Adelaide A. Hebert, MD

Experts explore the challenges of multi-product topical treatment algorithms for seborrheic dermatitis (SD).

Simplifying Treatment Regimens for Patients With SD

 When we go back and look at the clinical trial data and look at the areas that were treated, for the majority of patients, they were treating the scalp, but a lot of patients were treating the face and even the eyelids. So, James, when somebody has seborrheic dermatitis and it’s kind of creeping down on the face and it’s the glabella area and it’s the eyebrows and it’s kind of the whole central face [that] starts to get involved, in the past, what have you done if it’s in that periocular area?

 It’s a challenge, Linda, because we like to use topical cortical steroids as kind of a quick treatment, but we also know using steroids around the eyes can be getting to tiger territory, right? So glaucoma, cataracts, increased absorption, and so we have to be very judicious with using steroids in those areas. Topical calcineurin inhibitors has already been set. It burns, it stings, especially in those areas, and I found that topical azoles just don’t work quite that well either, so it’s great that we have a foam that’s highly efficacious and extremely well tolerated, even in these sensitive areas.

 What’s funny, because you’re talking about the azoles, patients just get into the mode of thinking, well, this is a fungal infection, this is ringworm, and you have to eventually try to break that cycle. It’s like, look, all these azoles shampoos and over-the-counter antifungals, let’s get rid of this, because it doesn’t have the mechanism that’s directed at the pathogenesis of the disease.

 And what’s interesting here is when we talk about the areas of involvement, as you mentioned earlier, and look at the patients who are in the clinical trials, the majority of patients had multiple areas of involvement. So [it’s about] simplifying the treatment regimen. We all have those patients who come into our office, they’ve seen a number of our colleagues, and they have the bag. I mean, do you all see the bag?

 The suitcase. The bag usually has some demon eggs in it too.

 And you know what happens is that we make treatments so complicated. I say we give patients so many things to do, and in this case, if it’s the scalp, it’s the face, it’s the body, and then they go home, and you give them several things, I say they end up incapacitated by fear, because you gave me so many things to do, I just don’t even know what to do, but say I have a little clobetasol, I know that that worked OK, my scalp was a little bit better, so maybe my face is a little bit better…. I had a patient this week who came in with very significant rosacea, and [the treatment] came from somebody, he’s like, “Well, I have something on it, I don’t know what it begins with, maybe it’s a B or something like that.” Turns out this patient was using a very potent steroid that he had gotten for somewhere else, but he started to notice that if he used it on his face, things went away faster. But then it becomes this vicious cycle, and you can get a steroid-induced rosacea. So I think the idea of simplifying and giving patients one thing to do once a day really helps with this whole process.

 That goes back to what we were talking about before with what else is concomitant, right? The acne patient who’s still got seborrheic dermatitis up here, but a lot of forehead involvement with comedones; the rosacea patient who’s got seborrheic dermatitis; even the tinea versicolor patient; we’ve seen overlap with those. So you’re right about trying to be a minimalist, but at the same time, we have to spell it out for them on what each step means to the process. We’re talking about the disease they’re not going to cure, right? This is something that they’re going to be treating, but maybe they can at least wind down to the number of things they’re using.

 Absolutely. So any other thoughts on the clinical trial? Anything that struck you in terms of the design? How important is it? And I want to know, we have lots of different treatments, and we have potentially once-a-day treatments versus twice a day treatments. Does that really matter? Shawn, I’m going to start with you. Do you care if something’s a once a day or a twice a day, or do you feel like you’re setting your patients up for better success if it’s a once a day?

 The once a day gives me a lot of ease, because I think it’s much easier to follow for patients. When we were talking about the different therapeutics, I was thinking about how we break particular topical steroids, for example, and then from our perspective, the provider perspective, we write, “Do not apply longer than 7 days to this area” in all caps, then we get a little bit worried. And how simple is it to just have a once daily preparation for patients? So I think that’s great for patients, it’s great for us too.

