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Hidradenitis Suppurativa Treatment, Biologics & Breakthroughs · The Science of Skin

• 0:08
  SPEAKER_02: Hello and welcome to the Science of Skin Podcast.
• 0:11
  SPEAKER_02: My name is Dr.
• 0:11
  SPEAKER_02: Ted Lane.
• 0:12
  SPEAKER_02: I'm your host for today.
• 0:13
  SPEAKER_02: I'm a board-certified dermatologist in Austin, Texas, and I am so excited to introduce our guest, Dr.
• 0:19
  SPEAKER_02: Steve Dave Lewey from Wayne State University.
• 0:22
  SPEAKER_02: How are you doing, Steve?
• 0:23
  SPEAKER_02: I'm doing great.
• 0:24
  SPEAKER_02: How about you?
• 0:26
  SPEAKER_02: Awesome.
• 0:26
  SPEAKER_02: I'm excited to talk today with a true world expert in hydratonitis superativa, which, if you don't know what it is, you will in about 30 minutes.
• 0:36
  SPEAKER_02: Steve is a full professor at Wayne State University.
• 0:39
  SPEAKER_02: He also leads the residence as a program director.
• 0:43
  SPEAKER_02: And otherwise, he lectures internationally on HS and other interesting topics.
• 0:48
  SPEAKER_02: But today we're just going to focus on the HS, Steve.
• 0:51
  SPEAKER_02: He also has an amazing beard and mustache.
• 0:54
  SPEAKER_02: And most male dermatologists at least have huge beard envy when we interact with Steve.
• 1:01
  SPEAKER_02: So Steve, if you don't mind, we're just going to jump right into it.
• 1:05
  SPEAKER_02: And let's kind of set the table here and talk about what is hydridenido superativa.
• 1:12
  SPEAKER_02: If you could, in your own words, just let us give us an idea.
• 1:15
  SPEAKER_01: It's funny because that is a question that we've sort of been debating.
• 1:18
  SPEAKER_01: You know, what is that succinct one-sentence description of HS?
• 1:23
  SPEAKER_01: And it's an inflammatory skin disease, but like a lot of our diseases, it's more than skin deep.
• 1:28
  SPEAKER_01: We know there's a lot of comorbidity, systemic inflammation.
• 1:32
  SPEAKER_01: We have really shifted away.
• 1:33
  SPEAKER_01: We used to hear people say a lot, like, oh, it's a sweat gland disease because it shows up in those areas that have our apoquin, apocrine sweat glands, like our axilla, our groin.
• 1:43
  SPEAKER_01: Um, but now we really understand the hair follicle seems to be at the center of it.
• 1:47
  SPEAKER_01: So you can get HS pretty much anywhere you have hair follicles, but it does tend to show up in those fold areas like the armpits, the groin, causes nodules, abscesses, they they scar, they form tunnels, and it just has such a huge impact on quality of life.
• 2:03
  SPEAKER_01: Like patients with HS, they everything they do is impacted by it, from their clothing choice to their activities, you know, they they can't ever forget they have HS.
• 2:12
  SPEAKER_02: Yeah.
• 2:13
  SPEAKER_02: It's probably the most impactful condition that we treat on quality of life.
• 2:19
  SPEAKER_02: I mean, just because even if if patients have what we call hurly stage one disease, so so early disease, we we stage HS into these hurley divisions based on essentially the amount of scarring as well as inflammatory abscesses and nodules and draining tunnels.
• 2:36
  SPEAKER_02: And it it's, you know, if you get one inflamed nodule or abscess, it is so painful, Steve, right?
• 2:42
  SPEAKER_01: Oh my gosh, yes.
• 2:43
  SPEAKER_01: And pain's the number one thing that brings people in to actually seek medical care.
• 2:47
  SPEAKER_01: Because sometimes if it starts off real mild, you might just try to take care of it at home, you know, a hot compress, a cool compress.
• 2:54
  SPEAKER_01: But that pain brings people in.
• 2:56
  SPEAKER_01: And the pain is so severe that sometimes patients, if they can't get access to say, go to the emergency room or in urgent care, sometimes they'll even lance the boils themselves at home because that little bit of pain of cutting a hole in yourself is a relief that leads to relief from the huge, excruciating pain of HS just tearing and stretching your tissues.
• 3:16
  SPEAKER_02: Yeah.
• 3:16
  SPEAKER_02: I'm a big fan of Seinfeld.
• 3:18
  SPEAKER_02: And I don't know if you've seen the the dermatology um episode from Seinfeld, and at the end, he's like, Why are there even dermatologists?
• 3:25
  SPEAKER_02: And he goes, skin cancer.
• 3:27
  SPEAKER_02: And he really should have said hydratinitis, because if we're thinking about the one thing where derms are truly so needed, it's to help with these poor, unfortunate people with HS.
• 3:38
  SPEAKER_02: Um so, Steve, let's just dive into kind of mechanisms of disease pathogenesis of HS.
• 3:44
  SPEAKER_02: It's super complicated, right?
• 3:46
  SPEAKER_01: So complicated.
• 3:48
  SPEAKER_01: We're right now collaborating with our friends down the street at Henry Ford and doing a genome-wide association study where you just kind of draw a bunch of blood samples from people, look at their DNA, and see where there tends to be little differences because it's not one of those easy genetic diseases of, you know, autosomal dominant, autosomal recessive, like blue eyes are.
• 4:07
  SPEAKER_01: Um, it's more complicated, but we're seeing mutations in the hair follicle genes, which makes sense to us because we know the hair follicles are involved, the immune system and the way it reacts to things, and then some of the like healing genes too, which may be why these don't really heal the right way.
• 4:24
  SPEAKER_01: Um, we think it all kind of starts at the hair follicle.
• 4:26
  SPEAKER_01: The hair follicle gets blocked up, that causes the oil to build up, the bacteria are already in there, kind of normal bacteria, but once they're trapped and they start really growing, the hair follicle ruptures, that triggers a lot of inflammation.
