← Derms on Drugs
Loading summary
Transcript157 lines
- [00:02]
A
Welcome to season two of Derms on Drugs, a video podcast brought to you by Scholars in Medicine. The best education platform in dermatology and provided no cost to medical providers. Derms on Drugs is where cutting edge derm meets hit or miss comedy. I'm Matt Ziers from Docs Dermatology and each week I'm joined by my residency buddies, Dr. Laura Faris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh, where we use our 60 years of combined DERP experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of derb and you'll actually have some fun listening. New episodes drop every Friday on Scholarship Medicine, Apple Podcasts, Spotify and other major podcast platforms, and reminder to everybody that there is a video component that has some of the key figures and tables 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?
- [00:53]
B
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 in 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 the first paper was in the jad. It was the effect of isotretinoin treatment for acne Bulgaris on height in adolescence. A retrospective cohort study using the Rochester Epidemiology Project. This is Ju et al. It's 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.
- [01:44]
C
I don't know how to say either one is probably okay.
- [01:47]
B
Okay, good. Epiphyseal closure in kids who are on high doses of isotretinoin. And this is generally not like the course of for acne. This is like neuroblastoma or ichthyosis. So in this study they looked at the Mayo Clinics like records link database, which is called the Rochester Epidemiology product. Is this in the famous Olmsted 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, 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, the rate of height gain. So they called that a velocity dip. But when it comes to adult height, it didn't matter. So, so the mean difference in final heights between the group was 0,67 cm, which was not statistically significant. There was no dose response. Just, you know, basically you might have this like little pause at starting in, in growth, but everybody makes it to the same height as an adult whether or not they used isotretinoin.
- [03:10]
A
So I'm not sure I buy that that outcome, like that was clearly what they want the outcome to be. And I think what all 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 the people in isotretino 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 intruder.
- [03:42]
B
It was, it was half a centimeter 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 in shorter courses. Right. So this may be a true issue in ichthyosis or retinoblastoma, 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 kid's 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 catch up period.
- [04:44]
A
So I'm, I'm still not convinced the, the figures that they had in there, figure one and figure two, those violin plots. Yeah, yeah, the violin plots. I've been 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 isotretino might make Their kids shorter because. 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 any. Doesn't make people any shorter. We should put everybody on Accutane. That's what I'm going. That's. That's my final answer.
- [05:35]
B
All right.
- [05:36]
C
Roundabout way of getting there, but yeah.
- [05:38]
B
I'm glad that you brought yourself.
- [05:40]
A
Zero.
- [05:41]
C
Zero concerns about. Zero concerns about height and Accutane.
- [05:45]
A
All right, all right, all right.
- [05:47]
B
And 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 a. What did she have? P. Good parenting. But, like, actually she had good parenting after having heart surgery and having improved cardiovascular, 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? 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. I think it is plausible that this is the case, and I think it's interesting. And now we can counsel people.
- [06:43]
A
All right, what. What's your second study?
