Hidden Gems: How Generic Systemics Still Shine in Dermatology

[Music] Hi, welcome to season two of Derms on Drug. A video podcast brought to you by scholars and medicine, the best educational platform in dermatology and provided in no cost to medical providers. Derms on Drug is where cutting edge dirt meets hitter miscomedy. I'm Matt Zeyers, each week and joined by my residency buddies, Dr. Laura Ferris at the University of North Carolina, and Dr. Dim Batten at the University of Pittsburgh, I by the way, am at Doc's Dermatology, and we use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It's everything you need to know to be on 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 podcast platforms. Just to remind you, there is a video component, and it has typically the key figures and tables from the articles we talk about. And then I want to introduce our guest for this week, Dr. Scott Drew, a fantastic dermatologist who is incredibly active in the world of philanthropic dermatology going overseas to underserved areas. And Scott also does a lot of teaching, serves on a lot of boards, those kinds of things, but he has been a busy private practice dermatologist for a good more years than I can even more years than I can count, but Scott did also just join Doc's Dermatology as well. So congratulations to join in us, Scott. And but with all that said, let's go ahead and get into our first article. Dr. Ferris, what do you got? All right. So today, I'm excited that we're going to talk about old school drugs. So I picked a combination of old school drugs. So this paper is pulsed as a thiaprin and lotus methotrexate versus standard osmethatrexate, treatment of patients with moderate to severe psoriasis, a randomized controlled trial. This is L, Komi at all. And this was published in clinical and experimental dermatology. All right. Before you go too far here. So Dr. Drew, what do you consider to be low dose methotrexate and standard dose methotrexate? What numbers you guessing the papers, 75 milligrams a week of methotrexate, like on a Monday and then full of acid on the other days. Okay. Patent, what do you think low dose is going to mean? Or did you read the paper? Do you already know? Yeah, I did. I read, but that was low dose for me, seven and a half, 10. Okay. So yeah, I think of low dose methotrexate is 10. I think of standard dose methotrexate is 15. And in today's world, I think of anything above 15 is being like, wow, what are you doing here? Could you do? Was there nothing else you could get them on? But let's, all right, fairs, go ahead. So you got a narrow therapeutic window there. Narrow therapeutic window. And to 15. All right. I have no problem with going up to 25 on methotrexate. I don't think that. All right. Okay. Okay. So this is straight out of Cairo University. And this is a small clinical trial, 67 patients, half got what we would call classic standard dose or Matt might call ridiculously high dose methotrexate, 17.5 to 25 milligrams a week. And then the other half got what I think we all agree could be low dose methotrexate 10 milligrams a week. But they also got once a week, 300 milligrams of azithioprint. So they picked one day and like in the middle of their methotrexate dosing and they got 150 BID. So 300 milligrams twice. So no folic acid here. Do you know, do you know if they did thiopurine methotransferase less? So I don't I haven't written a script from methotrexate in years. But I do remember you got your response check thiopurine methotransferase level TPMT. For a reason, you got to check it. Yes. I believe that they did in the study. So yes. Okay. Okay. Primary endpoint that they looked at was Pazzy 75. Now they also looked at Pazzy 90 and 100. So you know, problems if you step your primary endpoint and you got a small study. You know, that gives you challenges with the data, but here is sort of the top line results. It was that the patients who actually did really well were the were are sorry the end point that was actually really significant was actually the Pazzy 100 rate. Okay. So if I said to you, hey, this new biologic has a Pazzy 100 response that I think's really good. What do you think that should be met? Since we know you didn't read the paper really good. Pazzy 100. I mean, anything above 50% I think of is really good. But if you really like, if I was to be like, wow, I'd be I'd say 75% of people get into Pazzy 100. I would be stunned. Okay. So Pazzy 100 at week 12. It was for the was 35% in the combination arm in 10% with metatrexate alone at week 16. It was actually like half of people 47% in the combo versus 20% in the metatrexate arm. Now, I will say that this was with sub Q metatrexate, but I don't think that that's. That's a huge deal side effect wise safety was good. There's a little more GI side effects, but that was actually in the metatrexate only group. So relapse rates, you know, 20% of patients did have their psoriasis come back within two to three months of stopping, but we're not really shocked by that. So, you know, this was actually a randomized controlled trial. It was actually a head to head study. These are like super affordable drugs. It was a small study. You know, I think that this was kind of a helpful tool to have. So, you know, one, if I've got a patient who is, you know, doing maybe doesn't have a lot of options financially. I don't love that they're creeping up on their cumulative metatrexate dose. You know, maybe I can move them down to a low dose like 10 milligrams a week, where I'm not really worried about cumulative dose and then add in a low dose of azithioprin. A low dose meaning 301 a week or a low post. Yeah, yeah, yeah. Yeah. 300 milligrams once a week. So, so Dr. Drew in the real world, which Dr. Drew and I are both in the real world in private practice. Him much more than me as I primarily do research nowadays. But could you imagine ever doing this? Like, it's hard for me to imagine ever actually, if, you know, if I, if I couldn't, if somebody couldn't get on anything for psoriasis, that was, that was a good drug. Maybe, maybe if someone moved to my town from Seattle and said, I'm on this regimen and I like it and can I continue it, I would think about that. Some of the data Laura shared surprised me because I think back in the pivotal trials, which, like back in like 72 or 73, the Pazzy 50 numbers on metatrexate as monotherapy was 50% at moderate dose 17 milligrams at 16. So, to get those kind of numbers was, you know, I'm shocked by that. Yeah, so they're Pazzy 50. So Pazzy 75 wasn't actually statistically significant between the groups at week 16 was about 70%, which is pretty high. But Pazzy 50 rates were up to 90%. You know, so this is in Egypt, right? So we might not have as like obese of a population as we have in the US, right? A lot more sun as well. A lot more sun. Yeah, so baseline BSA, median BSA was like 25 and 28, right? 