Serious Medical Derm: Hot Topics & Clinical Controversies—Derms on Drugs Style

[MUSIC PLAYING] Welcome to Derms on Drugs. A video podcast brought to you by scholars and medicine, the best educational platform in dermatology and provided to no cost to medical providers. Derms on Drugs is where cutting-edge dermis comedy, a Matt Zeyers in each week from joint by my residency buddy, Stuckters Laura Ferris and Tim Patton. We use our 60 years of combined derm experience to discuss debate and dissect the hottest topics in dermatology. It is everything you need to know to be in the cutting-edge of derm and you'll actually have some fun listening. New episodes drop every Friday on Scholars and Medicine, Apple Podcasts, Spotify and other major platforms. Just a reminder that we've got a video component. So if you want to see the key figures from the tables, go ahead and jump onto the Scholars and Medicine website. As well, we've got all the links to the articles if you want to see the articles. All right, so let's go ahead and get into it. We've got one of our patented six pack episodes where we're going to go over the six most interesting things we've seen literature recently. Dr. Ferris kick us off. - All right, I am going to be presenting a paper from the New England Journal of Medicine, Danny Rishan at all. And this is the results of the C-posts trial. So Agibent Submit Blamab or Placibo and high-risk, cutaneous, squamous cell, carcinoma. So I've been kind of excited for this to finally get published and it just did like two days ago. So this is a phase three randomized trial where patients were enrolled who had local or regional cutaneous, squamous cell carcinoma after they'd already had surgical resection and postoperative radiotherapy. So these patients had to be, as you can imagine, at high risk for recurrence. And so the features that they used for defining high risk for inclusion criteria were either like nodal features which were extra-capular, extra-captular extension with the largest node that was 20 millimeters or more in diameter or with three nodes involved or high-risk non-nodal disease, which I, this kind of reason why I'm doing this is that I think we end up seeing a lot of these patients in dermatology, which was defined as any of the following. In transit meds, radiologic or clinical evidence of perinural invasion of a named nerve. So this is like big time perinural. T4 primary tumor, so with bone invasion or local recurrence with at least one other adverse feature. So these are patients who were not just like, oh, is that a bad squame or not? Like these are pretty bad squames. And so other the adverse features could be nodal disease, T3 lesion, T3 or higher lesion, diameter greater than 4 centimeters, poor differentiation, recurrent lesion of greater than 20 millimeters. So those are sort of those, the local recurrent bad features. So patients were assigned one to one to either get adjuvant submiplimab. There's about 200 per arm or placebo. So their dose of submiplimab was 350 milligrams every three weeks for 12 weeks. And then they sort of had this interim protocol amendment where they increased them to get 700 milligrams but every six weeks. So less frequent visits for patients. And so that was for another 36 weeks. So they were treated for 48 weeks total. Primary endpoint, disease-free survival, secondary endpoint, local freedom from local regional recurrence or distant recurrence and then of course safety. So patients you had to have had both surgically, surgery with curable intent and, you know, microscopic risk or section of all disease and this post-off radiation therapy or chemo radiation at a biological equivalent of at least 50 gray within two to 10 weeks before randomization. So in other words, these were people with really bad swathes. - These were people with what we would consider pretty bad swathes. Now these are maybe people who we wouldn't have always done adjuvant radiation. I think this is sort of a sticking point and this trial is not every site would do adjuvant radiation after a resection of high risk disease but they did have to have it to sort of have some standardization. So primary endpoint disease-free survival. So that is the time from randomization to the first documentation of either disease recurrence or death due to any cause. And so if we look at the number of events, there were 65 events of recurrence among those who got placebo but 24 in the submittal maharm. So that hazard ratio for recurrence or death was 0.32. So that is a 68% reduction in recurrence or death. That is really, like that's a huge hazard ratio for an oncology study. Secondary endpoints were freedom from local regional recurrence. And if we look at that, there were 40 patients in the placebo arm with local regional recurrence. Nine in the submittal maharm hazard ratio, 0.2, 80% reduction basically. And then the estimated percent of patients free from local regional recurrence at 24 months was 90, basically 95% in the submittal maharm versus 77% in the placebo arm, 0.35. So this was like a really statistically significant, highly successful adjuvant study, which is interesting. There were two deaths of people from each group. There were