Why you shouldn't ever use Bactrim for acne (and other new info you don't want to miss)

Welcome to season two of Derms on Drugs, a video podcast brought to you by scholarship medicine, the best educational platform of dermatology and provided no cost to medical providers. Derms are drugs as we're cutting into dermis, hit our miscommunity. I met zyres from Dr. Dermatology in each week. I'm Dr. Marizancy but instructor Laura Ferris from the University of North Carolina, Dr. Tim Batten from the University of Pittsburgh. And 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 done. The cutting edge of Derm and they have some fun listening. New episodes drop every Friday on scholarship medicine, apopodcast, modify the other major podcast platforms. The video component has the key figures and tables from the articles that we talk about. This week we've got another one of our fantastic six pack episodes where you're going to get into the latest, greatest, coolest stuff in the literature. And I've got to throw a plug. You better listen to the end because there is a new thing out there that is not going to get into the world. It is a huge medical legal risk for dermatologists. But let's go ahead and get started. Dr. Ferris, what do you got? Okay. My first paper today is from JAMA Dermatology. It is called Mediterranean Diet and Patients with Saraiasus, the Medi-Sau, randomized clinical trial from Perez-Butello. At all, these are a bunch of spaniards who did this study. Mediterranean authors for a Mediterranean diet. Exactly. The diet is as Mediterranean as the authors. That's the way it is. All right. Javier Perez-Butello. And I'm sure I'm saying that right. It's probably Boutillo or something. Anyway. Okay. Patients always say, "Hey, what can I do to change my diet?" Or some patients actually ask like, "What a Mediterranean, gluten-free, whatever diet helped?" So, normally we're like, "We don't really have a lot of data for that." But now we actually have some. Okay. This was a study that was an open label single center, a evaluator blinded, randomized clinical trial done in Madrid. So patients had to have mild to moderate Saraiasus like a PASI of 2 to 10. They had to be on stable topical therapy only. And then they were randomized one to one to either get a Mediterranean diet intervention or just a standard, you know, the advice like, "Hey, eat a good, healthy, low fat diet, but no real other intervention." Okay. This was small, 45 patients screen, 38 patients randomized. So 19 per arm, 97% of them completed 16 weeks of follow-ups. That was pretty good. And everyone kept using their like topical, steric, calcipitrine regimen. Nobody could start on a systemic therapy. So the Mediterranean group, they got like the full on Spanish grandma kind of treatment. It was, they had a dietician guiding them. They gave them counseling. They gave them educational material. They called them once a month for 20 minutes, which is probably more than my grandma even did for me. And they also got, this is the best part of it. I would have gone into it just for this free extra virgin olive oil. And they had to eat at least four tablespoons a day. Okay. And then, yeah. That's point, biologics are cheaper. No. That's not true. The talk is cheap and so is extra virgin olive oil. Okay. Controls got a one time low fat diet handout and know like they didn't have the dietician supporting them. So obviously you could not blind the patient to this, but you could blind the evaluator. And primary endpoint change in Pazzy score. And then they also looked at stuff like, did you actually adhere to the Mediterranean diet, DLQI, sleep, I don't know why, anxiety and depression with the hands, with the hats. And then they also did look at things like BMI, some, you know, site, some like metabolic parameters. Okay. So what actually happened? So baseline groups, the medium Pazzy was like four to five BSA was four percent. So these were definitely more mild. They were pretty well matched to weight cardio, cardio metabolic profiles. So they had some anxiety. They did have higher elevated CRPs. All right. I get to it. Did the diet work? It worked. Pazzy improvement, the estimated mean change in Pazzy was a decrease in 3.4 in the Mediterranean group versus zero in the control group. And where did the, where did their past? Could you let me talk? This is not the MAPA Cyrus podcast. All right. So in the Mediterranean arm, 68% had a Pazzy 50, 47% had a Pazzy 75 and 26% had a Pazzy 90 and 11% had a Pazzy 100. In the control arm, 11% had Pazzy 50 and nobody hit 75, 90, 100. So that's pretty good. Wow. They also looked at like diet adherence. So you could say, well, some people in the control arm, maybe they started following the Mediterranean diet. So there's a way to measure this. And it went up by 8.2 points in the intervention group, but only by 1.3 in the control. And that was statistically significant. So it wasn't just that the control people started eating better. Now what is a couple kickers? So you're probably like, well, yeah, I mean, we know that obesity is associated. They just lost some weight because they ate right. Right. There was no meaningful between group difference in body weight or waist circumference. So they did not lose any weight. They just ate better and their psoriasis improved. Yes. They ate a better profile of food and then you know, 16, I guess you can lose weight 16 weeks. But yeah, they had better improvements in DLQI insomnia, anxiety and they trend toward less depression, but it wasn't statistically significant. Now, their lipids did not improve. Their hemoglobin A1C did on the Mediterranean diet. So I thought that was