25 20. So that's more severe. Sorry, baseline BMI was like 28 to 30, which is a little lighter than what we see in a typical US. So I just got back from Egypt. I was there for two weeks and the other interesting thing about that, not only are patients more, are Fitch Patrick three, four and five. And if you go south like towards Sudan, there's actually six. And most people spend a great deal of time outdoors and it's sunlight 15 hours, 16 hours a day. So I'm wondering if there is in some additive effect of quote unquote, photo therapy, if you will. Yeah. And it's into the additive effect of whatever agent you're using. So it's triple therapy, a's a thiaprin, methothexate and UV light. Yeah, yeah. Okay. So. But I thought it was interesting. Like it seems safe, subcue. They didn't use full agacity, which was kind of interesting to me. But, you know, again, like I know you practice in the real world, but like I think I practice in a different real world, which is in, you know, the real world where patients sometimes don't have insurance and patients sometimes have Medicare and can't afford anything. And so, you know, you deal with like, what am I doing? I'm up against a cumulative. I don't want to reach a cumulative dose of methothexate where I feel like now I've got to think about liver biopsy or fiber scan. And so I think this could be an option for some of those. And I'll be interested as we get further into today's discussion after we're done with our articles to talk about if we ever recommend liver biopsy. biopsies and fiber scans and those kinds of things on methotrexate. But let's jump onto our next paper here, Dr. Patton. What do you got? Yeah, before I do that, the other thing I would say is like 16 weeks safety for amurina methotrexate, I would like I think over time you're going to have problems. You know what I mean? I mean, just the two of those together. And you know, he's a thigh print, a bad actor for skin cancer. Obviously with darker skin populations, that may not be a concern at all, but long-term immuran. I mean, those skin cancer patients, that's one of the ones we try and get them off because we do think it contributes to aggressiveness and frequency of SEC most. And I'll put it. Yeah, question is though 300 milligrams once a week, do you have to worry about it as much? I don't know that we know the answer. I don't know. And Dr. Patton, Dr. Patton, so practices at the University of Pittsburgh, which is organ transplant capital of the world as for Dr. Fair's practice for years as well. So lots of experience there with transplant patients on drugs like esothiaprint long-term. Matt, if I could pipe in for the one added benefit of this article, I think speaks to the avoidance of switching for those that engage in, you know, later stage therapeutic. So if you're doing someone on an aisle 23 or an aisle 17 or anti-12, anti-13, 23 or even a tick or a jack, this may be an operational opportunity to do something your different MOA because if someone's getting Pazzy 72 or 84, yet still not perfectly clear, do we want to go through the idea of switching or as Mark Lebel often opines with data should we not add something and oftentimes we'll talk about adding a Tesla or should I stick to and maybe perhaps something like this drug based on that study might be an option with different MOA. And I would say in there that the drug that I would really think about adding now for, you know, talking about adding a Tesla roflumalast orally, right, which is basically more potent than a Tesla, same side effect profile, not immunosuppressive and most importantly generic. So you can get it for like six bucks a month and not have to do a prior off as an add-on therapy. But it's a good point, right? Adding something else on that's very safe rather than going through the whole shenanigan of switching for somebody who's doing okay or doing pretty good on a, you know, on a biologic, not a bad idea at all, especially the non-immunosuppressive biologics or the ones of very minimal immunosuppression if any like the I-17 and 23 inhibitors. All right, Dr. Patten, what do you got? All right, my deep dive is pre-proof article from the JAD, available online July 2025. Lower oncogenic risk with dermatologic use of mycophinalate moffatil compared to transplant prophylaxis, a retrospective study by E at L. It was a retrospective studies at a single institution comparing malignancy rates of three groups of patients. Derm patients prescribed MMF, transplant patients prescribed MMF and dermatologic patients that were not prescribed any immunosuppressive therapy. So when counseling patients about MMF, I go into this field. It's an immunosuppressant, anytime you suppress a immune system, there might be an increase risk for malignancy. But I would say, you know, patients, you know, we see those malignancies and transplant patients who are significantly immunosuppressed and we don't know if the same sort of risk happens with monotherapy, treating, derm diseases. But I couldn't say where I really got that data, probably like Wolverton or it just sounded good so I went with it. I don't know if there's ever been a more direct comparison like the one seen in this paper. So they had 126 MMF patients, 226 transplant patients and 296 derm non-immunosuppress patients. Average MMF dose was actually higher in the derm patients around 1400 milligrams compared to 800 milligrams in the transplant group. That is like the opposite of what I usually told patients, like one of the things was, I would tell them is the dose of myocaphyl that we, that the transplant patient is to get is way higher and that's why they see all these problems. I would also go into transplants being on more drugs, but it turns out the dose was higher in the derm group. So I'm not going to be saying that anymore. As I said, concommentant immunosuppression was more common in the transplant patients. So compared to transplant patients, the derm patients on MMF at a lower risk of malignancy, especially in cutaneous and oncologic reproductive malignancies, and the