more grade three events in the submittal maharm group than in the placebo. Of those deaths in the submittal maharm, there was one pneumonia that was considered not to be related to submittal maharm. And there was one death due to myocytis, which was considered to be related to submittal maharm. So that's kind of interesting. All right, so first, we have actually this every single time you bring these damn drugs up. What is submittal maharm again? Sorry, it is an anti-PD1 drug. So it is a inhibitor of PD1. So it's one of these checkpoint-- Let's say checkpoint inhibitor. All right. So where's this going to be relevant, most relevant to germs? So we're not going to be prescribing this. Is it going to be in the category of talking to a patient who's got a high risk claim and be just so that we at least know, hey, there are some really good treatments for you if this goes south? So I think that there's a couple ways that this is relevant to us. I mean, one, this really reinforces the need for a multidisciplinary team to care for these patients. So also realize that submittal maharm has also been shown to be very effective in the neoagevant setting. So advance tumor, give them submittal maharb, then do surgery or look to see if they look for evidence of response. And/or now this is also showing that we can do this in the adjuvant setting. So do the surgery, maybe do the radiation. If you're going to follow the protocol, do it the same way, then give them submittal maharb. So one, I think we can't just manage these patients by ourselves. We need to have this discussion on ecology. And then the other thing is that sometimes these patients, they won't go to oncology. And I just want it off right now. So we can do that. But we really should then be referring them for a discussion of adjuvant therapy after resection. Because I mean, this was an incredibly successful response. Most recurrences were observed in the first year after resection and in that completion of adjuvant radiation. So this is also like we don't have years and years to-- it's not like melanoma like these recurrences happen pretty quickly. So I think having that team on board is important. The other kind of fascinating thing I wanted to point out is that there was another phase three trial of adjuvant PD1 therapy called Keynote 630. This was basically a similar study, but with adjuvant pemberlism app, just a different PD1 inhibitor. And that-- we don't have publications on that. But it was actually stopped for futility after it did not meet a pre-specified endpoint and interim analysis. So it's really interesting that two similar studies with two similar drugs had very different outcomes. It's like completely and totally fascinating, right? I mean, because semiplimab and pembero, they are FDA approved for some similar cancers, right? Metastatic squames, non-small cell lung cancer. And it's not like there's a huge difference in their effectiveness in those particular cancers. And people are talking about like, well, this is the importance of trial design. But, man, how would you go from 68% reduction to stopping a trial because of futility solely based on trial design? Is that possible? Does that make any sense to you? Yeah, I don't know. And I haven't seen the keynote 630, you know, this is basically press. release level data. You know, I don't there has been, I think that the you had to have slightly more advanced disease to go into C-post the one that I just talked about than you did for keynote 630. So, you know, therapies, work, and patients to see a reduction in death and recurrence, you need to have a high risk of death and recurrence in the first place. So maybe that was it, it was just a higher risk population, but you know, fascinating and you know, not a huge study, but in terms of safety, but you know, I think it's going to be interesting to see how we do this. And I just think also like for germs, we cannot like be like, if I can cut it out, the doctor treats it and we're done, right? Like we really need to be taking care of these patients in a multi-disciplinary setting and being the greatest most surgeon in the world, you can cut out the biggest thing and go down into the prodded and into the neck, like is not enough. That doesn't mean you can be their only cancer doctor to me. This really says like, we need to be able to offer this option to our patients. Do we send people to a medical oncologist for this or medical oncology would be the one who would give this? And you know, my plug for multi-disciplinary care, it doesn't have to be like we all sit in a room and look at things or you know, this is like we can all get on zoom. You can have a multi-disciplinary tumor board through zoom. You can all be in different locations and share photos or scans or have discussion and you know, triage the patient. You don't have to be in an academic medical center. It can be you know, this is my good medical oncologist, this is my surgical oncologist and you know, and I'm the dermatologist and it can be as simple as that. So I just think it's important that we really start working toward giving this level of care to our patients. All right, Patton. What do you get? My first six-packed