What Else Is New? Treatment Updates for 2025

What's new in dermatology? DEF Advisory Council Members address some of the latest approvals and therapeutic updates of the past year. Hear from Joe Gorelick, MSN, FNP-C; Andrea Nguyen, DMSc, MPAS, PA-C; Kara Gooding, MMS, PA-C; and Alexa Hetzel, MS, PA-C, as they address new developments in atopic dermatitis, psoriasis, and hidradenitis suppurativa. Plus, winter skin care tips and a fresh take on JAK inhibitors from Brad Glick, DO, FAAD.

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Transcript

Transcript provided as a courtesy. It has not been reviewed or edited for accuracy.

Welcome to The Dermalorian™ Podcast from the Dermatology Education Foundation. This independent podcast is made possible with support from UCB Pharma. The start of a new year offers a great opportunity to look back on treatment developments over the past 12 months. 2024, saw two cosmetic dermatology updates, with a new botulinum toxin approved. Letybo from Hugel America is approved to treat moderate to severe glabella lines in adults. Late last year, Botox Cosmetic received approval for the treatment of platysma bands. There were numerous approvals in the medical dermatology space, including in atopic dermatitis. DEF President, dermatology nurse practitioner, Joe Gorelick kicks off with a look at emerging and new treatments for atopic dermatitis.

Joe Gorelick:

One of the newer and emerging pathways is the Ox-40 or the Ox-40 ligand. The Ox-40 is critical for the development of Th2 cells. So Th2 is the primary lymphocyte, a foundational lymphocyte, driving the disease of atopic dermatitis. And the regulator of T cells is Ox-40. So a very interesting potential future implication, or target, to treat the disease. So when you look at atopic dermatitis, pathophysiologically, something happens with the barrier function. There may or may not be a genetic predisposition, with altered development of barrier cells because of genetic mutations causing issues with filaggrin, that may or may not be present, but there is a disrupted barrier.

When you have a disrupted barrier, antigens and microbes can trigger chemical messengers that are called alarmins. Alarmins are the first drivers of disease. IL-25, TSLP, IL-17C, and IL-31 are the alarmins that tell the dendritic cells to differentiate. When the dendritic cell gets activated, it stimulates the T cells, which are naive, to turn into Th2 cells. A Th2 cell, again, the primary lymphocyte for atopic dermatitis produces IL-4 and IL-13. In the inflamed state of atopic dermatitis, you have elevated rates of all of these pro-inflammatory mediators as well as IL-31. So when these cells are activated, they cause further disruption, and through inflammation of the barrier function of the skin, and itch.

So when you look at targets to treat atopic dermatitis, they're going to be surrounding the Th2 cell. So think about IL-4 and IL-13. There's opportunity to prevent or decrease their activity by blocking their receptor. That's what dupilumab does. There are two other agents that we have in this extracellular space that bind specifically to IL-13, and decrease the levels of IL-13, and decrease the amount of pro-inflammatory cytokines downstream. These are tralokinumab and lebrikizumab.

Next you have other agents that are in development to look at alarmins to decrease the differentiation of the dendritic cell. And then, now, we have a drug that's very specific for the itch cytokine IL-31 that is approved for prurigo nodularis. That's called nemolizumab. Then lebrikizumab, newly approved for patients with moderate to severe atopic dermatitis, down to 12 years of age, has one dose. It's a 250 milligram device that if, patients are 40 kilograms and above, they're candidates for treatment at 12 years and above. The dosing is the same for everyone. At baseline, they're dosed, and two weeks later, they're dosed again with a 500 milligram dose. That's two injections. After that, the approval is every other week, out to 16 weeks. And at 16 weeks, it's up to you whether you want to continue every two-week dose at 250 milligrams, or you want to go to every four weeks. Based on how your patients are doing, you can make that clinical decision.

Andrea Nguyen:

[inaudible 00:05:17], it's a small molecule, and it works in by regulating our activity of this aryl hydrocarbon pathway. So we have a downed regulation of Th17 cytokines. So this is why we see reduction in inflammation in psoriasis. But we also have an up regulation antioxidant activity via the Nrf2 pathway. So we have up regulation in those antioxidant activities. Therefore, we have reduction in oxidative stress, which we know sometimes can trigger some of these inflammatory disorders. We also have up regulation of some of the components of our skin barrier, such as filaggrin, loricrin, and involucrin. So this helps normalize the skin barrier. And then we also have a down regulation through the Th2 cytokine pathway, which is a reduction in atopic dermatitis.