incidence was actually comparable to derm patients that weren't on any immunosuppressive therapy whatsoever. This supports the theory that Michael Finalate, Moffatil Monotherapy and Dermpatients doesn't seem to confer an increased risk of developing malignancy. So the thing that I would tell patients still seems to be true, and now I think we have probably the best data to support that. So do you, I remember seeing articles before showing that transplant patients on Michael Finalate actually had lower rates of cancer compared to people not on Michael Finalate. And so I've always kind of thought of Michael Finalate as not really having a malignancy risk. Is there definitely a malignancy risk associated with it? There was one paper and it may have only looked at maybe skin cancer. But there was one paper that suggested higher doses of Michael Finalate were worse than lower doses. Like the risk ratio was higher in the higher dose Michael Finalate patients. So based on that, I would say, yeah, okay, Michael Finalate does seem to be associated with some sort of malignancy. Okay. So lower risk. Was that in monotherapy patients? Or, you know, how do we tease it out from all the other drugs and transplantation? Yeah. So I think that's what's tough. Right. And I didn't go through that paper when I was doing research on this paper. I saw that as a title of one of the articles that was referenced. Okay. So we. Because, yeah, I've yet to ever see. And I'm kind of in the background here doing a little bit of a lit search to see if I can find anything showing if Michael Finalate monotherapy. If there's any data showing an increased risk of malignancy with that, and so far, I've not shown anything. But, right, Michael, that study's probably never been done because. I think that higher dose versus lower dose wasn't transplant patients and transplant patients are never on. Right. So, and Will, when we get into our general conversation, we'll talk a little bit more about what, you know, we're going to get into how do we all monitor these drugs? What risk do we really talk about? What do we do to try and avoid those risks? Let me see what I found in my quick lit search here. Large cohort, registry studies, and transplant pulmonary populations. Either a lower or similar risk for patients on MMF monotherapy compared to cowcinern inhibitors or similar drugs. Let's see here, if I brought a lung disease, systemic sclerosis, cancer risk among MMF therapies very low, not significantly different from untreated patients. So, I think to take away both from the article that Dr. Patton did and from the background literature does support if there's a risk of cancer associated with long-term Michael Finalate, it is extremely low. Is what I would take away from it. Maybe we should add that to the methotrx state instead of azithioprene. Maybe once a day, Michael Finalate. Maybe that's going to be the magic. It works better when you stick to drugs that start with the same letter, right? Yes, true. That's been proven. That's strong. They're strong data for that. Dr. Drew, anything that doesn't seem like there's a whole lot to add right now, we'll chime in more about Mike Finalate as we go further, but just wanted. If there was something you were dying to put out there, wanted to give you a chance. I want to make sure I earn my keep, right? But the only people I see on MMF are those that come to me on it from room or transplant onk or some other case that I'm my role in is, what else can I write or not write based on their pharmacopeia? So I have very little primary experience as a prescribed group. Yeah, and I use it very little in, I'd say the last 10 years. I can't care about the last person I started on it. I've tended to use it most commonly in back before we had good at topic dermatitis drugs and I still have a few people on a long term from that. And I would use it in Pemphagoid patients, either that or methotrexate. But we'll get to more of that discussion as we go forward. Let me jump into our next article here, which was mine. So this was drug survival of duplomab methotrexate and cytosporin A in children with a topic dermatitis. This was in jam. dermatology and the first author was Vandorist RijST. And so this was an article I really like studies that look at drug survival. So drug survival to me is a very good, I don't want to say very good, is one of the best markers of really a total picture of a drug because it basically says if we started 100 people on this drug and follow them for three years, how many would it work well enough in and have few enough side effects in so that they'd still be on it after three years. And the big takeaway here is exactly what you would have expected. And by the way, the three years or something magical about three years, that was just kind of the number that they used here. I'm actually not certain that they used three years. That usually it's just how long did people stay on it. But exactly what you would expect to, Pilomep had much higher drug survival. The numbers were completely in line with what we generally expect about 10% of people discontinued it due to inefficacy. That seems to be 5 to 10% seems to be across the board when you look at drug survival about that many people, 5 to 10%, it doesn't work well enough in for them to stay on long term. Another about 8% discontinued it due to side effects, such as the ocular side effects that we're all used to talking about. And then 5% discontinued it due to shots. Methatrixate and cyclosporin survival, the thing that was most interesting, and just out of note, metatrixate had better survival than did cyclosporin. Cyclosporin was commonly discontinued due to inefficacy. But that's got to be a dose-related thing because cyclosporin always works if you give a high-- essentially always works if you give a high enough dose. But the most interesting thing to me in this article was that metatrixate and cyclosporin, their drug survival was much higher in the pre-dupillumab era. So they looked at this as once you-- once Dupy came out, what was the likelihood of drug survival versus pre-dupy? And exactly, I think we all would have predicted in the pre-dupy days drug survival would have been higher because you didn't have another option. So you were willing, if people were doing better, but not good, they don't really have any other options. So I'm going to keep you on it. Or they're getting nauseous, really bad on the metatrixate. But I'm really, I'm really on