article, Pre-Proof article published online, JAD May 2025. It's by Kau at all. It's titled, "Efficacy Safety, B-cell Depletion Capacity of Three Retuxement Dosing Regimens in the Treatment of Modern to Severe Pemphigus Valgerus and Pemphigus Folliaceous, a 52-week clinical trial. It was a single institution, prospective open label. Patients had to have moderate or severe PV or PF had to inactive quit disease control with corticosteroids and immunosuppressant medications. Specific doses, specific medications weren't specified. Difficulty tapering steroids, they did not really define that either. Patients receive systemic corticosteroids 0.5 makes per cake for moderate disease, one makes per cake for severe disease and also received retuximab on days 0 in 15. And the doses of retuximab varied, standard dose, which is 1000 milligrams, two doses, two weeks apart, low dose, 500 milligrams given in the same regimen, and then ultra low dose, 100 milligrams because of a higher percentage of B-cells tested at we 26 patients in the ultra low dose group, got an additional dose of 100 milligrams of retuximab at we 26. So it was kind of like two doses for those higher doses, three doses for the group that was in the 100 milligrams. 26 patients in the 100 milligram group, 13 each in the 500 and 1000 groups. Table one was all the baseline characteristics and there may be some differences in the groups of none of them reached statistical significance. Couple of numbers stood out to me patients and the 100 milligram group had a disease duration of 18 months, 18 months versus 36 months. That's a huge difference. Again, didn't reach statistical significance so maybe it doesn't matter but that that number jumped out at me. baseline predisode dose varied from 20 milligrams in that middle retuximab dose group. Up to 40, I think that's a big difference but I don't know maybe it's not. Primary endpoint was remission after disease control. So disease control, no new lesions, old lesions starting to heal and then you start to taper the steroids. And then the authors looked at who goes into remission following that point. There were some secondary end points as well. Primary secondary end points all measured at week 52. So table two goes through those. Every group achieved disease control. Almost every patient achieved complete remission. It was 13 out of 13 in the two higher dose for tuximab groups and 24 out of 26 and the 100 milligram groups. This wasn't considered statistically significant. And the only statistically significant difference between the two was in the number of days to achieve disease control but it was a difference of one day between groups and I don't think that that's clinically significant. Everything else cumulative steroid dose, time to complete remission, percentage of patients that relept, et cetera. No statistically significant differences between the groups. Series infections occurred in 15% of the standard dose. Almost 8% in the 500 and no series infections in the 100. None of the adverse events were significantly different between groups. No mortality or withdrawal because of adverse events was reported. So it seems like, you know, basically low dose 100 milligram. I mean that seems like a reasonable option because of that higher because of the additional dose that they had to get at week 26. Maybe I'm not going all the way down to 100 milligram dose but I think the next time I treat a panifigous patient, especially if it's not like, you know, the worst panifigous patient that I've ever seen, I think I might do those two doses at a lower dose like 500 milligram and just kind of see what results I get. I mean, it's not going to be an issue with insurance or anything like that and maybe this will be the next thing and how we manage a retux map. Just trying to pursue that lowest dose possible. I don't know. What did you guys think? This seemed like kind of a big deal. I thought it was a huge deal whenever I saw this. Yeah. Not that I treat any panifigous or use any retuximab but like that if you could read this as like, we've been giving people 10 times the dose they need. Yeah. And you know, occasionally retuximab is FDA approved but yeah, occasionally patients get stuck with like 3,000, 5,000, you know, I don't, they're probably still going to have to hit that minimum on whatever their insurance is but, you know, cost, effectiveness, the lower side effects, serious infections. It was a lower percentage even in that middle group now wasn't statistically significant but I think there's a lot of pretty good reasons to maybe start doing lower doses on these guys. And with numbers this small, it would have to be a huge difference to be statistically significant. So it makes total sense to me and yeah, to me, this should now be state of the art 500 max and maybe over time like people are going to decide it's 100. But yeah, interesting. All right, let's move on to my first one of the day. So this was a two for, so there were two things that came out that were really good. Number one, why do we see increased rates of cardiovascular events with tofocidinibin rheumatoid arthritis? And really what here's what was interesting about this. So it turns out TNF and