again, Dr. Sled was an author on this and it has a phenomenally good flow chart that really is a pretty comprehensive overview of all of the different therapies. I mean, you guys killed it with this. You've got Linazelid in there, which is by far my favorite therapy for helping in the acute setting. You've got, I think, oral reflumelast in here. Like, you guys really brought everything good in. I just think it's such a phenomenally good resource. Just bravo. Bravo was kind of my takeaway from it. Thank you. Yeah. Yeah. Dr. Schaul was, I think, in your author, I'll give her like the bulk of the credit and I came in and sort of helped in a few ways. But yeah, it's nice because it covers a lot. It's kind of all there. It's also maybe overwhelming of like, where do you actually start or what, which, you know, what do you actually follow? Because it is just there's so much different stuff you can do when it's unpredictable. So it's easy to get lost too. Yeah. So it's so that's the matter. Anything that talks about oral reflumelast off label. So you really, like you had them out reflumelast, but do you actually use oral reflumelast at all as a, at, obviously not as like monetary, but as an adjunct in HS, have you done it? Yeah, every now and then I mean, the PDE4 inhibitors probably are just not that great in HS. I mean, they're only so, so in psorias when it comes down to it. And like, you know, a third of patients get too much stomach cups that were full of last just like with a, like a primal last. And so it's got its limits, but you know, it's super cheap to get it from like, you know, like we'll get it from like more Cuban pharmacy for, you know, 20 bucks or something like that a month and it can fill a gap for somebody who's not quite ready to be on a biologic or doesn't want to be on for some reason. You know, maybe we're adding it on top of their biologic. I've tried it sometimes for things like that people get the sort of psoriasiform eruptions with whichever biologic they are on to see if we can calm that down. And maybe it has modest effects sometimes. I will say that I don't think I have a single patient on Rifu in the last right now. And so it's not something that I'm doing all the time, but you know, it's in the back of my mind is an option that's cost effective if, you know, somebody's having trouble accessing other things. And then one other question because one of the things I think that's a, that had an amazing when I've seen it done, I have not done it, but is irtipenum, IV irtipenum. How often do you use that? How would you say for like the average dermatologist who's listening who maybe isn't like, oh, I've got an order set for getting a pick line put in and blah, blah, blah. Like how do you use it? When do you, what's your off ramp from it? And how hard is it to actually get for patients? Yeah. So, I mean, first of all, you know, it's not the long-term fix, you know, antibiotic, you know, resistance is a real issue. We're mostly doing this in the outpatient setting. So it's less of a problem than when you're sort of incubating super bugs in the hospital and putting everybody on strong IV antibiotics like that. But you still have to be careful. And it's a, you know, it's a bit of a burden. People have to get their pick line plays. They got to keep it wrapped up and protected. It's, you know, somebody who's young and active physically, they have to be careful with exercise and stuff like that. I'd probably use it, you know, once or most twice in a month. And so, and I see a lot of patients with terrible disease who wouldn't be unreasonable. But again, you know, I'd say maybe a third of the time I offer it, somebody actually does it and I offer again a few times a month, something like that. I mean, even though it's a hassle, it is like, you say, it's like miraculous sometimes. I mean, people who are like your worst patients bedbound, three weeks later, like up and at it, doing things and, you know, they get the problem is they get worse once they go off. You know, they got a little bit of a tail. Maybe, you know, a few weeks on the short end or sometimes three to six months where they can be pretty good after they come off. If we do it for 12 weeks, but it is a bridge, right? Or it's a rescue. Somebody who's just falling apart, you have to kind of get them out of the house. You're trying to not make them get hospitalized and have bad things happen to them. It is a way to rescue or to, and at the same time, I'm starting, and I'm usually making some other big change in the background of what is the long term, like you said, exit strategy. So, it's either somebody who's terrible that we're starting up for the first time getting the ball rolling and other things or I've had them on something for a while. It's just not working. They're falling apart. Okay, let's transition into that next thing or get you teed up for surgery for some of those worst areas. Just get it calm down and less inflamed to begin with. But it, it's not, it's complicated. It seems like the first time you do it, everything is really complicated. I mean, I never did like influx a map during my residency. I never set up an IV drug. And so I do that all the time now still. With this, you know, I basically send like a pre-writmed order template that I just wrote out, you know, I've heard a pen and one gram daily, you know, CBC, CNP, ESRC, RAP, every two weeks. And I sit, the fact that I have a contact at one of the home infusion companies, option care, or