interesting. There was really like no cytokine difference. So they did this high dimensional cytokine panel. It's kind of not a huge difference. Fibreglass, fiberglass growth factor, 23 was a little bit higher. It decreased, it held that higher actually decreased more in the control group. It doesn't really explain anything. So and then also 63% in the Mediterranean diet group de-intensify their topicals versus 17% of controls. So you know, I kind of like some good data that if you eat, you know, the Mediterranean diet, which is like olive oil, fruits, grains, lower meat, that you know, that is something that we can tell people to do. So this is, these results are impressive and it's hard to like, I can't remember in my whole career if somebody ever coming in and being like, yeah, my eyes says this is a lot better because I'm eating better. No, I have had that happen a couple times. Like where patients have said, I've really gone to like a high vegetable diet and I have done better and it wasn't really significant weight loss that it was associated with it. I also like, we can go down this rabbit hole at some point later, but I really think diet probably matters for some of these diseases like HS. You know, why do, why do some areas and some pockets get horrible HS and other areas that have a lot of obese people don't, you know, not everybody with obese with HS is obese. I really firmly believe that there's got to be something environmental diet seems to be the most obvious candidate. I don't think so. I really, really horrible scalp psoriasis and we were at the point where we were discussing biologics and when she came back in for a visit, her scalp was completely clear and that's what she said. She goes, oh, I changed my diet. And I was kind of like, huh? And like, I didn't go into details of what she exactly did, but I mean, it's impressive. It's very viable from a microbiome perspective, right? It's a Mediterranean diet, it's also good for your microbiome. And like, for example, an AD and it should matter in psoriasis as well. When you've got a healthy microbiome, you produce these endol metabolites that activate the arrow hydrocarbon receptor, right? The exact same thing that Fatima does. So a good diet, maybe it's like Fatima systemically, whatever you, is one of the effects. Yeah, I mean, there's a lot of this. So like, fascinatingly in the melanoma world, there's a lot of evidence for microbiome impacting response to immunotherapy from fecal microbiotal transplants actually making people go from being PD1 resistant or progressing on PD1 inhibitors to then becoming PD1 responders to, there is data that patients who are prescribed and given a high fiber diet actually have better responses to PD1 inhibitor than patients who are not. There's evidence like having antibiotics prior to starting immunotherapy decreases your response to immunotherapy. So like, there is real stuff, I think. I used to kind of think it was all a little like crystals and, you know, chakras, but I actually think there's something real to it. Is, did they say how hard or easy it was to, like how hard is it to just switch your diet over to Mediterranean diet? You know, people did do it. So they didn't do a lot of like how hard was it. But I, you know, I think it's probably what people with resources and knowledge would tend to do, right? People with resources and knowledge tend to be good at saying I'm not going to eat as much, you know, processed food. I'm going to make sure I eat more healthy, you know, vegetables and grains and, you know, cook with olive oil and not, you know, butter and all those things too. So, I think I'm just moving to Greece or Spain or something. there's the answer. Okay. We'll find a time to record our podcasts while you're there. Having in to grease Spain and Italy. Main thing I think is those, they just so sweet. They do, it is so laid back and chilled. None of these people hustle at all. It's been my main takeaway from Italy, grease, Spain and Portugal. Yeah. And the food is different, right? Like they are eating, like real, like when I go to those places, I feel I don't feel disgusting versus like going to like an all inclusive resort or something, right? Like you eat grilled fish, you eat vegetables, you know, you don't have massive quantities. There's not like grocery stores full of, you know, prepared processed food. I mean, it does make sense. I saw some interesting stuff about gluten sensitivity this week that gluten sensitivity. And for people who are just listening, I'm using air quotes, gluten sensitivity spiked in 2006, 2006 was also whenever they figured out that glyphos fades in particular roundup. If you apply them to wheat right before you harvest the wheat, it desiccates the wheat. So dries it out and it stores much better and much longer. And so there's some now believed that all of these people with non-sealiac gluten, you know, gluten sensitivity. It's actually more because wheat has a whole bunch of glyphos fades in it now. And that also explains why some of these people will say, well, I can eat European. When I go to Europe, I've not gluten sensitive anymore because in Europe, their wheat is not treated this way. If any of that's true or not, I have no idea. But it was just interesting. My dad worked for Monsanto going up. So Monsanto funded my childhood. So we're going to be like. Nothing bad was around it. No, Monsanto, great company. Great company. But it is an interesting also AI use that I think it's gotten much easier because you really can't, if you go in and ask chat GPT or any of them about the Mediterranean diet, like, could I eat this? Should I eat that? You actually can get good