• 4:39
  SPEAKER_01: And then is when we get that abnormal healing process where instead of just kind of draining and healing, it starts to form these under-the-skin tunnels.
• 4:47
  SPEAKER_01: And it's strange, it's and this is one of the big challenges in HS is the pathophysiology kind of changes.
• 4:53
  SPEAKER_01: So in the early stages, really centered on the hair follicle, and that's why something like laser hair removal can be really effective.
• 4:59
  SPEAKER_01: But once you get the tunnels, they get these tertiary lymphoid structures, we call them, all around it, where it's so packed full of inflammation and T cells and B cells, it looks like a lymph node.
• 5:09
  SPEAKER_01: So then those are just sort of this nidus of ongoing inflammation.
• 5:13
  SPEAKER_01: And that's why a lot of times we'll see patients where medical therapy gets them so far, but then they need some surgery for the tunnels.
• 5:20
  SPEAKER_01: And once you take the tunnels out, then like everything is really calm because you've gotten rid of that source of inflammation in addition to sort of treating the underlying inflammation and preventing new spots from popping up.
• 5:31
  SPEAKER_01: But yeah, we're constantly learning more.
• 5:32
  SPEAKER_01: And every time I hear the people who are doing awesome research in HS pathophysiology, each time I hear a talk, I go, Oh, you figured it out.
• 5:40
  SPEAKER_01: And then the next talk comes up and I go, Oh, you figured it out.
• 5:43
  SPEAKER_01: Oh, and then I'm like, how do I put this all together?
• 5:45
  SPEAKER_01: There's neutrophils involved and macrophages and T cells and regulatory T cells are super low in HS, which maybe is why the inflammation is so out of control.
• 5:54
  SPEAKER_01: Um, but it's a hard one in clinic too, because patients go, okay, why did I get this?
• 5:58
  SPEAKER_01: And it's like, it's complicated.
• 6:00
  SPEAKER_01: It has to do with your genetics, maybe the microbiome that lives on your skin, your hair follicles.
• 6:05
  SPEAKER_01: But the big thing I always emphasize to patients is it's nothing you did.
• 6:09
  SPEAKER_01: It's not your fault.
• 6:09
  SPEAKER_01: It's not because you smoke, it's not because you're overweight or obese, it's not because something you ate or your hygiene, it's nothing that you did.
• 6:17
  SPEAKER_01: HS is not your fault, which is a good message for the patients because sometimes in their journey, they they don't get that message.
• 6:24
  SPEAKER_01: They do get a little bit more shame and blame from pay providers who sort of misunderstand some of those comorbidities and think that that that's the cause of HS is obesity or smoking versus just it's a comorbidity.
• 6:37
  SPEAKER_02: You know, I call it a kitchen sink diagnosis because we we throw all these different treatments at it, um, just trying to help these patients.
• 6:44
  SPEAKER_02: We we deal with the hormones, right?
• 6:46
  SPEAKER_02: We um Spronolactone, for example, birth control in females as well.
• 6:50
  SPEAKER_02: We deal with the microbiome, and it might be a topical antibiotic, or we talk about nutrition, we talk about bathing.
• 6:56
  SPEAKER_02: Um, the inflammatory component certainly that that's huge, as we know.
• 7:01
  SPEAKER_02: It's just so difficult to treat these patients.
• 7:05
  SPEAKER_02: Uh, and I feel for young dermatologists just coming out of residency or trying to figure their way out, and they get these HS patients and they may not have very much experience, but it's truly one where you need multifactorial treatment in order to really alleviate the symptoms for these patients.
• 7:21
  SPEAKER_02: And I think I'm so happy that we have so many biologics now that that are approved.
• 7:26
  SPEAKER_02: We have so much in the pipeline, which we'll go through.
• 7:28
  SPEAKER_02: But otherwise, Steve, if you're seeing an early stage one or two patients, give us some practice pearls.
• 7:32
  SPEAKER_02: Like what are you thinking about?
• 7:34
  SPEAKER_01: Yeah, and I love the way you phrase that question because I think it really is that the staging or like the severity really does make you look at patients differently.
• 7:43
  SPEAKER_01: So those early stage diseases, sometimes it's so early you're not even 100% sure if you can call it HS yet, right?
• 7:49
  SPEAKER_01: Like they've had a couple nodules come up and you're going, well, maybe just bad luck you've had two of them, but let's keep an eye on it.
• 7:57
  SPEAKER_01: Usually those patients I'll tell them, you may have this thing called HS, and then I spell it out for them because no one knows how to spell hydradnitis separativa.
• 8:05
  SPEAKER_01: But I tell them, don't freak out.
• 8:06
  SPEAKER_01: If you go home and you look this up online, don't freak out when you see how bad it can get.
• 8:10
  SPEAKER_01: We're not gonna let you get there.
• 8:12
  SPEAKER_01: You're with us, we're gonna get it under control.
• 8:14
  SPEAKER_01: Um, but the good thing is a lot of those early treatments kind of overlap.
• 8:18
  SPEAKER_01: Like you said, the the antimicrobial washes.
• 8:21
  SPEAKER_01: So we've got like benzoyl peroxide, um, chlorhexidine, we've got even the hypochlorite bleach and um zinc, like the zinc uh perithione washes can have shown benefit.
• 8:34
  SPEAKER_01: None have been studied with trials or or rigorous studies, but they're kind of like expert opinion.
• 8:38
  SPEAKER_01: We've all seen that they can be helpful, especially in early disease.
• 8:42
  SPEAKER_01: Even in later disease, I still give them to patients.
• 8:44
  SPEAKER_01: I say, I don't know how much it's helping, but like you said, we need all the help we can get.
• 8:47
  SPEAKER_01: It's all hands on deck.
• 8:48
  SPEAKER_01: So if it helps even a little bit, it's worth it.
• 8:51
  SPEAKER_01: Then we usually do like a topical clindamycin antibiotic.