I'll use, there's a couple other ones I'll use sometimes. I just send that to them and they set up home health. They set up, you know, all the drugs get older through the pharmacy and stuff. It's actually like very easy. Kind of like if you set up IV infusions at another clinic where once you set the order rolling, like all the, like they handled authorizations, they get everything kind of set up. Maybe 10% of the time there's somebody who's got a high coat, like you know, a high out of pocket cost and they can't do it for that reason. But it almost always gets approved. It's just a matter of whether something at the last minute they get a high quote of what it's going to be every week to have somebody come out. And the nurse goes out once a week, does the drug, like kind of, make sure the pick line looks good. But for the most part of the patients are taught to do it. That's pretty easy after that first day. And then you just set them up. We pick line. Are you sorry, Ben? How long do you keep them on it? 12 weeks usually, you know, the like the early literature was aiming for like six weeks, but usually 12 weeks, you know, by the time they hit six weeks, they've been good, pretty good for a few weeks. It's 12 weeks, you know, things settled down a bit more. You get more of a break and you've got more time to work with it because it just, you know, by that time they're on the third line by a lot, you can be having to wait for the insurance approval. If you do six weeks, half the time you get there and they've like barely started that next thing. So the question about her to pen them, because I have used it on a couple of patients. We're fortunate enough there's a person in the infectious disease department who does it. Like we just e-mail her and she said, yeah, I got it and takes care of everything, pick line placement, all that. Like the response is blew me away so much, so that I was like, what are we like what are we doing with H.S.? If we're calling it, it's inflammatory and TNF and it and antibiotic absolutely kills the disease. So is this all bugs? Is it all bacteria? I'm giving my theory a question. I want to give my theory for you. I think it is a inflammatory reaction. I did not ask doctors. I want to see what Dr. Sy, thinks about my theory is that it is skin commensals that people are having inflammatory reactions to because skin commensals are resistant to all normal antibiotics. All of them, I think it's like a inflammatory reaction to staff that be or to some other distance so you can't clear it. But yes, that is my theory that it isn't an excessive inflammatory reaction to a skin commensal. All right, Dr. Sy, what's the real answer? Yeah, yeah. I mean, I'm thinking is very much along the lines of that is that there is something abnormal in the immune response and I think people argue whether there is a defect in the immune response so that you don't sort of contain them and sort of limit the certain types of bacteria on the skin to trigger that response. So there could be a defect of some kind that allows altered proliferation and then an overactive response to that or there's just an overactive response happening. There is something about probably the innate immune cell responses like, you know, NK cells and mate cells and things like that that react to, you know, preserved bacterial antigens across lots of different species of bacteria that trigger that initial insult, you know, alert the rest of the immune system to respond like there is an infection presence. So it mimics the response to infection. And so that that may kick it off and it's possible there's like some effect on the gut microbiome as well and that also sort of fuels that inflammatory response that could certainly be playing a role too because yeah, it doesn't make sense. I mean, it's not anti-inflammatory antibiotic. I think you really are shifting, reducing the microbiome and then you kind of take the fecal out of the fire and doing so. And I mean, erdi-penum like in some ways it gives me hope that we're going to do better. Like, you know, if you look at Adelimab, Cosintix, Benzellus, like there is a little bit of a step up between those therapies, but they don't touch erdi-penum, right? Like, you know, it is like 95% of the time of home run. And so there is somewhere in there, you know, a signal or a cascade that if we can block it more specifically, like we should be able to get better drug responses over time. Like it is possible. I don't think it's an impossibility that we find something that hopefully does that well over time. I just don't know that we're always looking in like the right corners of the immune response so far. We don't have, you know, easy targets, you know, where drug companies are sitting on things that are T-cell and V-cell specific or whatever else and they just, you know, don't have that in their stable to try yet at this point. So to me, at least, is a glimmer of hope that we're going to do better as time goes on. We should probably move on to surgery, right? - Really? - At this point. Yes, but there's one more drug we've got to talk about. So the, I think it is because most terms are really not going to use erdi-penum. Just not. Linazelid is phenomenally effective. I use it all the time as rescue therapy now. For people who haven't used Linazelid, 600 milligrams BID. If you want to do it for 10 days or less, it's got an incredibly benign safety profile. Do it for more than 10 days. Just start to get into risk of