 Yeah, and Adelaide, we go back to the mechanism of action, and we have the other topical PDE4, but there’s a difference here, right? That one [is] twice a day versus once a day, ointment versus a foam, which is also available on a cream. What about for a kid? Does it matter once a day versus twice a day?

 I think it’s huge. I think every parent is very grateful if we have a product that they can just use once a day. Now many 9-year-olds are mature enough to take over some of their own skin care. It varies with the child in the household, but I think anything that simplifies the regimen is a value added. I also think that, we haven’t mentioned it, going to the pharmacy and having just 1 co-pay instead of the 3 co-pays for 3 products, which patients could confuse, is another value added. That wasn’t part of the study, but that’s the reality that our patients face when they have to buy medicines in multiples, and we want to simplify that part of their life as well.

Transcript was AI-generated and edited for clarity. 

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Experts explore the challenges of multi-product topical treatment algorithms for seborrheic dermatitis (SD) and the value of once-a-day solutions in fostering adherence, improved quality of life, and overall better outcomes.

Dermatologists discuss the safety and efficacy of roflumilast for seborrheic dermatitis (SD).

The Safety and Efficacy of Novel SD Treatment

 We have a lot of really interesting data, and maybe you can help us…understand what about the safety and tolerability?

 We actually, from the phase 2 study, have 24- to 52-week open-labeled data for roflumilast. It was well tolerated with low rates of adverse events. Actually, there were no imbalances between the treatment arm and the placebo arm and most of these adverse events were mild or moderate in severity. Most patients with hypo- or hyperpigmentation experienced a full resolution as well.

 OK, so do I have to worry about this? The scalp has really tremendous penetration, right? We all know if we do a scalp biopsy, for me, I usually hit a blood vessel almost every time. We’re going to be bleeding, and we know penetration is great. Do we have to worry about systemic absorption? Is that something that would concern you or not really?

 Not from the trial data because we know this is also going to be very localized areas and we didn’t see any signals there in terms of any adverse outcomes.

 And we know that [oral] PDE4 is used in dermatology and it’s safe, and so I agree. It’s not something that would concern me. When we think about a nonsteroidal, the first thing that comes to mind for me is, and this is true for psoriasis or atopic dermatitis, when we think about nonsteroidal, the first thing I think about is maybe very modest efficacy, but I also think about stinging and burning.

 Yeah, and that was the knock, unfortunately, on the few predecessors that came to market. Some of that was probably more vehicle-driven. Some of it was activity on the active rash that was perceived, because you put some of those same medications on normal skin and there was no stinging and burning. So, a lot of it you could also blame on the rash itself. It’s contributing to that. But from what we saw in the studies, the foam didn’t contribute to any of that, which is good. Again, seborrheic dermatitis doesn’t have as many open areas. It’s probably not as fissured. It’s not as volatile for some as atopic dermatitis would be on the different parts of the skin. That being said, though, a nice, elegant foam is going to lead to long-term adherence, which I think is just as pivotal to the long term about using nonsteroidal drugs because I want to be able to give someone 6 months of this and say, “Let’s just go to work.” I don’t want to worry about atrophy. I don’t want to worry that they’re using too much or doubling the dose. And even more so, when we go back to where we’re treating, think about the chest or even the intertriginous areas, if there

is seborrheic dermatitis there, especially scalp and face, you really don’t want to have to be thinking about how many prescriptions do I have to limit, or are they going to go out and shop this from somebody else? The vehicles that incorporate nonsteroidals will not have the issues. But again, we can’t blame our predecessors for what we have now. Now we have to think about where we’re going forward with incorporating the right molecule in the right vehicle.

 I also wanted to add to that because I think as trialists, one of the things we notice that with the patient in short hair or long hair, they all valued this vehicle. They found it was really great. They weren’t applying the vehicle or the medicine all the way down the hair shaft, but I found that male and female patients equally found it acceptable, tolerable, and whether the patient was 9 years old or 50 or 60 years old, there was really good acceptance of this product. And many of them commented about they liked the way it actually made their hair feel. That wasn’t a captured comment, but they just spontaneously brought that up during the course of the trial.