- [06:45]
B
Okay, my second one was. Was a little bit of the opposite. Decreased risk of regre. Of reduced linear growth among children with atopic dermatitis receiving dupilumab. A co. 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, you know, a couple questions. Do kids with AD end up shorter than kids without ad? And for kids who are. Who do have ad, does dupilumab rescue them from being shorter? And so they. How did they do that? They had the ad, the non AD cohort. They compared those two. Then they looked at a. A doopie cohort, and then they compared it with this conventional systemic immunomodulator group. They know patients are on things like methotrexate and cyclosporine. So this is a retrospective cohort study. Propensity score matching adjusted for things like bmi, sleep, because sleep can impact height, systemic steroid use, lots of stratification. When you've got that many people, you can, you know, stratify into age, sex, bmi. They excluded kids who had, like, Turner syndrome and Noonan's and all that kind of stuff. Okay, so what did they find? So in part one, 372,523 people with kids with AD matched to the same number without. And the, the mean age was six months. And in part two, they had 6,124 patients who, the, the DUPY cohort was like 3,000 and then they are about 3,000 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. So I thought that was kind of interesting. I've not seen that done before. And what was the result? 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 in the group with 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 corticosteroid 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 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, dilumab was, was also significantly associated with a lower risk of being under height percentile compared to immunosuppressives. That's a very back way of saying the kids on dupixent actually got taller. It, this association was strongest in older children, boys, kids with a BMI over 20. So the kids who like weren't underweight and so the doopy kids were more likely to reach normal height. So I thought that was also interesting. So you know, why does this happen? Persistent inflammation has been suggested to interfere with growth hormone insulin, like growth factor one. And you know, they're also, we know that like IL4 and IL13 can be, can disrupt chondrocyte activity and bone growth. And so there has been shown to be, you know, DUPY 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 in, you know, drugs can impact height in kids. We saw, sort of saw two different things. Warren Heyman 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 Accutane, and we can use it to encourage our parents to. Who are hesitant to put their kids on dupixent. So I think we worry about the bad side effects, but we don't necessarily, in terms of dupixent, think about the risk of not treating.
- [12:03]
C
Right.
- [12:03]
A
Fair. As I was looking at table three.
- [12:09]
B
Yes.
- [12:09]
A
Here's what occurred to me. So where it's body height less than the 50th height percentile, only, like looking.
- [12:18]
B
At the cohort one, part one, which is AD versus no AD, or part two, which is AD with doopie versus conventionals.
- [12:26]
A
Either one. Okay, here's. 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.
- [12:56]
C
Right.
- [12:56]
B
So it's body height less than the 50th percentile.
- [13:01]
A
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. I. There's got to be an explanation. I just don't know what it is. Just it. It was kind of like the. How 90% of people think they're an above average driver, like.
- [13:19]
B
Right, right, right.
- [13:20]
A
That work that way?
- [13:23]
B
Yeah. So the 25th percentile part makes more sense.
- [13:30]
A
Yes. So I, like, I just don't. Like, there's got to be an explanation. I just don't know what it is. And I did. I didn't think about it until I, you know, looked at this.
- [13:40]
B
Yeah, I was focusing more on the difference ratio and the difference. All right, I'm gonna figure it out while you guys do your other papers.
- [13:49]
C
All right.
- [13:49]
B
But there has to be an answer to this.
- [13:51]
A
I agree. All right, Patton, what do you got?
- [13:54]
C
All right. My first six pack paper from October 2025, Jamaderm, entitled Transcutaneous Auricular Vagus Nerve Stimulation treatment for. For erythematotelangectatic rosacea by Lee et al. If I've ever heard of transcutaneous vagus nerve stimulation as a treatment for rosacea, I don't remember it. Nope. But ETT rosacea 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 rosacea greater than six months, severity of two or more. Out of a scale of zero to four, half the patients received trans auricular VNs. That's vase nerve stimulation. 30 hertz, pulse width 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 zapping 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 at weeks 15 and 27, primary outcome was something called a CEA score, which was statistically significantly better in the active treatment group at week three. And it remained 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 rosacea 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, PHQ, Q9, blah blah blah. Figure 2 has some line graphs that depict some of the data. Figures E and F compare the proportion of change in CEA between the two treatments. And I mean it's like way better for the vagus nerve stimulation. 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 rosacea patients.
- [16:21]
A
I'm a hundred percent on board here. So there's so first for, for. So as somebody who's interested in like 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 disorder is 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 up regulating people's parasympathetic nervous system, which then changes these body sensations that people interpret as anxiety. So and there's like really good data around vagal nerve stimulation for various things. And there's now even some for vagus nerve stimulation for like rheumatoid arthritis and psoriatic arthritis. Like it, it may have some real immunologic effects. I was surprised that it worked for rosacea because I kind of like would picture this as being more related to like cranial nerves, which I don't think of is particularly vagal responsive. But like the results were impressive. Like it was like there wasn't change.
- [17:39]
C
Yeah, impressive change in numbers.