answers really quickly. So it made me a week long Mediterranean diet, dinner plan. I like these things. I don't like these things and you could get it. I'm interested in these. Yeah. So no, I think it's good data. Eat the Mediterranean diet. Fish, meat, vegetable, vegetables, whole grains, olive oil. Yep. All right. Easy, Pat. What do you got? All right. My first six pack was December 2025 issue of transplant, no transplantation direct and is titled Consensus-based Recommendations on the Management of Immunosuppression. After Sclaims Cell Carcinoma Diagnosis in Kidney Transplant Recipients and International Delphi Consensus Statement by Whitley at all. So as we all know, transplant patients are at a higher risk of developing cutaneous SEC. They get more of them and the ones they get are bad dudes. They're really challenging cases. They can be. There was a Delphi panel of germs that was published in 2021 and JAMA Derm address this a little bit. One of the things come out of that article was the actinic damage and skin cancer index, the ADSEI went from one to six, one being patients with photo damage, but no AKs, six being high risk, the development of a high risk cutaneous Sclaims Cell Carcinoma. Based on the 2021 study, discussion with the transplant team regarding immunosuppression should be initiated for stages five and six. So stage five is invasive, multiple invasive Sclaims Cell Carcinomas. They grouped it into five A and B, lots of, not many versus lots of them. And then stage six, which was a high risk cutaneous Sclaims Cell Carcinomas. But for stage four patients, first invasive, low risk, cutaneous SEC, no consensus was reached. So this Delphi panel, the one that I'm talking about now, that was the JAMA one. This one had a few dermatologists on it that most of the participants were Kidney people. They called themselves International Transplant Nephrology Experts, but I'm calling them Kidney people. There were three rounds. They focused on ADSEI stages four, five, and six. So again, four, that's your first invasive Sclaim, five, multiple low risk invasive Sclaims. And six is a high risk invasive Sclaim. Is high risk like, oh, you got one on your ears. So now that's, it's a high risk or is it like high risk based on tumor characteristics? So they, the bring them and women's risk thing. So it's to be and higher was high risk. And I think with to be you have to more risk factors, risk factors being like parinural invasion, size greater than two centimeters. Helping out here. You're differentiated tumor. Yeah, poorly differentiated. Yeah, stuff like that. So truly high risk tumors, not like, oh, yeah. Not like, oh, it's on your scalp. Yeah. Okay. So they asked the respondents if changes in immunosuppression would be made in what would these changes be, the complete surveys and the supplementary materials. There's kind of long lot of questions. 31 panel is completed all three rounds. And the results are nicely summarized and figures one and two. So for stage four, ADSEI, that's, actinic damage skin cancer index. Is that what I called it? Yeah, that's it. Actinic damage skin cancer index, you had one low risk SEC. They wouldn't consider changing immunosuppression. So they kind of like the stage four where there was not that consensus with the germs with the kidney people. They're like, no, we wouldn't one low risk. We're not going to really bring up that conversation. Multiple low risks and high risk SEC. There was consensus to modify immunosuppression. Immunosuppression if the patient was in is a thigh print, which I don't really see that much. So I don't know how relevant that is. And there is near consensus. So close to like 70% that with multiple SEC's consider modifying the metabolite if it's micaphenylate morph till and then switching either this the calcinerin inhibitor or the anti metabolite to an mTOR inhibitor if patients are having a high rate of SEC's or high risk SEC. Other factors that they took into consideration probably more detailed than what a germ is going to do, you know, history of T cell or antibody mediated rejection. It was kind of straightforward. And so I think for us as germs, you have your transplant patient, you know, lots and lots of AKs. I think everyone kind of agrees that's not the person where you need to call up the transplant team and say, hey, we should switch something. They get one SEC maybe bring up that conversation and certainly with multiple and high risk then you bring it up. The percentages of physicians that changed immunosuppression after a few low risk SEC's was higher than like my personal experience. Fair number of times transplant docs are happy with the fact that a transplant is not being rejected. And if a patient has some low risk SEC's like if you think about a few on the trunk, they're they're, you know, well differentiated. There's no pariniral invasion. I have not had them be really that open. They're just kind of like I would just kind of keep everything the same. So the percentage in this particular paper was higher than what my personal experience was. But other than that, it was pretty straightforward. Did you guys have any other takeaways? So this is probably not a question you can answer. But why isn't everybody who gets a kidney transplant just on rapamycin? Like if if squaking, if squaking a squain or such a big deal and rapamycin is so protective, why don't they all just go on it right from day one? Is there a big downside? I don't know about. They it does have a worst side effect profile. I couldn't get into details, but they don't like the side effect profile and they don't think it works as well in prevent rejection. Right. I mean, that