Transcript
Speaker 2 (00:31):
Welcome to the Practical Dermatology Podcast. This month we have an update from Dr. Jason Hawkes on psoriasis, an interview with Dr. Lisa Swanson and Dr. Ted Rosen, and the latest news. Now here's Jason Mazda with Dr. Jason Hawkes.
Jason Mazda (00:44):
I'm Jason Mazda of Practical Dermatology, and I'm joined today by Dr. Jason Hawkes to talk about a consensus statement from the National Psoriasis Foundation that he was involved with, “Defining On-Treatment Remission in Plaque Psoriasis.” Dr. Hawkes, thank you for joining me.
Dr. Jason Hawkes (00:59):
Yeah, thanks for having me. Excited to be here and talk about this important topic.
Jason Mazda (01:03):
Absolutely. So tell me, what is remission like and why was this an important topic that you wanted to be involved with this consensus statement?
Dr. Jason Hawkes (01:11):
Yeah, this was an effort that was really coordinated within the National Psoriasis Foundation, or the NPF, April Armstrong really spearheaded the effort so she gets really credits for that. But I was one of many members on this effort and participated in this consensus statement because it's important for patients, and I think that was really the entry point for this project was what's important to the psoriasis patients. And what was important is to try to get to a state of remission, which has had variable definitions, but for them it ultimately came down to simple things which was trying to get clear, and conceptually that makes sense.
(01:59):
The problem was that there was all these contradictory, or conflicting, or variable definitions. So, this was an attempt to say, "Let's talk about remission, what does it mean?" And let's be specific that we're talking about remission as it relates to being on treatment as opposed to remission that we talk about in maybe the oncology space where they're in remission but they don't have to undergo treatment in some situations. So, it's being a little bit more specific, it's focusing on a high value for clinicians and patients, and it's trying to do that in a systematic way using psoriasis experts, and also including a cardiologist and some rheumatologists. And I think that is really why this is an advance on what's been done in the past.
Jason Mazda (02:52):
And I know that remission was this consensus statement, you actually defined benchmarks for what on-treatment remission is. So, what can you tell me about what those benchmarks are, and what the impact of this decision is?
Dr. Jason Hawkes (03:10):
Yeah, so the paper specifies that obviously this is an important value among patients where this effort really started, but it also goes broader. It brings in other stakeholders. So payers for example, multiple providers, those that really know disease, it clarifies we're talking about on treatment rather than off treatment. And what was clear to patients is their highest value or the way that they looked at remission was to be disease-free and symptom-free. And so, naturally that correlates with clinical measures that we often use. So things like body surface area, if patients get to a body service area of zero then they don't have any active disease, and that usually correlates with not having any active symptoms. And you could do that with other measures like the Investigator's Global Assessment or the IGA score of zero, and that would be that they're clear from a disease.
(04:13):
So, it became obvious from the patients and also payers who recognized that this measure made sense trying to get to completely clear skin, which would often correlate with not having symptoms. And I think what came out from the consensus from both patients and providers, and also stakeholders I think in the voting, was that you could do that in a couple of ways, either the IGA zero, again being clear, or achieving a body surface area percentage of zero where there wasn't any active psoriasis. And those were the two statements that basically identified as being the best measure, or at least the measure that the group felt was the most representative of this concept of achieving symptom clearance, but also disease clearance. And that was really what came out of this effort was the BSA involvement of zero, IGA score of zero.
Jason Mazda (05:24):
Was it an easy process? Was everybody pretty much in agreement right away or was there a lot of deliberation before coming to this consensus?
Dr. Jason Hawkes (05:34):
What's nice with these type of efforts is that occasionally you'll get 100%, but it's pretty rare. You tend to have a distribution. And that Delphi process I think inherently reflects that, that you're not saying we're only going to move forward if we have 100% agreement because that's difficult. And there's some valid reasons for why someone might feel strongly about not using body surface area of zero, for example. So, even though the majority either strongly agree or agree, you're going to have some that are maybe neutral or some that even disagree. And you find that with some of the other options that were put out there in the voting process, so obviously this is a voting process. You're looking for consensus among those voting, and the ones that have the strongest consensus that's what you're reporting in the final, the Delphi definition. And so, here you still have some variation, and there's again, some reasons for that.
Jason Mazda (06:41):
Excellent. So, is a consensus statement for off-treatment remission in the works?