- [17:42]
A
But on his, on a zero to four scale, I agree with you. I don't know what the CEA is either. So I. But on a 0 to 4 scale, if you go from a 3 to a 1, that sounds pretty damn good.
- [17:54]
C
Yeah. And like starting off, Nobody was at 0 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 0. And then without any other additional treatments by week 15 and by week 27, even higher percentage of patients reach. I mean. Right. And everybody starting had to be greater than two. So if you have patients going from two to zero, like woohoo.
- [18:24]
A
Yeah, I'm in. 278 bucks is not like a lot.
- [18:30]
C
Cheaper than a capitalist.
- [18:35]
A
The hair helmet maybe.
- [18:37]
C
I got a hair helmet. Yeah, I wear a hair helmet. My vagus nerve stimulation, I look like Frankenstein. I'm going to bed. It's pretty sweet.
- [18:46]
A
I like it, I like it.
- [18:47]
B
And is it just the air? It's just the erythema that it changes?
- [18:51]
C
Yeah. This was ETT specific and you know, there were exclusion criteria. So like papules and pustules. It was, I don't, I think that like excluded patients. I'm pretty sure.
- [19:02]
A
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 they used an OTC one.
- [19:13]
C
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.
- [19:21]
A
Yeah, you're right. I'm thinking about the rheumatoid arthritis one that I saw. That was the 600 prescription one.
- [19:28]
C
Yeah. And just right 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.
- [19:46]
A
So as somebody who's. Who's again been to lots of anxiety workshops, this is why they think that oming works. Because the vibration of the OM stimulates your vagus nerve in your neck. And so that's where they think the oming helps. It's why it's not like he. Instead is. There you go. All right, all right. Moving on to mine.
- [20:20]
B
Sorry.
- [20:21]
A
All right. So first one was just. I'm always looking for cheap, safe supplements that do stuff. So. Effectiveness and safety of oral and acetylcysteine, a combination with narrowband UVB phototherapy compared with narrowband UVB phototherapy alone. A pilot study. So this was a, you know, randomized, blinded, blah, blah, blah. It was a very small study, only 16 patients, eight in each group. But they did show a meaningful difference in how well people responded to the phototherapy. Whenever they added the N acetylcysteine on it wasn't like a huge difference, but it was a difference. Now, I'll also say I think they used doses of N acetylcysteine that were too low. So they used 600 milligrams twice a day. You should be using at least 1200 milligrams twice a day. But, you know, we've got. There was that data a few years ago of N acetylcysteine helping with trichotillomania. There's been some data since then. Psychiatrists now actually kind of routinely recommend N acetylcysteine for obsessive compulsive disorder and anxiety. Uh, so acetylcysteine does something. The other thing.
- [21:35]
B
And I'm just gonna. Because I don't think you actually said what disease they were studying.
- [21:39]
C
It's.
- [21:39]
A
I said vitiligo in the.
- [21:40]
B
You did? Okay, yeah, I said it very quickly.
- [21:43]
A
Sorry. So the maybe. Oh, the other thing that there's been a study for an acetylcysteine 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 N acetylcysteine before you went out drinking. And the people who took the N acetylcysteine had less of a hangover than the people who did not take the N acetylcysteine.
- [22:14]
C
And I would bet $1,000 you test this on yourself.
- [22:18]
A
I have a big bottle of N acetylcysteine at home. That is correct.
- [22:23]
B
Draw your own conclusion.
- [22:24]
C
How did I know.
- [22:28]
B
The other one is dihydromyrcitin. That is also a hangover. Prevention in clinical trials. Huh?
- [22:36]
A
I didn't know that. Have I, Have I told you guys that I tested disulfiram on myself?
- [22:43]
C
Yes. Yeah, yeah.
- [22:44]
A
So I gave, put myself on disulfiram and then slowly, like I took one sip of wine. Okay. One night I felt okay. At about a half a glass of wine. I started to get hives and like a full feeling and a cough in my throat. So it took me about a half a glass of wine before the disulfiram really caused any noticeable symptoms. That was just.