This is their clinical trials in ADORING 1 and ADORING 2. Basically, it was a two-to-one randomization between active treatment arm and vehicle control, 1% once a day, as compared to vehicle. And, here, one thing about their clinical trial, which is amazing, is they had over 80% of their clinical trial population be pediatric patients. That's outstanding because, generally, in clinical trials that are actually very, very hard to recruit are pediatric patients, especially of the younger age groups, just because if you put yourself in the position of parents, how many parents are going to be enrolling their children into these clinical trials? So it's really outstanding that we have such a large study population being paed, and we have about 50% of patients being skin of color.

We were looking at clear, almost clear with the two-grade improvement. And, again, EASI-75. So this is their IGA scores, zero one, but that leaves that two-grade improvement from baseline at week eight. So we see here on active treatment 45%, as compared to 13.9% on vehicle. And then, in ADORING 2, very comparable percentage, 46.4%, as compared to 18% of vehicle. So very consistent data across the two clinical trials. And then we see the same thing being repeated in EASI-75, so EASI-75. Again, we're talking about topicals. We're not talking about systemic therapy. And the fact that we can also really look at these high measures of skin clearances, very reflective of this amazing time that we have, these advanced topical therapeutic options. So 55.8% of patients achieving EASI-75 in ADORING 1, and 59.1% achieving in ADORING 2, up compared to 22.9% and 21.2% on vehicle only.

And then this is looking at a clinically meaningful PPMRS. So four point improvement or more having that reduction of itch at week eight. We see here 55.8% as compared to 34.2%, and 52.8% as compared to 24.1%. And then the treatment AEs were mild to moderate in their clinical trials, folliculitis, headache, nasopharyngitis, but discontinuation rates were very low. So 1.9% in active treatment, 1.5% in active treatment in ADORING 1 and ADORING 2 respectively.

Speaker 1:

That was DEF Advisory council member, physician assistant Andrea Nguyen. Nemolizumab, by the way, received FDA approval for moderate to severe atopic dermatitis in individual age 12 and older.

For this episode's Dermalorian Clinical Clip, we turn to another form of eczema. For Winter Skincare Day this month, DEF advisory council member and physician assistant, Kara Gooding, offered strategies to manage seasonal hand dermatitis.

Kara Gooding:

Isolated hand dermatitis, which is really a big problem this time of year, especially when we shift from the more humid summer into the drier winter, we see a lot of flares of hand dermatitis. I, myself, have it. I don't have it in the summer. I wash my hands the same amount of time. But I found myself, this past week, having redness, dryness, starting to have a little bit of cracking and bleeding on my own hands. And what I do is, make sure I moisturize frequently throughout the day. So find your favorite barrier repair moisturizer. And then I love to do Aquaphor or Vaseline overnight with a thin pair of gloves to help restore the barrier.

Speaker 1:

As we refocus attention on newer therapies, we'll stick with Kara Gooding as she addresses psoriasis.

Kara Gooding:

So bimekizumab is our newest agent. It is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy and phototherapy. And, more recently, it got the indication, very recently, for PSA as well. It is the first biologic approved to selectively and directly inhibit both IL-17A as well as IL-17F. We saw earlier that the earlier agents only are going to inhibit the IL-17A. So this is going to include both the IL-17AA homodimer, as well as the FF homodimer, as well as the heterodimer of IL-17A and IL-17F. And we're going to look at, really, the robust efficacy that we see because of that over the next few slides. Inhibition of IL-17F, in addition to the IL-17A, does result in rapid normalization of keratinocyte biology, as well as key inflammatory IL-23 and IL-17 pathways. And I would say that that rapid normalization is really what we do see with this medication.

There are some things in the package insert for bimekizumab to be aware of so that you can discuss with your patient. One is that you do need to screen the patients for depression. It does say in the package insert that there is a possibility that it may increase your risk for suicidal ideation and behavior. The very interesting thing is it was studied proactively in these patients. And bimekizumab was doing extensive studies and questionnaires while they were in the clinical trial. The numbers were very, very low. And actually in the package insert elsewhere, it says that there has been no causal relationship between bimekizumab and suicidal ideation and behavior that has been identified. So you can use that information. We know that depression is something that we see in a high incidence in our psoriasis patients.

