Welcome to season two of Dermtond Drugs, a video podcast brought to you by scholars and medicine, the best education platform of dermatology and provided no cost to medical providers. Dermtond drugs is where cutting edge dermis, hit or miss comedy. A medzires from Dr. Dermtology in each week and joined by my residency buddies, Dr. Laura Ferris from the University of North Carolina, Dr. Tim Baden from the University of Pittsburgh, where we use our 60 years of combined to experience to discuss debate and dissect the hottest topics in dermatology. There's everything you need to know to be on the cutting edge of Dermt and you actually have some fun listening, new episodes drop every Friday on scholarship medicine, Apple podcast, Spotify and other major podcast platforms. Remindered everybody that there is a video component that has some of the key figures and cables from the articles we talk about. So this week we've got one of our patented six pack episodes and we are going to kick it off with Dr. Ferris. What do you got? All right, Matt today I'm going to talk about height. So I'm going to talk about two papers that recently came out talking about height and kids coming from me who doesn't see any kids and who isn't very tall. So I thought I was the perfect person to cover this. Okay, so first paper was in the chat. It was the effective isotretinoin treatment for acne bull garrison height and adolescents. A retrospective cohort study using the Rochester epidemiology project. This is you adults, John Barbieri's group. So first of all, I like a good study that did not involve trinetics. So it's a different cohort. Okay, so what do we why do we worry about this? So there are case reports of premature epiphyseal epiphyseal. How do you say that word closure? I don't know how to say either one is probably okay. Okay, good epiphyseal closure and kids who are on high doses of isotretinoin. And this is generally not like the course of for acne. This is like neuroblastoma or Icthiosis. So in this study, they looked at the Mayo clinics like records link database, which is called the Rochester epidemiology product. This is in the famous Olmstead County. And they looked at at so they took kids who are adolescents who started isotretin before age 15 for acne. And they compared them to kids who got antibiotics for acne. And they did adjust for things like sex age and systemic steroids. And what they looked at was height velocity. And final adult height recorded at 18 years. So what did they find isotretinoin may temporarily slow the rate of height gain. So they called that a velocity dip. And it comes to adult height. It didn't matter. So the mean difference in final heights between the group was 0.67 centimeters, which was not statistically significant. There was no dose response. Just, you know, basically you might have this like little pause at starting and in growth. But everybody makes it to the same height as an adult, whether or not they used isotretinoin. And that was clearly what they want the outcome to be. And I think one of us want the outcome to be. But this is one of those deals where like when I look at this and there was a clear change in height velocity. And people in isotretinoin were a little bit shorter like it wasn't statistically significant, but it makes me think that if you got enough people, it might actually make you like a half an inch or two. It was point it was half a centimeter, which is different, right. That's hard to really say that it matters. And then also, you know, this may be why they, you know, looked at acne and shorter courses, right. So this may be a true issue in the osysterretinoblastoma. But, you know, let's face it, these are serious conditions that height may not a half a centimeter may not matter, right. So I, and you know that the height velocity thing is kind of interesting, right. So, you know, in the end, do you care about if your kids shorter a little bit shorter for six months versus are you really concerned with their ultimate height, you know, in adulthood. And I would argue it's probably the latter. So, I don't know, I thought it was interesting. And I thought because you could have, I thought it was helpful in terms of guidance. And people are like, but look, they're not growing at the same rate. Like it's reasonable to be able to say that's actually been studied and there is this ketchup period. So. I'm still not convinced that the figures that they had in there figure one and figure two. Those violin plots. Yeah. Yeah, the violin plots. I live in this way. I am going to pretend that I believe it one way or the other because I don't want to have to talk to the patients about that the ice treadmill might make their kids shorter. Because, but and it was not statistically significant. So it it that we can legitimately say the data shows that. And I still I guess what am I talking about? Yeah, it doesn't make people in these doesn't make people any shorter. We should put everybody on acutate. That's what I'm going. That's that's my final answer. I'm glad that you brought your. Zero zero concerns about zero concerns about height and acutate. All right. All right. Alright, first, what's ever. One, I will say just kind of anecdotally. I had a daughter who had, you know, like a heart heart disease basically, pulmonic stenosis ended up having. No, not what did she have pulmonic stenosis good parenting. But like actually after that. Yeah, she had good parenting after having heart surgery and having improved cardiovascular act like activity. Like basically she went through a growth spurt after that. So it kind of made me realize