• 8:54
  SPEAKER_01: Some people will reach for resortinol, which is commercially available outside of the US, like in Europe, but here you have to get it compounded.
• 9:02
  SPEAKER_01: I've just had trouble with my patients being able to afford compounded meds, so I don't use it a lot, but some people do reach for it if that's something you want to look into and get into.
• 9:11
  SPEAKER_01: And then a lot of times it's a little course of one of our antibiotics, like doxycycline, minocycline, clindamycin.
• 9:17
  SPEAKER_01: Um, a few years ago, we used to, the original studies we used a lot of clinda plus rifampin, both 300 milligrams twice a day.
• 9:24
  SPEAKER_01: And then some very smart people realize rifampin is a strong CYP3A4 inducer.
• 9:29
  SPEAKER_01: So when you take both of them, after a while your clindamycin levels are zero.
• 9:33
  SPEAKER_01: So now they did a study that showed Clinda alone was just as good and no increased risk of side effects as the duo.
• 9:39
  SPEAKER_01: So now I've switched.
• 9:40
  SPEAKER_01: I just do the clindamycin 300 milligrams twice a day by itself, and I'm seeing similar results to when I was using it with the rifampin, and now I don't have to warn people about orange tears and secretions.
• 9:52
  SPEAKER_01: But the other, the other important thing with those early patients is when do you really pull the trigger and talk about a biologic?
• 9:59
  SPEAKER_01: Um, because we have a big problem of waiting too long, and part of it is the patients often don't get to us when they're early.
• 10:05
  SPEAKER_01: It's getting better, I think, with with social media and with increased disease awareness and just more info out there.
• 10:11
  SPEAKER_01: Patients are kind of self-diagnosing sooner, and even doctors, the frontline doctors in primary care are getting to like know HS a little more, recognize it.
• 10:20
  SPEAKER_01: Um, so one of my favorite is definitely if a patient has any kind of evidence of tissue damage.
• 10:25
  SPEAKER_01: I think about it like acne.
• 10:27
  SPEAKER_01: You know, I see scarring, we're talking isotretinoin right away.
• 10:30
  SPEAKER_01: I've got to stop any more scarring from going on.
• 10:32
  SPEAKER_01: So if I see tissue damage, which is like significant scarring or even a tunnel forming, then I know, all right, we got to turn this off right away.
• 10:40
  SPEAKER_01: But even before the tunnel is that tricky one of when do I start a patient?
• 10:44
  SPEAKER_01: And so I like to use in Europe, they have a scale they call the IHS4.
• 10:49
  SPEAKER_01: And you basically count up the abscesses, nodules, tunnels, they each have a point value.
• 10:53
  SPEAKER_01: And with that, if you have three inflammatory lesions, either abscesses or nodules, at the same time, that counts as moderate disease.
• 11:00
  SPEAKER_01: And so sometimes I'll even ask patients that when they're still on that early side, like, have you ever had three active spots at the same time?
• 11:06
  SPEAKER_01: Because that's just a predictor that they're probably gonna go on and it's probably time to start talking about something to really get it under control if we haven't been able to.
• 11:14
  SPEAKER_01: Um, other things I love are in early disease, like you said, sporonolactone for female patients.
• 11:19
  SPEAKER_01: I love it.
• 11:20
  SPEAKER_01: I've started to use a little more phenasteride because you can use it in men or women, and in the studies, or it was just case series, not studies yet, so not a ton of evidence, but they sometimes started at a lower dose, but everyone ended up on the five milligrams daily.
• 11:33
  SPEAKER_01: So I just jumped to the five right out of the gate.
• 11:36
  SPEAKER_01: And then you're gonna make sure you see the patients back because that early disease, you want to make sure you are sort of keeping it on your radar, and if it starts to get worse or if they're not responding to therapies, you're going to that next step and adding to their regimen.
• 11:48
  SPEAKER_02: Yeah.
• 11:49
  SPEAKER_02: Steve, do you ever use acutane or isotretinoin?
• 11:52
  SPEAKER_02: I I think when I was in training, isotretinoin was first line.
• 11:55
  SPEAKER_02: Uh, but again, I was in training a while ago.
• 11:58
  SPEAKER_02: Uh so uh what what are your what are your thoughts on isotretinoin?
• 12:02
  SPEAKER_01: Same for me.
• 12:02
  SPEAKER_01: It was back then we had like nothing for HS, right?
• 12:05
  SPEAKER_01: So we had antibiotics and isotretinoin and prednisone.
• 12:08
  SPEAKER_01: And that was like all we we could really do for people.
• 12:11
  SPEAKER_01: Um I still use it sometimes.
• 12:13
  SPEAKER_01: I definitely reach for it in those patients who also have the nodulocy acne.
• 12:18
  SPEAKER_01: And I usually tell them I'm using it for your acne, but I hope it's gonna help your HS a little.
• 12:22
  SPEAKER_01: I have some colleagues who do like using it in combo even with the biologic.
• 12:26
  SPEAKER_01: Um, and I haven't reached for it a ton there, um, but I think that it's an area to explore.
• 12:32
  SPEAKER_01: We had some early studies that showed maybe an early disease.
• 12:34
  SPEAKER_01: It works okay, but later on it doesn't work so well.
• 12:37
  SPEAKER_01: It's also hard because, like you said, those studies were from a while ago.
• 12:40
  SPEAKER_01: We were probably including our most severe patients, like we usually do when a study comes out and you go, let's try this new thing.
• 12:47
  SPEAKER_01: So I think it could have a role.
• 12:48
  SPEAKER_01: Um, you can also use acetretin.
• 12:51
  SPEAKER_01: Um, so sometimes that's a little easier to get patients on long term because you don't have to deal with eye pledge and all the monthly issues that you have.
• 12:58
  SPEAKER_01: Still important to do your contraceptive counseling and and you know, use contraception, especially because a lot of HS patients are childbearing age females.