IL-17 induce a pro-therombotic state in your endothelial cells. So basically the way that those two cytokines, the pathways that they activate drive this pro-coagulant, that makes some stuff go up, some stuff go down, but they drive a more pro-coagulant thing for TNF alpha and IL-17. And essentially what it comes down to is that tofa doesn't reverse it. So it's a Jack 3 and it really doesn't counteract this innate pro-therombotic state of rheumatoid arthritis. Now the next question is, well, would, not that we're treating rheumatoid arthritis and derm, but would would, would, would, would, Rinvoke be different and it may be because it doesn't lower IL-10, because it has a different Jack selectivity. It maybe doesn't lower IL-10 as much and it may be suppresses IL-6 more. And both of those things would have a different, they would make it less likely to have any pro-therombotic effects. But the really relevant thing is the, the next article that I want to talk about, and this was when I was a co-author on, Izupatisidinib, IE Rinvoke, Cardi Protective and chronic inflammatory diseases, review of major adverse cardiovascular events and venous thromboembolism and atopic dermatitis. And there's a really nice figure here that really shows that for, with all the studies that we have looking at the rates of Mace and VTE, the background rates in atopic dermatitis, they are lower on Rinvoke than they than the expected rates in the generally top of dermatitis population. My personal belief is that there's this Kaiser article where they specifically looked at a cohort that was intended to mimic the cohorts in the AD trials for all drugs. And that's to me my favorite comparator. And you know, the rates, if somebody came out with data nowadays that showed me that that Rinvoke increased the rate of Mace or VTE in atopic dermatitis, I would be like flabbergasted, like flabbergasted. I think there's so much data around this now in multiple different ways. And it makes sense because now that we understand better why Tofa might have a pro-therombotic effect. or at least not to be anti-thrombotic. It's actually kind of a little more believed that it's just that it's not anti-thrombotic, is disease-specific. So it's in a disease that's TNF and IL-17 driven that's innately increasing the pro-therombotic risk and Jack's just might not reverse that, the same way that drugs that directly target IL-17 or TNF or IL-23 do. So it really looks like these drugs act differently in the two different disease states. And that was kind of the, but it was interesting, it was the first time I've really read something that I was like, okay, now I think I get it. I think I get now more about why we see this pro, this increased risk of Mason VTE in psoriasis and rheumatoid arthritis, while we don't see it in atopic dermatitis in LAPI Shariaida and other diseases. So that was kind of my, it just was, now I feel like I finally have an answer for this that I've been wondering about it for a long time. - Interesting, I've always thought it was just the different patient populations. It's just a lower risk population with AD, right? They're younger, they don't have all the comorbidities, but there were some VTE events in the studies, but you're just saying not like we just like anchor onto them because we're looking for them. - Yes, and it's in, in mubotor arthritis, I believe the risk of Mason VTE is literally double compared to a matched population that does not have the disease. And in AD, there is not. There is not an increased risk when you compare to a matched population that does not have the disease. - I thought that the fact that the Jack inhibitors were up against the TNF, like specifically up against the TNF alpha inhibitor, like TNF alpha inhibition in RA is decreasing clot risk. And it's not like Jack's are making it worse, but if TNF reverses it, - If they're just not reversing it, then compared to a TNF blocker, it's not gonna look-- - Yes, and I have never seen any data that shows, 'cause we're never gonna get like a placebo control. Hey, for your rheumatoid arthritis, go on placebo versus, you know, Rinvoke for five years. - We're never gonna see that study. It's always gonna be Rinvoke versus, they're not Rinvoke, Rinvoke, TOFA, whatever, versus something. And TNFs, and probably Ios have a teens, you know, they reduce the risk. So it's, but this was first, 'cause I always think it was just inflammation, it's inflammation. And the takeaway from this was that, no, Ios have a TNA and TNF, specifically induce a pro-therombotic state in your endothelial cells. - And when you say that, they matched the control. So, you know, one of the things I thought of with clinical trials, if you were within six months of having some cardiovascular event or VTE, that was exclusionary, you wouldn't be in the trial. If you're just looking at an atopic dermatitis population, you're gonna have those people. So aren't the trials like selecting out maybe healthier people that aren't gonna have the clotting issues, or were you saying that one of the studies controlled for that? - Well, I think I was more talking on an epidemiology level, if they look at these people with the disease, versus without the