Dr. Jason Hawkes (06:47):
That's a good question. Certainly those discussions are happening. It's particularly interesting right now because as our medications have gotten better over time, as we've moved from broad acting immunosuppressants, these oral medications, methotrexate, cyclosporine, we went through the TNF inhibitors, which worked pretty well. They were a dramatic improvement on the ability to manage and treat psoriasis. But the newest therapies, IL-17s, IL-23s for example, these inhibitors, they're actually pushing a huge proportion of patients, in fact, the majority of patients into PASI-100, so that's 100% improvement in their PASI score. So, the reason we can have some of these conversations is because we finally have medications that we can get a large proportion, the majority of patients actually in these categories that fit with the consensus guidelines for on-treatment. But the emerging concept is if we optimize the dose, maybe it's an increased dose, maybe the frequency is different in terms of how the medication's given, we actually can push disease clearance in those patients for longer periods of time.
(08:05):
And I think this was clear from a study that was done at our center along with the University of Michigan, the KNOCKOUT study, which was giving very high levels of IL-23 blockers in patients with psoriasis, and then seeing how their disease did. And many of those patients actually in the trial, most of them achieved complete clearance, but they also had clearance for a long period of time. So, that's part of this definition is that the final conclusion for this paper is that patients maintaining a BSA of 0% or an IGA score of zero for at least six months while on treatment, and that treatment includes both prescription and non-prescription interventions. But the nuance to that is what happens at 8 months, 9 months, 12 months, 24 months? And so, we will have these continued efforts and interventions, and new trial designs, which are going to start looking at is there a way to keep people clear longer, beyond six months when they're not on treatment?
(09:18):
Because this is on-treatment. Can you keep their disease controlled off-treatment? And I think the real reach, the silver bullet to all this would be can you do something at either early stages or in the middle stages of their disease where you can get it under such good control that you might be able to even shut off the disease? And I think that's the real goal for some of these chronic inflammatory diseases like psoriasis. So, I do think you're going to see more efforts like this in the future with the on-treatment, or even these prolonged states of remission in these two different circumstances.
Jason Mazda (10:01):
Well, is there anything else about this consensus paper that's out, or about this topic that you would want to say before we wrap up?
Dr. Jason Hawkes (10:08):
No, really just driving home that point that while we have really good therapies, there's some limitations. One is not everybody gets 100% clear, and we still don't have a really good understanding, because some of those patients that we have with psoriasis, they clearly have psoriasis. They phenotypically look the same, yet they don't respond to medications that work in most other psoriasis patients. So, we really don't have a good understanding of that. We don't know why somebody can stay clear for two years, three years, five years on one medication and then it suddenly stops working. So, we haven't figured out those molecular mechanisms, and we don't even have good biomarkers to predict those patients. So, that's going to be another key component of this, is that we need to understand why patients lose control of their disease when they stay on the same therapy, because that's important, particularly for our industry partners that are developing these medications. It would be critical for them to understand why does a patient lose efficacy over time?
(11:19):
And if we could help avert that problem, that helps our industry partners, also patients, it helps providers. So, we need to understand that process. We really need to understand some of these subtypes where they just don't seem to respond perfectly in terms of complete clearance with specific medications. So, that's a gap that we're exploring. And of course, there's all these other subtypes of psoriasis. We frequently talk about plaque psoriasis, but we know there are other types of psoriasis, pustular psoriasis, guttate psoriasis, inverse psoriasis, palmoplantar psoriasis. So, there's these other subtypes, early onset disease, late onset disease, we need to still work out the nuances here. So, this is really the tip of the iceberg, it's the beginning of these conversations about let's take the most common subtype, let's take the most common scenarios, and what would be the ideal goal here that would meet the needs of all these different stakeholders involved?
(12:19):
But as I mentioned, there's a lot of nuances that haven't been addressed in this same methodical way, and that will be an important effort in the future.
Jason Mazda (12:30):
Excellent. Well, thank you so much Dr. Hawkes for joining us.
Dr. Jason Hawkes (12:33):
Thanks for having me today.
Speaker 2 (13:00):
Now here's Dr. Lisa Swanson with this month's featured conversation.
Dr. Lisa Swanson (13:03):
Hello everybody, and welcome to another wonderful podcast from Practical Dermatology. I'm Dr. Lisa Swanson of Boise, Idaho. And get excited you guys, because we have the guest of all guests. This is like when New Heights had Taylor Swift, you guys. So get ready, buckle your seat belts. We have Dr. Ted Rosen with us today. Dr. Rosen, you want to introduce yourself?
Dr. Ted Rosen (13:33):
Yeah, I'm Ted Rosen from Houston Republic of Texas. I had to get that in there. If you're going to plug Idaho then I’ve got to remind you that we're our own republic. Well, we used to be.