• 13:06
  SPEAKER_01: Um yeah, so it's it's in my arsenal, but I tend to use it a little more when they have the acne and the HS.
• 13:13
  SPEAKER_01: Or, like you said, when I'm running out of options, you you always get one of those HS patients where their HS just will not listen to you and you've got to bring in something new, try something different.
• 13:24
  SPEAKER_01: It keeps you on your toes.
• 13:25
  SPEAKER_01: Always, always trying to figure out new ways to help people.
• 13:28
  SPEAKER_02: What about intralesional kenalog or steroids?
• 13:31
  SPEAKER_02: Um, you know, something that you can do in the office in addition to drainage, even de-roofing, if you if you do some IOK.
• 13:38
  SPEAKER_02: How what are your thoughts on that?
• 13:40
  SPEAKER_01: I love it.
• 13:41
  SPEAKER_01: I, all my new patients, I tell them if you have a flare-up, you can call our office and the staff knows they don't even have to ask me.
• 13:48
  SPEAKER_01: If you say my HS is flaring, I need an injection, they'll just add you to the schedule that day or the next time I'm in, um, and you'll get in real quick.
• 13:56
  SPEAKER_01: And then I told all my staff, so they do know that.
• 13:58
  SPEAKER_01: Um, but I love it.
• 13:59
  SPEAKER_01: And I actually recently in the last few years, there were a couple publications out of Europe that showed higher dose, like the 40 milligrams per cc, can lead to sometimes permanent resolution of nodules, abscesses, and even some small tunnels.
• 14:14
  SPEAKER_01: Wow.
• 14:14
  SPEAKER_01: So I've started to just use that as concentration, even if it's the first time a spot is showing up.
• 14:18
  SPEAKER_01: I go with 40 milligrams per cc.
• 14:21
  SPEAKER_01: Depending on the size of the spot, sometimes it's a quarter CC, a half.
• 14:24
  SPEAKER_01: Um, I'll do, I try to keep my maximum to like three CC's in one session because they might start to get a little systemic absorption at that point, but not the worst thing in the world if they're flared up and a little steroid gets in the system.
• 14:36
  SPEAKER_01: Um, but yeah, and I found it it can be pretty good.
• 14:39
  SPEAKER_01: I've even had a couple patients where we scheduled a deroofing for a small tunnel, and I said, All right, while you're here, let me just inject it, but let me know how that goes.
• 14:46
  SPEAKER_01: And the patient calls and says, I don't need the surgery anymore.
• 14:48
  SPEAKER_01: It did when after you injected it, it closed up, it doesn't drain anymore.
• 14:52
  SPEAKER_01: So it's you know, prevented a couple surgeries.
• 14:55
  SPEAKER_01: But yeah, I'm a big fan of it.
• 14:56
  SPEAKER_01: And one of the key, I think, techniques that sometimes people run into is when it's a nodule, you can go right into it.
• 15:03
  SPEAKER_01: Yeah, but if it's an abscess or a tunnel, you don't want to go in that pocket.
• 15:06
  SPEAKER_01: Um, especially if it's not open and you go in an abscess, they'll scream in pain because that that stretching is already causing so much pain.
• 15:13
  SPEAKER_01: So you're actually going perilesional, kind of feel for normal skin right next to it and kind of plant it just next to it.
• 15:19
  SPEAKER_01: Um, and in a tunnel, it'll just leak out if you're in the pocket.
• 15:22
  SPEAKER_01: So then it's not gonna do anything.
• 15:23
  SPEAKER_01: Yeah.
• 15:24
  SPEAKER_02: Oh, you you stole my next question.
• 15:26
  SPEAKER_02: That's exactly what I was gonna say.
• 15:27
  SPEAKER_02: I've I've I've realized you have to kind of flood the area with the higher concentration of ketalog in order to achieve any kind of meaningful response.
• 15:35
  SPEAKER_02: And so just such a great practice pearl there, Steve.
• 15:38
  SPEAKER_02: Thank you so much.
• 15:39
  SPEAKER_02: Higher concentration.
• 15:40
  SPEAKER_02: Don't be afraid to use more than you think you need.
• 15:43
  SPEAKER_02: Flood the area and don't go straight into something that's inflamed.
• 15:46
  SPEAKER_02: I mean, your patients will hate you.
• 15:48
  SPEAKER_00: Yes.
• 15:48
  SPEAKER_02: Uh, and and you know, these poor all you're trying to do is help these people, and you're actually making them in so much worse pain.
• 15:54
  SPEAKER_02: So just be careful there.
• 15:55
  SPEAKER_02: Um, okay, that's just Steve, love this.
• 15:58
  SPEAKER_02: Let's go into biologics, okay?
• 16:00
  SPEAKER_02: What is currently available, as we know?
• 16:02
  SPEAKER_02: We've got adolymumab, secu, and bimekizumab.
• 16:07
  SPEAKER_02: Uh, what what are your thoughts on those three?
• 16:09
  SPEAKER_02: Is there one that you kind of turn to first?
• 16:11
  SPEAKER_02: And I don't want to get you in trouble.
• 16:12
  SPEAKER_02: I know you work with a ton of industry, but uh as do I, but but I think that you know we all kind of have our favorites, and or we we are able to determine maybe you have uh a decision-making algorithm in your mind as to which biological use for a certain type of patient.
• 16:30
  SPEAKER_01: Yeah, yeah, great question.
• 16:32
  SPEAKER_01: And I'm so glad we have three now.
• 16:33
  SPEAKER_01: I'm excited that soon we're gonna have a JAC inhibitor, we're gonna have more options.
• 16:38
  SPEAKER_01: Um I definitely, of course, like all of us, insurance dictates a lot of what we do.
• 16:43
  SPEAKER_01: So whatever I can get covered first line, I'll get covered first line.
• 16:46
  SPEAKER_01: But if I have any option, um, if they have inflammatory bowel disease, I'm definitely gonna go for edilemumab because the 17s, it's not an absolute contraindication, but if I can, I'm gonna avoid them.