disease, kind of a matched control, that there's this big increase in RA, that's above and beyond just what are your innate risk factors. - All right, let's move on here, Ferris, what's your next article? - So my next one is clinical utility, findings of a transcriptomic psoriasis, biologic test, demonstrate altered physician, prescribe me the havers and improve patient outcomes, drover at all, this is basically, and this is endometallologic therapeutics, so this is the MIND PX, this MINDERA test that is supposed to help you to predict which biologic for psoriasis your patient should get. So what they did was they basically randomized patients who had moderate to severe psoriasis to either who are either starting a biologic for the first time, or switching to their second biologic, to either get the, so everybody got this MIND PX test done, and in one arm, the physician got the result before they picked their biologic, and then in the second arm, the physician just had to make their decision as usual, treatment as usual. So the primary outcomes they're looking at is physician prescribing behavior, and then also the patient's reach of Pazzy 75, yes or no, at weeks four and 12. So 210 patients completed, although they enrolled 310 or screen, so it's kind of a higher dropout rate than you might expect. So how often did the physician pick what the test said to do? When they knew the result, 93% of time, when they didn't know it, they picked the right drug 65% of time, so this was statistically significantly different. So here's where I'm like, does this, I don't know what I think about this. They looked at Pazzy 75 responses. So first of all, Pazzy 75, we can do better than that, but that's the output, that's the outcome primary, clinical outcome that they looked at. And so more patients had a Pazzy 75 in the informed versus uninformed arm, both at week four and week 12, and they said, oh, this is like consistent with what we saw on historical controls. So of the patients who reached, who completed the study, 81% reached Pazzy 75 in the informed arm versus 54% and the treatment of the treatment as usual. So that's kind of a low number. So I was like, all right, I mean, what is like the expected Pazzy 75 response? So even with no guidance, I think it should be higher than what they saw, than 54%. So I was like, let me go back and look at week 12 Pazzy 75 response. For E-Tanersept, it's like, you know, 49%, for Adalimimab, it should be more like 65 or 70%. And, you know, for IL-17s and IL-23s, it's kind of more like 80-ish percent, right? Did they maybe count dropouts as did they do like an intent to treat analysis? Is that, is that not that's not what I got from the methodology of this paper. So the other glaring omission is like, what drug did people actually get in both arms, right? So if everybody in the, you know, in the, in the test, you know, we saw the test result got like, risen Kizimab and everybody in the treatment is usual got E-Tanersept, then that would explain it to you. And then what's that? I could do the same, I could do the same test by putting my finger on the patient. You will respond better to risen Kizimab. Yes. Exactly. I mean, in theory, this could be really good if it told you-- Like a defining rod or something like that. That'll be the next one. If it tells you the two thirds of people who are going to do good on a, umira biosimilar, like this could save a huge amount of money. Agreed. So that would be like where this would be helpful. I just think like they didn't share enough data on like exactly what drug everybody got. And then like, you know, they didn't, I presumably in the standard of care, like arm, they still had to go through insurance, right? They didn't just say pick a drug and we'll give it to them. So like, there was also probably a little bit of a, a bias in terms of like, you know, what insurance dictated and maybe with the result, they were able to follow the guidance of the test better. If they had the insurance, if they had that result. So I think, you know, the jury still out to me on this test. All right. So Ferris, I got this chart that you made. Yeah. The Passey 75s, which AI did you use for that? Because it's really good. Herplexity AI. Don't give away secrets. Yeah. And you put it-- you put in like a prompt, like make me a table of the-- Well, week four and week 12 Passey 75 responses for, and I gave the names of the drugs. And you didn't have to upload the papers or anything. You just make me this day. I had it go look for it and made it for me. Yeah. Did you tell it to get it from the package inserts? I didn't tell it. I let it pick where to get it. OK. But I mean, I kind of did like a little quick spot check that actually wasn't like, you know, all AI hallucinations. Yeah. OK. That's pretty interesting. Yeah, mind to PX, mind to PX. Maybe great. Maybe not hard to tell from this paper. Yeah. The other thing is like, I think about some of the papers we did recently where we're like, they failed 1-I-23. Should you switch to another one? And the answer we kind of all came up with was, yeah. They do pretty well. So it's hard for me to say you're a responder to a whole class based on all of the like within