Dr. Lisa Swanson (13:50):
I love it, I love it. We each have our claims to fame. Well, we're going to tackle a delicate topic during our podcast today. And I feel like we should have the REM song, It's the End of the World as We Know It, playing in the background, because we are going to be talking about antimicrobial resistance, which is a hot topic that I care a lot about, I know you care a lot about, and I've heard you give some awesome talks on this recently. And I always emerge from them feeling a little bit depressed, but also empowered to make better choices in the future to impact people's health and the world as a whole. So, go ahead and take us through your feelings, where do we stand on antimicrobial resistance?
Dr. Ted Rosen (14:43):
Well, people worry about the world coming to an end because of nuclear Armageddon, or alien beings landing somewhere, and that's not where the problem's going to be. The problem's going to be with bacteria, or fungi, or viruses. They've been around for billions of years, and they've learned to live. We think that we're the top of the food chain, which I guess we are, but they've learned to live what we throw at them. And I think if I could leave the audience with any message it's this, you need to know what's going on in your area, because resistance patterns are highly geographic. But let me just give you an example. So a common thing, and one that would be near and dear to your heart, Lisa, is we have a kid with impetigo, or an adult with impetigo. It doesn't really matter very much.
(15:45):
And if it's not very significant, you're reflexively going to reach for Mupirocin. Or if it's not impetigo, maybe it's a superficial infection, you might reach for doxycycline or trimethoprim-sulfa because that always works. None of that is true anymore. So, there was a really, really good global study about Mupirocin resistance, it's about 8% globally. But if you look at the range of resistance, first of all for MRSA, generally globally it's up to 14%. And there was a paper from Miami that was 20%, and there's a paper, it's a little older, but it's from New York City, every borough was different, but Upper Manhattan was 40% resistance. In the county that I reside in Houston, it's almost 60% resistant.
(16:49):
And then, let's just quickly talk about oral agents for MRSA, MSSA, strep pyogenes. We used to not have to worry about doxy, resistance was about 1 to 2%, and you didn't have to worry about trimethoprim-sulfa at all, it always worked. That's not true anymore. 2024 study, looking at that throughout the United States, isolates collected from all over the U.S. We're looking at about 9% resistance. That's not a zillion percent, but it's more than zero for doxy and about the same thing for trimethoprim-sulfa. So, oh my gosh, you need to know whatever it is that you're isolating from a bacterial standpoint is actually going to be sensitive to what you treat it with. And it isn't the patient's problem, it's that they may be totally adherent. Or if it's a kid, it's not the parent's problem. They didn't stop applying Mupirocin, it's the drug is failing and you need to understand that.
Dr. Lisa Swanson (17:59):
And I have a question, a practical clinical question about this, because I feel like my inclination in the past, if I see something like impetigo, I've always been a culturer. I'll culture it because I want to know if it's staph or strep, and I want to understand the sensitivities, but I usually will go ahead and get patients started on treatment at that visit. Because I had impetigo when I was in college, it was devastating. I wanted to be better. It was on my face, it was awful. And so, I wanted to be better super fast. And so, I'm just programmed, get them started on treatment. We'll see what the culture shows in the end. Should I still be doing that, or should I actually be waiting to treat until I get the sensitivities back?
Dr. Ted Rosen (18:42):
Oh, no, what you're doing is perfectly fine. But it's that first step that you mentioned that a lot of our colleagues frankly don't do. "Okay, I know this is going to work, so I'm going to do it and I'll worry about it later." Well, later, it's already spread or it's gotten worse, or it can scar. Or if it's something that's more than impetigo it can get in the bloodstream. And now you've got to really worry, and you don't know what your step two is going to be because you haven't cultured. And let me just mention viruses for example. Same difference, herpes virus we have acyclovir and all its relatives, yes, in a normal host population that's going to be resistance, maybe a percent or two.
(19:29):
But what's happening in society now, we have so many immunocompromised and immunosuppressed individuals, cancer patients, HIV, immunosuppressives for collagen vascular diseases. Well, in that group it can be 10 or 20% acyclovir resistance for HSV-I or HSV-II, doesn't matter. So you need to know, is this going to work or not? Luckily, we do have a new drug coming, Pritelivir, which works in a totally different manner than acyclovir, and all its analogs should be out next year so that we have a backup. But right now, if you're using something that's not going to work anyhow, you need to have step two in mind. And in an immunocompromised or immunosuppressed patient, that can really be important.