- [23:08]
C
Yeah.
- [23:09]
A
Another experiment.
- [23:10]
B
Thank you for sharing that.
- [23:11]
A
Yeah.
- [23:13]
B
All right.
- [23:13]
A
All right. So next study that I, that I did, this one really interesting. So title of this optimized combination isotretinoin in conjunction with oral tranexamic acid for the treatment of moderate severe acne. Vulgarish randomized double emphasis control trial. I have no idea what made somebody decide to, hey, maybe we should put together isotretinoin and tranexamic s. But the study, 72 patients, 60 of them completed, it was kind of a weird isotretinoin regimen. 20 milligrams a day for 12 weeks and then randomized to receive either 250 milligrams bid of tranexamic acid or placebo. Big difference. So 90% reduction in inflammatory lesions at 12 weeks. 82% of the people who got the tranexamic acid and isotretinoin versus 30% who only got the isotretinoin. Two great improvements. 73% in the combo group, 30% in isotretinone alone. Better transepidermal water loss, better hydration. Post inflammatory erythema, improved more. Post inflammatory hyperpigmentation, improved more. There was less itching, burning and dryness. And at 24 weeks, there were zero relapses in the tranexamic 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 it, you know, if this would matter with like a normal full course of isotretinoin. Don't know. But like it was a big difference. The, the, the efficacy. So did you say the dose, the dose of Tranexam at. They did 250mg twice a day and isotret was the right. Same kind of doses that have been used for melasma. But the isotinone 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, some efficacy. And then just another paper to kind of go along with this one. Obviously the thing we all worry about with tranexamic acid is the, is there a risk for thrombosis? So this next one was an example of a terrible, terrible, terrible study. Trinetic study. Oral tranexamic acid use for melasma is not associated with thromboembolism. Findings from a multicenter propensity score match Electronic health record.
- [25:36]
C
Coh.
- [25:37]
A
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, they, 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 because there were 10 events out of 628 people in Trinetics, if there are less than 10 events, they say 10. So there's, 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 you know 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 like a, you know, 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 tranexamic acid group and 21 out of 582 got a doppler in the. No tranexamic Acid group. Otherwise, there was not a single group that I thought was anything comparisonable in, because every other group had. At least one of the Two groups had 10 people in it, which could have been one 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 tranexamic acid stuff, which I do now think of as standard of care for melasma. Tranexamic acid and iron oxide containing sunscreen might be in the two things. Those. Those were the two I had.
- [27:49]
C
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 so you want to do it.
- [28:03]
A
They use it at 10 times the dose.
- [28:07]
C
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.
- [28:14]
A
You got. Yeah, you got to work on your spiel patent. That's a big.
- [28:17]
C
Have you done it?
- [28:18]
B
Fair. No, I. I have had the same thing. I've tried, like, twice to get people in. I'm like, it's really safe, other than maybe, like, a risk of blood clots probably not going to happen. And then they. They're like, I don't want that. Yeah, I got to listen to somebody who sells it better.
- [28:33]
A
So my. My spiel is this. Oh, there's this medication, by far the most effective treatment we've got for melasma. Now, it's a weird medication. It'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 like that. 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.
- [29:19]
C
Blood clots happen, right?
- [29:21]
A
Blood clots happen to people, Right. All right, let's go. Ferris, what do you got for.
- [29:26]
B
I'm gonna go back. I figured out the answer to your question about why is it less than 50% of people. Why should.
- [29:33]
C
Why isn't it that she's been ignoring us for the last 20 minutes?
- [29:36]
B
So, like, I have been trying to figure it out, but I got there.
- [29:39]
A
All right, what is it? What is it?
- [29:40]
B
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. Okay. So it might also help me be nicer to everybody, too. So there's a lot of.
- [29:55]
C
A lot of good things, very little downside.