like this does happen with kids, right. And then you can have something that temporarily gets in the way of growth. And you can have like a sort of stunting early or like a delay this velocity dip. But they ultimately get to the right place. So I, you know, I think it is plausible that this is the case. And I think it's interesting. And now we can. Council people. So what's your second study? Okay. My second one was, it was a little bit of the opposite decreased risk of regroup of reduced linear growth among children with atopic dermatitis receiving dipilyamab, a cohort study. So now this is using trinetics. And this included. So it looked at a couple things 745,000 kids 18 and younger. And it asked a couple questions. Do kids with AD end up shorter than kids without AD. And for kids who are who do have AD does do pill you mad rescue them from being shorter. And so they, how did they do that? They had the AD, the non AD cohort they compare those two. Then they looked at a doopy cohort. And then they compared it with this conventional systemic immunomodulator group. And then they looked at patients who run things like met the trexate and cyclosporine. So this is a rapture, spective cohort study propensity score matching adjusted for things like BMI sleep because sleep can impact height. Systemic steroid used lots of stratification when you got that many people you can, you know, stratify into AH sex BMI. They excluded kids who add like Turner syndrome and new N's and all that kind of stuff. So what did they find? So in part one 372,523 people with kids with AD matched the same number without. And the the mean age was 6.7 and in part two, they had 6,124 patients who the doopy cohort was like 3000 and then they are about 3000 each matched. And so they they used this the part two, it was interesting. They used an as started design. And what they said is what we did was we basically took each one. And then we compared them for when they started. So they're like, this is sort of like an attempt to treat methodology that we would use for a randomized controlled trial. But we're doing it in a retrospective way. And I thought that was kind of interesting. I've not seen that done before. And what was the results. So the kids who had AD did have a somewhat higher risk of reduced stature more so in boys and in those who were over six. And then the group was sleep problems in the group who had had like chronic steroid exposure. And when they stratified by BMI and immunosuppressant use the association between AD and lower height remained pretty significant. So, but when they looked at, but however, when they looked within the kids who had had sleep disturbance or within the chlorodicosteric group, it didn't seem to they didn't see a significant association with AD. So what would that suggest? The sleep disturbance is probably
probably really critical to the height. I remember one time a patient saying, kids grow when they sleep and I was like, that doesn't make any sense. And now I actually think it does. Yeah. And so then, so that being said, DuPilliumab was also significantly associated with a lower risk of being under height percentile compared to immunosuppressive. That's a very backwards way of saying, the kids on DuPixent actually got taller. This association was strongest in older children boys, kids with a BMI over 20, so the kids who weren't underweight. And so the DuPi kids were more likely to reach normal height. So I thought that was also interesting. So why does this happen? Persistent inflammation has been suggested to interfere with growth hormone insulin like growth factor one. And, you know, there also, we know that like IL-4 and IL-13 can be, can disrupt condorcite activity and bone growth. And so there has been shown to be, you know, DuPi is associated with markers of increased bone turnover, which is like markers of growth, like bone alkaline phosphatase, which may signal enhanced bone formation. So I thought this was kind of interesting. So, you know, drugs can impact height in kids. We saw sort of saw two different things. Warren Hamon wrote a little commentary on the two papers, which was we can use this to help reassure our parents who are hesitant to put their kids on Acutane. And we can use it to encourage our parents who are hesitant to put their kids on DuPixent. So think we worry about the bad side effects, but we don't necessarily, in terms of DuPixent, think about the risk of not treating. - Right, Ferris, as I was looking at table three, here's what occurred to me. So where it's body height less than the 50th height percentile, only like-- - We're looking at the cohort one, part one, which is AD versus no AD or part two, which is AD with DuPy versus conventional. - Either one. - Okay. - Here's what I don't understand. If it was the 50th percentile of height, shouldn't like 49.9% of people be in that group and they've got like 5% of people. It is impossible that 95% of people were above the 50th height percentile. Right? I looked at this paper several times and it didn't occur to me till just now to think about, to wonder that. Right? - So body height less than the 50th percentile. - Right, but so that should be 49.9% of people should have a body height less than the 50th percentile. Like there's, I just, there's gotta be an explanation. I just don't know what it is. Just, it was kinda like the how 90% of people think they're an above average driver. - Right, right, right. - So that's what I did work that way. - Yeah, so the 25th percentile part makes more sense. - Yes, so like I just don't, like there's gotta be an explanation. And I didn't think