would say to them like, Hey, let's switch off of this tachyrilitis over to sear alimus. They're like, yeah. Like if it's a heart, they're like, we need to save the heart and switching over to sear alimus, that would concern us more. That's been my experience. I couldn't give you numbers. But you know, that's why one of the ones was, you know, it may be taking mycophinolate away and adding the mTOR inhibitor as opposed to stopping the CNI. That's why they kind of set it up in this trial as they have an option. You could stay on a CNI, but maybe instead of the mycophinolate, that's where you add in an mTOR because they like the CNIs. They like tachyrilitis. It's good at preventing rejection. Yeah. What would be interesting would have been to combine this with like the germ guidance, like to me, you know, looking at this, if you were in that group that was like the couple one to two lower squames, like maybe that's where based on some of the data, we should think about nicotinamide, right? And then like I would also like guidance on where do we talk about field therapy? Like should like, you know, should we be doing field therapy once somebody is any AKs, we're like, if you have AKs, you got to do field therapy at least once a year. You know what? That jamma, derm consensus, address that, hold on. I have that like right here. I pulled that up for a second. A consensus based recommendations. And they use that same actinic damage and skin cancer index. And so what they said, this was the 2021 jamma, derm stage one photo. damage skin only preventive bangerers, education, sun protection, sunscreen, blah. Discrete AKs, so you had scattered AKs, cryotherapy, oral chemo preventive therapy should not be initiated. Grouped AKs, same thing, field, that's when you have field therapy, oral chemo preventive should not be initiated, but if they have thick lesions, then you do field therapy, fluorosil, base modality, blah, blah, blah. Field cancerization, field therapy, transplanting, don't discuss immunosuppression. You're right, they didn't get into nicotinamide. The kidney people, they actually did talk about that. - They did, okay. - Feel treatment or nicotinamide with like your stage two, three diffuse, actinic damage things. - Okay, so they don't have an objection to that. They're like, yep, sounds good. Okay. - No, yeah. They liked that recommendation. - Good, I like it. Thank you. - And would we guess, now that we know that the reason that vitamin D, cusp of trying, and fluorosil works so good together is this long lasting immune response. I don't think there's any reason not to use them together, but my guess would be that you wouldn't get as much benefit in transplant patients compared to five FU alone, because it seems like the immunosuppression is gonna make it less likely you're gonna get the immune surveillance you're hoping to get. - I think we just don't know. - Yeah. - Until we do the study. - Yeah. - We've got to do the study. - Thank you. - Fuerris. - Get UNC Dermodet Fuerris. - All right. - All right, let's jump on to mine. So first one was association, just came out literally today, association between the topic dermatitis and contact sensitization and updates, systemic review and meta-analysis. So this is a long-running question of our people with AD, more likely to have contact-ermed than other people because they're barriers impaired and they use more products, or are they less likely to get ACD compared to other people because their immune system is skewed to H2, TH2, and contact sensitization is more or less a TH1. Take away from this article was, it was a big review with like dozens and dozens of studies included in it, and there's no big difference. So if you look at people with AD who get patched, just compared to people without AD who get patched, just did no big difference. The only things that were of interest, people with AD were more likely to be allergic to sesquatorping lactones. So things like chrysanthemums and merigold and some weeds, they don't have a good explanation for that. The best one that I've got is that aquafore has sesquatorping lactones in it. So it's got ingredient in it. One of the aquafores that's the common background one, it's got an ingredient called bissabolo, which is an extractive German chamomile, but they also said it could be airborne, whatever, but the main takeaway was, we're now can be pretty sure that people with AD or there's no more or less likely to be allergic to anything compared to everybody else. That was kind of the big takeaway. - That's the flowers, get your AD friends chocolates, not flowers, that's the takeaway. - That's good, get them chocolate, not flower, I like it fairs. All right, let's buy second one, which is a little bit more sort of clinically relevant here. Efficacy and safety of duplomab and Haley Haley disease, multi-center cohort study. And to be honest, it was impressive. So this obviously it's not a randomized controlled trial, right, but there's this, they had 20 patients with Haley Haley 14 got like dramatically better. Like so 70% got like shockingly better for improved, but it wasn't shocking. And there were only two who didn't get any better. They didn't get any worse, but they also didn't get any better. It was pretty darn impressive. And it's really interesting. We now have data for duplomab and both Haley Haley and Darius. And I have no idea why it works. Like none. Like it certainly seems like it does. - But I read a thing on aisle four and aisle 13 bind to something called Spork, and that can affect intracellular calcium. And so if you block aisle four and aisle 13, they're not acting on that thing and calcium intracellular