some woodshed. I'm going to keep you on it. Whereas once Dupy came out, like, OK, like, well, it's not working well enough, we've got another option. Let's try switching you over. So that, to me, was the most interesting thing. Was exactly as you would have predicted. This article was basically like, OK, what I thought would make sense. Make sense, right? Was the primary takeaway here. Comments from you guys on these key takeaway. I think it's hard to retrospectively get the real reason for stopping. So did you really stop cyclist-born because it wasn't working? Or did you write that down? Because you knew that there was a better safer option for them, right? Like, I'm looking for any reason to stop cyclist-born by six months because I know that I'm increasing risk. And so oftentimes, payers don't take, like, I shouldn't use it past six months. It's working fine, but I'd rather put them on something safer. Usually, it doesn't fly. So yeah. Yeah. Yeah, it's a really good point that you're trying to capture the true reason. And if it was well, it's not working well enough at this dose. So rather than increasing the dose because there's a side effect that their creatinine's going up a little bit. So what are you going to call it? You got to pick one or the other for why they stopped it. Yeah. Agreed with you completely. Patent, anything, any comments here? No. This is, like you said, this is what you would kind of expect. Yep. Scott, Dr. Drew, I'm just going to Scott. Forget this Dr. Drew. I'll ask you to rest out. Yes. So somewhat scarily, Sucka Sporn is a drug of choice for Pemphagoid and AB in Idogina. So at the adult and children's hospital in Saigon, they have entire inpatient wings, wards of 30 rows and 20 columns of beds of people who have Pemphagoid and AB. And the drug of choice is IV celluloid medral and Sucka Sporn. And you push the dose, you start it 4 1/2 mix per gig. And that's-- Yeah. --children. And you just go. And you monitor it with, are they peeing? And so the idea that this is some archival type of data-- I'm sad to say that's not the case, because Viet Nam is like the 20th most populous nation in the world. And you can get lasers and Botox and filler in Viet Nam. But if you have an inflammatory skin disease, there's no depiction. So it's pretty scary to see a four-year-old on 4 milligrams of a 4-mix per gig of Sucka Sporn for a year. And no dentist comes into clean the teeth. You don't get hyperplasia. But that's what they have. It's a really interesting thing to me, the idea. So let's break it off now into our general discussion of use of these older drugs. And kind of where I want to start this discussion is the idea of if we were in a different society, one that wasn't so litigious, where there's element of CYA, but there's also just an element of like, I want to do what's best for the patient and cost be damned. Because we've done our drug cost episode, and I'm certainly a believer that the patient's sitting in front of me is the only thing I'm thinking about. I'm not thinking about what's the cost of society, because I don't know what the cost of society is. Maybe we're going to get the drug for free through a patient assistance program. Maybe the drug company is going to give it to him on a bridge program, whatever. But I don't know the cost of society, but I know the person sitting in front of me is suffering. But if these older drugs, you, Pat and Fareson, I will train at the same time, right when Humeera came out. And when I look back on AD, I think for the 15 years, I practiced without Dupy. I threw everything at people and wasn't able to get them better on drug regimens that I would become able to take in myself. You know, in the prebiologic days, did, you know, what was it like taking care of Saraya's his patients? Did you hit him hard with this method of treating and psychosporin and they did okay? Or was it the patient's miserable? Inpatient Poova and Saraya Tane, and I grew up in the era of Amavive, and I remember Kevin Cooper invited us all up to Cleveland for a big gala when psychosporin was approved by can 19, 1994 and '95, something like that. We thought we'd, you know, died in gone to heaven. This is before narrow band. And when someone was getting married, you know, you'd tell their, though, the psoriatric mother, you could inject three injections of a catalog into their proxful nail fold and then 27 more injections. And well, let's do it once a month to get nails clear. It was, you know, I likened to what HSS is now, or was maybe a year ago before we had, you know, it's like, oh my God, Saraya, I just dread it. And we all had Poova units and we had narrow band units and we had mixed units. And yeah, we had, it was, it's a great time to be in Durham. And one comment I'd like to make about the cost of society, I've never seen a slide in my 40 years have been this industry. I've never seen a slide ever that said, what is the cost of doing nothing? You know, if you have bad HSS or bad psoriasis or bad AD or bad anything, you know, you sit home, you don't engage, you don't date, you don't go to school, maybe you're suicidal, you maybe you're depressed. I really challenged people to consider the cost of the, the lack of human socialization relative to quality of life of skin disease. So I'm with you, Matt, on the my contract is with the person sitting in front of me who's gotten the hood spot and come to my office and take their clothes off and bear their stories after being told before they're too fat, they're too lazy, they're too this or too that. And they're, they're here to hear what we have to have to make. - So Scott, to see in things like you see in Sagan where there are wards of, you know, tons of people on, you know, fairly hydrocyclist born for fairly long periods of time. Does that make you come home and feel more comfortable using these drugs or is it more, it makes you be while you're there like, oh my God, I'm glad I don't live in Vietnam. - It, well, I never gonna plan again when a rep brings me coffee and not cappuccino, right? So that, that's one thing. But it makes me go to more investigator meetings. It makes me wanna like figure out what can we do. It makes me keep my farm people on speed dial. Like, hey, I'm going to, Peru next week, I need 50 shots of this and I need a continual stream so we can keep these people going. And it makes me come on podcasts like this and recruit other physicians to come because it's easier when I 25 germs than if I have