about it till I looked at this. - Yeah, I was focusing more on the - The difference. - ratio and the difference. All right, I'm gonna figure it out while you guys do your other papers. - All right. - But there have to be an answer to this. - Yes. - All right, Pat, what do you got? - All right, my first six pack paper from October 2025, Jamaderm, entitled, Transcutaneous or Rikular Vegas Nerve Stimulation Treatment for Arithmeto, Telegangec, Tatic Rosacia by Lee at all. If I've ever heard of Transcutaneous Vegas Nerve Stimulation as a Treatment for Rosacia, I don't remember it. - So, but ETT Rosacia is really hard to treat. It's like maybe we try some topicals and refer to a laser specialist. So if there's another potential option, that would be great. This was a single center randomized double blind sham controlled trial patients were 18 and older. ETT Rosacia graded in six months, severity of two or more out of a scale of zero to four. Half the patients received Trans or Rikular VNS, that's Vegas Nerve Stimulation. 30 Hertz pulse widths of 200 microseconds. I don't know what any of that means. 30 minutes per day for three weeks. So time consuming, but you're just kind of sitting there with this thing to zap in your head. Follow-ups were carried out for another 24 weeks. So a bunch of assessments were done weekly during the active treatment and then it weeks 15 and 27. Primary outcome was something called ACEA score, which was statistically, significantly better in the active treatment group at week three and it remains statistically, significantly better at weeks 15 and 27. I don't really know the CEA, like is that a clinically significant difference? I don't know, I've never done a rosaceous study. There's no photos anywhere in the paper or in the supplements. So it's hard to discern what these numbers mean. All the other measures were better in the active treatment arm PSA, GFSS, GAD7, PHQ9, blah, blah, blah. Figure two has some line graphs that to pick some of the data. Figure E and F compare the proportion of change and CEA between the two treatments. And I mean, it's way better for the vague snourst simulation. Cost of these devices varies. Two of the more prominent companies that sell these products online, Vagustim, probably saying that wrong, 300 bucks, TruVaga, 500 bucks. There was a review of these devices, found the cheapest one to be what's called the pulsetto light unit, 278 bucks. So I mean, one study, and I don't know what these numbers mean, but it's really hard to treat. And I think I may kind of mention it to my sort of red, fleshy rosaceous patients. I'm 100% on board here. So there's-- so first for-- as somebody who's interested in anxiety treatment, in particular, I've looked at these before. So basically, the idea here is there's now for anxiety, at least. There's now a general-- some consensus that anxiety disorders often a parasympathetic sympathetic imbalance where people get a sympathetic response to stuff they shouldn't. And so by stimulating the vagus nerve, you're upregulating people's parasympathetic nervous system, which then changes these body sensations to people interpret as anxiety. So there's really good data around vagal nerve stimulation for various things. And there's now even some four vagus nerve stimulation for rheumatoid arthritis and psoriatic arthritis. It may have some real immunologic effect. I was surprised that it worked for rosacea because I kind of would have pictured this as being more related to cranial nerves, which I don't think of as particularly vagal responsive. But the results were impressive. Like it was like-- It was an impressive change-- Yeah, impressive change in numbers. But on a zero to four-- I agree with you. I don't know what the CEA is either. So I put on a zero to four scale. If you go from a three to a one, that sounds pretty damn good. Yeah, and like starting off, nobody was at zero and decent percentage of patients. And actually, after treatment was stopped. So at like week three, you had a percentage of patients that went all the way to a CEA of zero. And then without any other additional treatments, by week 15 and by week 27, even higher percentage of patients reached out. I mean, right, and everybody starting had to be greater than two. So if you've patients going from two to zero, like woo-hoo. Yeah, in 278 bucks is not like a lot. Like more than a capillus with some of the things for hair helmet. Maybe with a hair helmet? Yeah. Where a hair helmet, my vagus nerve stimulation, I look like Frankenstein going to bed. Pretty sweet. I like it. I like it. It is just the-- it's just the erythema that it changes. Yeah, this was ETT specific. And you know, there were exclusion criteria. So like, papules and postures, it was-- I don't-- I think that excluded patients. I'm pretty sure. And I think in this study, they used a prescription only one that's like $600 a month, you have to rent it or something. I don't think that is an OTC one. I was trying to find the device. I mean, they gave-- it was like a serial number thing that they gave. And I tried to look it up. But-- All the websites were in Chinese. Yeah, you're right. I'm thinking about the rheumatoid arthritis one that I saw. That was the $600 prescription one. Yeah. As Matt was saying, these are marketed for more-- like right now, it seems more psychiatric, like, helping you sleep, anxiety, things like that. So this is maybe a new application, anti-inflammatory, neuroimmune modulation. There was somebody who's-- again, been to lots of anxiety workshops. This is why they think that Oming works. Oming, because the vibration of the oom.
