Announcer:
0:00
Welcome to MedEvidence!, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts Hosted by cardiologist and top medical researcher, Dr. Michael Koren.
Dr. Erich Schramm:
0:11
Hello and welcome back to the MedEvidence! podcast. I'm your host, Dr. Eric Schramm, sitting in for Dr. Michael Koren. Today he's out on
Dr. Michael Bernhardt:
0:20
Maternity leave.
Dr. Erich Schramm:
0:21
Maternity- leave.
Dr. Erich Schramm:
0:22
That's right. It's my pleasure to be here with you. Just a little background for myself for those who don't know me I'm a long-term clinical research investigator and have been with the ENCORE Research Group for more than 20 years. My training and background is in family medicine. I'm a board-certified family physician and have been in primary care practice for more than 20 years, though more recently I'm specializing in cannabis health, so I help patients, guiding them on their journey for healing in the medical marijuana space. I'm very excited to be here with longtime clinical research colleague and one of my favorite dermatologists, Dr. Michael Bernhardt.
Dr. Michael Bernhardt:
1:04
Thank you.
Dr. Erich Schramm:
1:05
So Dr. Bernhardt and I go back a long ways. I recall the time that back in my residency training he took me under his wing, had a great rotation as a family medicine resident in his clinical dermatologist office and came away with a lot of practice pearls from that that I still find useful today when I'm seeing patients. So that is greatly appreciated. Thank you so much. Mike has a great background in clinical medicine probably three or four decades at this point, I think and as well as thinking about his background in academics recently teaching at Florida State University, the residents and the med students there Is that right?
Dr. Michael Bernhardt:
1:51
Correct.
Dr. Erich Schramm:
1:51
Yes, sir
Dr. Michael Bernhardt:
1:52
Helped run a residency program for three and a half years.
Dr. Erich Schramm:
1:55
That's right. And also touching base on long-term clinical research experiences and background in clinical research, and I think that was going back to 2010. Is that right?
Dr. Michael Bernhardt:
2:09
I've been here since, I think, 2008 or 2009. I remember we started doing some of the early phase three clinical trials for drugs which are now almost fading out of the market Things like Taltz, Cosentyx, Siliq, and some of the topicals. So we've been at this for a while.
Dr. Erich Schramm:
2:26
Yeah, and that's actually. You know, we'll be talking today, we'll sit down, we'll kind of do a psoriasis 101 discussion, really kind of drill down on some of those things, and we can talk about the treatments and kind of the evolution of those treatments because, you know, 25 years ago in my training in your office, we really weren't talking about those kind of therapies because they didn't really exist at that time. So that's going to be kind of an exciting topic to get into. Anytime, I'm sitting across the table from a clinical researcher. You know, one of the first things I want to know is hey, what got you interested in this and got you wanting to pursue research?
Dr. Michael Bernhardt:
3:08
You know, it's really kind of an interesting evolution, because I started doing this, I think, in 2008, 2009. And a couple of things. I mean back then, really up until the early 2000s, I used to call it institutionalized mediocrity in terms of how we treated our patients, because the therapies that we had were institutionalized mediocrity in terms of how we treated our patients, because the therapies that we had were institutionalized standard of care. They were garbage. I mean literally garbage. All we had back then were drugs like methotrexate or cyclosporine, which are great drugs they have the use, but in psoriasis they were really suboptimal.
Dr. Michael Bernhardt:
3:40
And then around 1999, 2002, a drug called Amevive came about and it was the first injectable drug for psoriasis and in the 15% of patients that it worked, it was a home run. People got clear. The problem was the other 85% didn't really do much. And then around 2004, somewhere around that time, Embryol came along and Enbrel was a game changer. Enbrel and Remicade were absolute game changers. They blocked an inflammatory molecule called tumor necrosis factor, TNF1. And at that time we all thought TNF1 was the central hub that drove all the inflammation in psoriasis, which of now we know is not true.