- [29:59]
B
Yeah, exactly. What could go wrong? Okay, the reason is Trinetics 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 percentile for height less than the 25th. Okay, so got it. Does that make sense?
- [30:23]
A
Yes. So it was.
- [30:24]
B
So it is. Did you have that coded as an event? So most kids don't have any kind of coding, but you are more likely to less likely to have that coded if you are on dupixent.
- [30:35]
A
Okay, so that is like parents come in, but I think my kid's 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.
- [30:46]
B
So there you go. I've answered it. Okay, my next paper is about hs efficacy and safety of ruxolitinib cream in patients with mild to moderate hedrenitis. Separativa results from a randomized, double blind vehicle controlled phase two study. So kind of cool that we have a topical study and mild to moderate obsolete.
- [31:09]
A
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.
- [31:17]
B
Well, you're going to see that the answer might be something in between. So this is Martina Porter et al. Okay, so this is phase two study. This is patients who had 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 Opsler on the skin.
- [31:51]
A
And just as an FYI there, 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 occluded areas. And so they didn't want to like, give people so much that they got systemic levels.
- [32:04]
B
Gotcha. Okay, good. And then patients, 50% got 1.5% ruxolitinib cream, 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 change. Was change. And combined what they call the an, which is abscess and inflammatory nodule count at week six. 16. Okay, so 60. This is pretty small study. 69 patients randomized. Median age was 29, mostly women. And so. And what did. So starting with that primary endpoint at 16 weeks, the mean an count dropped. Dropped by 3.6 in the rocks group versus 2.42 for the vehicle group. So a greater drop in the number of inflammatory nodules in the RU 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 account? And it was 79% in the rucks 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% in the rux group, 12% in the vehicle group. So kind of roughly twice as many patients hit each milestone with ruxolitinib than with vehicles than with the vehicles.
- [33:43]
A
Does something, huh?
- [33:45]
B
It does do something. So they also looked at pain and itching scores, which, you know, pain with hs. Yes, itch. Do I think of that as a huge thing. But everybody had to have a pain or itch NRS of at least 1 to get in the study. The average was about 4. There was no statistically significant difference in those scores. Okay. They looked at high score 50. More patients with ruitinib than vehicle achieved that like 79 versus 50% at week 16. And high score, they saw similar trends for high score, 75, which was 50, 54% versus 25% at week 16. So, you know, safety good, you know, well tolerated, no grade 3 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 stady steady state trough of the concentration was 19.5 nanomar. So what does that mean? The threshold for myelosuppression is 281 nanomolar. So like greater than tenfold 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 intertriginous, you know, area about myelosuppression. So, you know, low sample size. Interesting. You know, the average baseline an count was 5.44, which is actually greater than like usually the, the a minimum an count to go into a moderate to severe biologic study for HSS5. 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 Hurley stage one or two, but they did have, you know, a highish an count and something comparable to what would get you into your app. Like, so some of these patients could have gotten into a biologic study.
- [35:49]
A
Yeah, this seems like it will be an ideal treatment for people who like get two or three at a 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 gonna 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 whenever you get one.
- [36:15]
B
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 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 gonna like have zero disease activity because you got follicular trapping, blah, blah, blah.
- [36:40]
A
So this could, this could really be something that again, if insurance companies had half an 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, Cosentyx or Bimzelics, probably.
- [36:59]
B
Cheaper than, you know, than Opsler at this point.
- [37:02]
A
That might be true.
- [37:03]
B
Putting that out there, but yes, you're right.
- [37:05]
A
Well, but as we're about to find out from Dr. Patton, I think those biosimilars may not be all they're cracked up to be. Dr. Patton, what do you got?
- [37:15]
C
They may not. You are correct, are my second six pack. October 2025 edition of JAD International. It was titled Originator versus Biosimilar Adolimumab.
- [37:27]
A
By the way, I prefer that to be pronounced JAD International.
- [37:33]
C
But then it would be spelled with a C. Internacion. Okay, I'm going international.
- [37:39]
A
Fine.