stimulates your vagus nerve in your neck. And so that's where they think the oaming helps. It's why it's not like he and said is, oh, there we go. All right. All right. Moving on to mine. Sorry. All right. So first one was just a-- I'm always looking for cheap safe supplements that do stuff. So effectiveness and safety of oral and acetylcystine in combination with narrow band UVB, phototherapy, compared with narrow band UVB, phototherapy alone, a pilot study. So this was a randomized blinded, blah, blah, blah. It was a very small study, only 16 patients ate in each group. But they did show a meaningful difference in how well people responded to the phototherapy, whenever they added the an acetylcystine on. It wasn't like a huge difference, but it was a difference. Now, I'll also say I think they used doses of an acetylcystine that were too low. So they used 600 milligrams twice a day. You should be using at least 1200 milligrams twice a day. But we've got-- there was that data a few years ago of an acetylcystine helping with trecatelomania. There's been some data since then. Psychiatrist now actually routinely recommend an acetylcystine for obsessive compulsive disorder and anxiety. So an acetylcystine does something. And I'm just going to-- because I don't think you actually said what disease they were studying. It's a lot of-- I didn't think I'd go in the name-- We did, OK. Yes. I said it very quickly. Sorry. So the-- maybe the other thing that there's been a study for an acetylcystine for. So it, right, is what you give people who have Tylenol overdoses. So it's hepatoprotective. And there have been some studies that, especially in women. It was worked in women, but not in men. They did a randomized controlled trial of taking an acetylcystine before you went out drinking. And the people who took the anacetylcystine had less of a hangover than the people who did not take the anacetylcystine. And I would bet $1,000 you tested this on yourself. I have a big bottle of an acetylcystine in home that is correct. For all your own conclusions. How did I know? But the other one is dihydromyocetin. That is also a hangover prevention in clinical trials. I didn't know that. Have I told you guys that I tested disulfuram on myself? So-- Yes. Yeah. So I gave-- put myself on disulfuram. And then slowly, I took one sip of wine, OK, one night. I felt OK. At about a half a glass of wine, I started to get hives and full feeling in a cough in my throat. So it took me about a half a glass of wine before the disulfuram really caused any noticeable symptoms. That was just another experiment. Thank you for sharing that. Yeah. Yeah. Self-perimentation. All right. So next study that I did, this one really interesting. So title of this optimized combination, isotretinone in conjunction with oral tranacxamic acid for the treatment of modern severe acne and vulgarish. Randomized, I'm going to be a little-- I have no idea what made somebody decide to-- hey, maybe we should put together isotretinone and tranacxamic acid. But the study, 72 patients, 60 of them completed. It was kind of a weird isotretinone regimen, 20 milligrams a day for 12 weeks, and then randomized to receive either 250 milligrams BID of tranacxamic acid or placebo. Big difference. So 90% reduction in inflammatory lesions at 12 weeks, 82% of the people who got the tranacxamic acid and isotretinone versus 30% who only got the isotretinone. Two great improvements, 73% in the combo group, 30% in the isotretinone alone, better trans-referred water loss, better hydration, post-inflammatory erythema improved more, post-inflammatory hyperapigmentation improved more, there was less itching burning and dryness, and at 24 weeks there were zero relapses in the tranacxamic acid group versus 19% of the people in the isotretinone group. Now, several problems with this study, the biggest being that like who treats acne with 20 milligrams of isotretinone for 12 weeks, like nobody. So if this would matter with a normal full course of isotretinone, don't know, but it was a big difference the efficacy. So-- Did you say the dose? The dose of tranacxamic acid, they did 250 milligrams twice a day. And isotretin-- same kind of doses that have been used for malasma, but the isotretinone dosing was low, which was weird. But like-- so this might for somebody that you want to do really low dose, maybe, would have some efficacy. And then just another paper to kind of go along with this one. Obviously, the thing we all worry about with tranacxamic acid is there a risk for thrombosis. So this next one was an example of a terrible, terrible, terrible study, a trinetic study, oral tranacxamic acid used for malasma is not associated with thromboembolism, findings from a multi-centered propensity square mass electronic health record cohort. I think that the people who did this study didn't actually understand how trinetics works. And I don't think the reviewers from the journal understood either, which is why I say this is a terrible, terrible study. So the reason I say this, in this study, when you look at it, there were lots of people who had-- there were lots of groups that had 10 events. And then they reported like, well, 1.6% of people, there were 10 events out of 628 people. In trinetics, if there are less than 10 events, they say 10. So you don't know if it was-- so you know if there's 0, and you know if there's 11, but between 0 and 10, it could be 1 or it could be 10. You do not know. And so all of the statistics that they did, you don't know because they apparently didn't know this because they treated it as if there were 10 events in all of these groups. So the only one that was, I think, remotely usable because it was the only one where there were more than 10 people in both