Dr. Lisa Swanson (20:25):
Yeah. Oh, definitely. Definitely. And speaking of cultures and things, if I was confident in a diagnosis of tinea, I wouldn't culture. I didn't necessarily care about speciation. Now I always culture before I start treatment, I order speciation and susceptibilities. In fact, our stuff goes to a lab in Texas. So you'll be proud, proud of your Texas lab, because we have seen all of this resistant tinea now.
Dr. Ted Rosen (20:57):
Yes, this is now a dime a dozen. And here's the sad thing, I have a paper coming out talking about how to get those studies. It's easy for us to say, "Oh, well culture for your fungus, and make sure that you know what it's susceptible to." But the sad reality is the vast majority of labs can't do susceptibility for dermatophytes. They can for candida because that's an FDA approved test, but they can't for saprophytes, they can't for dermatophytes, and I'm talking about state labs now. The vast majority cannot do this, they cannot identify by genomic methods some of the very species we're most concerned about, like trichophyton indotineae, and trichophyton mentagrophytes subgroup VII, which are known to frequently be resistant. They don't have the genomic capacity.
(21:53):
There are literally a handful of labs that can do that. So, you could very easily end up giving one of our major drugs for tinea, or for candida for that matter, and have resistance, and you don't know it until maybe weeks or months later when you have clinical failure. In Europe, they're ahead of us because they do PCR, do sensitivity testing always. It's routine for them. For us, it's hard to even find anyone who can do that. So, we need to catch up.
Dr. Lisa Swanson (22:32):
Well, and it takes time. I do the swab in the office and I send it off, and usually it's a month or two before I get the results. And so, when I'm seeing a patient with tinea capitis say, I have started to have turmoil over what to choose first while I'm awaiting those results. Do I choose griseofulvin, terbinafine, itra? I don't want to overuse itra. What are you doing when you have that initial visit and you're like, "This is fungus. I know it's fungus, I'm going to do the culture," what are you starting first?
Dr. Ted Rosen (23:07):
So, it's the same thing that you would do with bacteria, your same protocol. I start with what I think it should work. So, for most dermatophytosis, terbinafine ought to work for those species that it's not sensitive to. It's up to 80% resistance for itraconazole, which would be my first drug if I isolate a saprophyte out of nails, for example, where that's not uncommon. So, most of the time itraconazole will work, whether you give it continuous, whether you give it as a pulse therapy really doesn't matter. It's your preference. But when you come to some species that are resistant now, like trichophyton indotineae, 20 to 30% of those will be resistant. But I start with a drug I still think will work first, and then I have a culture waiting with sensitivity that'll tell me what do I do if what I started doesn't work? That's the key.
Dr. Lisa Swanson (24:13):
Yeah, I love that. I love that. And if you would have one piece, one word of wisdom about antimicrobial resistance in the world today, what would you impart to our listeners?
Dr. Ted Rosen (24:27):
Number one, I'm going to give you more than one word. I'm sorry. Number one, culture. Number two, know what you're treating. Don't guess. Number three, which I think is really important, know the dose and duration. If you under dose or short duration of therapy, you are literally helping breed resistant organisms. So proper dose, proper duration, culture so you know what you're really dealing with, and sensitivities so if number one step doesn't work, what should be your proper number two step?
Dr. Lisa Swanson (25:06):
Okay, I love it. I love it. Now, in our final moments, Dr. Rosen, we're going to do my favorite part of the podcast, two truths and a lie. And so, I'm going to ask you to tell me three things about yourself, two are true, one is not. And then, I'll ask you some questions and try to guess which one is the lie.
Dr. Ted Rosen (25:26):
You ready for this?
Dr. Lisa Swanson (25:27):
I'm ready.
Dr. Ted Rosen (25:28):
You asked for it. All right.
Dr. Lisa Swanson (25:29):
I did, I did.
Dr. Ted Rosen (25:32):
I am a lifelong fan of the Chicago Cubs. I started collecting gold coins when I was eight years old. And I was a virgin when I got married. There you go.
Dr. Lisa Swanson (25:49):
Oh my gosh, I'm loving this. So Chicago Cubs, did you grow up in Chicago?
Dr. Ted Rosen (25:54):
I did, in Skokie, Illinois. It's a suburb of Chicago.
Dr. Lisa Swanson (25:58):
Okay. And have you ever been to Wrigley?
Dr. Ted Rosen (26:02):
How many times? I can't remember how many times.
Dr. Lisa Swanson (26:06):
Did you ever get to go to one of the World Series games there or the playoffs?
Dr. Ted Rosen (26:11):
In the year that the Cubs won the World Series, one of my friends has season tickets and I flew there and went to one game.