neuropathy. But I have a fair number of patients who are like on a biologic and then are also getting 10 days a month of Linazelid. And they get, like, there'll be good, there's 10 days, they'll be great. Usually about 10 days after they'll be good. And then the last 10 days, they're like back to normal. But it's better than, like it's in its chief. right? It's dirt cheap. I thought dirt cheap is like 50 bucks for 10 days for 10 days if you have to pay cash Do you if I it is possible. I've just been super lucky Tell me how you use Lynne's a lid. I'm assuming you use it Which what's your play? Yeah, like you said it's not something where there's long-term safety I mean lots of antibiotics have a long track record of safety whether it's like you know We've you've freak out about backroom But you know people use backroom for prophylaxis for you know decades and it's not a problem So there's plenty of things you can use long-term but Lynne's a lid is short term like 10 to 14 days is kind of a rescue You know it people talk about using triple therapy with metronite is all moxie flux and and a refamp and in that you can do for a couple of months or a few months The Alan aze lid is like a short-term flare rescue can be very reasonable. I haven't put somebody on like every month due 10 days There's a way to kind of you know have them on an ongoing adjunct But it's an interesting idea and something that yeah like it it it probably can work pretty well It's not as good as our depenum, but it's it's probably better than the average antibiotic is Okay, yeah, it's a it's an easy drug to use and for a patient who says oh, I've been on so many antibiotics never the Lynne's a lid will work like it is if reliably effective It's alright now. Let's one last question before we move on to system surgery Of the ancillary drugs the metformin this for an lactone Refluemolasse we mentioned already You're in a really very very useful Do you have many people on those in addition to their biologic? I mean probably my favorite thing in that I mean like spirulactoma form and like I said like DAPS on I'm not very impressed with like They're all sort of okay. I mean oral contraceptive pills if you do contain like for patients who flare before their menstrual cycle If you do continuously active pill and suppress cycles consistently you do get quite a bit out of that sometimes And so that's a pretty easy thing where you just It's four packs for three months apply You know throughout the sort of last or a pills go straight to the next pack and most patients who suppress cycles for Some will have spotting and it's a regular and you can't keep it up But it does get around those pre-minstal flares for a lot of patients And influx map is probably I mean I use as much influx map as like any other biologic even though it's off-label and you have to fight for because it is it is probably still Like the fastest and most consistent of them like it probably you know, it's good as been the kids matter better It's just you know It's more of a hassle to do infusions the approvals are kind of hit or miss and like J&J used to do a free drug program for Remake aid they've stopped it for salar and remake in the like starting this year for any new enrollments for people who can't get it to Rinsurance or you don't have insurance and so that's been kind of a blow actually because usually we could fight the insurance and if we couldn't get it We have now but now we're kind of stuck and none of the other biosomalers you offer free drug programs for off-label use in particular for HS So it is a you know an issue that they're sort of some advocacy for I told my wouldn't sick anybody on them yet But yeah, if you ask your J&J reps about you know what happened with the free drug program and you know If they're supporting all the patients they care so much about like why why have they taken away this drug It's very important to some of them Fair fair so that my takeaway answer there was none of thoseance layer drugs or that great So I think that's a good point that this is a chance for us to try to advocate for patients This is and Fliximab is not expensive for the company or the biosomalers should not be expensive for Pairs it would be great if we actually had this as an option for HS patients So hopefully the more that we all speak up the more we can get this Yeah, but it so Chris isn't it so I had a patient who actually wanted to go on in Fliximab They had failed humor. They were placed on Cocentics the the growing disease got worse And so they asked about in Fliximab And at first the insurance company said It's not FDA approved and I said well Benzellix is and it's a lot more expensive So don't you want to do the infliximab? I mean and they did they paid for the infliximab Do you see that with insurance companies where like infliximab is a cheapest option? So so they still fight you on it sometimes so You know it's off label so it's easy for them to reject it if it's not in their algorithm a lot of Insurancees do have it in their formula for treatment of HS and so for some they'll go along with it pretty easily It is very expensive even with biosomalers like the dose we use because it's 10 mix per gig Sometimes the patients can be heavier like you know We're not talking about two or three vials for like a you know R.A. patient who weighs 60 like you know a hundred pounds or something like that like this is it adds up quick Some time and so it can be like very very costly When you do it especially