Dr. Michael Bernhardt:
4:26
And then when, around 2008, 2009, when we had the big recession, I had people coming into my office who were literally facing foreclosure of their house, repossession of their cars, and when I started talking to them about some of these drugs, like Humira and Remicade and Enbrel, their eyes would glaze over because they lost their insurance, they didn't have money.
Dr. Michael Bernhardt:
4:53
And then, by coincidence or out of serendipity, I was contacted here to become part of the research team. And you talk about a benefit, an amazing benefit for patients. We were able to give them state-of-the-art drugs. I mean, at that time, Taltz and Cosentyx were were state-of-the-art drugs and there was no out-of-pocket cost to patients. So not only were we able to use drugs that really delivered on the promise, I mean, people got clear, their skin became uninflamed, their joints became uninflamed, side effects were absolutely minimal and they didn't have to pay any money for it. So we really accomplished a lot of good, and that's what really kind of was the hook line that got me into clinical trials.
Dr. Erich Schramm:
5:37
That's a great story and some really important examples to talk about. Now let's unpack some of that and let's talk. Tell me, give me, a good definition for psoriasis, so we know what we're dealing with here.
Dr. Michael Bernhardt:
5:50
So you know psoriasis comes from the Greek word psoare P-S-O-A-R-E, which means to itch, and that's about the extent of Greek that I actually know. I don't even know how to say where's the bathroom in Greek, so it's challenging if I ever went there. But that comes from the Greek word psoare, which means to itch, and the irony is only about 20% of people with it actually itch. So we now know that, unlike in the early 1980s, late 70s, when I was in training, where they used to teach us that psoriasis was a condition from rapidly proliferating keratinocytes Skin cells were growing too fast, which we now know as codswallop.
Dr. Michael Bernhardt:
6:30
It's an inflammatory disease and it's really part of the whole metabolic syndrome associated with things like cardiovascular disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis. They're all kind of integrated with each other Psoriatic arthritis, so we know that. So all the people that I used to teach when I was teaching the residency program, they all know that I'm kind of what they call a cytokine geek. I like to really dive down and see what the primordial step is. And we're getting close.
Dr. Michael Bernhardt:
7:04
We don't really know what the primordial step is in psoriasis, but we know that it's a consequence of inflammation. There are cells that are innate to the skin and that also circulate in the blood, called dendritic cells, and they release a molecule, a pro-inflammatory molecule, called interleukin-23. And interleukin-23 has a feedback loop relationship with other inflammatory cells and other keratinocytes and it stimulates the release of interleukin-17, which really is like the analogy would be putting the key in the ignition and turning the switch. Or, for those of you who have cars newer than that and don't understand about putting a key in and turning a switch, putting your thumb on the start button and pressing it, and that starts the whole inflammatory cascade which leads to skin proliferation. And since the skin is proliferating so fast and piling up if you visualize a big mound of seashells when you get to the top of that mound it's got to go somewhere and it peels off his scalp.
Dr. Erich Schramm:
8:03
Right. So that's very interesting because a lot of times people have that kind of question about how a condition that is systemic manifests itself at the level of the skin. So we're talking about autoimmune diseases and abnormalities, immune system-related abnormalities that result in a process that ends up relating to the skin conditions, right? So, getting back to understanding and you were saying at the top of the discussion, you mentioned a lot of the biologics involved, , this kind of early development of the biologics and how they came in and why they ended up being real game changers in this, and so you've mentioned interleukin-23, interleukin-17 as important precipitators for this and ultimately, as they um from that level in the dermis to the epidermis and you end up with um with the.
Dr. Michael Bernhardt:
9:11
It's hard to keep both these and all those multi-syllable words there, Erich, it's Friday.
Dr. Erich Schramm:
9:14
I know this is you know you know, uh, it's so interesting because right, and so you know, truth is uh about.
