From deucravacitinib to roflumilast to tralokinumab and everything in between, James Del Rosso, DO, previews his upcoming Winter Clinical Miami session on new therapies.
2022 saw some blockbuster FDA approvals for dermatologic therapies, and 2023 is shaping up to bring clinicians even more tools to add to their toolchest. Ahead of the inaugural Winter Clinical Miami meeting, held February 17-20, 2023, conference co-founder James Del Rosso, DO, previews his session on what’s new in therapeutics. Del Rosso is an adjunct clinical professor of dermatology at Touro University College of Osteopathic Medicine, and co-director and co-founder of the Fall and Winter Clinical dermatology conferences.
This transcript has been edited for clarity and length.
Dermatology Times: As one of the co-founders, what was the motivation behind launching the inaugural Winter Clinical Miami meeting?
Del Rosso: Well, this all started with Darrell Rigel, Mark Lebwohl, and myself, and the first meeting we had was in 2001 in Las Vegas a month after 9/11. That's how I remember, it was 2001…so close to that bad time. But it was a great meeting, and we had the full attendance of people that were intending to come before that event and so it started off in Las Vegas, and then grew into the Winter Clinical [meeting] in Hawaii. Over time, we've added some other meetings for residents and nurse practitioners and physician assistants in dermatology Board Immersion course. And then the idea came up about having a meeting on the East Coast, because a lot of what we were doing was [on the] West Coast. There was an initiative to start it. Also, the administrative people that are involved and the behind-the-scenes leadership of the group has grown exponentially and there are new people that have new ideas, they bring things to the table, and [things] just happen. There's a lot a lot of momentum in our organization.
Dermatology Times: You will be chairing a session and delivering a talk on what's new in therapeutics. Can you provide a few of the key takeaways from the session?
Del Rosso: Sure, I'm happy to. It's called “New Therapies: What You Need to Know.” A focus of this Winter Clinical Miami meeting—which Dr. Mark Nestor who's now one of the co-directors with us [and who] is very involved, he lives in that area—is to present more case-based presentations, and then present information around that. That being said, when you're [talking] new therapies, there's a large catalogue of things you're going to talk about. There are some cases weaved in to try to bring those therapies to life.
I do talk about visible light and the fact that it's not only ultraviolet light [anymore]. When I came into dermatology, everything was ultraviolet light. We have broad spectrum sunscreens that cover a lot of the spectrum of ultraviolet light, but we don't have sunscreens that really do such a great job on visible light. Obviously, if you are using a physical occlusive, you'll get that effect, but visible light is very important. It does have some damaging effects that can create a photoaging [and] may contribute to skin cancer and, in darker skin individuals especially, leads to more dyschromia and pigmentation change. There are some sunscreens, and there's 1 line in particular that has a 5-antioxidant shield, and those antioxidants are what protect us against the effects of visible light because visible light stimulates reactive oxygen species and free radicals that create a lot of the damage, so we talk about that.
I also talk about Polypodium leucotomos extract; Polypodium leucotomos and Polypodium leucotomos extract are not created equal. The vast majority of the data show the actual effects that are beneficial are with 1 particular brand that, in the United States, is Heliocare, and that has effects in mitigating visible light—not alone obviously—[and] other photo protection and also pollutants, which create a lot of damage in the atmosphere. That’s why we're trying to control the amount of pollutants in the atmosphere because they create a lot of damage [and] we don't necessarily see what's going on, so we're going to be talking about that.
There have been new topical therapies that became approved this year for plaque psoriasis—topical tapinarof and topical roflumilast, both of them are once daily. They’re for patients with mild moderate to severe plaque psoriasis, they’re topical drugs. Tapinarof is an aryl hydrocarbon receptor agonist modulator and that's a new mechanism of action for us in dermatology. It's an important one because when tapinarof ligands with those receptors, which serve an antioxidant function in the skin in many cases, it actually stimulates changes that can benefit a variety of different skin diseases so the drug is approved for plaque psoriasis, but it's also being looked at for atopic dermatitis, and we expect that to come along relatively soon.
Now, topical roflumilast is a phosphodiesterase-4 (PD4) inhibitor and we've had other ones, but this one is very different; they're not all created equal. This one is more potent in terms of its activity, so we expect, and I believe we see, a greater therapeutic effect than what we’ve seen with previous therapies, though 1 of the PD4 inhibitors is oral for psoriasis, so it's hard to make a comparison. But, in terms of activity of the actual mechanism of action, in my mind, it's more potent, and the formulation, the vehicle, was brilliantly designed [to target] irritation, stinging, [and] burning in psoriasis…Also, the data now we're seeing in atopic dermatitis where it's also being evaluated and not yet approved, and also seborrheic dermatitis…the results we are seeing with roflumilast therapeutically are excellent. We don't have to worry about [the] side effects that we might see with topical corticosteroids. Roflumilast is also approved for any severity of plaque psoriasis, like tapinarof is. We don't have to be concerned about the topical corticosteroids side effects, so with either of these agents, you could keep using it and you'll see some patients kick in faster and some may take more time, but you can keep pushing it and not be concerned about how long the patient is using it or even where they’re applying it to get an effect. Roflumilast in a foam formulation is also being evaluated for seborrheic dermatitis, not yet approved.