• 16:58
  SPEAKER_01: I don't want to risk flaring up the IBD.
• 17:01
  SPEAKER_01: Makes sense.
• 17:02
  SPEAKER_01: Um, same thing if they have really bad nodulocystic acne that hasn't really done well with isotretinoin.
• 17:08
  SPEAKER_01: There's some pretty good evidence for the TNF alpha inhibitors for really bad acne.
• 17:12
  SPEAKER_01: Um, whereas there's not as much for the IL-17s, so I tend to reach for it there too, thinking, all right, kill two birds with one stone.
• 17:19
  SPEAKER_01: Um interestingly, I don't have an opinion yet about arthritis.
• 17:23
  SPEAKER_01: Sometimes you get the HS patients who just have that like arthritis and room goes, we can't figure out what this is.
• 17:28
  SPEAKER_01: And I say, it's just from their HS.
• 17:30
  SPEAKER_01: It's just HS can bring this arthritis.
• 17:32
  SPEAKER_01: And I don't have an opinion of if anything works better.
• 17:35
  SPEAKER_01: We know for psoriatic arthritis, the 17s and TNFs can both work.
• 17:39
  SPEAKER_01: Um, so I haven't really figured out a difference there yet.
• 17:42
  SPEAKER_01: Um, and then 17 inhibitors I like for patients if they're really kind of want less frequent dosing, that's one of the benefits that you get there.
• 17:51
  SPEAKER_01: Um the Bemikizumab is a nice option because it blocks the IL-17A and F.
• 17:56
  SPEAKER_01: So it does seem, I mean, there's no head-to-head, so technically I can't say it's more effective, but just looking at the numbers from the trial, they are a little higher for the people getting those high score 75s and 90s.
• 18:07
  SPEAKER_01: And I feel like in practice, it it does seem to have pack a little more punch.
• 18:12
  SPEAKER_01: It can come with a few more side effects.
• 18:14
  SPEAKER_01: Like I've had a couple more cases of oral thrush with the machizumab versus securinomab, but usually mild, treatable.
• 18:22
  SPEAKER_01: I've started recommending um, so there's these studies from diabetes that show xylitol containing gum can reduce candida, can inhibit candida growth.
• 18:33
  SPEAKER_01: So they had patients chew gum and it lasted about 12 hours.
• 18:35
  SPEAKER_01: So I tell my patients if you get this gum that has xylitol for the sweetener and chew that twice a day, it can hopefully decrease your risk of thrush.
• 18:43
  SPEAKER_01: Hasn't been studied in HS and in BIME, but it works for diabetes.
• 18:47
  SPEAKER_01: You know, I'm just kind of extrapolating it through.
• 18:50
  SPEAKER_02: Wow.
• 18:51
  SPEAKER_02: Um, that's a great practice, Pearl.
• 18:53
  SPEAKER_02: Uh, love it.
• 18:54
  SPEAKER_02: So uh totally agree with everything you said.
• 18:56
  SPEAKER_02: I think that Bimzelix or Bimekishimap does have obviously it's just there, right?
• 19:01
  SPEAKER_02: By fact that we just see greater high score 75, high score 90.
• 19:05
  SPEAKER_02: Uh, and we have such experience with it in PSA and PSO as well.
• 19:09
  SPEAKER_02: Um, feel very comfortable with both of those drugs, as well as as the TNF alphas.
• 19:14
  SPEAKER_02: But you know, what's interesting also, Steve, is what's in development.
• 19:17
  SPEAKER_02: Like the pipeline, as you you've already alluded to, is so rich and full, including a couple of drugs that are focused on the IELT 17 pathway.
• 19:26
  SPEAKER_02: Uh, so we got Sonolik Sonelokimab.
• 19:31
  SPEAKER_02: These names, man.
• 19:32
  SPEAKER_02: Right.
• 19:32
  SPEAKER_02: Sonelokimab, which I love the name of the company making it, Moon Lake.
• 19:36
  SPEAKER_02: I just I just I don't know there were lakes on the moon.
• 19:39
  SPEAKER_02: Uh and um, and so and it's targeting 17 ANF via a nanobody technology, which honestly I I was gonna ask you, I'm not familiar with the nanobody technology.
• 19:51
  SPEAKER_01: It is pretty cool, and that that makes me so excited for the Sonalocomab.
• 19:56
  SPEAKER_01: And so nano, it's a lot smaller.
• 19:58
  SPEAKER_01: So, you know, usually our biologics are these antibodies and they're pretty big.
• 20:02
  SPEAKER_01: You know, that's why you can't really take them orally, you've got to inject them, and they're these big particles that stay in the circulation.
• 20:09
  SPEAKER_01: So the nanobody is much smaller, and then it's actually not a biologic.
• 20:14
  SPEAKER_01: So the biologics are called that because they put genes into microorganisms to create these antibodies and then harvest the antibodies, and so it's a little bit more of a process.
• 20:24
  SPEAKER_01: The nanobody is a little bit more like organic chemistry, just kind of putting the molecule together.
• 20:30
  SPEAKER_01: Um, so the advantage of it being a lot smaller is in theory, and I think we've seen it in some of the studies, it penetrates the tissue better.
• 20:37
  SPEAKER_01: So we know like there's all that inflammation in around all this scarred and fibrosed tissue, but you've got to get there.
• 20:44
  SPEAKER_01: And so it kind of penetrates in there a little bit better.
• 20:47
  SPEAKER_01: It's also cool because since they're not a biologic, we can sort of design them.
• 20:51
  SPEAKER_01: So in the future, we may have nanobodies with two targets.
• 20:54
  SPEAKER_01: So maybe we'll have one that covers TNF and 17, or Ox40 ligand and TNF.
• 21:00
  SPEAKER_01: Um, so that's kind of cool too, that they have a little bit more potential in the future.