five. But it doesn't make you come home and say, well, there were 600 people on cyclosporine in Saigon. Maybe instead of, you know, what, four milligrams per gig for, you know, 20 years, isn't that bad? No, no, no, no. No, there's a whole conversation about AVM affirmations and Vietnam that just curl your toes. But no, it makes me want to bring what we have both medically and, you know, investigationally. At the same time, it's partnering with them because they teach me and all of us the way they do things, which is sometimes better, you know, and communicatively and culturally. And so we learn and we teach and we share. And but I do think it makes me a better Durham having gone there and come back. I think I treat my, I think I think I'd better for that having gone. Okay. All right. Can I ask you, Scott, are there any, like, based on the fact that, you know, you see things like this? Are there any drugs that you're like, maybe we overreact to that one. Like, I guess, you're saying cyclosporins, not it. Like, have you seen, you know, maybe where you've gone, there's a lot more methotrexate use. Have you seen the bad things or methotrexate or would you say, are there any times that you're like, we probably overblow or worry about the risk of this drug? Yeah. So like, for the great example, low-droit methotrexate, I wrote more methotrexate last week than I've written in 15 years because that's all there is. And so, Pazzy 50 is better than Pazzy 2. So yes, would I do that here? I would not. And sometimes there are, he just the word "fad," but, but, like, right now there's a lot of serriotene usage going on in Peru. I suspect because someone found a warehouse full of serriotene. I don't have, I asked and they said, well, we don't know. I'm like, how did that happen? Maybe there instead of drug shortages like we have here, they have the opposite. We're like, hey, we got to put serriotene now, right? We all, we all moan collect live when someone says, low-trishone. But there is no fear, no fear of topical steroids in the non-industrialized world. In fact, Clobetazol mixed with Clotrimazol is over the counter there. It's called Clovisone. And you can buy a nice 120 gram, two of it, for about a buck and a half and the same letter drug, same concept. Yep. Yeah, there you go. Clobetazol would be great. Right. All right. So let's get into talking some about these older drugs. So, and the ones we're really going to cover today, Methatract, Scythus Boran, Micophanolate. I kind of lumped Rolflumolest in here now because I think of these more as like cheap, small molecules that are immunologic drugs. We're not going to talk about Rolflumolest today because it doesn't really lump in with the old school drugs. I'm going to not really talk about these as a thiaprin because I think that's a drug that probably gets extremely infrequently used by any of our listeners. But so we're going to start off Dr. Ferris with our discussion about Methatract, Scythus Web, Dr. Patan lead, RMMF discussion. Then I'll talk about Scythus Boran. So Dr. Ferris, you know, what you, so psoriasis patient comes in. You know, they've got 15% BSA Medicare. So they, you know, you could get them on a biologic, but they, you know, it's going to cost them a couple hundred bucks a month, $167 a month, sorry. So they're like, no, you know, is it there something a pill that I could just take? What's your starting dose? What's your spiel? What's your, you know, monitoring for, you know, average psoriasis? So average psoriasis average, you know, depends on the patient. So you know, my questions are going to be like, you know, one I'm going to look and are they, how obese are they? Are they a type two diabetic? Those are the things that I think are going to have a bigger impact on safety. I will ask them about alcohol use and I will tell patients, you know, if I said you could only have two drinks. Wait, what's the obesity in the diabetes? Why? Because you're worried their kidneys are going to have, they're going to have a low creatinine or because you're worried about fatty liver and having a, so fatty liver that you're not going to pick up because your ALT and AST is going to be normal. Okay. Yeah. Or just that there, I mean, there are studies that show high risk of developing fibrosis if you're, you know, obese and type two diabetic. Okay. So I know that they're at higher risk. So I'm going to look at that alcohol use. I don't want to do this in somebody who's a heavy drinker. But, you know, I'll, like I will tell people, if I said you can have two drinks a week, would you be okay with that? And if they say yes, I don't care if they have two drinks a week on not the tracksate, I'm fine with that. What about two drinks a day? They're going to have a six pack a day. It's a different story. What's up? Two drinks a day. Two drinks a day, I say that's a little much. Okay. You know, so also with people admitting to two drinks a day, I'm not entirely sure that it's really only two drinks a day. Right. So when people say, oh, sometimes I'll go to something and I'll have a drink. If I say two drinks a week and they're like, oh my gosh, I have like three drinks a year, then I know I'm fine. If they're like, I could try to cut it back to two a week, then we're going to be talking about a little bit. So in your, so in your initial discussion, obesity, diabetes and drinking or your three big things, all right. Yeah. Keep going. And then, you know, yes, I mean, are they at risk of, you know, renal failure? So I'm monitoring creatinine and creatinine clearance and older patients in particular when they're on. And then when do you do your next set? So I do my baseline. I'm, you know, I screened our way for hepatitis B and C because so many people have hepatitis C, but you don't know it, particularly in Pittsburgh for some reason. So I screen everybody as long and the screening guidelines are everybody should, every adult should have a one time hepatitis C screening. So if they have not had it in a few, you know, five years or something like that, I will go back and screen them. I get, so I start them on 10 milligrams a week and then I check labs in a month. Okay. When you test dose, there's nothing like when do you see them back to see if the 10 milligrams is is doing anything three months. Okay. So you do it. So let's say you see back a one, you get their labs at one month. Okay. They're fine. You see them back at three months and their psoriasis says, hey, they responded