Dr. Erich Schramm:
9:21
Every friday we work together. I have an opportunity to pick your brain and be like Mike. Tell me a little bit more about IL-23 and IL-17 and interferon 1, tumor necrosis factor, and to try to bring this down to. I always joke with him. I say, hey look, you've got to dummy it down for me. I'm a family practice doctor.
Dr. Michael Bernhardt:
9:45
One of the smartest I ever met and one of the smartest I ever trained by.
Dr. Erich Schramm:
9:49
Ok, thank you. So that's, we have mutual admiration society going, thank you. So you know, I'm always trying to kind of think of this in terms of really kind of the basic premises. Here We've got a, we have a very important immune system functions.
Dr. Erich Schramm:
10:07
But now we see what's I think fascinating about psoriasis is if you look at the approved therapies out there, they're hitting so many different pathways and whether it's interleukin or TNF, you have phosphodiesterase inhibitors, and so it's such a diverse cascade of these inflammatory processes. And so you, as you alluded to you, had been involved in some of those clinical research trials you mentioned. Taltz was kind of very important and pivotal. And the other thing that's interesting, I think, in these medications you start to see this evolution. They went from injectables and then at some point maybe you could talk about some of the JAK-STAT inhibitors out there and understanding, hey, you know, these treatments went from injectables to orals. That was a big leap in, you know, being able to offer oral medications to patients. So maybe you could touch a little bit on that,
Dr. Michael Bernhardt:
11:18
Yeah, I mean, you know it's funny, Erich.
Dr. Michael Bernhardt:
11:20
Everything goes in cycles, you know, and prior to the onset of the biologic age, you know which the primordial era was Enbrel and Humira. But the modern era probably started with Taltz, and you know our site. We had like 40 patients in the study. So I had hands-on experience with over 40 patients on Taltz before the drug ever came to market, so I was always very comfortable with it. But now we are. We're gravitating back into an oral realm. You know there's an oral IL-23 inhibitor in development. Phase II studies have been published by Johnson Johnson which looks like it's going to be an amazing drug. The JAK inhibitors are an amazing drug. So one of the things that I try to impress upon people like there's a difference between autoimmune and autoinflammatory, and I think psoriasis is probably more accurately conceptualized as autoinflammatory rather than autoimmune
Dr. Erich Schramm:
12:20
Can you tell me a little bit how you define that difference?
Dr. Michael Bernhardt:
12:23
In other words you get inflammation rather than autocratic destruction.
Dr. Michael Bernhardt:
12:28
So in psoriasis you're upregulating a huge inflammatory cascade rather than tissue-targeted destruction. So that's why I tend to think of it as autoinflammatory. One of the ways I try to teach when I'm teaching residents either dermatology residents or internal medicine or family medicine residents is when you're thinking about the immune response or the inflammatory cascade. You know all the things that you see, everything is done to linear. You know 23 leads to 17 leads to this. I tend to think of it as a series of interlocking gears where one primes the pump for the other and allows other processes to turn on. And I think that you know, I think, some of that. The linear aspect of thinking about this is just. I think, part of a fundamental limitation of human thinking that we can only think of one thing at a time. But with autoinflammation you've got to think of interlinking parallel gears and a lot of these. I call these autoinflammatory cytokines. I call them the usual suspects Because if you look at a lot of diseases, a lot of diseases are using the same pathomechanism in different body parts, right?
Dr. Michael Bernhardt:
13:45
So there's data that shows that ulcerative colitis and Crohn's disease is driven by an interleukin-17-23 cascade. There's data that shows that multiple sclerosis, you know, is driven the experimental model for that is driven by interleukin-23. There's some data that I read in one of the throwaways where terrible diseases like ALS may have an IL-17 derivative to it. So a lot of these usual suspects, these evil suspects not really evil, but the effects that they do are evil pop up in different areas because these were originally designed to fight certain things off and what happens is there's either a genetic or an environmental miscue that ramps this system up. So if you think about the inflammatory process I used to use the analogy it's like thinking about NATO and the Warsaw Pact.