• 21:04
  SPEAKER_01: Um, so I'm excited for that one.
• 21:06
  SPEAKER_01: And they saw really good results in their phase three trials.
• 21:09
  SPEAKER_01: Um, they actually went for the high score 75.
• 21:12
  SPEAKER_01: So most of the trials go for the 50 as the bar to get approved.
• 21:15
  SPEAKER_01: They went for the 75, um, which we were like, good, impressive, go for it.
• 21:20
  SPEAKER_02: Finally raising the bar, right?
• 21:22
  SPEAKER_02: I mean, it's just as these newer therapeutics come out, we're raising the bar for what we expect in terms of um efficacy.
• 21:28
  SPEAKER_02: Uh yeah, you know, I'm just thinking as you're talking about these nanoparticles, these small molecules, you know, Icotrachindra is that small peptide, you know, approved just very recently for PSO.
• 21:41
  SPEAKER_02: And uh again, the idea is greater tissue penetration.
• 21:44
  SPEAKER_02: So I this is something that we're gonna see more and more.
• 21:46
  SPEAKER_02: I mean, as we look further into the pipeline, there's Azocobep as well, which is a small protein inhibitor of IL17A.
• 21:54
  SPEAKER_02: Also looking at high score 75, uh, that's an interesting molecule, also.
• 21:59
  SPEAKER_02: It It's it's a different technology, but I guess kind of the same idea.
• 22:03
  SPEAKER_01: Right, right, exactly.
• 22:04
  SPEAKER_01: And it'll be interesting to see, you know, like now we've got uh Sekokinumab as just the L17A antibody and then Bimikizumab L17 A and F antibody.
• 22:14
  SPEAKER_01: And then as we have these nanobodies coming out targeting IL17s, you know, what's gonna be it's gonna be interesting to see what our algorithm is.
• 22:22
  SPEAKER_01: Where do we start?
• 22:23
  SPEAKER_01: Where do we go?
• 22:24
  SPEAKER_01: Do they sort of replace each other, or like what role does each of them play?
• 22:28
  SPEAKER_01: And then it's exciting too that there's things coming out with new mechanisms of action or different things.
• 22:34
  SPEAKER_02: Yeah, so let's go into one of those.
• 22:35
  SPEAKER_02: Atrechobart from Lily.
• 22:38
  SPEAKER_02: Uh, this targets the chemokines to inhibit neutrophil uh chemotaxes.
• 22:42
  SPEAKER_02: So it's a it's a brand new therapeutic target, right?
• 22:45
  SPEAKER_02: It's essentially, I think of chemokines as like chumming the water, right?
• 22:49
  SPEAKER_02: For for the um the poly the PMNs to come in.
• 22:53
  SPEAKER_02: And here we're targeting those, we're decreasing that chum in the water.
• 22:57
  SPEAKER_02: And so we are hopefully limiting the inflammatory component of HS that way.
• 23:02
  SPEAKER_02: And they had a well, I was just looking 49% high score 50 at week 16.
• 23:06
  SPEAKER_02: So pretty impressive efficacy.
• 23:08
  SPEAKER_02: I don't know what their high score 75 uh is, but but that's an interesting new molecule, also.
• 23:14
  SPEAKER_01: Yeah, yeah.
• 23:15
  SPEAKER_01: And it's kind of like we were we were talking a little earlier where there's these varieties of HS presentations.
• 23:21
  SPEAKER_01: And so I think it's gonna be really interesting to see where different things might come into play.
• 23:26
  SPEAKER_01: Like if someone has a lot of drainage, is something like a trekkobart that targets the neutrophils, because we know really pus tends to be a neutrophil thing.
• 23:34
  SPEAKER_01: Neutrophils generate the pus.
• 23:35
  SPEAKER_01: So, like, will that work really well for them?
• 23:38
  SPEAKER_01: Um, and we sort of saw that with there was uh uh an IL or a uh C5A inhibitor that had a phase three trial a while back, and it it wasn't able to hit the high score, but it did really well for the draining tunnels.
• 23:52
  SPEAKER_01: And that's one of the downfalls of the high score is that if you decrease the abscesses and nodules, great, you can pass.
• 23:58
  SPEAKER_01: But if you decrease the tunnels, it doesn't help you.
• 24:01
  SPEAKER_01: The increase in tunnels can hurt you, and then you don't count as a responder, but in helping the tunnels doesn't really help, which was when they designed the high score, they were kind of thinking like medications don't really help tunnels, they help abscesses and nodules, but we just want to make sure you're not converting to tunnels and getting more.
• 24:18
  SPEAKER_01: Um, so that'll be interesting to see too.
• 24:20
  SPEAKER_01: Like these an anti-neutrophil agent, does it is there some characteristic about their HS that makes me lean for that?
• 24:26
  SPEAKER_01: Like if they have copious drainage, or does it just work for all of them?
• 24:29
  SPEAKER_01: Because, like you said, it's you know, that chum in the water that's just pulling in all this inflammation.
• 24:33
  SPEAKER_01: Can we just turn it right down?
• 24:35
  SPEAKER_02: Yeah.
• 24:36
  SPEAKER_02: Steve, you make you you bring such a great point into the conversation, which is the limitations of the endpoints that we use.
• 24:43
  SPEAKER_02: Um, and and I completely agree with you, like that it just doesn't encompass, it would be very difficult to encompass every aspect of HS, right?
• 24:51
  SPEAKER_02: And so we really, when you're looking at the data, I think you have to take it with a grain of salt and that high score, as you mentioned, really focuses on that abscess and nodule component, but doesn't focus on on the draining tunnels, which for many patients is is just as impactful on their quality of life as you can imagine, trying to change bandages and deal with draining uh tunnels, especially on your backside when you're trying to sit all day or something like that.
• 25:17
  SPEAKER_02: It's just it's really horrible.
• 25:19
  SPEAKER_02: So thank you for bringing that up.
• 25:20
  SPEAKER_02: Super important point that I had failed to mention.