class versus interclass-- interverses, interclass switching papers we've talked about. Although there was this day recently that-- I don't know if we covered on the show-- that did show a better response rate for treatment and attic-- for treatment. They didn't do good enough. A better response rate with interclass switching. But I think it was mostly a second I/O-17 or switch to I/O-23. But the interclass switching did seem to be better. But it wasn't like failing one drug predicted the other one isn't going to work. It was just it's a little less certain it's going to work right. Yeah, we did cover that. Okay. All right, Pat and what do you got? Second six pack was from May 2025 edition of Journal of Coutanis Medicine and Surgery. It was by Steertun at all. It was titled, "The Reputed Drug Monitoring and Hydride Nytus Upper T Patients with suboptimal treatment," response to Adelimimab. Cross-sectional study 62 patients with HS managed at a single institution. So to be one of the 62 patients, they included, "Yadab, Moderna to severe HS." So this was based on Hurley alone. So Hurley Stage 2, 3. They were on Adelimimab 40 or 80 milligrams weekly and a suboptimal clinical response, meaning is. Is that is that difference just based on weight? Is it a weight like I don't really use a lot of you merit for treating HS and put them on a clinical trial. What do you. Why were some on 40? What are some on 80? The pay. So, you know, this. Having it at a single institution, I think impacted this paper a lot because the way that they would practice at this institution is if you were on 40 and you were a suboptimal response and you were subtherapeutic on your Adelimimab level and they just said it at a particular level, like 10.6 whatever, micrograms per something. So if you were on 40, suboptimal response, subtherapeutic level and had no anti-drug antibodies, you got bumped to 80. That was just how they did it. So if they're on 80, when they did this cross sectional, it's just one point in time, but that's how they got to 80. Okay, so it wasn't. It wasn't like if you're over 220 pounds, you get 80 or something. Can you get 80 from insurance? Is that like. Yeah, so I mean, I kind of get into that at the end of the paper, but that's the. There's a lot of things in this paper that may actually be moved because of when it was done, but we can talk about that at the end. All right, go ahead. So suboptimal clinical response meant worsening of their HS despite being on therapy for a minimum of three months. We talked about they would do therapeutic drug monitoring and they bump them up to 80. So in the final analysis, 51 patients on 40, 11 on 80, percentages of similar were between the two groups. It was like a 60, 40 split between therapeutic and sub therapeutic drug levels. So in the 40 suboptimal responses, 60% of the patients were suboptimal even though they had a therapeutic dose, whereas 40% were at a subtherapeutic drug levels. And it was that same breakdown, kind of 60, 40 in the 80 milligram weekly group. Tables two and three compared to clinical characteristics. Nothing really stood out except that. And I'm probably going to say this wrong, but I don't know, we'll make a chart. Most patients with therapeutic levels were early stage two. So 78.1. This was just in the 40 milligram weekly. Most patients with subtherapeutic levels were early stage three. So 57.9 in the subtherapeutic were, were, were, were early stage three versus whatever. Yeah. Drug antibodies didn't seem to play a huge role, but that was, this was very confusing. So overall, only for the 19 patients with the subtherapeutic drug levels and the 40 milligram group had anti drug antibodies. So this is not subtherapeutic because you have anti drug antibodies. It's just subtherapeutic. They don't know why, but at one point in the paper, they're like, we only check anti drug antibody levels. If the, if the dose is like barely like essentially zero. So did they really check anti drug antibodies in everybody? I don't know. Another thing that stood out in the 80 milligram group over 70% of those patients were on additional immunosuppressants that weren't characterized. Was it immunosuppressants to treat the HS? Was it immunosuppressants to decrease the likelihood of developing anti drug antibodies? They didn't really say. So it seems like without stating it or maybe they did stated explicitly. The authors would recommend that in patients with subtherapeutic control on 40 milligrams weekly, you would do what they do. Check drug levels, drug antibodies. If levels are low and there are no antibodies, bump them up to 80. Again, how did they do that with insurance? This was a study that was done in Canada. So maybe Canadian health system. Yeah. This should be getting easier for us to do though with biosimilars. Like who cares? Once you're paying for, who cares if you give a second dose? Yeah, that's true. They don't really propose to what to do if you're a suboptimal response and on the 80 milligrams. Like you bump it up to 120, 160. This was all done before. So in Canada, you can get the IL-17s. They are approved. So this was done before that was an option. So it was almost like this was the only option