Dr. Michael Bernhardt:
14:32
You have two armies head to head and on one side you have the interleukin 17 AF derivative, which is designed to cause inflammation, and then on the other side you have interleukin 10, which I always say is kind of like Snoop Dogg. You know, give them a joint, cool them out, chill them down, let them go to sleep and let them stop being inflamed. So these two are butting heads and when there's active inflammation, 17 AF wins, il-10 loses. When that inflammation's damped down, il-10 wins, 17 AF loses. So there's always that kind of push pull going on in the body and the question is what's driving it? Why does it happen? We don't know why it happens in psoriasis. We do know that psoriasis is a genetic condition. It can run in families. Two of my brothers had it, my mom had it. What can set it off? A lot of things. Stress, alcohol consumption, certain medications, particularly beta blockers, can trigger it. Trauma, injury and sometimes rule 17, which is stuff happens.
Dr. Michael Bernhardt:
15:36
And it just kind of happens. And back in the old days before in the modern era, you know, counseling someone with psoriasis was very discouraging because all we had was topical steroids and maybe methotrexate Cyclosporine you couldn't use forever because you had to watch blood pressure and kidneys, as you know from being an internist, um. So we had limits on what we could do and and it was very frustrating as a physician to do the best that you could and know that you're only going to get these people marginally better right. And then when the Taltz and the Cosentyx phase three pivotal trials came out, they were huge because for the first time ever we were getting PASI 100s. And for those of you who don't know what a PASI is, pasi stands for psoriasis area severity index and what we do is, through a very tedious process, we quantify how much of the body surface area is involved with psoriasis, how thick the plaque is, how severe the scaling is, and we kind of cook that up and boil that into a number. So a PASI of 2 or 1 is good, a PASI of 20 is very bad.
Dr. Michael Bernhardt:
16:38
And in the old days when people had these high PASI scores, topical steroids would only go so far. Now with these injectable biological drugs, whether it's Taltz or Cosentyx or some of the 23 inhibitors, the norm is to see people clear or almost clear. That's the norm, and the beauty of it is that that visit has been reduced from a 30 to a 45-minute visit that mostly consisted of hand-holding to gee, you're great. Are your labs up to date? See you in six months. Any problems from the drug? No, see you in six months, wow.
Dr. Erich Schramm:
17:08
So they really hit a home run.
Dr. Michael Bernhardt:
17:10
Yeah, it's Grand Slam Bases, loaded bottom of the ninth Grand Slam,
Dr. Erich Schramm:
17:17
Right. So the other day it was interesting, you're in the office and you're talking to one of the coordinators and you were showing them your hand and said talking about body surface area, so what's the significance of the handprint?
Dr. Michael Bernhardt:
17:29
It's a peace sign.
Dr. Michael Bernhardt:
17:39
So usually, when you usually, when you usually when I can't split my fingers like Spock used to do.
Dr. Michael Bernhardt:
17:41
But no, usually you use the patient's hand and it's not really the whole hand, it's the palm. Use the patient's palm as an indicator of body surface area. So one one area the size of the patient's palm should correspond to 1% body surface area as a rule and that's what we use.
Dr. Michael Bernhardt:
17:58
We use the palm. Now in real practice, most patients' hands are about the same size, unless you're talking to someone you know, like maybe one of the guys on the Jags or one of the professional basketball players. But for most normal people, most mere mortals like us, most palms are about the same. So we all kind of use our own palm in clinical practice to get an idea of what their body surface area is.
Dr. Erich Schramm:
18:19
So for those patients suppose that they don't meet the criteria to consider the newer therapies, biologic or one of the DMARs or something like that what do you have to offer somebody that isn't that severe? So?