calcium homeostasis somehow gets fixed. - That was the bet. - Because right, we think of Haley Haley as a, I mean, you could have secondary inflammation I get, but the primary problem is like just cellular. - Adhesion. - Adhesion, right? - Yes. - That's not an inflammatory process as far as I would think of it. - Yeah. - Yeah. - So those pictures are like dream-mad. - That's perfect. - Yeah. - Yeah. - It's crazy. I have seen, I tried this like off label once with somebody with Haley Haley and she definitely did get better. It'd be great to have, I mean, having stuff like this is really helpful in terms of advocating on behalf of our patients to get coverage for these things. - And just as I was digging into this, a few other things that if you, if you can't get to do be covered, you don't have samples. None of this stuff, do I think, works great, but it's stuff that's outside the door and that has some data and literature to back it up. Oral magnesium. And so it's 300 milligrams a day of elemental magnesium, could be magnesium chloride, magnesium chloride, hexahydrate magnesium glycine, whatever, but it's 300 milligrams of elemental magnesium. And that makes some sense because we know the magnesium is calcium, calcium mymetic, somewhat mimics calcium effects in cells. So since Haley Haley and Dairy A's are a problem with calcium transport, makes some sense that magnesium could play a role, can't hurt and it is dirt, dirt cheap. The two other things. - We, magnesium glycinate is a good adjunct first insomnia. - That's right, calm, calm, mag calm is one of the things that I see advertised all the time. - Okay. And then the other things that have some data out there. So a premalast, so oral reflumalast, worth a shot in these people. If you've got a difficult patient and then topical dichlofenac. So mostly 3% is reported, but topical 1% dichlofenac, which is generic over the counter and super cheap. Also reported could help with the pain, but also did seem to help with healing the lesions. And then glycopyrilate, either orally or topically, also adds some benefit in Haley Haley. So, but the big thing here, Dupy 20 patients look really strong and just useful to have in your back pocket if you see it a tough Haley Haley patient. Okay, that's really-- - Well, you have to move this paper that we should talk about at some point is, now we've renamed, there's been this whole effort to rename everything. It's no longer called Haley Haley disease. Now you wanna call this ATP2C1 associate non-sodromic epidermal differentiation disorder. - Yeah. - 'Cause that rolls off the tongue. - I'm just gonna call it Haley. The one Haley was a great guy. The other Haley was a big jerk. - Okay. - Can we call it the 90-million pempagus? - BFP, is that what they used to call it? - BFP, yeah. - Yeah, the line familiar. That protein was smoc1, S-M-O-C1. - Smoc1. - Okay. - And you wanna keep being attracted to it. - I heard it here first. - Hey, I wanna say that that atopic derm study, I think, aren't you, you're selecting for patients that wouldn't got patch tested? And I would argue that, yes, genetic atopic derm, lifelong history, blah, blah, blah. Okay, fine, that's one group of people. But the other people that you're sending to get a lot of patch testing done are these late onset atopic derm, that don't have the lifelong atopic dathesis. So, aren't you comparing atopic derm with atopic derm? - So, yes, what I think is happening with a lot of patients is they have derm and they don't know if it's derm, AD contact derm or whatever. And so, I think there's a lot of diagnostic, like this person has a diagnosis of AD, this person doesn't, blah, blah, blah. It is a difficult situation. And there's some, they did kind of break it up into pre-2016 and post-2016, because back pre-2016, more likely, like if you got called AD, you had like classic AD, post-2016, it was more likely to be on your called AD or you don't really have any. And they saw not that big of a difference in pre-2016, there was actually negative correlation. AD patients were less likely to have contact derm, but it was this very small effect. And post-2016, so from 2017 on, they showed no effect. But I agree completely, the whole sort of space of non-avvious dermatitis, it's hard to make heads or tails of any of the literature, right? because the only time you know something. somebody has contact germ is once they get better whenever they avoid something, right? Because you can have a topic dermatitis or just dermatitis, we don't know why. And a positive patch test that seems relevant doesn't mean the passive patch test is relevant. You know, it's almost like saying that everybody would joint pain in a positive A and A has lupus. No, you can have joint pain and a one to 80 speckled A and A and you probably don't have lupus. So, bagry, takeaway. Take away, I agree. It's hard to figure out. All right, let's go to our next one. Ferris, we got. Okay, moving on to big things like cancer, but still squamous cell carcinoma. Efectcy and safety of Cosa Belamab and advanced cutaneous squamous cell carcinoma results from a pivotal open label study with a median follow-up of greater than or equal to two years, Emily Ruiz. And so, what is Cosa Belamab? It actually sounds very Mediterranean to me. That's my theme of the day. If you had to come up with it, it's brand name is Unlocksit, which is kind of a cool name too. Okay, so Cosa Belamab is not, it inhibits the PD1 pathway, but it is a PDL1 inhibitor. So what does that mean? It is, it binds to PDL1, which is the ligand versus, or it is the ligand versus receptor. So it blocks the PD, if it's, blocks the, let me start that over, Cosa Belamab