they had because in FlixMab also from what I understand, I mean, the quick reading I did, which might not be accurate. But it's also hard to get in FlixMab up there too. Whereas in at least my experience, it's not that hard to get in FlixMab for HS patients. So yeah, would I would I would I mess around with the Adelimimab and doing all that and bumping them up to 80 if they're sub therapeutic without it. Probably not at that point, I would say we need to switch either to in FlixMab where we can wait to wait base dose it. And the other thing that's nice about insurance with in FlixMab is if you say I want to do it every six weeks, they're like fine. And then if you call them and say, well, I want to bump up the dose and I want to do it every four weeks, I have not had problems with insurance is saying no, no, no, you can't do that. They really cover like once they say, okay, I'll cover the in FlixMab, they they'll cover any dose, any frequency. Where I am at now with HS though is do I do that before the 17s? I do think the TNFs might be a little bit more effective and it's very nice with in FlixMab to have that flexibility with those seen frequency. But if you have a failure in Adelima Mab, where are you where do you think you guys are going next? 17s or FlixMab? I mean, I think the TNFs are clearly riskier than they and I don't think it's a huge risk because our people are dying, you know, keeling over with horrible infections. But I think of the TNFs riskier. I don't know, I don't know. I would say infectious. Yeah, in fact, in a FlixMab has a higher infection risk than Adelima Mab. I mean, probably just because of the doses, particularly that therapy doses. I'm going aisle 17 if my first pass TNF, if my Adelima Mab doesn't work, if I can get aisle 17 and aisle 17. Yeah. The thing I'll throw in there is throughout sprinkles and reflumalastin, right? If they're if they're like not doing well enough because there's no reason to not use reflumalast together with a biologic, right? There's no additive immunosuppression, right? Might be easier than trying to switch over to a to a whole different drug and get a, you know, another product. I don't need any need to do. Another prior off, right? All right, I'm going to jump over. We're going to jump to my last article, which was Scabies, right? So the first, let me give you my Scabies pearl. Do not ever say the word Scabies to a patient until you are sure they have Scabies. So the way that you, oh, you've got to sit you rash. I'm really excited. I think you might have this weird skin infection. It'd be the best thing that you could ever have because it's totally curable. So I'm really hoping that this is what you've got, because otherwise you're going to really suffer with this for a long time. But if it's this infection, you're just we're going to cure you easy piece of cake. Like, oh my god, go, I hope, I've got it. I hope I've got it. But was there a name to it? I don't worry about it. I'll tell you after I go look at this into the microscope. You wait, do you get a lay with that? I'd be like, wait, you don't know the name? Well, at some point, you got to tell. I just don't look it up. But you got to, you build it up first. You build it up. Is this is what you want to have? All right, you get them excited. You get them excited. I do tell people that all the time. I do give them the name scabies. But I say like the best. I'm really hoping you have scabies. But just throw the scabies. So really what happens? I have that whole discussion. They're like, oh, they're all excited. And then they're like, what's it? What's the name of it? Then I'm like, it's called scabies. And then they're like, oh, I'm not dirty. And I'm like, I know you're not dirty. But let's really hope you've got this, right? The other thing that I tell people at times that I think scabies is way less contagious than it used to be because of just better personal hygiene that, you know, we're shower in every day. We're using all of our soaps, everything else. But I was told people that it's just, I think it's bad luck because scabies happens to live in the skin in the web in the, in the spaces between your fingers. So it's just you shake hands with the wrong person. You catch it. And then you're just never going to get rid of it until we treat you the right way. How do you, that's that? Come on. I don't think you can get from scabies. There's a different kind of understanding contact that believes the major risk factor. But God, maybe also like the people who get her piece from toilet seats, they might also get scabies from shaking hands. Right. That's, you know, it's possible. It's possible. It's possible. Right there in your fingerwebs. This article, scabies management outcomes identification risk factors for treatment, disaster failure. Basically, they, Susan Germany where they have like very strict guidelines. And so basically they looked at people who either their scabies quickly cleared or quickly did not. So it's relatively short follow. up and I think if you had scabies for a long time, it takes longer to get better, but relatively short follow up. And here's what they found. So first 97% of people got per methamphetamine mostly twice. But