Dr. Michael Bernhardt:
18:34
there's gradations of severity, right, and the standard is typically how much body surface area there is. Now the other things that you have to think about is areas of involvement, not just body surface area. Scalp involvement Do they have scalp involvement? Why is that important? Because people with scalp involvement have four times the risk of developing arthritis from the psoriasis as people without it Do. They have little pits in the nails where it looks like someone took a safety pin and tried to chisel a hole in their nail. Well, if the answer to that is yes, it means they've got what we call a matrix disease. And nail matrix disease is three times more likely to develop psoriatic arthritis as the rest of the population. So those are areas of special interest and that's the reasons why.
Dr. Michael Bernhardt:
19:17
The other area, facial involvement or genital involvement. Facial involvement people feel marked, they feel like lepers. Genital involvement involves, you know it impairs psychosocial function, impairs relationship formation So for people with those areas, even though there's limited body surface area, we still in the AAD, they still consider that an escalation basis to ramp that up as a severe disease. And then I'd be more aggressive with them. People that don't have those areas, that maybe have 3%, 4%, 5% body surface area. There are a couple of oral drugs out there. Otezla is one which is a phosphodiesterase inhibitor. Typically, how does a phosphodiesterase inhibitor work? Long story short, it indirectly decreases tumor necrosis factor one. It affects cyclic AMP and ATP formation, but the end run is that it decreases TNF inhibitor.
Dr. Erich Schramm:
20:13
Right, and that can be combined with other modalities right.
Dr. Michael Bernhardt:
20:17
Yeah, topicals you can use with topical steroids.
Dr. Erich Schramm:
20:19
Whether you're inhibiting interleukin or
Dr. Michael Bernhardt:
20:22
It's a great drug, it's definitely got its place. I think we're looking at doing a clinical trial on a TIK2 inhibitor right, which is tyrosine kinase, which is one of the inflammatory systems, and those work really well too. I mean, there's one tyrosine kinase inhibitor already on the market, but we're looking at a competitive one for clinical trials. So it offers a nice alternative because there are some people that don't want to inject themselves.
Dr. Erich Schramm:
20:48
So, with the new drugs coming on the market, what would you like to see better in terms of these new medications?
Dr. Erich Schramm:
21:01
What would you like to see improved upon?
Dr. Michael Bernhardt:
21:07
That's a tough question, because if you'd asked me that 10 years ago, I'd have given you a laundry list. But now, I mean, if we can achieve the same thing with an oral without having to self-inject, I think that would be very nice, although I take Repatha and I pinch a big roll of fat which I have way too much of and click it and it's really not a big deal.
Dr. Erich Schramm:
21:25
But you're working out. I see that.
Dr. Michael Bernhardt:
21:26
I know
Dr. Erich Schramm:
21:28
You're looking pretty good these days
Dr. Michael Bernhardt:
21:30
I work out, but it's like gee. I worked out. Now I can eat 10 pieces of chocolate. You know it's the whole cycle of balance. But so if we can achieve the same things orally that we do with injections, I think that would be beneficial. Now, you were talking about the JAK's before.
Dr. Erich Schramm:
21:45
Right, that was kind of where I was leading to is what kind of issues were there with that particular class?
Dr. Michael Bernhardt:
21:52
I mean the way I think of JAK's. I think of them as the prednisone of the 21st century. They do a lot of things that steroids do do, JAK's. So the intellectual basis for JAKs is every cell has a receptor, right. The psychographic for that is, if you think of putting a straw in a cup of chocolate pudding, all right, the chocolate pudding is the cell the straw goes in, that's the intracellular environment. The part sticking out acts like the receptor and binds some of these cytokines. So let's say, a cell receptor binds to a molecule of interleukin-23. What happens next? Well, there's what I call an inflammatory synapse, just like we have neuromuscular synapse. This is an inflammatory synapse where the receptor binds. There's like a little impulse of transmission that goes down where the receptor binds. There's like a little impulse of transmission that goes down through the receptor, through the membrane, into the interior of the cell, and that transmission fires off a stimulation of these JAK, which is Janus kinase molecules. They're enzymes.
