James Song, MD, FAAD: Advanced Strategies for Alopecia Areata, Refractory Dermatoses, and Emerging Non-Steroidal Topicals

At this year’s Fall Clinical Dermatology Conference, James Song, MD, FAAD, director of clinical research and associate chief medical officer at Frontier Dermatology, as well as a clinical Instructor at the University of Washington, shared top tips for fellow clinicians.

Song participated in a session titled, "20 Tips for 20 Minutes."

He spoke with Dermatology Times to share the top clinical pearls and key takeaways from the panel discussion.

Transcript

James Song, MD, FAAD: I had the chance to share 4 clinical pearls, just from my my clinical experience. The first pearl is how to treat severe alopecia areata when a patient isn't a candidate for an oral JAK inhibitor. I actually shared a case of a patient that also had generalized vitiligo, so his entire body was depigmented. I warned the patient, if we put him on an oral JAK for his scalp, his color may repigment again, and then that was not something he was interested in, just because he's lived for years without having any color in his skin. We had to pivot and look for a different treatment option. We used, actually, DCPC. This is also known as diphenylcyclopropane. It's an oldie, but a goodie, and it's a form of contact immunotherapy where we're trying to trick or distract the immune system so it doesn't pay attention to the scalp. It pays attention to a dermatitis that we're causing by applying that product.

The challenge of DCPC, though, has been more along the lines of logistically: How do we get it ordered? How often do we use it? Does it have to be applied in the clinic, or is it something that a patient could do at home? There's a lot of different variations of the protocol, and I think that's why people haven't been using it as much as they should. I gave a simple, no nonsense, modified protocol of how I've been doing it. Essentially, I skipped a sensitization period, meaning you don't have to put the product in the office. You don't have to carry it. I start them off at the lowest dose, which is 0.1%, and have them apply a little bit to the affected area, anywhere from once a week to 3 times a week. I will increase it by tenfold every couple of weeks, and I'll just be sending in a new prescription until they get to a point where getting a low grade dermatitis for about 4 to 5 days. Once we get to that point, they just continue to use it on a 1 to 3 times weekly maintenance dose. It has worked extraordinarily well for some of my most recalcitrant patients, even in patients who failed oral JAK inhibitors. Don't forget about DCPC.

The second tip is going to be for a refractory discoid lupus erythematosus, a very tough condition to treat. We know that once it starts to scar, we can't really reverse those changes, so we want to be aggressive in treating this condition up front, and we've tried traditional immunosuppressants, whether it's methotrexate, mycophenolate, azathioprine. These medicines have a lot of side effects, and quite frankly, they don't work all that well either. We've been using deucravacitinib, which is an allosteric TYK2 inhibitor as my treatment of choice now as a steroid-sparing agent in DLE, and that's because we know that there are higher levels of type 1 interferon signaling in patients with lupus erythematosus and deucravacitinib blocks TYK2, which also signals those key interferon type 1 interfering cytokines.

Now, there's actually an ongoing phase 2 study looking at deucravacitinib for systemic lupus erythematosus, so sometimes we will use that as a way to get this drug approved, because it currently is off label. But when you actually look at how well it's treated lupus, when you look specifically at the skin manifestations, it did actually very, very well across all the different dosing regimens.

The third tip is using upadacitinib. This is an oral JAK1 inhibitor for refractory dermatomyositis. We know that dermatomyositis could affect many different organ systems, including the skin, the muscles, and the lungs. There's been actually a number of studies that have looked at various different oral JAKs, whether it's using whether it's upadacitinib, ruxolitinib or baricitinib. What we have consistently seen is that these JAK inhibitors, they work quite well for the skin, but also for lung improvement, lung function improvement, and even overall survival. A lot of these patients, unfortunately, they pass away because they get rapidly progressive interstitial lung disease. We do now have some data to suggest that using oral JAK inhibitors could actually improve, not just quality of life for these patients, but also the actual mortality benefit in using these drugs as well.

Then, last but not least, I've talked about a various acantholytic disorders that can be treated with biologics and JAK inhibitors as well. It's interesting that whether you have Hailey-Hailey disease, Grover's disease, or Darier disease, some of the skin barrier defects that we associate with these conditions could give way to a type 2 inflammation, and that type 2 inflammation then could affect calcium mobilization and keratinocytes, which can affect desmosomal integrity.

We've had biologics like tralokinumab and dupilumab to target that type 2 inflammation, and in those refractory cases, we even use oral JAK inhibitors to treat pretty much all 3 of those conditions, Hailey-Hailey, Darier, and Grover's. When you're running out of options for those patients, think biologics that target type 2 inflammation and oral JAKs.

Dermatology Times: What advice would you share with fellow clinicians who may be hesitant to try DCPC therapy for their alopecia patients?