groups was the diagnostic testing for thrombosis. So how many people got a Doppler or something? And it was equal numbers in the two groups. So 21 out of 500 and some people got a Doppler in the trinacemic acid group. And 21 out of 582 got a Doppler in the no trinacemic acid group. Otherwise, there was not a single group that I thought was anything comparable in because every other group had at least one of the two groups had 10 people in it, which could have been 1 or could have been 10. So an example of a really poorly done trinetic study, but the little bit of data that it did give us that there were no additional people tested for thrombosis that was useful for trinacemic acidity stuff, which I do now think of as standard of care for malasmus. Trinacemic acid and iron oxide containing sunscreen, being the two things. Those were the two I had. I just haven't been able to get anyone on it because I think I totally freaked them out. Because I'm a little freaked out, probably inappropriately about blood clots. And so I'm like, oh, they use this thing to clot the blood. So you might get a blood clot, but do you want to do it? They use it at 10 times the dose. I know. I know that, but I'm not, so I'm not selling it. I'm not making it sexy. I need to work on my spiel. You got it. Yeah, you got to work on your spiel pattern. That's a big. You got it, Far? No. I have had the same thing. I've tried twice to get people in. I'm like, it's really safe. Other than maybe a risk of blood clots, it's probably not going to happen. And then they're like, I don't want that. Yeah. I got to listen to somebody who sells it better. So my spiel is this. Oh, there's this medication. It's biflar. The most effective treatment we've got for malasmus. Now, it's a weird medication that's usually used for helping to get people's blood to clot more. But we're going to use it in 90% lower dose than is normally used. So like 10 times less. And with that dose, there has been no evidence at all suggesting that it affects how your blood clots. Now, I can't tell you 100%. There's definitely not any risk. But the data has been like, we really don't think there's any risk. That's my spiel. And if that was recorded and they got a blood clot and it got played in court, I'd be like, yeah, I stand behind what I said. Like, there isn't any evidence. But I didn't tell them that there was no risk. I told them as far as I can tell, there's no risk. Blood clots happen. Right. Blood clots happen to people, right? All right. Let's go. Ferris, what do you got for? I'm going to go back. I figured out the answer to your question about why is it less than 50% of people? Why shouldn't, why isn't it that? She's been ignoring us for the last 20 minutes. So like, I've been trying to figure it out, but I got there. All right. What is it? I've listened a little bit. I've learned things. I might be getting a vagal nerve stimulator for my rosacea. I feel like this has been a productive podcast for me. OK. So it might also help me be nicer to everybody too. So there's a lot of good things that come off. Very little downside. Yeah, exactly. What could go?
wrong. Okay, the reason is, trynetics does not say, here is this kid's height. What it says is you're looking at, did you have a visit that was coded as being less than the 50th percent of the night, less than the 25th? Okay. So, does that make sense? Yes. So it did, did you have that coded as an event? So most kids don't have any panic coding, but you are more likely to, less likely to have that coded if you are on dupexen. Okay, so that is like parents come in. I think my kids too short. Actually, they're at the 48th percentile, but you're still going to document that like they were below the 50th. Okay. That makes sense. Yep. So there you go. I've answered it. Okay. My next paper is about HS efficacy and safety of ruxilitinib cream and patients with mild and moderate hydranide separative results from a randomized double-blind vehicle controlled phase two study. So kind of cool that we have a topical study and high-alt moderate. Absolutely. Yes. I've been dying to see this data because it like I could imagine it working great. I could imagine it not working very well at all. Well, you're going to see that the answer might be something in between. So this is Martina Porter at all. Okay. So this is phase two study this is patients who had or adults with early stage one or two. So like three to ten abscesses or inflammatory nodules, but no draining tunnels less than 20% of their BSA involved. I don't usually think of HSA HS and BSA, but that is what they did. But if you think about it, it's partly the indication for using obsular on the skin. And just in FYI, either I'm doing the phase three for this. And that's exactly what it is. Their FDA was concerned about we're putting it in included areas. And so they didn't want to like give people so much that they got systemic levels. Gotcha. Okay. Good. And then patients 50% got 1.5% ruxilin of creve 50% got vehicle cream, BID for 16 weeks. Everybody crosses over to open label rucks as needed through week 32. And so the primary outcome was changed, was changed and combined that what they call the AN, which is abscess and inflammatory nodule count at week 16. Okay. So 16, this is pretty small study. 