every four weeks I mean that being said it does just work the best and so you get something out of all that for a lot of patients where they're Especially those that have like terrible pioderma and HS overall app like those in flamets like sort of Inflammatory syndrome with patients, you know they high dose infliximab is like the one thing that works for them most of the time So yeah, so it's it's a challenge with some insurance is it's in guy It's you know the old treatment guidelines of 2019, you know talk about infliximab like other international ones talk about So there is plenty of precedent for it a decent number of studies usually within a P.O. You can get a cover but there is you know 10% where they won't budge They'll tell you can only do five mix per gig every eight weeks, which never works well enough Or patients you know lose insurance and they've been on it for five years and all of a sudden they have no way to get access to it anymore So yeah, it presents some challenges Right, so I know we're running low on time, but one if people wanted to learn more about surgical intervention Which I just think is so key and underutilized A) what's the procedure you would tell people to learn to do and B) what's the best way to learn how to do it? Yeah, I mean there are like a fair number of videos online now that kind of walk through the roofing You know I always tell people if you ever want to come hang out with me like I have plenty of people who come through the clinic and spend a day or two and it's not like rocket science I mean the residents that we train you know I'll get some exposure and almost all of them go out and they're like How do I order those probes afterwards? They're all they're doing at the community now So if you know somebody else doing them and you can watch a few and you've done plenty of other skin surgery for things like skin cancers Like you have all the basic tools already. It's just kind of like okay. Where do I look? Where do I numb that kind of stuff? Yeah, there's the shsa meeting which is I mean we don't always do like Sort of like the nitty gritty of how it works But there's lots of meetings where somebody's giving a server will talk on hs They're gonna shake some videos and walk you through it. You know you can reach out to me like I'll send you some videos or talk to you about it The hs community in general is like super willing to help and teach others Um, so I don't think you have much trouble if you know somebody's doing them to join them for a day or something Or again like just have a phone conversation look at some pictures and videos and talk it through it's It's scary at first Do you have a video repository for this? I have some videos that we've taken in a few that are like published, you know And sort of review articles about surgery and stuff like that where you have to go and you have to dig for a little bit We did one on like there's one on our website now that I just did that goes through like It's more patient directed of like this is what to expect for your procedure Like it's got a video of what the procedure itself looks like and what the wound care looks like how to take care of it afterwards Um, so we just posted that in the last couple of weeks and then And it's on YouTube right now if you look up probably like slide deep roofing or something like that I would guess it would pop up. I don't know exactly how to get to search it but But yet there's lots of videos that talk through you know how to go about doing it at this point I'm gonna make a suggestion here that I think would would Take that Lousy Durham department and UNC that's kind of really struggling and put it on the map would be and for cheap and easy right You get a medical student An iPhone camera would probably be good enough But a medical student and it's in camera to come and spend a couple of weeks with you or do a one month research rotation And really and then you know at the AI video editing tools now are so good Uh, edit them together into here are 20 D roofings here are You know wide local exit like a medical student could easily put that together and If there was somewhere that I have that a bunch of high quality videos I think that could be a real Needle mover in the world of interest. I mean Yeah, we have some like Paid for right there are codes they get it paid for which also becomes a barrier sometimes to people doing it so Yeah, but it's yeah, there's a good way to do small things Yeah, the codes pay well for small things if you're doing big stuff all the time then yeah, it's You can spend a lot more time than what you're getting back compared to treating skin cancers, but it's kind of a wash like you know Some patients where I treat three things that are small in different locations and that reimburse is really well And then somebody else you know doesn't work as well for but it it's all fine in the end Dr. Ferris hadn't fired me for not meeting our view expectations yet. So I it's it's working out. Oh yeah, right yeah All right, right any There's said anything that we haven't touched on that you want you know that so it would be where the the biggest podcast in The dermatologist listen to and Durham providers. Is there anything that you want to get out there? Uh about Hs that we haven't that we haven't talked about already Yeah, I mean, you know, it's it's getting better all the time, you know It's still challenging to manage but like when you get these patients better You know the patient