 There wasn’t any residue. There wasn’t anything that they felt like, “Oh, I’ve got to redo my hair.” And even more, we’re still reminding them, “Treat your scalp. Let’s focus on where the disease is, which is in your scalp.” Or in the case of what we could do for it, different hair-bearing areas around the neck or the upper shoulders or the mid-chest and men, these are all areas that have all been difficult to treat with the wrong vehicle.

 Now we’ve talked about the vehicle and patients with skin of color. And I had patients who had various hairstyles, various skin types, and I agree. It was uniformly accepted, even in women who have skin of color who maybe wash their hair once a week or even every other week, and still found that this was an acceptable vehicle, an acceptable topical that they could use every day without a problem. And I want to go back to something interesting about foams, because not all foams are the same. In the past we’ve had hydroethanolic foams that when you put them on, [they have] high amounts of alcohol that sting and burn. This is not this is not the same foam; it’s different.

 Well, it goes back to the excipients. The excipients are going to cause irritation or potentially be an allergen. That’s going to be very dose limiting. But to your point about the spread, like think about someone who wears their hair in braids or cornrows, someone who has longer [hair], or, like Adelaide said, maybe some shorter hair, application of the foam into the scalp still has to be the pivotal way of delivery that everybody has to be taught. So if the right foam is going there and it has an easy spread and it’s not going to leave residue or sting, then I then will maximize adherence for the long run.

 Neal, I just wanted to add, I’m glad that you mentioned excipients, [as] we know not all vehicles are the same. The main purpose of the vehicle is to get that active ingredient…into the target [area], and depending on what excipients you’re using, it could be poorly well tolerated. We do a lot of patch testing, and we are seeing a pretty significant amount of propylene glycol allergies. I think it’s important to recognize that this does not have propylene glycol in it; it’s extremely well tolerated.

 Now, Adelaide, this was tested down to age 9. Are you comfortable using a topical PDE for inhibitor, even one that’s much more potent than the ones we’ve seen in the past, on a 9-year-old child?

 Absolutely. Based on the safety data we have from the study as well as a maximum-use study, this drug was very well tolerated; the patients really liked it. The other thing [is], I think because patients had tried things before that that weren’t that good, that’s why they kept coming back. When they finally got to a product that benefited them, that was well tolerated, they liked it on their hair, they were really exceedingly happy to finally discover that there was hope for the future, [that] we might get a medication in a good vehicle that could really help them with their seborrheic dermatitis. But I think the children tolerated [it] absolutely as well, at least in my experience, as the adult patients we enrolled.

 So, [it’s an] interesting study. Interesting in the fact that we looked at kids we looked at adults we looked at mild, moderate, or severe. We have a 0.3% foam. Shawn, going back to [what I] asked you before, now I’m coming into your office. I’ve used over-the-counter products, maybe I’ve used a prescription or 2 or 3. How would you incorporate this into [treatment for] a patient who has maybe moderate seborrheic dermatitis? Maybe I have it in my scalp, but I might also have it on the body.

 I have a lot of confidence in roflumilast foam in particular, because we have the clinical data back in and up. For these other agents that we are using, we actually don’t have much data, if any at all, in seborrheic dermatitis. So that gives me a lot of confidence, and I think the mechanism of action of the drug being able to target these different ends of inflammation, as we talked about, makes it for me a clear frontline choice. I would probably go with it first.

 Yes, it goes back to what we were talking about before, bringing drugs to market so they can get FDA-approved. There’s one thing to be FDA-approved, there’s another thing [for it] to work. If it actually works, then we can actually go back to saying, look at all the data behind it, even though there’s no phase 3 study with X amount of patients in it to bring it to a market label. So, again, that comes back to us, being able to talk to the patients and say, “This is the most effective treatment on the market based on the trials.”

 And sometimes we get a new drug in an area where there are so many drugs approved, but here we’re getting a new agent where there is nothing.