Dr. Erich Schramm:
23:01
Right, so like little machinery factories right.
Dr. Michael Bernhardt:
23:05
When those enzymes get tweaked, they cause stimulation of the second phase of that which is the STAT stat complex, and when these stats get activated they then transmigrate to the nucleus and upregulate inflammatory genes. So if you stop the JAK, you stop stat, you stop inflammation.
Dr. Erich Schramm:
23:25
So really treating it right at the core.
Dr. Michael Bernhardt:
23:28
It's a big yeah. The JAKs are more like a shotgun than a sniper rifle. So the 23 and the 17 inhibitors are more like a sniper rifle because they're picking off the specific cytokine. The JAKs are a broad shotgun and they just shut down everything.
Dr. Erich Schramm:
23:47
Well, I think, well, in terms of the you know of the interleukin inhibitors, I think it's being a little more downstream right Versus if you're arresting that at the point from a cellular level right, so you're just shutting it down at the cellular level.
Dr. Michael Bernhardt:
23:57
For example, JAK1, right. JAK1 upregulates a variety of cytokines, right. Things like interleukin 3, interleukin 5, interleukin 7, interleukin-9. So those all get upregulated and they all have specific functions. Like interleukin-7 is a broad T cell stimulator. Right. Interleukin-9 upregulates killer cells. Interleukin-15, right now I'm just blanking on what 15 does. But so you're downreg regulating a huge inflammatory cascade, right. Right, interleukin 2 is responsible for driving interleukin 6, which is one of the main pro-inflammatory cytokines for a lot of tissue destructive
Dr. Erich Schramm:
24:35
right, so kind of the pros.
Dr. Erich Schramm:
24:37
There are broad uh suppressant of these wide range of inflammatory molecules right, but the downside is there could be collateral damage in that right. In that immune system, or whether it's infection, or
Dr. Michael Bernhardt:
24:54
that's why these drugs aren't on the candy aisle.
Dr. Michael Bernhardt:
24:56
I mean drugs are drugs and they can cause great things. They can do terrible things. So I was doing a lecture last night to some of the doctors that said, part of our job as learned intermediaries is to be able to figure out what drug is going to be in such a state where we've mitigated the downside risk and maximize the upside potential. That's our job as physicians and that's why I don't think AI will ever really replace a good physician. You know, even though patients come in all the time, Dr. Google said I had to do this, this, this and this. They said well, Dr. google's office is right next door. Feel free to go see him there.
Dr. Michael Bernhardt:
25:32
This is how we're going to do it here. That's right.
Dr. Erich Schramm:
25:34
No, I appreciate
Dr. Michael Bernhardt:
25:35
But the JAK's are great. I mean, they're really, they're a brave new world. Um, a lot of people have developed what I call JAKophobia. They're afraid of the JAK's and that really bothers me. And the reason for that fear was there was a study, there was a problem with Xeljanz about about 12 or 13 years ago.
Dr. Michael Bernhardt:
25:54
Xeljanzis a pan-JAK ,JAK one, two and three which blocks everything. It's a great drug and it has its use. But there was a cohort of patients with rheumatoid arthritis who were on comorbid prednisone and methotrexate and they were using a dose double what we're using today and there were some problems. Some patients had pulmonary emboli and deep vein thrombosis. And then, about four years ago, there was a study where they compared one of the TNF inhibitors to one of the to Xeljanz in the same cohort population. You know, methotrexate and prednisone treated rheumatoid arthritics and they showed that there was what they call not. They were not able to establish non-inferiority. Okay, so they couldn't say that the JAK was non-inferior.