69 patients randomized. Media and age was 29, mostly women. And so and what did so starting with that primary endpoint at 16 weeks, the mean AN count dropped by 3.6 and the rux group versus 2.42 for the vehicle group. So a greater drop in the number of inflammatory nodules in the rux group. Okay. Then they also looked at milestone reductions as secondary endpoints. I think these are kind of more interesting, helpful. So they said what percentage of people had a 50% or greater drop in their AN count. And it was 79% and the rux group 50% 56% in the vehicle. If they looked at a 75% reduction, it was 54% versus 25% and for that really high 90 to 100, it was 21% and the rux group 12% in the vehicle group. So kind of roughly twice as many patients hit each milestone with ruxilin than with vehicles. So it does something. It does do something. So they also looked at pain in itching scores, which you know, pain with Hs. Yes, itch. Do I think of that as a huge thing? But everybody had to have an pain or itch NRS of at least one to get in the study. The average was about four. There was no statistically significant difference in those scores. Okay. They looked at high score 50. More patients with ruxilin than vehicle achieved that like 79 versus 50% at week 16. And high score, they saw similar trends for high score 75, which was 54% versus 25% at week 16. So, you know, safety, good, you know, well tolerated, no grade three treatment related adverse events, no injection minimal injection site. And then they did look at plasma levels, which I thought was sort of interesting. So the mean steady, steady state trough of the concentration was 19.5 nanomolar. So what does that mean? The threshold for myelose suppression is 281 nanomolar, so like greater than 10 fold higher. And even like the peak that they saw was 153, which still doesn't hit that. So, you know, not being worried with the inter-trijianist, you know, area about myelose suppression. So, you know, low sample size, interesting. You know, the average baseline, AN count was 5.4, which is actually greater than like usually the minimum AN count to go into a moderate to severe biologic study for Hs. 5. So these patients didn't, you know, like they were, they fit, they didn't have the drain, they didn't have the tunnels, they were early stage one or two, but they did have, you know, a high-ish AN count and something comparable to what would get you into your app. Like some of these patients could have gotten into a biologic study. Yeah, this seems like it will be an ideal treatment for people who like get two or three to time, you know, and sometimes don't have any, and it can be like, okay, the second you feel one coming on, start putting this on, that's going to be the really, it's a shame they couldn't do it that way because I'm sure the FDA would not allow such a study, but to just have it be PRN, whatever you get one. Well, it was, if once you switched over, week 16 to 32 was more like using it as needed. Okay. So, you know, so I think it's going to be interesting. I mean, the million dollar question in Hs is, is there a therapy that we started early and we prevent the late stage scarring and tissue remodeling? Because once you have that, you can have the best drug in the world, but you're never going to like have zero disease activity because you got follicular trapping blah blah blah. So, yeah, this could really be something that again, if insurance companies had to have a ounce of intelligence could save them a ton of money if like, you put people on this early and they never ended up going on Humira or, you know, Cossentics or Bim Delic, whatever. Maybe cheaper than, you know, that might be true. Putting that out there, but yes, you're right. Well, but as we're about to find out from Dr. Patton, I think those biosiblers may not be all there. Correct. That to be Dr. Patton. What do you got? They may not. You are correct. Are my second six pack October, 2020, 25 edition of JAD International. It was titled "Originator vs. Biosimilar at a Limonab." By the way, I'd prefer that to be pronounced JAD International now. But then it would be spelled with a C, International. Okay. Fine. Going international. Fine. Biosimilar at a Limonab in Hydro-Edenitis Subroutiva." A multi-center real world analysis of clinical response maintenance of response and switching and wise by Aghajani at all. Retrospective study, 3HS clinics in Australia. First, cohort bio-neighe patients, biosimilar versus originator. Was there a different synephycocase second cohort patients who were switched from originator to biosimilar at week 16 after achieving response and that response, I'm almost positive with the high score 50. So these patients were matched with, so the crossover people, better the switchers, let's call them, these patients were matched with patients who remained on originator. First cohort, 313 patients, 186 on originator 127 on biosimilar. Week 16, not huge differences in high score 50, 75, IHS 455 scores between the two groups, but at week 52, originator was statistically significantly more effective using those three measures. So there's a retrospective study, so take that. A lot. Like a lot. Wow. Yeah, so I mean, if you wanted to go through numbers, well, yeah, I think I talked about that a letter. Let's see, also difference in loss of response between the two groups. So median time to loss response was 100 weeks in the originator versus 52 weeks in the biosimilar group. I mean, that's just a big difference. Wow. In the switchers, median, the median time to loss a response, 87 weeks in the patients who were remained on originator versus 50 weeks for the switchers. You know, we looked at that other European study. It was like three big databases in Spain and Germany and something. And it seemed that perceived differences in adalimumab effectiveness was more of a no-cebo effect. That was for psoriasis, right? No difference in actual efficacy, but a perceived difference because patients feel like they're getting an inferior product in the biosimilar. You know, the authors say no-cebo could still be playing a role, but in those differences are so big that maybe there is a true efficacy difference. It would be odd, but maybe.