• 25:23
  SPEAKER_02: So um as as we look further into the pipeline, Remy brutinib, I find that to be so interesting, Steve.
• 25:29
  SPEAKER_01: Me too.
• 25:30
  SPEAKER_01: And it's funny, before before we started talking about Remy brutinib, I didn't really know what brutin's tyrosine kinase was.
• 25:36
  SPEAKER_01: You know, like these drugs teach me new things.
• 25:38
  SPEAKER_01: I'm like, what is it inhibit?
• 25:39
  SPEAKER_01: I gotta go read up on that.
• 25:41
  SPEAKER_01: And it's an interesting one because we see some of these overlaps, right?
• 25:44
  SPEAKER_01: Like all three of the drugs that were approved for HS also were approved for psoriasis.
• 25:49
  SPEAKER_01: So it was kind of like, okay, that we we get it, some similar pathways.
• 25:53
  SPEAKER_01: Well, Remy Brutnib is approved for spontaneous urticaria.
• 25:56
  SPEAKER_01: And so you're going, oh, this is kind of interesting.
• 25:58
  SPEAKER_01: What's this overlap in inflammatory pathways through this BTK with, you know, because that's not one that I typically think of.
• 26:06
  SPEAKER_01: You know, I think like arthritis and HS, yeah, you see some sometimes together.
• 26:11
  SPEAKER_01: Um, but yeah, the urticaria isn't one, but it is kind of funny because we've come to recently appreciate how much important itch can be in HS too, where a lot of the patients are really itchy.
• 26:22
  SPEAKER_01: Um, so yeah, that's an exciting one to see how it's gonna, and it the trial's underway.
• 26:28
  SPEAKER_01: So hopefully it'll be coming out soon.
• 26:30
  SPEAKER_01: I do have one patient I've treated with it because she did have urticaria and HS, and it was perfect timing.
• 26:36
  SPEAKER_01: I go, hey, there's a new medication for your urticaria, and we're gonna start it because you also have HS, and I I have reason to believe it will work for both.
• 26:45
  SPEAKER_02: Yeah, yeah, we're involved in that trial, and and I'm blinded, right?
• 26:48
  SPEAKER_02: So, but I'm just so excited about the idea.
• 26:50
  SPEAKER_02: It's it's such a well-tolerated, you know, and it's oral as well.
• 26:55
  SPEAKER_02: I mean, lots of great opportunities with Remy.
• 26:57
  SPEAKER_02: So I'm I'm I'm hopeful that this plays out well.
• 27:01
  SPEAKER_02: And then, of course, you know, the big kind of gorillas are the jack inhibitors that we actually haven't talked about, but so much support for the use of jack inhibitors in HS, right?
• 27:10
  SPEAKER_01: Yes, so much.
• 27:11
  SPEAKER_01: And we should be seeing Povor Sitnibs approval pretty soon.
• 27:15
  SPEAKER_01: So we'll have access to our first jack in HS, which is really exciting.
• 27:20
  SPEAKER_01: Um, because I think jacks do have that role of, you know, like if you have just the right cytokine, like in psoriasis, 17 or 23, and we've got our biologic is like the sniper who just takes that cytokine out, but it was the key thing, and everything just melts away.
• 27:34
  SPEAKER_01: Like we mentioned earlier, HS were not there.
• 27:36
  SPEAKER_01: You know, it's it's a messier inflammation, there's more stuff going on.
• 27:39
  SPEAKER_01: So you take out one of the pathways, and the other ones are still kind of lingering and going.
• 27:44
  SPEAKER_01: And so I think the jacks are a little nice for that, where they kind of hit on different pathways through that uh surface receptor mechanism where they kind of come together and converge.
• 27:55
  SPEAKER_01: Um, some people have asked me, well, are you a little more nervous?
• 27:57
  SPEAKER_01: Because with HS we have a higher proportion of smokers, obesity, cardiovascular risk factors, right?
• 28:03
  SPEAKER_01: And I said, Well, you know, it's a conversation we'll have to have with patients, but luckily we're a little spoiled in Durham that so far we haven't seen those boxed warning safety signals with RJAC inhibitors.
• 28:14
  SPEAKER_01: So I still tell that to patients, and even the pack, it's the one time I have them look at the package insert, right?
• 28:19
  SPEAKER_01: Usually I'm like, don't read the package insert.
• 28:21
  SPEAKER_01: But this is the one time where I go, no, look, actually, look, it says a different drug in a different patient population had this side effect.
• 28:27
  SPEAKER_01: They're just putting it here because your drug is in the same grand family.
• 28:31
  SPEAKER_01: And then I kind of like that they put it on the cream too, because then I go, they even put it the more this warning on the cream, you know, and then patients feel a little better.
• 28:39
  SPEAKER_02: Yeah, I think we're getting to the point where thankfully companies are producing more and more safety data as this drug is these drugs have been out, and we're seeing some great safety, uh, five-year safety data for one of them, for example, yeah.
• 28:51
  SPEAKER_02: That uh really allows me to it increases my confidence in these drugs, and I pull the trigger to use them much more quickly now than I used to.
• 29:00
  SPEAKER_02: Um so very excited about Povor as well.
• 29:03
  SPEAKER_02: Um, and and we were part of those trials long term also, and and I think that's gonna be a very, it's gonna be a great addition to our momentarium to treat our HS patients.
• 29:11
  SPEAKER_02: Um, Steve, uh one last question, if you don't mind.
• 29:14
  SPEAKER_02: Uh just the GLP1 agonists and how you what how do you consider using them, if at all, in your HS patients?
• 29:23
  SPEAKER_01: It's funny because I'm teetering on the decision of do I start writing them?
• 29:27
  SPEAKER_01: Initially I had been reluctant just because I thought, hey, we've got enough Pryroth burden for my staff to deal with.
• 29:33
  SPEAKER_01: I'm not gonna add on these drugs.