really well. When do you, what's your monitoring regimen going forward? So I like to get once a month for the first three months and then I'm every three months. Huh? Okay. Now, do I always succeed in that? Sometimes it's like I get it a month in, I get them back at three months and I get labs. Sometimes that like month two thing gets skipped. If I am going up, I will make sure that I get it. Okay. And some is just like the access issues that we have, but I will get them back at three months. I'll see all they're doing. We may go up if they, you know, I'm happy to go up to 15. If, you know, like Tim said, I'm happy to go up to 25. I will, my next jump up is 15, generally, do they monthly for three months if you go up to 18. Then they get, then they get once a month. I, you know, I don't believe that every time I go up by 2.5, I need to go back to monthly months. But if you go about five. Okay. So first, let me say I almost only use method tricks 8, 10 milligrams. It's rare that I ever go up. I check labs at baseline. I usually don't do a hep B and hep C. I'm sort of like, well, if your LFTs are okay, that's a very, very, very, very poor man's hepatitis panel. Maybe I should start doing hep B and hep C. And then I check labs at six weeks. See him back at two. So this is typically for dermatitis patients. I see him back at two months. And if I'm going to keep them on the method, I say 10 milligrams, I typically check labs. Every three months for about a year, then I'll go to twice a year. Now if I'm going to more than 10 milligrams, then I usually try to do labs every three months long term. But you know, when I've asked some of the guys, believe it or not third dermatologist, even older than Scott, when I've asked them, they probably don't have a computer though. So we couldn't have true. We couldn't have the podcast unfortunately. When I've asked the old guys, have you ever actually seen anything bad happen to anyone? Can you think of a single patient that something bad happened to on 10 milligrams of methotrexate? And I've asked it to a lot of old guys and all of them, when I say, I'm using the word guys in the gender neutral, when I've asked old dermatologists that every single one has been like, no, I've never seen, I really, at 15, maybe a couple at the really high dose. No, no, no. They all had liver biopsies. Right, but they weren't using 10 milligrams. They weren't using 10 because we all kept running charts on our paper. We would add the number of methotrexate milligrams you had. And once you hit a total of four grams, you had an open liver biopsy. Yes. Now, Scott, well, let me ask you, you count as an old Durham. Have you ever seen anything bad happened to anybody on 10 milligrams of methotrexate? Other than eye-atrogenic things like that. No, not from the garage. And now, I will say where I have seen it is every once in a while, somebody will give a patient on dialysis a single dose of methotrexate. And that will kill them. So I always warn the residents when I give that lecture about methotrexate. I'm like, if they are on dialysis, if they are, they really have, if they have significant renal disease, and certainly if they have end stage renal disease, and absolute their on dialysis, you cannot use methotrexate. That will kill them. And by the way, we're spending more time on methotrexate than we'll spend on the other drugs because I do think it's the drug that has the broadest spectrum of use since probably gets used the most by our listeners. Dr. Patton, what do you, so what's your typical starting dose? What are your methods of trexate? What's your monitoring rate? 15 to 20, first month. I do every two weeks. I'm paranoid about the cytophenias. Maybe that's because my starting doses are higher. So I do two weeks for the first month, monthly for a couple months after, and then three, four months long. Dr. Patton, do you give patients an option? Do you ever say to somebody like, hey, with this medication, usually I'll monitor, I have people get labs pretty frequently initially, like every couple of weeks, and once a month, really rare that I ever find anything wrong. Would you rather that we, you know, you want to do the same for edgment, you know, the more frequent labs, or is that going to be a big pain in the rear and you want to get them a little less frequently? Do you ever give people that option? I don't. I tell them this is what I want to do. I mean, you know, how good am I at following those or those some patients that come back, they only get them, they only get it at a month. And I've given them a month supply. Yeah, but you know, there is what I told them to do. So if I run into problems, I can at least. Dr. go back on that. Dr. Cress, our program director, told me as a resident, I'll never forget this was a DAPSONE patient. And you know, we ordered at the time we were going weekly labs on DAPSONE for the first like 12 weeks. And I was like, so, but like since I ordered it and documented in the chart that I told them to get the weekly labs, like if they don't get the labs, that's on them. That's what on me, right? And he was like, oh, no. If I agree, I think you'd still be liable. But just in the real world, you know, I tell them how I want them to monitor it and hope that that's what they do. The two weeks is probably too frequently. So if they're not getting it then, it's not like I'm freaking out. All right, Scott since you've been writing methods. I will say one more thing like worst side effect. And it's controversial, but I have had pulmonary fibrosis develop in a pentecostal patient. What dose? What dose? I don't remember. But even that's controversial. I mean, it was more than 10. It was more than 10. There's more than 10. Please say it was more than 10. They'll make us all feel better. No, because they were elderly. I don't push the dose in elderly patients. But again, that's not like that. He developed pulmonary fibrosis. Polynephibrosis can happen etiopathically. But that is something you see in methotrexate. So that was kind of like, uh, so you're saying, do you ever get ex-chessis? What kind of chisels? I mean, I mean, I mean, I mean, I mean, I mean, I mean, I mean, I mean, I mean, I mean, I don't know. You know, you know, you know, that that's happening. No, I don't ask questions to screen for it. And when I tell patients about methotrexate and, you know, the things that can happen, I say, it does affect internal organs. Bone marrow kidney liver lung. Okay. Scott, what's