Dr. Michael Bernhardt:
26:42
Granted everybody listening, I agree it's double talk, but that's just the way these things are done. This is done via bureaucratic methods, not our methods. But it showed that there was quote, unquote non-inferiority. So now the entire class JAK's have have this box warning about infection, lymphoma, deep vein thrombosis and cardiovascular disease. Yet when you look at these newer drugs that are not panJAKs, that are selective for just JAK1 or maybe JAK1, JAK2, the data doesn't reflect the warning, at least not the data that I've seen. Okay, they reflect the warnings. Now, if someone comes to me who's got a history of deep vein thrombosis, you know, or they have some of the metabolic syndromes that predispose them to blood clot formation, probably not a great choice, right, I'd go in a different direction. But for a lot of these other diseases, these JAK inhibitors are going to be the cat's meow.
Dr. Erich Schramm:
27:43
That's great, yeah, and thinking about those patients that were on prednisone and methotrexate, which are—.
Dr. Michael Bernhardt:
27:48
Which, of course, have no side effects at all.
Dr. Erich Schramm:
27:50
Yeah, I was going to say
Dr. Michael Bernhardt:
27:51
Totally benign drugs, totally harmless, Nothing to worry about.
Dr. Erich Schramm:
27:53
So that puts it in the context of what we think about. And you know, I think it's great to have someone with your clinical experience and your research experience so that you can take and give kind of a real risk assessment for patients and say, and you know, in doing the right thing for your patient,
Dr. Michael Bernhardt:
28:13
The problem, Erich, is and you and I have both dealt with this in our practices there's risks of taking the drug but there's risks of not taking the drug.
Dr. Michael Bernhardt:
28:23
You know, I'm not a rheumatologist, I don't treat rheumatoid arthritis, but I have a lot of patients with overlapping syndromes, you know. And the inflammatory environment is different. In rheumatoid arthritis it's more Interleukin-1 driven, you know, rather than Interleukin-4/13, like in atopic dermatitis, which is where we use most of our JAK inhibitors, and atopic dermatitis is our big use for that particular drug. It's a different pro-inflammatory environment. have Interleukin don't have 1-up regulation, they have 4/13. So the risk for that population of having a vascular event is really pretty low, probably no more so than the SEER data, which is the expected population-based data, right,
Dr. Erich Schramm:
29:07
so your take on the TYK2, tyrosine kinase 2 inhibition, some of the newer products here being developed, what's your comfort level with that?
Dr. Michael Bernhardt:
29:21
Very, very comfortable. You know there's one on the market that I've been using in patients. Like I said, there are some people with psoriasis who don't want to take a shot. So there's one of the TYK2 inhibitors is on the market and I've been using that for a couple of years and it's a little slower in onset than the shots. I can tell people it's the tortoise, not the hare, but at the end of the year you're basically going to be in the same place. You're just going to get there a little slower, knockwood. I've not seen any significant side effects to the point where patients would stop using the medication and it works.
Dr. Erich Schramm:
29:59
Wow, that's great. So you know I was thinking about this because I'm a big college basketball fan and watching March Madness
Dr. Michael Bernhardt:
30:08
oh my God Go Gators, what a great year for them.
Dr. Erich Schramm:
30:11
There you go, and what struck me—.
Dr. Michael Bernhardt:
30:13
And Auburn and Houston and Duke all the teams I met at the Final Four
Dr. Erich Schramm:
30:17
Give them credit for that.
Dr. Erich Schramm:
30:18
They were all great, great series. There are a lot of great games there. But what was really interesting were the commercials right. And so I was surprised at the number of commercials for psoriasis and the selling point for this one particular drug was it tackles or treats both types of interleukin-17. And I was like, wow, that is a really sophisticated advertising approach to direct a consumer. Advertising that's very sophisticated and so curious. Do patients come in, you know, saying hey, I saw this commercial on TV blocking both types of interleukin-17. Have you seen that in
Dr. Erich Schramm:
31:08
your practice?
Dr. Michael Bernhardt:
31:08
I'm waiting because I want them to give me a lecture about it and tell me that what?