Dermatologists discuss the safety and efficacy of roflumilast for seborrheic dermatitis (SD), highlighting its tolerability across backgrounds and age groups, safety in pediatric care, and the unmet need it fulfills.

Dermatologists discuss a groundbreaking agent, roflumilast, filling a void in seborrheic dermatitis (SD) treatment. 

Topical Foam: A Breakthrough in SD Treatment

 That brings us to talking about what is new, and it’s a new world. We have a very viable new option that actually fills the gap of what we’ve been looking for. We have a topical roflumilast foam. Adelaide, can you tell me, what is roflumilast foam, and why should I care?

 Roflumilast foam was compounded because we needed a product that could be successfully used on hair-bearing skin. And we knew that if we gave a regular cream, the acceptance was going to be extraordinarily poor. That just is not going to work. I wouldn’t accept that. I wouldn’t expect my patients to accept it. So with that in mind, and given that we have so few products, as you alluded to, roflumilast foam came of age. And I think it’s going to be a great advance. We’ve all had experience with it as clinical trialists, and I think it was very well accepted by the patients for whom we used it. In terms of the mechanism of action of roflumilast, we know that it’s a PDE4 inhibitor, and it reduces and controls cyclic AMP levels, so they stay normal. And in doing so, they actually reduce inflammatory cytokines. We know that this is an inflammatory skin condition. We’ve all talked about that. Ideally, we can control the inflammation, which will help repair the barrier and make the patient be less uncomfortable, less scaly, and less troubled by the disease state.

 So you mentioned a PDE4 inhibitor, and that’s not a new, novel concept for dermatology. We’ve seen PDE4 inhibitors before in dermatology. Are they all the same?

 No, fortunately, they’re not all the same. And this was a specially formulated agent in that we know it would have greater capability and greater bioavailability in some of the previous PDE4s that we’ve had for atopic dermatitis.

 So it’s interesting. So this is, as you mentioned, it’s a novel, kind of like topical steroids. When we say we have a topical steroid, it doesn’t mean that every topical steroid is the same. We have different formulations. We have different potencies. We have different vehicles. So this is, as you mentioned, topical PDE4. Love the fact that it’s a foam because for the scalp, vehicle matters so much because some people will want an ointment. Some people will say, “Give me something that doesn’t leave any residue.” We have a vehicle that actually is elegant enough to be used potentially on the face, on the scalp, or on the body. So we have a really interesting study where we looked at roflumilast, 0.3% foam formulation, and compared that [with] the vehicle foam. The exciting thing was we looked at this in kids. So, as you mentioned, it happens in kids. We looked at it all the way down to age 9. It’s a once-daily formulation, which is nice because if you give somebody something once a day, it’s a little bit easier to incorporate into your activities. You can put it on when you want to. [Patients] had to have 20% body surface area or less. And we did the head-to-head study, active drug versus vehicle, applying it once daily for 8 weeks. What’s interesting is we looked at patients who had mild, moderate, or severe disease, which is nice because we’re taking all comers, giving them one thing, once a day, that’s not a steroid. I always use the term one-stop shopping. I like to be able to say, “OK, I’m not giving you one thing for your scalp, one thing for your face, one thing that’s a little bit stronger for your body.” Here’s one medication that you can potentially use in any area that’s involved. And what we found was, when we look at the active drug versus the vehicle, we saw actually a statistically significant separation as early as week 2. And that difference continued over the course of 8 weeks. And we found that highly statistically significant, up to about 80% of patients getting to clear or almost clear. You know, you’ve been doing clinical trials for a while. For 80% clear or almost clear, is that something that you’ve seen before?

 That’s a very lofty mark to try to replace in any study. I think the bigger testimonial was that when the trial was over, patients did not want to give this up. They wanted to hang on to it no matter what.

 So this is actually very interesting. I wonder if you all see this as well. So, I know if a drug is going to make it out of clinical trials and be something that’s a winner, on the last day, people either forgot their medicine, they lost their medicine, right? Or I would get things back that had been emptied out at home. Sometimes the bottom’s cut out and squeezed, or the foams.