binds to PDL1. It blocks its interaction with PD1 and B71. So this is still like taking the brakes off the T cell activation and the tumor microenvironment side, but you're talking about blocking or binding onto the tumor side instead of the receptor side. The other twist is that the FC domain of this antibody Cosa Belamab has been engineered such that it can induce antibody dependent cellular cytotoxicity or complement dependent cytosatasticity, so you actually have direct tumor-litic activity. So in, like, real cancer where they're doing, and I know squamed your real cancer, but like, in lung cancer or whatever, wherever they're using PD1 inhibitors all the time, does this stuff work better? PD1L work better than PD1? So we have, you know, we have a Vellamab, which is FDA approved to treat marital cell carcinoma. And so it doesn't necessarily work better. They've just sort of been looked at in different tumors. Okay. Okay. So this was, again, these are, you know, it's hard to enroll people to these studies, so it was an open label study. Group one was metastatic, cutaneous squamed 78 patients, group two locally advanced, 31 patients that dozing's basically 800 milligrams IV every two weeks, but then there was a metastatic cohort that went on to get 1200 every three weeks. So just, you know, IV dosing every two to three weeks is sort of for us to think about. Did these people get less of the side effects? And I finished doing the result. Sorry, sorry, sorry. Okay. And then we could talk about that. Okay. Okay. Most people were treatment nine. So primary endpoint objective response rate and duration of response. Okay. So what were, what were the objective response rates for metastatic 50% had a CRR PR in 12.8% had a complete response. So like all their tumor gone. And for locally advanced 54.8% had a objective response. And then 25.8% had a complete response. Durability, median duration of response was not reached in either, but it was estimated for metastatic that the probability of maintaining response for at least 24 months was 72% in that that was about 80% for locally advanced. So I don't know exactly how you estimate that when you don't have it, but that's, you know, that's it. So that's what they found. So those responses actually tended to deepen over time. And so they, you know, patients had higher response rates, you know, as with extended follow-up, then they did it their original interim analysis. And so that was kind of, that was interesting. So you know, this is really not like drug works while you're giving it. This drug induces a mean response, mean response works, even when you're not on the drug. So PDL1 status, a lot of times when you look at these, I mean, therapy studies, they look at PDL1 status of the tumor. And you know, there was not a, did not clearly, it wasn't like, oh, only high PDL1 expressors responded and low ones did not. So that was kind of interesting. And you know, so kind of the take home about half of people are going to respond. And if they do, that's probably going to be a pretty durable response. So what about safety, you might ask? Yes. Yeah. If you looked across, their, you know, adverse event rates were like 94% of grade three or higher AEs. And immune related adverse events were about 27%. But only about 3.6% of these were grade three and there were no grade four, I mean, related adverse events. So if we, you know, that is, that is act that was higher in the other studies. So if we look at like some MIPLAMAB, which is a PDL1 inhibitor, the, the grade three or higher, immune treatment related adverse events have been like about 20%. And if we look at Pembrolyzumab, those rates were severe, I mean, related adverse events were about 8 to 9%. So, you know, and their, their efficacy objective response rates were in the sort of 50 or 50% range. So really what we're seeing is that the biggest difference is lower adverse event rates with the PDL1 inhibitor, COSABLAMAB. So that similar efficacy may be lower kind of higher grade adverse events. Huh. Does, does it ever make any sense? Does anybody ever get both a PD1 and a PDL1? I don't know, you don't do that. When we talk about switching drugs in our podcast or things like psoriasis or AD, you know, we have a lot of conversations where we're like, yeah, I mean, they're not responding to Giselke Mab. So I'm going to put them on Rizakizmab and we switch between classes all the time. They don't tend to do that in oncology. I think what will be interesting to see is how much switching happens from a PD1 inhibitor to a PDL1 inhibitor. If a tumor does not express PDL1, how in the hell do these drugs work? I mean, so there's a lot of, there's not a lot of standardization of how you measure PDL1 and it's really are they PDL1 low versus high. So I think that in general, you can find PDL1, but one, there's different ways to measure it. It's not standardized. And so, you know, what is called what's considered a high expressed or is it greater than 5% is a greater than 2%, how are you measuring that? So I think that that's so it's really not are you zero? Yes or no, it's lower high. I mean, if I had a squame and they were talking to me about their therapies, I would do the PDL1, like it just makes way more sense. It does seem to make more sense. Yeah. And so the question is like, you know, it'll be interesting to see if we have longer term data or head to head data, does one work better? It's probably be hard to power that study. Yeah, like the hepatitis, the colitis, the endocrinopathy's, I mean, those are horrible side effects. Those are the horrible side effects. Yeah. Huh. What if you combine to one of these drugs with those immune