Dr. Lisa Swanson (26:22):
Love it. And then the coins, do you have a prize possession coin?
Dr. Ted Rosen (26:30):
Yes.
Dr. Lisa Swanson (26:32):
And are you willing to disclose what it is?
Dr. Ted Rosen (26:36):
It's a coin that was minted in Italy with the face of Napoleon Bonaparte, the French leader, when France conquered Italy. And they minted very few of these because they didn't think he was going to last, which eventually he didn't. But it's a very oddball thing. And I actually bought it in an auction because everybody thought it was a common French coin because they saw his name, but the writing was in Italian.
Dr. Lisa Swanson (27:14):
Love it, love it. And then to your third two truths and a lie, you were virgin when you got married. How old were you when you got married, Dr. Rosen?
Dr. Ted Rosen (27:22):
22.
Dr. Lisa Swanson (27:24):
22 years old. And were you in college when you got married?
Dr. Ted Rosen (27:29):
I was in medical school.
Dr. Lisa Swanson (27:31):
You were already in medical school, okay. So, I think the lie is that you were a virgin when you got married.
Dr. Ted Rosen (27:39):
Wrong.
Dr. Lisa Swanson (27:43):
What? But you knew all about the coins and the Cubs. Which one was it?
Dr. Ted Rosen (27:47):
Well, the actual thing is if you listen carefully, I started collecting gold coins when I was eight. Who can afford those things when you're eight years old? You get a few bucks to mow the lawn, or a little allowance. No, I didn't start till I was 12.
Dr. Lisa Swanson (28:09):
Oh, 12. 12. Oh my gosh.
Dr. Ted Rosen (28:11):
That was the lie.
Dr. Lisa Swanson (28:12):
Oh my gosh, I love it. Dr. Rosen, you got me. I had gotten the answers right in my previous podcast. Yes, you were the first one to get me.
Dr. Ted Rosen (28:28):
There you go. That's what you get for inviting a Texan on.
Dr. Lisa Swanson (28:29):
There you go, I knew it was going to be a wild ride. Well, thank you so much, Dr. Rosen, and thank you so much to our listeners. We appreciate you tuning in, I hope you learned something today and had a little bit of fun. Thanks so much.
Speaker 2 (28:42):
And now for the news. In our top story, new research suggests biologics are among the most durable treatment options for patients with psoriasis who experience major adverse cardiovascular events according to new claims data analysis from Korea, published in the Journal of Dermatology. The retrospective study examined data from almost 4,000 patients who experienced MACE after initiating psoriasis treatment between 2008 and 2021. Among those actively receiving treatment at the time of the cardiac event, almost 80% of patients on biologics continued their therapy compared to just under 47% of patients on non-biologic system agents, and 47% receiving phototherapy. Patients receiving biologics post-MACE were more likely to continue therapy than for cyclosporine, methotrexate, or phototherapy. Nearly half of those on non-biologic agents or phototherapy discontinued treatment entirely, and switching therapies was rare. The authors said the data show the need for better clinical guidance and reimbursement support for post-MACE management, and that the study support the preferential continuation of biologic therapy in the post-MACE setting and highlight the need to consider cardiovascular safety in the long-term management of psoriasis.
(29:52):
Data from a recent Swedish cohort study indicates a potential link between early life stress and later development of psoriasis. Researchers publishing in the Journal of Investigative Dermatology followed more than 16,000 children in the All Babies in Southeast Sweden cohort, tracking early life stress events and psoriasis diagnoses. According to their findings, a new family structure before age one was significantly associated with future psoriasis. Statistical significance was reduced somewhat following multivariable analysis. Despite this, the study authors emphasize the clinical relevance of the findings, pointing to a substantial effect size despite the adjusted models. Finally, in the newest edition of C-Suite Chats, Dr. Rafael Amado, head of global R&D at Zai Lab, shared preclinical findings presented at the 2025 European Academy of Allergy and Clinical Immunology Congress on a novel bispecific antibody targeting IL-13 and IL-31 receptors in the setting of atopic dermatitis. Here is a clip from that interview.
Dr. Rafael Amado (30:51):
Recently, the EAACI Congress in Glasgow presented pharmacodynamic results in non-human primates, showing that a single intravenous injection of 1503 at a dose of 10 milligrams per kilogram completely inhibited IL-13 signaling, which is measured by Phospho-Stat6, and also inhibited the scratching that is caused by IL-31. The minimum time was 76 days, but in some animals it went out to 133 days, which is remarkable for a single injection.