Song: There's a lot of variations in the protocol for DCPC, so sometimes you just don't know where to start, or where to where to actually send the prescription to, how often you should be seeing these patients, how soon you should be escalating the doses. Everyone does it differently. I think without a standardized, formal protocol, people just don't feel comfortable using DCPC. The other challenge, though, is just logistically: How often does the patient have to come back? That could sometimes be a barrier, just because with the traditional protocols, people are supposed to come back every week, and you're supposed to carry in your office almost every single concentration of DCPC. Just practically speaking, it's hard to pay for all these products, keep it in your office, and it expires in a couple of months. You're going to have to turn it over and pay for the new product.

What I have found to be successful is really just kind of having the patients apply it themselves. You could show them in the office just how much they should be using, but sending a prescription to a compounding pharmacy that you could partner with, and that could recommend a bunch of different ones, and just sending it directly to the patient and letting them take charge of them actually using the product themselves, and then kind of reporting back to you what type of reaction you're actually getting.

Dermatology Times: What advancements in inflammatory diseases have excited you most this year?

Song: Let's start off with atopic dermatitis. This is an area where we've made a lot of progress over the last couple of years, but the reality remains that there's still a lot of patients that we can't get to clear or keep them at clear. I think that really speaks to just the complexity and the heterogeneity of this disease. We need more therapies, despite having a bunch of them already. We had one really important drug approval just a couple of weeks ago, actually, with lebrikizumab. This is also known as Ebglyss. This is an IL-13 inhibitor that targets the same pathway that our other 2 biologics dupilumab and tralokinumab target, but it does it a little bit differently, and we actually know that by binding to the key cytokine, which is Il-13, at a much higher affinity and holding it onto much more tightly, there are some potential benefits of this therapy versus our other 2 biologics. I'm really excited about that.

We also had the approval of nemolizumab. This is an IL-31 receptor antagonist. This is our second FDA-approved therapy now for prurigo nodularis, which has been, historically, I think, been an underappreciated and really a poorly understood disease, and as a result, a lot of these patients were undertreated. But now we have another novel drug. This is the first IL-31 antagonist that we have. The dosing is very nice. It's once a month from the very beginning, and the ability to lead to itch reduction in such, I would say, almost JAK-like speed. It works very quickly, and the depth of response that we're getting with itch reduction is really exciting for these patients, because it's really the itch that drives this condition.

As far as psoriasis we have a couple of therapies that are quite not approved this year, but they are going to be imminent, hopefully by next year or the following year, and this is mostly going to be from the oral space. We have an oral IL-23 peptide called JNJ-2113: extraordinary efficacy and speed, not just for an oral therapy, but really for any systemic therapy. Then we have 2 other oral TYK2 inhibitors that work on that allosteric domain, the same target as deucravacitinib, but they bind to it much more selectively and a much higher affinity, and that potentially could translate to even a better response. Even if you look at the phase 2 data, it seems to work fairly quickly, much more quickly that we see with deucravacitinib; honestly, is it's an effective drug, but it does take time for it to work. It's nice that we have potentially the same safety of deucravacitinib, but we can get to that finish line much more quickly.

Last but not least, topicals. This is what we as dermatologists utilize the most, and we've always been stuck between using a steroid which is more efficacious and non steroids which don't have the baggage with steroids, but they barely sting; they're just not quite as effective. There's really been a large unmet need for highly effective and well-tolerated non steroidal agents, not just for psoriasis, but particularly for atopic dermatitis. I'm pleased that we have now several options in the AD space, starting off with topical ruxolitinib 1.5% cream, currently approved for 12 and up. I would say objectively, this has been the probably most effective non steroidal topical that I've been utilizing, at least in my hands, when it comes to speed, depth of response, and tolerability, but currently it's only 12 and up. We do have data that was published from the age of 2 to 11, so even though it's currently not approved for that age group, we're hoping that by next year, we will have it down to that age, which I think is going to be very, very important, just because of how well this drug works.

The next is going to be topical roflumilast 0.15% cream. This drug is already approved for psoriasis at the 0.3% dose, as well as seborrheic dermatitis, but now we have half that dose for atopic dermatitis, 6 to 11. This is a second I was considered to be a next generation PDE4 inhibitor. It doesn't have the burning and stinging that we typically associate with this class. Very well tolerated once a day, and also works very, very well when it comes to skin clearance and its reduction. It's something I've really enjoyed using in combination with my systemic therapies, recause the one challenge we have with topical ruxolitinib is that, per the label, you cannot combine ruxolitinib with a systemic agent. I've been using a lot of roflumilast for those patients that are just breaking through the systemic agents.

Last but not least, tapinarof 1% cream. This is currently approved for psoriasis, not quite approved yet for atopic dermatitis, but they've already filed an application, and we should be getting a decision here sometime, hopefully within a month or 2. But really, the advantage of tapinarof would be the age of indication, if it gets approved, it will be approved onto the age of 2 years, and not right out of the gate. This is also a non steroidal once a day cream, and if you're familiar with some of the psoriasis data, and in many of these patients, if you could get them to clear and you stop the medications, and many of these patients still stay clear or almost cleared for for quite some time, and that is somewhat, I would say, unique to this mechanism of action.

[Transcript has been edited for clarity.]

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