stimulatory herbs that you talked about that make Dermatomyositis worse? You could have really bad Dermatomyositis. It seems like that would that would be a knockout. You'd be guaranteed basically to be cured of your cancer. There you go. Immunostimulatory herbs. Dermatomyositis, yeah. Right. Andermat, so you get Dermat-O, but your cancer's gone. Yeah. But no, I thought it was important for us to know about this. It is an FDA approved drug for the treatment of metastatic and locally advanced squamous carcinoma. It's a little different mechanism of action. A PDL1 inhibitor, Cosa Belamab. Yeah. Just the on the lookout for it. So, Semiplimab and Pembro have the same indication locally advanced metastatic, right? Yes. No, they've metastatic. Semiplimab has that adjuvant approval, right? Yes. After resection and radiation in the adjuvant setting, Semiplimab is FDA approved. Pembrolyzimab is not. This Cosa Belamab has that I'm aware of, no studies looking at it in that setting. All right. We're going to go to the next slide. Okay. All right. Pat, what do you got? All right. My second six pack was from December, Jammadur, entitled a novel tool for predicting malignant disease and adult patients with Dermatomyasitis by yay at ow. We're so 2023 International Myasitis Assessment and Clinical Studies Group. They put together that little. algorithm, we covered it in an earlier episode. I'm sure everyone remembers. Stratified dermatomyositis patients into low intermediate high-race groups. And then it made screening recommendations. So for that assessment, there were a lot of different factors, right? Would they have dermatode? Do they have, I always call it cutaneous only? I know it's clinically amyopathic, but cutaneous only is easier. Certain antibody profiles, if you had interstitial lung disease, there were just a lot of different factors and then you put people into low intermediate high-risk and they gave screening recommendations. The study was just kind of that, but narrowed down things a bit. A retrospective study performed that one institution in China training was done on cases that were done in the department dermatology and then they did an external validation that was done on 262 dermatomyositis patients in the department of room. Criteria, they came up with, they called it the tip CA model. So T is for anti-tif-1 gamma antibodies. I interstitial lung disease, P-pochlear derma, C, clinical diagnosis where they had DM or cutaneous only DM. And that was it. No, they're in anemia. And so it was like you get 1.0 points. Basically, if you have any of those, you get 1 point. The exception being interstitial lung disease. If you have interstitial lung disease, actually, that gets you a zero. And if you don't have interstitial lung disease, you get a point. This was a little bit weird. In the table, that's how they scored it. In the abstract, it was like if you have interstitial lung disease, you get a minus one. - Minus one. - Yeah, that was the one protective factor. It was. But they just, they did the math differently. They called it minus one in the abstract, but in that table, they're like, if you didn't have it at zero, and if you don't, no, if you have it, that's protective, you get zero. If you don't have it, you get a one. - It's not either a zero or, so it could be a zero one or it could be a zero negative one. - No, I don't need the abstract in the table were different. That's how it was like a almost like a maybe they'll publish an erratum. Because they say if you have a score of five, well, if you if interstitial lung disease is either minus one or zero, you'll never get to five. So I think it's zero. Let's just go with zero one. - Zero one. - Zero one. - And basically, if you have dramatic my side is, and you don't want cancer, then you'd rather have interstitial lung disease. Yes? - Yes. - That's it. Except that sounds kind of blousey as well. - Yeah, neither one's good. All right, so it's kind of an easier thing to use, I guess, than that other table. They use the cutoff value of 2.5. So if you were one or two on that little table, then that's below and if you were three, four, five, they use that in the validation cohort sensitivity was 82% specificity was 66%. So pretty sensitive, but right specificity takes a little bit of the hit. The authors didn't really go into what screening do I do for a patient with three, four, five. So that was kind of left open. The features of the tip CA model that aren't really in that earlier algorithm were poicular derma and anemia. So maybe just do the I cams model and maybe add anemia and poicular derma. I don't know. I just, it jumped out of me because hey, we have this cool tool. It's pretty similar to that I cams and I think the I cams is just a little bit more thorough. And what's nice about that paper, 2023, they actually go into, here's your screening for low risk, here's your screening for intermediate and here's your screening for high risk. So a little bit more of a complete panel. I don't know if this adds much. Yeah, I thought it was a good refresher of what is a risk factor versus a protective factor. Yeah. So basically, Pat, and this was the cheap Chinese knockoff of the higher end original brand name tool. I don't want to get into any of that. Very useful though, because it is such a, what's always interesting to me, and I guess they I think of duration of Dermatomyocytus is such a big part of it. Like whenever I see a new clinically amyopathic Dermatomyocytus patient, I'm always like, how long have you had this rash? And if they've had it more than two years, I'm like, ah, you're fine, you don't have cancer. And if it's less than two years, I'm