who comes in as a total disaster and it's like where do I even start here? I mean there is a path to getting those patients better I didn't understand that when I started it You know, I question myself the most that first year to when those patients that walk on the door I said I'm gonna be the Hs expert and then you know the bomb drops and it's like how do I even like start with this person It's got early three disease everywhere. I don't have any drugs that are approved but like over the course, you know It's a project it can take a year or two or a few years of you know Stabilize with medications and we've got more options for that now Again figuring out how to do some procedures yourself and sort of finding some servants who are willing to help you. But, you know, you can put life at the end of the tunnel. Like, I didn't even, I couldn't see it first because I hadn't seen that path sort of two weeks in in the beginning, but in patients have never seen it for themselves. And so they don't have much hope sometimes. But you can make a huge difference over time, even in those worst cases. And the better our drugs, I mean, there's 20 drugs in trials right now. Like, we are gonna have some step ups over the next five years that are gonna do even better. So there is absolutely a way. And like, you know, there is nobody else to do it, right? Like, you know, we, I mean, on the dermatology end, like, we know these drugs well, we know the procedures well, like, there is no place else for them to go. And so they, we really do have like a unique skill set where we can serve these patients in my mind better than anybody else can. You know, it's a team effort sometimes, but like, if you're not the quarterback for them, like, they're gonna walk out the door and be stuck right where they are and there is again, like, no needle being moved if we don't step up and do it for them. So yeah, just realize that you have the skills and a very unique power and like, place and society to help these people suffer terribly. It's just a matter of like jumping in and figure how to do that. - Okay. Last question, a problem. Jack inhibitors, when they come into H.S. So I'm going to the POVO trial. And I think it works better than any of the biologics is my take. You know, we're not gonna have that data, but that's what it seems like. But I'm nerve like, you know, the AE reports come through. And you know, these are immunosuppressive drugs in people who have abscesses. Like I'm kind of nervous about Jack inhibitors in H.S. Like, where do you see them fitting in once they get approved? - Yeah, I mean, you know, I think Jack's made everybody very nervous, you know, and it's all based on like, again, there's not enough time to talk about oral surveillance and sort of true risk around Jack inhibitors stuff. I'm, I'm smudding like, I feel like Jack and him is safer than a ton of the drugs we've used historically. Like they're very great options. And I think they get sort of an unfairly bad name. The safety profiles in the H.S. I think you're gonna look very similar to other drugs ultimately. You know, my take, you know, I've been part of like the Poverstatin of trials. Like, you know, I use a fair bit of you patissit and a bough label. And so, you know, they're not perfect. I think they're gonna come out like relatively similar to where like, Cocindix and Demy are probably. There's gonna be some patients who happen to respond better to a Jack and him better than to whatever biologics we've had them on so far. So it's gonna be a great, additional option. There'll be some patients who would rather take a pill than an injection. So for them, it's gonna be first line. For others, it's gonna be, you know, second or third, depending on what their preferences are. But I don't know that they're gonna be a step up as much as an alternative. I think both UPA and Polo are gonna be, you know, good options to have. It's gonna put, you know, another quiver, another arrow in our quiver, but it's not gonna be, you know, the thing that's the plants, everything else is number one efficacy. Like an atopic derm, like Jack's work better than all the biologics. I don't know that we're gonna see something similar to an efficacy standpoint in the chest though. That'll be good. I'm gonna be happy to have them. - And we are big Jack reporters on Dermjunt Drug. We've talked numerous times about why oral surveillance, it did not actually show that Tofe increases the risk. What it truly showed was that you were reduced, reduces the risk. Like it's, and that's what the label says. The label says compared to a TNF, the rate was higher. But, right, it was at the TNF lowered it, right? That's the key thing. - Yeah, yeah. Yeah, if you look at similar controls in like what's severe, might or severe rheumatoid arthritis, and all those risk factors, they had lower rates of those side effects in the trial than they had like what we expected in real life. So yeah, that is just, yeah, it's not a fair comparison. - Yep. Well Chris, I want to thank you for coming out. It's been a fantastic episode. I'm anybody who is an HF, SX, HS person is the saint in my, you guys are the saints of dermatology. No question about it. Just really appreciate you coming on the show. With our listeners, hope you learned a few things. Hope you laughed once or twice. Mostly, and we're hoping you're planning to join us again next week. Till then, I'm Matt Cyrus. - I'm Tim Patton. - And I'm Laura Ferris, and we are Derms on drugs.