Then we talk about dupilumab, and we know dupilumab is an injectable. It lessens the effect of IL-4 and IL-13. [It is] approved for atopic dermatitis, all the way down to children now. [It is] very, very effective and the safety profile is excellent. We occasionally see problems but they are uncommon, no laboratory monitoring mandated. Dupilumab has revolutionized the lives of people with moderate to severe atopic dermatitis, ones that haven't responded to other treatments, but it recently got approval for prurigo nodularis. Regardless of whether or not they're atopic in terms of other diseases like asthma, allergic rhinitis, or atopic dermatitis. In fact, in the studies, a significant number of the patients were not atopic and the ones that had atopic dermatitis were only mild so this drug works for prurigo nodularis. even if they're not atopic, and even if they don't have atopic dermatitis. It may take a little bit longer, but the effects and reducing the itching and the lesions…these patients have large numbers of lesions so that has been a major advance [and] the first approval we've had for prurigo nodularis and there was several other things we discussed.
Dermatology Times: Are there any innovations in the works this year or any upcoming dermatologic FDA approvals that you're particularly excited about?
Del Rosso: Some of the things that I am also discussing is we've had some major advances in disease states that we've struggled with. [For] vitiligo, we have topical ruxolitinib, which is approved topically also for atopic dermatitis, a Janus kinase inhibitor. Unfortunately, the FDA put the box warnings that we have with the JAK 1, 2, and 3 oral agents on the topical, which I think was not the right decision because if you look at the pharmacokinetic data, including maximal use studies, the amount that actually gets into the systemic circulation and gets systemic exposure is negligible. When you look at the amounts that patients are actually using with a topical, they're going to be 7, 8, 9, 10%, studied up to 20% body surface area, and negligible systemic exposure. And with vitiligo, up to 10% body surface area. Vitiligo takes longer so, you’ve got to remember, those melanocytes, the factories have been basically burned down so you have to wait for them to reform and it depends on the reserve that's in the skin that's been affected by vitiligo. But pressing on for months, you'll see many patients can get significant improvement especially on the face, and in hair-bearing areas. You'll be able to tell, generally, within the first 4 to 6 months if you're getting something, but some people may kick in slower. If you're seeing repigmentation, encourage those patients to continue on.
What we have with the oral Janus kinase inhibitors, like abrocitinib and upadacitinib for atopic dermatitis. I think a big advance there is we're understanding that even though they have the boxed warnings, which were based on tofacitinib used in older patients, generally over 60—old people like me, right?—they had rheumatoid arthritis and a lot of comorbidities and other systemic disease states where they had multiple risk factors where they would have more serious infections or maybe thromboembolism, cardiovascular events. But in the atopic dermatitis patients, and we're also seeing with baricitinib, which was approved for alopecia areata, another difficult disease, that in the younger populations that are typically treated with the absence of a major risk factors, the risk of those adverse events is exceptionally low. [That] doesn't mean they're zero, doesn't mean we don't monitor for them—and there are monitoring guidelines, which we review during this meeting, and other people have in other places that are published—but I really think that we have to pay attention in dermatology because we can get so many of these people better, as long as we understand the risks and monitor for them. In the populations where we're using these agents, usually in the majority of cases, the risk factors are much lower, and the risk of those events is much lower. That's what the data appear to be showing.
We also have bimekizumab that is an anti-IL-17, A, and F, so it has shown and based on the data, better results than we see with the other anti-IL-17s for psoriasis, which have excellent results, but the data with bimekizumab appear to be somewhat better, but that drug is also being looked at in psoriatic arthritis and hidradenitis suppurativa. Anti-IL-17s, like secukinumab, are being looked out for hidradenitis suppurativa. I think these agents are going to be a major advance for that disease. What we have to remember…[these patients] have chronic recurrent abscesses and inflammation and they develop scarring. Once they develop scarring and sinus tracts, it's too late. I think we're going to have to introduce these agents earlier in the course of disease so we can get these patients better. We had very little to treat these patients. We obviously had the anti-TNFs, like adalimumab, which is approved for that disease, but I think the ant-IL-17s are going to be a bigger advance above that.
In atopic dermatitis, we have an anti-IL-13 tralokinumab, but we have lebrikizumab, which has a different binding profile against circulating IL-13 and it’s showing very promising results for atopic dermatitis moderate to severe and IL-13. We expect that to come out this year; that's very exciting.
I'll end with TYK2 [tyrosine kinase inhibitors]. You want to hear about TYK2? Tyrosine kinase 2 is considered to be a Janus kinase enzyme, but it's distinctly different. The profile when you inhibit TYK2 is very different in terms of what kind of effects you might see and that would include the adverse effects. Deucravacitinib, which is a 6-milligram tablet given orally once a day for moderate to severe plaque psoriasis, given orally, has been shown to be superior to oral apremilast in a head-to-head study, which we've had for some time, which is an oral PDE4 inhibitor, but did not get the box warnings. The company had to prove, and other researchers had to prove to the FDA that TYK2 is different and it has to do with why TYK2 behaves separately because of the allosteric binding to that enzyme, and also the effects that TYK2 has. When you lock up TYK2 with deucravacitinib, you decrease IL-12 and IL-23, which is important in psoriasis and even some other disease states that will be looked at, but it's approved for psoriasis now…but you don't have those downstream effects where we see blood count changes or venous thromboembolism or cardiac events, so not having the concern or the need for the monitoring for those conditions [gives] deucravacitinib an advantage with regard to having an oral therapy for plaque psoriasis. That is a big breakthrough and it’s being looked at for other conditions.
Follow along with all of Dermatology Times’ Winter Clinical Miami coverage here.