Dr. Michael Bernhardt:
31:14
actually is kind of funny is, like I said, I'm a pathways geek, right. So what I was doing this morning in between surgical patients. There was a great article published this month in the British Journal of Dermatology where they did a genetic analysis of hidradenitis suppurativa and they looked at all 5,000 genes that are upregulated hidradenitis suppurativa and they found that there was a notch. You know, we've always known that there's more 17F both in the lesion and perilesional right, and F is a very powerful driver and I'll talk about that in a second. But in this study they looked at the gene sequencing and they found that not only was 17F upregulated in the follicle itself but in the perilesional dermis those dermal fibroblasts were kicking out more 17F. So 17A we already talked about it, it's released by dendritic cells stimulates the whole 17A loop amplification right.
Dr. Michael Bernhardt:
32:22
17F seems to be more tied in with upregulating other players in hidradenitis, like interleukin-1, which the whole interleukin-1 family is a very strong pro-inflammatory cascade upregulating interleukin-8. Now interleukin-8's job is to cause neutrophils, or white blood cells, to migrate into the lesion. So they're taking the position hidradenitis and and I think I agree with hidradenitis is is primarily a neutrophilic dermatosis and it's a biphasic disease, so it starts out as a pro-inflammatory disease. They know that there's a defect of this gene called secretase and secretase gamma. Secretase is important in the hair shaft and allowing the hair to turn into hair, when it's defective it forms cysts and that seems to be ground zero for HS. They form these inappropriate cysts and the other thing that they've found is through a process called epithelium mesenchymal transformation, where cells go from one cell to another type of cell, kind of like what we see in cancer.
Dr. Michael Bernhardt:
33:24
In hidradenitis fibroblasts will transform into epidermal keratinocytes within the dermis, which also drives inflammation. So IL-17, A and F get massively upregulated in hidradenitis. And the beauty of this new drug, by downregulating F and the AF heterodimer, is you can drive down that interleukin-1, tnf, interleukin-6 cascade. So that's why that particular drug has been successful in treating something, not just psoriasis and psoriatic arthritis, which it's great for, but I think also for treating a previously very difficult disease to treat, which hidradenitis suppurativa.
Dr. Erich Schramm:
34:06
Well, I think I hear the topic of our next podcast discussion coming up right, I think that's going to be in a couple of weeks.
Dr. Michael Bernhardt:
34:13
Skin is in baby.
Dr. Erich Schramm:
34:14
Yeah, you know I never get tired of hearing you talk about the inflammatory cascade.
Dr. Michael Bernhardt:
34:21
It's amazing.
Dr. Erich Schramm:
34:24
So, Mike, thank you so much. You know a ton of insight there, always appreciate that and you know whenever we can talk about science and Snoop Dogg and all of that. I love picking your brain on things.
Dr. Michael Bernhardt:
34:39
My pleasure.
Dr. Erich Schramm:
34:41
Any question you think I should ask you?
Dr. Michael Bernhardt:
34:45
Well, let's see. For those of you who are really on the edge of your seat, I found a great restaurant down in St John's.
Dr. Erich Schramm:
34:54
Do tell
Dr. Michael Bernhardt:
34:55
it's called Irons and Ember. Okay, and they do. All their cooking is in cast iron skillets. Everything is fresh, the seafood is fresh. The prices are reasonable. The service was great. We went there two weeks ago and it was the kind of place where my wife and I looked at each other and said when do you want to come back? And I'm like how about tomorrow? So the big unanswered question where should we go to eat this weekend?
Dr. Erich Schramm:
35:19
Okay, that's great. Well, no thanks for your insight, as always, and again look forward to talking to you in the near future. We'll pick up on hidradenitis suppurativa.
Dr. Michael Bernhardt:
35:29
Sounds great. It's an amazing disease state. Thank you,
Dr. Erich Schramm:
35:32
thank you,
Dr. Michael Bernhardt:
35:32
thank you.
Announcer:
35:33
Thanks for joining the MedEvidence podcast. To learn more, head over to MedEvidencecom or subscribe to our podcast on your favorite podcast platform.