I wish I knew of someone in the world who could like really talk about are the biosimilars actually like to say him like is there is there a theoretical explanation for this or they do you I don't yeah if any of our listeners are like the biosimilar experts and can speak to this I would love email me uh uh Matt Dodds
[email protected] Matt Dodds
[email protected] because I would love to talk about this because I don't know I just it seems like it should work the same but I could also imagine like if your process isn't quite right maybe the protein isn't quite folded right and that's more immunogenic or whatever like I just don't know fairs what do you think yeah I don't know I mean I've always been uh you know having done like biosimilar studies without a limb of map like you know the data and insurisists like the data are pretty good insurisists that if people don't know they're switching they and they don't know what they're on it it's like perfect so this is really a big difference um did they have like a and do we know like how many different biosimilars were in here I didn't miss that part with like it's in the supplementary material and every none of the links worked on any of the papers that I had that that information they said was in supplementary materials I couldn't get any of the links to work so okay yeah so we don't know if it's like oh they all had one and uh you know they had multiple I mean they at least said that they said there were multiple different biosimilars um right so okay okay yeah that one biosimilar I want to say like last month that it got FDA approved for pediatric HS down to age 12 which apparently like they had to do I was reading something about it where you know once once a biosimilar gets approved for psoriasis you could use it in anything so if you have an adult uh they got the biosimilars got approved for psoriasis but you could use it for any indication because of the one indication that it was studied it in okay pediatric apparently that's not like you actually do have to do a little bit more it's not it's not a clinical trial right I mean the biosimilar didn't go through a clinical trial and versus the originator but they did enough bioavailability and things like that they were like yes okay we are going to allow you to approve this for pediatric so I believe that was you know what I don't know what it was syltesio simlandi simlandi oh well simlandi well of course yeah yeah yeah I don't even know um so yeah kind of interesting I mechanistically doesn't make a whole lot of sense it was retrospective right so maybe it was something as simple as a patient got switched on on to the biosimilar and was like ah they're giving me this crap drug I'm not using it anymore yeah but the biosimilar the ones who started on a biosimilar like yeah oh yeah no right so that would be the switchers but maybe they did the same thing for the biosimilars like hey this isn't what's on the commercial I'm not using it okay yeah I mean that the multiple you could imagine maybe like you would make I mean it what would be interesting is if they looked at because they didn't look at like serum you know peak or trough or anti drug antibodies right like those are the things that would be really helpful to understand looking at these patients it was a short paper but I think it raised an interesting question and maybe that's the next step as somebody does a head to head yeah yeah because we've I'd have seen articles where drug levels are pretty predictive of at a limb and ab responsiveness in H.S. then we we talked about that somewhere with somebody that like if you look at non-responders their drug levels are generally lower and yeah it was like a Canadian study yeah because because they didn't have any other drug I don't I don't know if been beeny or cosentics are approved up there so it's like once once out of lime maps stops working they needed different plans so they were looking at levels and could they increase the dose and yeah okay I don't remember the paper at all but I'll go back and watch the episode okay it's what's great about these episodes hmm listen to yourself over and over again it's in the archives yeah all right here by here my last two so first uh ones I don't remember what study made me do this but I did kind of a deep dive into the question of right when you're looking at these long term oh I know what study it was it was a two-year follow-up study of some AD thing for long term whatever and it was like oh at three years and you know X percent of people using a Markov chain multiple imutation bootstrapping chain equation model like we just very representative of right so I was like this always sounds like baloney to me so I did a deep dive uh and found a couple of articles one called attrition bias so the question is all of those models like whenever there's like okay we have this long term study we started with 500 people three years later there were like 82 left and 90% of them were doing great but based on all of the modeling that 90% that really is 90% of people would do great based on all of our modeling it doesn't matter if everybody dropped out and I've always been like that sounds like such baloney but the statistic people hold no no no this modeling and the blah blah blah and they use all these confused so I did a deep dive and so attrition bias related to missing outcome data longitudinal simulation study and addressing missing outcome data and randomized controlled trials and methodological scoping review and all of these different Markov chain multiple imputation pattern mixture models mixed effect models expectation maximization algorithms Rubens rules for combining imputed data sets the heckman selection model the Kaplan Meyer Cox pH for dropout modeling the uh all of this beloved right what did it show literally all of them totally worthless the only way they are ever useful is if people dropped out at random so they they cause so there's missing at random and then there's missing not at random now if they're missing not at random because like people who are over the age of 40 were more likely to drop out they can fix for that what they cannot fix for if people who don't do as well on the drug are more likely to drop out which is anybody who does clinical trials