- [37:40]
C
It was titled Originator versus Biosimilar Adalimumab and Hydradinitis separativa. A multicenter real world analysis of clinical response, maintenance of response and switching and wise by Aghajani et al. Retrospective study, three HS clinics in Australia. First cohort bio naive patients, Biosimilar versus originator. Was there a difference in efficacy? Second cohort patients who were switched from originator to biosimilar at week 16 after achieving response. And that response, I'm almost positive, was a high score 50. So these patients were matched with. So the, the crossover people or 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. This is a retrospective study, so take a lot.
- [38:46]
A
Like a lot. Wow.
- [38:48]
C
I know. Yeah. So I mean, if you wanted to go through numbers. Well, yeah, I think I talk about that. A letter. Let's see. Also difference in loss of response between the two groups. So median time to loss of response was 100 weeks in the originator versus 52 weeks in the biosimilar group. I mean that's just a big difference.
- [39:09]
A
Wow.
- [39:10]
C
In the switchers, median. The median time to loss response, 87 weeks in the patients who 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 nocebo 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 than biosimilar. You know, the, the authors say nocebo could still be playing a role, but man, those differences are seem so big that maybe there is a true efficacy difference. Be. It would be. It would be odd, but maybe I.
- [40:01]
A
I wish I knew of someone in the world who could like really talk about. Are the biosimilars actually like the same. Like, is There a, is there a theoretical explanation for this? Are they. I just, I don't. Yeah. If, if any of our listeners are like the bio similar experts and can speak to this, I would love. Email me matt zyrusmail.com matt.zyrusmail.com 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. Ferris, what do you think?
- [40:55]
B
Yeah, I don't know. I mean I've always been a, you know, having done like biosimilar studies without a limumab. Like, you know, the data in, in psoriasis, like the data are pretty good in psoriasis 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. Did they have like a. And do we know like how many different biosimilars were in here? I didn't miss that part.
- [41:24]
C
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.
- [41:37]
B
Okay, so we don't know if it's like, oh, they all had one and.
- [41:41]
C
You know, they had multiple. I mean they at least said that they said there were multiple different biosimilars. Right. So okay, not a bad one. Yeah, yeah, that one biosimilar, I want to say like last month it, 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, 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 in with 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 pediatrics. So I believe that was you know what? I don't know what it was. Simlandi. Simlandi.
- [42:52]
A
Oh, well. Simlandi. Well, of course.
- [42:54]
C
Yeah. Yeah. I don't even know. 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 onto the biosimilar and was like, ah, they're giving me this crap drug, I'm not using it anymore.
- [43:13]
A
Yeah, but the biosimilar, the ones who started on a biosimilar, like yeah.
- [43:20]
C
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.
- [43:29]
A
Okay.
- [43:30]
B
Yeah. I mean the, the multiple you could imagine maybe like you would make. I mean 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.
- [43:43]
C
Like, right.
- [43:44]
B
Those are the things that would be really helpful to understand looking at these patients.
- [43:50]
C
It was a short paper, but I think it raised an interesting question and maybe that's the next step is somebody does a head to head.
- [43:59]
A
Yeah. Because we, I have seen articles where drug levels are pretty predictive of adalimumab responsiveness in hs. Didn't we, we talked about that somewhere with somebody that like if you look at non responders, their drug levels are.
- [44:17]
C
Generally lower and yeah, it was like a Canadian study.
- [44:21]
A
Yeah, yeah.
- [44:22]
C
Because. Because they didn't have any other drug. I don't, I don't know if, if bim, Bimi or Cosentyx are approved up there. So it's like once, once adalimumab stops working, they need a different plan. 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. That's what's great about these episodes.
- [44:45]
B
Listen to yourself over and over again.
- [44:47]
C
It's in the archives.
- [44:49]
B
Yeah.