how about you? So what's your usual starting dose? What's your usual right monitoring rate? So I'm a little more conservative. I go two and a half, three times a week with folic acid and I only go as high as 10. That's as high as I go. And I think about lab monitoring, the interesting metric about compliance with lab monitoring, the factor that predicts compliance is whether or not the patient has to get in a car after they leave your office to get blood work done. So if you can get the blood work done, either in your office or in the building where you are and they don't have to move their car, that increases, that's the single factor associated with that. One thing I'd like to say about prior awesome things is I used to be of the reality that some biologists were hard to get or small molecules were hard to get. And I find that when you do this work often enough, it becomes easier. And I'm not sure that's because the bioquart and it gets better. The insurance companies know you're serious where you get better at writing your notes or AI or whatever it is. But I have colleagues that say they can never get the biologic approved. And I can tell you in Ohio, I don't have step edits anymore. I don't have to worry about starting with that the trixate in order to get whatever biologic is the one that we're currently. Yeah. There's something that I'm going to say. So Scott, you said 2.5, 3 times a week. What did you mean you? Three tablets together. Oh. So 7.5 milligrams on Sunday. Okay. And then full of acid the other six days. Yeah. So that's in for hopefully no, by the way, if you're listening to this episode and thinking, okay, I've never prescribed methadrixate now. I'm ready. Don't do that. Go to scholars in medicine. There's a core curriculum in dermatology or read a chapter somewhere just to we're talking kind of about people who've used it some, but you know hesitant to use it a little bit more. That's kind of who we're targeting here. And so because we haven't even mentioned, you know, you want people to be taking 1 milligram of folic acid the six days of the week that they're not taking the methadrixate. You want to make sure that they know that it's only one day a week that they take the methadrixate. It's not, you know, four pills, once four pills a day, no, it's four pills once a week. You really emphasize that. And now the thing that I thought Scott was going to go with the lab monitoring thing, I think of the only labs that I think of a patient is going to get are however long I write the script for. So if I'm like, I'm going to have three months worth you get what labs in three months, you get a three month supply with no refills. If I want, if they want, if I think I mean monthly labs, you get a one month supply with no refills or maybe a six week supply with no refills. If I really want the labs, which right, if I don't really want them, I shouldn't be ordering them. That's the way that you give them minutes of pain in the butt because then you got to send in the refills and then the patient's calling, well, where's I'm out of my medication? You're like, well, you didn't get your labs. Well, I lost my cell. Well, we got it. Okay. We'll send you another script here. I'll send in a script for two weeks worth and they were not sending more to you get your labs. Right. That's that's the way I end up doing it if I really want to get labs on people. All right. Let's let's move on to our next structure, Dr. Patten, microphenolate. So just initially for our listeners, the big thing with microphenolate to me is there's a huge range of dosing. So I've seen regimens up to 40 mix per gig per day recommended down to I've got some exome patients on 500 once a day, which is probably three mix per gig. So Patten, what's your dosing? We're talking in run of the meal, Pemphagoid patient, run of the meal, A.D. patient, something like that. What's your dosing? What do you put people on? I had two Ohio State University professors, both of them happened to be Indian descent who had Pemphagos that were not clear on retoxin. And I put them on an off label dose of Pemphagos, not Pemphagoid, an off label like 400 milligrams a week of dupliumab and they both got clear and off of retoxin. And they were better on retoxin but not clear. Anything can happen. You have to get rid of antibody titers and I don't know that Dupy does that. It works in Daria's and Haley Haley and it shouldn't. Maybe it has an effect of stabilizing the desmosomes. Yeah, yeah. maybe, but I want to say with Derry A's and what was the other? >> Haley Haley. >> Yeah, I guess those aren't as inflammatory. Yeah, I don't know. >> Yeah, it's an interesting thing. >> Maybe TH2 inflammation does more than we thought. >> So do you check any labs and? >> Yeah. >> Wait, wait, wait, wait, wait, I'm >> I'm in it there, Patten. >> Why? >> What? >> Bruce Strober published in the blue journal that there's no need to check labs. >> And then microfinally patients. >> That's fine, but I would still do that. I get the baseline infectious stuff. You don't want to give somebody hepatitis B. >> Okay, fine. >> Microfinally. >> All right, so hep B, hep C, fine. >> Ep B and the quant gold. And then CBCCMP, I would get monthly for three months, and then I do like every three or four months just keep it. >> So that's interesting, because I mean, the literature really is that there's no monitoring requirement with MMF. >> Yeah, I know. >> And it just, I wasn't trained. >> And I occasionally do, I will check CBCs maybe once or twice a year, because actually I'm trying to induce a mild lymphopenia. There's some evidence that that's a good marker of drug level and efficacy with my ventilators mild lymphopenia. And I mostly use it in AD patients and in dermatomyocyte dyspacines. Again, not a ton of them, but those are the two things that historically have been. >> Yeah, I would say connected tissue immunobulose. I would put in a plug for CSU patients. Like I actually go to cell sept before cyclosporin. Now we have dupe dupe de pili-mab and we're going to get remy. So those enter into the mix. But I had patients who failed cyclosporin and I put them on cell sept and they had an amazing response. And then I'm like, I would rather prescribe cell septence cyclosporin. And there are actually, I've seen some guidelines that said, it's not unreasonable to go to cell sept first because of its side effect profile compared to. >> What dose and duration do you do? >> The same, two grams and then