like, I'm going to think about it. And that's when, and so I'm just interested that duration of disease that it doesn't, doesn't play into these. Yeah, it wasn't, wasn't for that other one either, that I can't. Yeah. They don't factor duration. Yeah, it's interesting. It's interesting. You just, that's a mental thing, because if you're like, well, you've had this for a long, if you, if it was associated with cancer, you'd be dead by now. I'm sorry. Yeah, exactly. Yeah, that's exactly it. And it has been in an article. It was in a guideline or a recommendation somewhere that like for the first X years, you should be, you know, screening these people. And then after so long, you didn't need to keep screening them every year. Okay. I think, I think that's where I came up with that somewhere. All right, so get around my last two. One more, Matt, you're, you're, you're, you're, you're cut off. You got one paper. The, the, with the one barely counts. It was basically that like, people who go on, Lotus, Oral, Monoxidil, essentially all of them, if they are a man, get hypertricosis on their arms, but they don't care. And that was, it was five milligrams a day. And it was man. And it's, like I said, essentially, all of them got some, not even essentially, all of them, all of them, essentially got some element of hypertricosis, especially if they were under the age of 41. So just interesting, it might be something worth talking about to patients whenever you start them on Lotus, Oral, Monoxidil, your body might get hairier. But this is quality of life didn't, didn't affect it at all. The much more interesting thing. And this is the big medical legal risk for dermatologist. I, and maybe everybody else in the world of derma was all about this, but I had never heard of it that there is now like a very specific warning from the FDA about using backtrum in young healthy people that there is every time you prescribe backtrum to a young healthy person, if it's for more than seven days, there is a one in three thousand chance that they will die from acute respiratory failure. And it is specific to young people. Now they don't know if it's specific to young people because young people are the people who get longer courses of backtrum because they're getting it for acne. So this has been specifically associated with backtrum for acne. And so maybe older, you know, fits for a UTI or a, select, you know, whatever an infection, maybe you only get a seven day course, whereas if you're getting it for acne, maybe you get a three month course, so you're more likely to get it. But it's a very specific, lung injury, unlike normal lung injuries from other things. And it's one in three thousand. When this was been reported from a bunch of cases from like one of the children's hospitals here in America, this was a Canadian large database study. And the attributable risk is about one in three thousand. They compared it. Your odds of getting this lung injury after getting a moxasillin, your odds of getting it after a cephalosporin and your odds of getting it after backtrum. And one in three thousand people more got it after backtrum compared to the others. And so did you guys go about that? Yeah, they controlled well for baseline risk for people getting in. It wasn't like, well, because they all had lung infections like they controlled for that. Yeah, this is really important. I hate backtrum as like a drug for acne. And I'm always happy to have a reason not to give it. And so it's very important to me for that. But no, I think people sometimes give this out a little to Lucy Goosey for acne when we do have other options. And so I agree, people need to counsel patients and say, you know, there's this risk. And maybe it'll also help patients not to be like, oh, just take the antibiotic. Yeah, I mean, I'd say where I probably use it the most is, you know, community acquired MRSA. I'm always used doxy, but I, you know, I think backtrum probably works a little bit better. So sometimes for skin infections or HS, I'll use backtrum. And this may make me think of backtrum as more of a last, even more of a last line option than it already was because of Stephen Johnson and TEN kind of stuff. Right. And this is actually a way higher risk than Stephen Johnson or TEN. Seems like it to me. I mean, I'm one in three thousand seems like a, yeah, I mean, if one in three thousand people we treated with doxy cycling got Stephen's Johnson or, you know, are even with backtrum. It's a, yeah, that's a much lower risk. This is a meaningful, real, higher risk. Right. Thank you for bringing that to our attention. It's our, I tried to cut it you off. Right. If you think about it, if you're a Durham and you prescribed backdrum twice a week, that's going to be a hundred times a year. If you have a 30-year career that's going to be a three thousand people, you will kill one person from this reaction. If you prescribe backtrum twice a week for your whole career, we should just go back to Chloram Fennecoll. That was, that was an old time acne drug. But I like it. I just thought about this now because I barely ever give backtrum. I give a ton of DAPSOM. Is this backtrum specific or sulfon? Did they look at other sulfonamide antibiotics? Did DAPSOM did not come up as I was digging into this? I see a trinetic study in your future. Oh, I loved apps. Don't take it away. It'll be okay. We'll report back. All right. Why I want to thank everybody for joining us this week. We hope you learned a few things. Hope you laughed once or twice and mostly we hope you're planning to join us next week. Until then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Ferris and we are Derms on Drugs.