The other thing that you do need to screen for is, it's in the package insert to test for liver enzymes, alkaline phosphatase, and bilirubin at baseline. And then, basically, at your discretion thereafter. If this is something you feel that the patient is maybe a high risk for elevation of their liver enzymes, you may want to check it more than annually, but that is really left up to your discretion.

Alexa Hetzel:

What is HS? What is hidradenitis suppurativa? So it's really thought to be a disorder of some of the terminal follicular epithelium within the apocrine glands. And those apocrine glands are really the sweat glands, which is why we see a lot of HS pop up in sweat bearing areas around the hair. So the axilla, the groin, inframammary, and neck areas. That doesn't mean though that these patients can't have them everywhere. You have patients who have it suprapubically. They can have it all down their legs, their trunk. I have one guy who has a really big beard. He's got really horrible HS within his bear., and that can be difficult sometimes if it's only in those areas, if it's not in those classic areas that we see, like the axillary groin. So just don't necessarily brush those patients off that they have regular acne. Look a little bit deeper at the lesions and how they look.

Secukinumab which recently got approved as well as bimekizumab, which just got approved. Great options. We did the clinical research for bimekizumab in our office, and our patients did very well. Unfortunately, with adalimumab and secukinumab, high scores of 50, so 50% improvement or better is what we're seeing. With bimekizumab, you can see anywhere from 50, 75, and actually high score 100 data they have. So it's pretty impressive how we're getting a little bit more targeted and a little bit more focused for some patients that are truly suffering.

Speaker 1:

That was DEF Advisory council member, physician assistant Alexa Hetzel. Other new drug approvals in dermatology in 2024 included zelsuvmi for the management of Molluscum, and Unloxcyt, a PD-L1 inhibitor for advanced skin cancers. You can read up on these on the DEF blog at dermnppa.org. There's more ahead in this episode of The Dermalorian Podcast, an independent program made possible with support from UCB. For our Dermalorian Derm Decoder, let's hear from dermatologist, Dr. Brad Glick, as he addresses what he calls the biggest misconception regarding JAK inhibitors, the belief that they are dangerous.

Dr. Brad Glick:

That is a true misconception. No, they're not without consequences. There are drugs that modulate the immune system. When we block intracellular processes, when we inhibit cross phosphorylation of Janus kinases, protein, kinases, intracellularly, when we blunt the dimerization, the coming together of stats, JAK stats pathway, and we decrease those genes that are responsible for transcription in a variety of skin diseases. We may get not only what we want in down regulation of important cytokines, but patients may get infections. They might be risk of infection. Some patients in these clinical trials did indeed develop cardiac events. But, nevertheless, we're talking about disease states, like atopic dermatitis, where there may be background cardiovascular disease. And we see this in other disorders as well too, that we have to take into consideration what the background rate is of malignancies, and those adverse events of interest, based on the disease state itself versus the drug itself.

Again, to reiterate, they're not without side effects at all. But I think, like all therapeutics that we have in the toolbox, and in comparison to our older therapies that we've had, like I referenced before, take cyclosporine. A wonderful drug, but it has a lot of side effect baggage, if you will. And I really feel like JAK inhibitors have fewer. So it's about counseling our patients, providing the warnings accordingly, being transparent about the fact that JAK inhibitors when we talk about misconceptions. But, indeed, some of the misconception is provided by the fact that there is a black box warning, or so-called box warning, for these therapeutics. And, unfortunately so, it includes the topical therapy, which is topical ruxolitinib 1.5% cream, which is approved for mild to moderate atopic dermatitis. And, ironically, the oral form of this therapeutic, which was approved in 2011, does not have a boxed warning. So that's a little confusing. But, nevertheless, that's where we are at this current time. And so there are some misconceptions. I think it's about counsel and appropriate transparency with our patients regarding these therapeutics.

Speaker 1:

That concludes this edition of The Dermalorian Podcast from the Dermatology Education Foundation. The Dermalorian Podcast is produced for the DEF by Physician Resources. You can hear previous episodes of the podcast wherever you listen to pods. If you like what you hear, be sure to share with a colleague. Thanks for listening.