- [44:50]
A
All right. Here by here, my last two. So first 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 limitation bootstrapping chained equation model like we, that's very representative of. Right. So I was like, this always sounds like baloney to me. So I did a deep dive 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 that everybody dropped out. And I've always been like that sounds like such baloney. But the statistics people, oh no, no, no. This modeling and the blah, blah, blah, and they use all these confusion. So I did a deep dive and so attrition bias related to the 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, Rubin's rules for combining imputed data sets, the Heckman selection model, the Kaplan Meier Cox PH for dropout modeling. The. All of this, what did it show? We don't know what it is. Completely worthless. Literally all of them, totally worthless. The only way they are ever useful is if people dropped out at random. So they, 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 as 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. And so all you can say is if, and especially when they oh, we've modified nri. We did an nri. It's a modified bullshit. It's not a modified, 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 trick us into thinking they can. So a little bit of a soapbox there.
- [48:23]
B
Just a little bit.
- [48:24]
C
Yeah, a little bit. Man.
- [48:29]
B
On Drugs. That podcast instead, that was like that.
- [48:33]
C
Movie network when he was mad as hell and he wasn't going to take it anymore. This is math. Mad as hell movies.
- [48:39]
B
That's it. All right.
- [48:42]
A
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 had formaldehyde in them, and there was like this big whoopty whoop of whatever. Well, it turns out that what they replace the formaldehyde 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 that are formal. When they made them formaldehyde free, they actually turned them into they. A lot of what they added was an ingredient called glyoxylic acid. G L, Y O X Y L, I C. And examples of these products. Cezanne Classic Keratin Smoothing Treatment. Kerasilk Smoothing Lotion. Oxo Organic Hair Straightening System. Fanola Smoothing Liquid Gussy at Home Keratin Treatment. The problem is this glyoxylic acid. If even 1% of it gets absorbed into your scalp, it can cause kidney damage. And so at worst. So There are like 30 reports in the 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 want to say probably.
- [50:46]
C
There it is.
- [50:47]
A
It is possible that everybody who gets one of these keratin treatments to make your hair shinier and smoother is getting mild kidney damage that can be cumulative and is increasing their risk of getting calcium oxalate kidney stones. So, like, l' Oreal 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 Heyman 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 derms. It's especially an issue in like 40% of the people who reported with acute kidney injury they had scalp rashes. So if you've got impaired, if you've got seb, derm, psoriasis, you know anything and then you use this, you get increased absorption. So like we should now be telling all of our hair, you know, scalp, seb, derm, scalp psoriasis, scalp anything. Hey, if you're, 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, these.
- [52:12]
B
Are in, these are at home things. Not like you go to the salon.
- [52:16]
A
There are both.
- [52:18]
B
So they are, both were associated.
- [52:21]
A
Yeah, well, the, 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, 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, it's a significant thing. I've, I've been emailing some of the nephrologists who have published on this, but nobody has gotten back to me yet to like, like this is nuts. Like it because, because who would, you know, somebody goes to their PCP gets annual, you know, CMP and their creatinine is 1.7. Is there PCP can, oh, do you get keratin treatments? Like, no, nobody's. Or they get a kid. Do you get keratin treatments? No, nobody's, nobody knows to ask that.
- [53:31]
B
Right.
- [53:31]
A
But it's, it's, I think it's probably going to turn out to be a big deal. So again, glyoxylic acid, not glycolic they have studied glycolic because a lot of them have glycolic. Glycolic acid is fine. It's only glyoxylic acid in these keratin or smoothing treatments. Highly nephrotoxic. Highly, highly nephrotoxic. That's it. Anything? Yep. That's saving lives here. We're saving lives.
- [54:04]
B
All right.
- [54:04]
A
We're saving lives. All right.
- [54:06]
C
I've always had silky smooth hair. I'm just blessed. Just blessed. I don't have much of it.
- [54:13]
A
Very. Yes, that's. It does look good today. It looks good today. All right. I want to thank everybody for joining us this week. Hope you learned a 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.
- [54:28]
C
I'm Tim Patton.
- [54:29]
B
And I'm Laura Farris. And we are germs on drugs.