 My favorite line was, “I’ll go back and get it.” [That] never happens.

 Never, never. And so that’s how you know this is a medication that potentially does well.

 Which boasts your point about 80%. Because, remember, the patients have to fill out surveys also. But the same investigators seeing the same patients, seeing that change not just in the scale, not just the erythema. But again, when you walk in the door and you see how much better they were, that’s your global assessment that says, OK, now we’re getting somewhere.

 Now what was also interesting, and I’m wondering what you all think about this, is clear or almost clear, we always throw this into a basket together, and I’m not saying that clear is not a really wonderful thing, because that means there’s just maybe a little bit of residual, maybe a little bit of pink left, maybe a touch of scale somewhere, but we saw that about 50% or more patients got to completely clear. Does that [resonate], Shawn?

 Totally resonates, because a lot of the therapeutics we have right now don’t get you that close at all.

 Completely clear is completely clear. That is a hugely high bar, especially when we’re looking at patients who came with mild, moderate, and severe. So, James, earlier you were talking about the impact on quality of life, and a lot of these patients are really, really itchy. When we’re looking at the clinical trial data, is that impactful for you? Do you want to know how they did in terms of itch?

 Yeah, absolutely. For all of our clinical trials, we will have a clinician-reported outcome, whether that’s clear or almost clear, and then we’ll have various patient-reported outcomes. And for seborrheic dermatitis, I think absolutely itch reduction is the right patient-reported outcome to be measuring. That’s very clinically relevant. And what we saw from these studies, it worked very quickly, right? And oftentimes it gets even, the itch reduction happens even before the skin clears as well.

 Yeah, and we saw over 60% of patients getting that 4-point reduction of itch. Shawn, I want to ask you to comment on the itch. When we talk about a 4-point reduction of itch, what does that mean?

 That’s clinically meaningful. So, if someone has a 4-point drop, that matters for their overall quality of life. And another thing I’d say about itch is, it’s a check on our eyes, and us making judgments, that someone does or does not need therapy. So I regularly ask folks, how severe is your itch, just 0 to 10? And I can’t tell you the number of times I’ve thought a rash may not look that bad, but then I hear how severe the itch is, and it’s made me be more aggressive with therapy. So that’s a really important metric that I think we can use as a clinical marker of disease severity.

 It’s interesting because I think we all understand when people have a flaky red scalp, they’re probably scratching their scalp and it’s itchy. But I don’t know that we necessarily think about it all the time in all of our seborrheic dermatitis patients. You know, to say how itchy are you and what’s going on with that.

Transcript was AI-generated and edited for clarity.

Dermatologists discuss a groundbreaking agent, roflumilast, filling a void in seborrheic dermatitis (SD) treatment. These experts highlight patient-reported response to this novel treatment and their own experiences in clinical trials with this drug.

Dermatologists discuss patient presentations and effective treatments for seborrheic dermatitis (SD).

Navigating SD Challenges: Expert Treatment Strategies

 Shawn, I’m sure by the time somebody comes to you, they’ve already gone to their local CVS or Target. They’ve tried some of the over-the-counter products. How do you approach these patients when they walk in? And if I come in and I say, “Well, I used the over-the-counter products. I’m not getting the results,” How do you approach that patient? Where do you start?

 That’s a great question. Neal brought up a great point about the immune signatures in seborrheic dermatitis. And one thing that I’ve noticed is there’s a lot of heterogeneity in how patients present. James is talking about the hypopigmented areas that we see in skin of color patients. Or you can see bright erythema, scaling, and intense itch. So, actually, that’s a microcosm of different immune axes also being involved. We know that Th1 activity is important. You have some forms of seborrheic dermatitis that are very scaly, can even be called sebo-psoriasis. And you know you may have a little bit more Th17. Then you have some forms that are really itchy, and you think Th2. So, I use that when I’m treating. If it’s on their face, if it’s really itchy, I’ll often times give a topical steroid, very low potency, and hope that they do not use it chronically, every day. I’ll also use the topical calcineurin inhibitor if needed. I think many of us probably use the antifungal washes, ketoconazole or ciclopirox. I’ll tell you what though, in the scalp, it can be very damaging, as James mentioned, in skin of color patients. I have so many African American female [patients] who’ve said they can’t tolerate ketoconazole.