• 29:34
  SPEAKER_01: And when they first came out, you couldn't even get them anywhere, and it was just a nightmare.
• 29:38
  SPEAKER_01: Um, but we've had that we've had a couple smaller studies.
• 29:41
  SPEAKER_01: One was prospective, one retrospective that did show benefit.
• 29:44
  SPEAKER_01: One of them, when they did their multivariate analysis, the benefit for HS was actually independent of weight loss.
• 29:51
  SPEAKER_01: And we've seen that with some of the psoriasis studies too, where they the psoriasis starts clearing up before they really have significant weight loss.
• 29:57
  SPEAKER_01: So I do believe that it's got those inflammatory pathways that it's blocking too.
• 30:02
  SPEAKER_01: Um and I've seen, like I said, I haven't written them for patients.
• 30:05
  SPEAKER_01: I've written once because well, patient longtime patient, of course, talked me into it, but it went well.
• 30:10
  SPEAKER_01: Um, but um, I've seen patients come back and I've had some of those patients where we're a little bit stuck on their HS progress, you know, kind of hovering in that like better, but could be doing better.
• 30:20
  SPEAKER_01: And each visit, we're tweaking things, and then all of a sudden they get on a GLP one and it's like, wow, now you're doing considerably better.
• 30:26
  SPEAKER_01: So I do think they're gonna play a pretty big role, and it will be interesting to see, even in that sense of like dual inhibition, is that gonna be something we do sometime?
• 30:35
  SPEAKER_01: Like you're taking a GLP one and a TNF at the same, like one drug, you know, take it together.
• 30:42
  SPEAKER_01: So, so I think that'll be really exciting.
• 30:44
  SPEAKER_01: And of all our drugs, you know, you always have to kind of talk to patients, get them talk to them off the ledge about the side effects, convince them that it's a good idea to take it.
• 30:53
  SPEAKER_01: They're apprehensive, not GLP ones.
• 30:55
  SPEAKER_01: They're like, give it to me.
• 30:56
  SPEAKER_01: I love it, I want it.
• 30:57
  SPEAKER_01: You know, you're like, Can we talk about side effects?
• 30:59
  SPEAKER_01: They're like, nope, just give it to me.
• 31:02
  SPEAKER_02: That's so true.
• 31:03
  SPEAKER_02: Uh yeah, that's an easy win, right?
• 31:05
  SPEAKER_02: With the GLP one.
• 31:06
  SPEAKER_02: Yeah, like, oh, it's a shot.
• 31:08
  SPEAKER_02: I don't care.
• 31:08
  SPEAKER_00: Yeah.
• 31:10
  SPEAKER_00: You might be on it for life, no problem.
• 31:12
  SPEAKER_00: Um, right.
• 31:13
  SPEAKER_00: Every other drug, they're like, Do I have to take this forever?
• 31:15
  SPEAKER_00: You're like, can we just get your disease under control before we talk exit strategy?
• 31:19
  SPEAKER_02: Yeah, yeah, it's it's so true.
• 31:21
  SPEAKER_02: Uh I I I have maybe a little bit more experience than dealing uh using GLP1s for my HS patients, and I found them to be incredibly helpful.
• 31:30
  SPEAKER_02: I I think that the anti-inflammatory component really does make a difference.
• 31:34
  SPEAKER_02: I mean, we just saw, you know, Lily just released their um data on on trzepatide plus TALTS plus Ixakizumab, and we saw incredible synergy there for PSA or excuse me, PSO.
• 31:46
  SPEAKER_02: And here were, you know, just my anecdotal experience really impressive what the it what it can do.
• 31:53
  SPEAKER_02: I mean, certainly not, it doesn't knock out the disease, but again, with the idea of how can I improve my patient's quality of life, I feel like it's worth it uh for them.
• 32:02
  SPEAKER_02: Um, so anyway, Steve, listen, thank you so much.
• 32:06
  SPEAKER_02: I really appreciate your time and your in your incredible expertise as well.
• 32:10
  SPEAKER_02: And I've enjoyed this so much.
• 32:12
  SPEAKER_02: So uh everybody's Dr.
• 32:13
  SPEAKER_02: Steve Dave Lewey, he's a full professor at Wayne State University, uh, just an incredible guy.
• 32:18
  SPEAKER_02: If you ever get a chance to to hang out and talk with Steve, you will not regret it.
• 32:23
  SPEAKER_02: And um uh my name is Dr.
• 32:24
  SPEAKER_02: Ted Lane, I'm a board certified dermatologist leading the uh this podcast in the science of skin.
• 32:30
  SPEAKER_02: Thank you so much for listening.
• 32:31
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• 32:33
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• 32:35
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• 32:38
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• 32:44
  SPEAKER_02: We try to produce content that is right at the cutting edge and is also relevant to your practice.
• 32:49
  SPEAKER_02: So thanks again for listening, Steve.
• 32:51
  SPEAKER_02: Thank you.
• 32:52
  SPEAKER_02: Uh, how can people get it get it a hold of you or find what you're doing, Steve?
• 32:55
  SPEAKER_02: Do you have an Instagram?
• 32:56
  SPEAKER_02: Are you active at all?
• 32:57
  SPEAKER_01: I do.
• 32:58
  SPEAKER_01: So my Instagram, not surprisingly, is at Dr.
• 33:01
  SPEAKER_01: like spelled out D-O-C-T-O-R underscore beard underscore M D.
• 33:07
  SPEAKER_01: So Dr.
• 33:08
  SPEAKER_01: Beard M D.
• 33:09
  SPEAKER_02: That's awesome.
• 33:10
  SPEAKER_02: Okay, got it.
• 33:12
  SPEAKER_02: Well, everybody please follow Dr.
• 33:13
  SPEAKER_02: Dave Louie.
• 33:14
  SPEAKER_02: You you will learn something every time.
• 33:16
  SPEAKER_02: Okay.
• 33:17
  SPEAKER_02: Thanks again for listening.