when they get clear, try and peel it away every three months or so and see if they stay clean. >> Okay. I will say with my confinolate, the one thing that I do with all of my patients is put them on 500 of allyl cyclovir once a day because I've seen so much disaster. Back when I used to use it a fair amount, I saw a lot of disaster. Even now that was in the pre-good vaccine days. So I don't know if they've been vaccinated, should I get them vaccinated? If they haven't been vaccinated, the blood, the blood, the blood. >> You should get them vaccinated. They should get schingrux. >> Yes, but even if they've had it, I'm still probably going to profile ax them because it's certain. >> That is no data. There is no data to support that. >> But there's no data to not support it. So in other words. >> I mean, maybe I'll give them a chocolate chip cookie every day because there's no data to not support that too. >> So what do you like me more? >> Give me what your rationale is for. Because right, my rationale is my confinolate. If it's if I've got an adequate dose that it's suppressing lymphocyte proliferation and activity, lymphocytes are necessary for antibody production. And schingrux's main efficacy is from cell mediated immunity. So it makes really good sense to me that my confinolate would reduce the efficacy of the vaccine, even if they got the vaccine before they were on the my confinolate. So why not give them Valley Cyclovere 501s a day, which is dirt cheap and has really no risks associated with? >> Aha, see. >> They've got pre because they have circulating antibodies after they've been vaccinated. But the main effect of the schingrux vaccine is cell mediated immunity. I only know this because there was just an article looking at Renvoque, people getting vaccinated while they were on Renvoque. And while the vaccine, Gricks did still work, it did not work nearly as well as it did in people getting vaccinated while they're not on Renvoque. And that's why I now know that cell mediated immunity is the main thing. Scott, do you use my confinolate at all? And anything you want to add to this conversation? >> I don't, but I will buy, I'll take 35 seconds to say the one drug that we haven't talked about that I do use a ton of is DAPSOM. >> Oh, yeah, I need to talk about DAPSOM. >> Talk about DAPSOM. So let's, so let me give my 30 second and not 30 second, two minutes to be on cyclosporin. Cyclosporin, incredibly effective drug for almost everything. Really good, you know, rapid efficacy and at very low doses. So I've had, so when you think about cyclosporin, you think about modified cyclosporin is what you want to prescribe to people. Four makes per cake per day is the maximum dose. If I can get somebody down to one to two makes per cake, and they get good efficacy long term, I'm very comfortable keeping people on one to two makes per cake long term monitoring them, monitoring their creatinine in particular every three to six months at that low of a dose. Mainly, of course, I've used that for a topic dermatitis, and it's very reasonable to use it as add-on therapy, especially at like one make per cake for, you know, add-on therapy for a biologic that is non-eminent or suppressive. I would not use it for add-on therapy with a jack inhibitor, but very low dose cyclosporin is actually a quite safe drug in my experience. I take up the literature, baseline, you know, CBC, CMP, HEPB, HEPC, in theory, you want to check a magnesium level as well, you want to check a lipid panel, that, and typically I check labs at about six weeks, and then every three to six months, if I'm at low dose, which in today's world would be, it's hard for me to think of a situation which I would be using anything other than one to two makes per cake long term. Rest of you guys thoughts on cyclosporin? I like it. You see you monitor blood pressure. You get baseline and monitor it every time they're in the office or tell them to monitor it themselves. I tell them to stop and CVS's and get it done. But we, I generally don't monitor it whenever they're in the office. Not unreasonable though. I monitor it in the office. I like it low dose combined with sometimes like a biologic, also sometimes for really bad CSU patients who are, you know, on Omalizumab and for you know, his main and throwing in 100 milligrams of cyclosporin can help. I am more careful with cyclosporin. I do see them. I would never go. I mean, I pretty much get monthly blood work when they're on. Even if even if they're on like 51 today, maybe I'd be a little bit more, but I feel like I almost never have anybody on less than 100 a day. So which I know is kind of low, but I'm, I'm careful with it. I worry about the creatinine. Okay. Yeah. I've never, I've never, at the one to two make per cake, I haven't seen creatinine effects. And whenever you look at the old data on why we were so much about creatinine, it was really with some super high dose. It's really peak level of cyclosporin that's more of an issue than the steady state level. So 50 of psychs born twice a day is probably better than 100 milligrams once a day in terms of renal effects. Scott, use any cyclosporin little. I used to use it a lot for like I'm getting married in two weeks, kind of psoriasis. I think we have better agents now. My fear of cyclosporin is, you know, we all have that end of one or two. And I've had two cases of horrific gingival hyperplasia, which just were jaw dropping and I'm afraid it's great. You smarter that a little bit. So it's a hyperplasia gingival, gingival hyperplasia. Where the gums, yeah, and then further than the teeth. And part of that I think may have been with poor dental hygiene to begin with, but that gets my attention. I agree with Dr. Ferris or Laura that I like it as an additive to a biologic, not my first choice, but I debts where I mainly use it these days. Okay. Wow. So everybody that has been a phenomenal discussion so far in some of these oldy but goody drugs. And we're actually going to make this a special episode where we're going to split it and we're going to have the second half of the discussion with Dr. Drew next week to cover some more of these oldy but goody drugs. So I want to thank you for joining us this week. I hope you learned a few things. I hope you laughed once or twice and mostly hoping you're planning to join us for the rest of the discussion next week. Until then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Ferris and we are Derms on drugs. [Music]