 It’s funny because you mentioned ciclopirox, it probably had the best activity against ptero-sporin species than the other, especially the azoles. And yet, we don’t find it anymore. It’s hard to get prescription ciclopirox, and all we get are generic substitutes for all the azoles.

 And I’ll mention too, in terms of pediatric care, we see some parents that are so vigorous. They actually have the child’s hair coming off and the scalp bleeding. So overtreatment is problematic even within the pediatric realm. So we have to keep counseling, and I agree with the leaving the shampoo on. If we have a medicated shampoo, we really need to go down into the follicular level. We give our patients and parents a handout with the chemical formulations listed in all the possible shampoos in that chemical group, so that they can pick and choose. And we also want to rotate these shampoos because of the issue of tachyphylaxis, where after you use the shampoo for a while, it won’t work as well anymore. It’s not like antibiotic resistance, but it is an important teaching moment so that they don’t think they have to keep using the same shampoo forever, and they’ll feel disappointment when it no longer gives them the results that they had hoped to have as their outcome.

 That’s an important point. And given the fact that this is often on sensitive areas, including the face and around the mouth, James, do you go to the nonapproved topical calcineurin inhibitors? I know they can sting and burn, and this is a condition where they’re already a little bit sensitive. What’s your thought on that, or do you stick with a steroid or an antifungal?

 That’s a great question, Linda. I would say that for a lot of our topical calcineurin inhibitors, they do have the burning and stinging problem, and the vehicle is something that left to be desired. Oftentimes it’s greasier, especially if you’re applying it to a hair-bearing area. It’s harder to put on. So I generally do stick with more topical cortical steroids and azoles in general. I love what’s already been said, but sometimes, when you have really severe seborrheic dermatitis, I may have to reach for a systemic agent as well. I don’t do it all that often, but especially if it’s diffusely on the scalp and you’re starting to get some body areas, even systemic azoles, like fluconazole, just doing a couple courses of that. There are some studies looking at very low-dose isotretinoin. That also has been shown to actually help as well. I don’t do it all the time, but for a recalcitrate seborrheic dermatitis, that’s something I will reach for.

 And you realize that this is something that’s impacting this patient’s, not just their overall quality of life, but their work, their relationships. I think we really underappreciate [that].

 And part of that goes to what else is lying under the hood. You talk about patients with HIV, anyone with debilitating neurologic disorders, dementia, Parkinson [disease], what have you, then you’re dealing with a whole different approach, on top of the fact that your adherence levels are going to be small if they don’t have the wherewithal to apply everything, or if they’re institutionalized, then you’re even in bigger trouble.

 One other key point that I make, if I happen to be using a ketoconazole cream formulation, I tell the parents it comes in handy to have it at home for diaper rash, just generic diaper rash, as well, if that’s caused by 

. So that’s a good selling point. They like to have that product around, and they will use it on an as-needed basis. They understand treating diaper dermatitis, pure diaper dermatitis, not seborrheic dermatitis but regular diaper dermatitis with ketoconazole if it’s due to a yeast, and they know that it’s intermittent use. So that is a reinforcement that I can give with another example with which they’re already familiar.

 So it sounds like we have kind of an unmet need. We talk about what’s FDA approved—well, not a whole lot. But what research have we been doing? For years and years we’ve all been doing research for pretty much our careers, and we haven’t really been looking at seborrheic dermatitis front and center. And so, it’s kind of time for a change.

Dermatologists discuss diverse patient presentations and effective treatments for seborrheic dermatitis (SD), addressing over-the-counter product challenges, immune signatures, and treatment nuances in pediatric care.

Adelaide A. Hebert, MD

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