knows that is the case right somebody who's like not doing great way more likely to drop out they there's zero ability to fix for that at all like none no matter what model they use it is literally impossible to correct for that and so every statistician every you know stats KOL expert who's ever total total bullshit complete bullshit if people are more likely to drop out because the drug didn't work as well cannot correct for that totally impossible it's all you can say is if and especially when they were modified NRI we didn't NRI it's a modified and a bullshit it's not a modified it it's totally meaningless the only two things you can look at true NRI you assume that everybody who dropped out failed as observed you just look at you know of the 80 people left how many were doing good the real number is somewhere between there nobody can make up anything more than that all those statisticians have gotten paid trillions of dollars to try and and trick us into thinking they can't so a little bit of a soap box there just a little bit yeah a little bit man yeah that's what you want to keep that is decisions on drugs that podcast instead that was like that movie network when he was mad as hell and he wasn't going to take it anymore this is mad as hell moment that's it all right you can't run so don't there's statistics lies lies and damn lies they all just they're making it up all right so that was number one the number two is another example of the world of medicine completely failing patients like failing it horrendously all right so you remember a few years ago it came out about the Brazilian blowouts head from out of hide in them and there was like this big whoop did a whoop of whatever will it turns out that what they replaced the from out of hide with is probably much worse so there are now a bunch of reports of people getting acute kidney injury like going to the ER like they're not peeing their kidneys like got horribly whacked and it turns out it is directly related to keratin treatments so these replacements for the old Brazilian blowouts with it that are from out when they made them from out of hide free they actually turned them into they a lot of what they had it was an ingredient called glyoxylic acid G-L-Y-O-X-Y-L-I-C an example of these products sezon classic keratin smoothing treatment carousel smoothing lotion oxo organic hair straightening system phenolous smoothing liquid
Gussie at home, keratin treatment. The problem is this glyoxylic acid, if even one percent of it gets absorbed into your scalp, it can cause kidney damage. And so at worst, so there are like 30 reports in a literature now of severe kidney damage from this, but it is very likely that almost everybody who uses any of these gets a little bit of absorption, and then the glyoxylic acid gets converted into oxalate, which calcium oxalate is both what causes kidney stones and can cause direct kidney injury. So that probably, I don't wanna say probably, there it is possible that everybody who gets one of these keratin treatments to make your hair shiny or you're in smoother is getting mild kidney damage that can be cumulative and is increasing their risk of getting calcium oxalate kidney stones. So like, Lori Al has completely, they won't use this stuff like because of this, but all of these other companies are putting this in there and nobody is sounding the alarm in the world of medicine. Like, Warren Haiman did do a commentary when this first came out, but it was only talking about the acute kidney injury, and now they are much more thinking that there's gonna be long-term effects from this of people, and especially for us as germs, it's especially an issue in like 40% of the people reported with acute kidney injury, they had scalp rashes. So if you've got impaired, if you've got sub-derm psoriasis, anything, and then you use this, you get increased absorption. So like, we should now be telling all of our hair, you know, scalp sub-derm psoriasis, scalp anything. Hey, if you get any keratin treatments or smoothing treatments or hair straightening, you gotta make sure it doesn't have this glyoxylic acid in it because it could whack your kidneys. And like, this is just not out there. Like, people are not talking about this. - These are in, these are at-home things, not like you go to the salon and-- - There are both. So they are both-- - Okay. - So the both were associated. - Yeah, well, the most of them have been salon ones, but there's no regulation that says you can't sell them for at-home, and there are now at-home products for it. And you know, the manufacturers recommend, don't get it on the scalp, don't get it on the centimeter of hair closest to your scalp. So if done perfectly and correctly, there may be, but the thing is, it only takes 1% of it to get absorbed for it to have like 10 times more than your kidney's ability to excrete, oxalate safely. So it's like a significant thing. I've been emailing some of the nephrologists who have published on this, but nobody has gotten back to me yet, to like, this is nuts. Like it, 'cause who would, you know, somebody goes to their PCP, gets annual, you know, CMP and their creatinines 1.7. Is their PCP gonna, oh, do you get keratin treatments? Like, no, nobody's, or do they get a kid, do you get keratin treatments? No, nobody knows to ask that, right? But it's, I think it's probably gonna turn out to be a big deal. So again, glyoxylic acid, not glycolyc, they have studied glycolyc, 'cause a lot of them have glycolyc, glycolyc acid is fine. It's only glyoxylic acid in these keratin or smoothing treatments, highly nephrotoxic, highly, highly nephrotoxic. So that's it. Anything. - Awesome. - Yeah, that's saving lives here. We're saving lives. - All right. - We're saving lives. All right. - I've always had silky smooth hair. I'm just blessed. I'm just blessed. I don't have much of it. - It's very, yes. It does look good today. It looks good today. All right, I wanna thank everybody for joining us this week. Hope you learned the thing or two. Hope you laughed once or twice, but mostly I hope you're planning on joining us again next week. Until then, I'm Matt Zyrus. - I'm Tim Patton. - And I'm Laura Ferris and we are Derms on drugs.
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