what mattered, leaving it on longer than 12 hours was more likely in the treatment success group, getting someone to help you put it on. So you get it in all the cracks and crevices that mattered and then second adding Ivermectin mattered. So just both using Ivermectin and doing two doses of Ivermectin that would people were more likely to be in the treatment success group and to me this is, this is one of the first places I've really seen this, but to me that should be standard of care for oscabies now is permetherant like you do permetherant and Ivermectin on the same day, then a week later you repeat the permetherant and Ivermectin. Because we know permetherant if you use it correctly is more effective than Ivermectin, but it's just like sunscreen right? People don't put it on thick enough, they don't get everywhere, the blob of blah. So to me now this really supports the idea that standard of care should be permetherant plus Ivermectin orally because Ivermectin is such a cheap safe drug. And it's the counter and lots of places. So if you're right going over the counter now, which yeah that's an interesting whole another debate. But then the other thing they also looked at treating the environment and things that correlate with being more likely to be in the treatment success group was changing your bedlin in daily for four days after application, storing your clothes and plastic bags for four days, seem to make a difference and then vacuuming carpets and car seat seem to matter. There are a bunch of things that didn't seem to matter. Things like getting your carpets disinfected, getting them professionally cleaned, disinfecting your car seats didn't seem to matter, getting your car seats professionally steamed cleaned or whatever didn't seem to matter. So it seemed like vacuuming was a useful thing in general and then the changing the bed the bed sheets and the putting your clothes. But this wasn't like a randomized trial where they told you know do this, don't do that it was it was so it you know who knows maybe the those measures were just a marker of they put the promets are on better or something like that. But but those were the the big takeaway so vacuuming your your furniture, your car seats and your carpet seem to matter, changing your bed sheets daily for four days after each treatment seem to matter and then for clothes, put in the plastic bag and leaving them in there for four days seem to matter. Those those were the the big takeaways. What what do you guys tell people to do? But you know when you when you do you like really go into the like whoa you got to really clean everything and the or you're like the drug the drug's gonna work just yeah I also think like if you use both drugs together it's generally gonna work. I tell them wash their sheets the morning after their application of permatherin and then you know each time that's kind of what I say and like wash all your clothes and that's all that I tell them to do. Same yeah okay I will be very honest the way that I treat scabies whenever I'm sure it's scabies I do I've remect in 400 micrograms per kilogram so double the normal dose combined with permatherin and I repeat a weekly for four weeks because like why not treat the hell out of them is there you know they're such they're such safe drugs just that makes way way way more sense to me to treat them very aggressively like that so that's that's my my scabies pearl the other thing if you don't know about this most useful diagnostic advance in the history of dermatology in our lifetimes do you guys I don't know if you're talking about scabies floresces and it's a very specific obvious thing on wood's light so the mite floresces are bright yellow and then the burrow floresces like a pale white behind it unlike if you think somebody might have scabies you should never scrape them until you have wood's light at them because it is the first thing ever that tells you where to scrape like dermoscopy was worthless because it's still the dermoscopy in the right spot the woods you can look like their whole body in like 30 seconds and it tells you exactly where to scrape and to me it is by and this and I'm making this up it's well published like a couple of studies looking at this it's just woods lighting scabies is like a big like that was a big advance I can't believe nobody figured that out like 50 years ago very disappointing in our in our ancestor colleagues now I have not used wood's lamp I do used dermoscopy I do actually sometimes find it helpful for finding where the mite is but I need to start doing wood's lamp because that's sometimes it's like where exactly do I look so yeah and it yeah it just makes me feel better about what I'm like I don't think I got scabies I'm now a lot more certain that somebody doesn't have it but so that's the the takeaway all right so I want to thank everybody for joining us today I've got questions comments ideas for topics which cover on the show shoot us an email questions at germsandbrokes.com who've learned a few things hope to last once you twice and mostly are hoping you're planning to join us next week till then I'm Matt Zyrus I'm Tim Patten and I'm Laura Ferris and we are Derms on Drugs