Brad Glick, DO, MPH

What are you excited about? What’s up and coming? Linda, what’s coming for patients with plaque psoriasis?

 I’m excited about seeing how well some of our medications do in combination. I’m excited about new molecules. I’m excited about topical therapy. We can’t forget about topical therapy. I’m so thrilled that we have these 2 new nonsteroidal options. I want to make sure we continue research and development in the topical arena because if you have moderate to severe plaque psoriasis, I can do wonderful things for you. Patients who have localized disease can be more challenging to treat. I’m excited to continue to see the research and development and continue to see work on getting us even better treatment. We’ve come so far, but we have a little ways to go.

Mona, what’s in your crystal ball? What are you excited about?

I have a great interest in treating patients with skin of color who have inflammatory skin disease, in particular psoriasis. Newer dedicated studies of patients with skin of color are underway, and they can potentially change the game. They’re important because patients with skin of color have historically been underrepresented in clinical trials. Whether it was for systemic agents or topical agents, these individuals have unique needs. They may not respond in the same way to our topicals or systemics, and they may have different safety signals that we have to worry about. These newer studies are going to give us insights into the diagnostic and treatment nuances of psoriasis in skin of color. Hopefully, if we learn more about these special considerations, we can allow for our patients to get high-quality care in an inclusive society.

I’m most excited about these oral biologics. We have several companies potentially bringing to market oral IL-17 and IL-23 inhibitors. The fact that we might finally be able to deliver a protein therapeutic via the GI [gastrointestinal] tract is exciting. It’s crazy to think we can do it, but the early phase 1 and 2 data are compelling, so we’ll see if we can get that through. Janssen and some other companies have those therapies. That’s what I’m most excited about.

Mona, tell us some clinical pearls that you have in managing patients with plaque psoriasis. Give us a couple of thoughts about some approaches that you have.

The most important thing I try to teach my residents or talk to patients about is that psoriasis goes beyond the skin. That multidimensional burden is key, and it keeps the whole patient in mind. Screen them for comorbidities, ensure that they’re plugged in with a primary care doctor. We’re dermatologists, but we’re also doctors. We have to treat the patient and not dump them on the next specialist. We have to ensure they get comprehensive care, so they can lead better lives.

Linda, some pearls from you as we close out.

 One of the most important things I’ve learned is that it’s important to stay up to date on what’s new in terms of treatment options. There’s so much research and development going on. We owe it to ourselves and our patients to understand the new treatment options and not always fall back on traditional medications that we’re comfortable with. We have to get outside our comfort zone and learn the new medications. That way, we’ll be able to choose the right medications.

That what’s been nice about the dermatology space: this expansion of the dermatology-focused pharmacy. They’re everywhere. They’re not just in Manhattan. Patients think they have to go to the local pharmacy. When you show them that there are dermatology-focused pharmacies that are good at getting tapinarof and roflumilast covered. They see that and then end up getting the therapy. A lot of times, individuals run into issues with these newer topicals because of access, and they have this perception that they’re not going to be able to get their patients the drug. I work with local pharmacies, the ones that are more dermatology focused, to get it. When you say 

 to a patient, they’ll do whatever it takes to get it. Patients don’t want to use steroids. That’s my experience. Lastly, another perception about branded topicals is the cost to the health care system. Let me assure you, clobetasol is not cheap. There are only a few manufacturers of clobetasol ointment in the country. You can look up the cost. It’s not much cheaper than these branded nonsteroidals. Those are just a few pearls.

Linda, Mona, and Michael, thank you for a great experience discussing topical treatments for patients with psoriatic disease. It was really enjoyable. I’ve had a great opportunity to interview a number of individuals, and this was a rewarding experience. Thank you to the 3 of you.

Thanks to all of you for this rich and informative discussion. Thank you all for watching this 

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Videos

Brad Glick, DO, MPH; Mona Shahriari, MD, FAAD; Michael Cameron, MD, FAAD; and Linda Stein Gold, MD, comment on the future of plaque psoriasis treatment and share clinical pearls on the management of plaque psoriasis.

The Future of Plaque Psoriasis Treatment

How do you envision these new nonsteroidal topical agents impacting our clinical practice for our patients with plaque psoriasis? How are they going to fit in the treatment landscape? What has your experience been? We went over that a little already. I’m going to throw out another question: are we seeing a paradigm shift? Mona?

For me, nonsteroidals are the next generation. They’re going to represent a new standard of care because of their impressive efficacy; that once-daily dosing; the ability to use them for mild, moderate, or severe psoriasis on any affected area—the face, the groin, the trunk—for any duration of time. We aren’t concerned about local systemic adverse effects or tachyphylaxis, which makes them an incredible addition to our toolbox. I’m noticing that paradigm shift in my practice, where I’m reaching for them over my topical corticosteroids. As long as access isn’t a barrier, and that tends to be the biggest issue no matter what aspect of dermatology we’re prescribing medicines in. But the conversation with my patients is shorter, the adherence to therapy is better, and patients come back having an overall better experience because they don’t feel like a failure for putting the wrong stuff in the wrong place. They feel empowered to effectively treat their disease.

Steroid phobia does exist. We have to discuss it, and we have to channel the use of corticosteroids properly. This takes it away. Linda, what are your thoughts?

 We need a lot of tools in our toolbox. No one medication is going to be effective for 100% of patients. There will still be a role for potent topical steroids and midpotent topical steroids in patients who need to be clear tomorrow. Nothing works as quickly as a potent topical steroid. They’re always going to be a very important tool. But I think of them as a Band-Aid. This is a long-term, chronic problem. We might need them on a short-term basis, but these nonsteroidal options are the workhorse of the treatment options we have in front of us. The beauty is that we have several treatments to choose from. We need each of those treatments because our goal is to get our patients to a point when they no longer think about their psoriasis.

When we look at the time line of drug development for psoriasis, they came out in the 1950s and 60s. They looked at coal tar, saying “What?” We’re still using coal tar. We look at the use of topical steroids in psoriasis as crude, like how we look at coal tar now because it’s such a better instrument than a topical steroid. When you use clobetasol, it goes away but comes back right away. We’ve all seen now the remittive effect of tapinarof, for example. It behaves…like a class 1 steroid. We had the trials at Mount Sinai [Hospital], but what’s different from clobetasol is that it stays away for 3 to 4 months on average. You can make a compelling argument to the PBMs [pharmacy benefit managers] and the payer groups: we might keep the population off biologics for 3 to 4 months if we’re having this remittive effect.

I’m trying to answer your initial question. I get all my patients with psoriasis on these nonsteroidals when I can get access because that’s what I’d give my sister. It’s a better therapy than a topical steroid. It fits in the biologic space as an add-on but also in the mild to moderate space with Otezla or as monotherapy to try to keep patients off biologics.

When someone has a pretty good flare or mostly localized disease, do you think we’d go to our corticosteroid first? Then we can treat to complete with these new nonsteroidals. Mona?

That’s definitely a possibility. But it’s going to vary from patient to patient based on that individual’s treatment goals. That’s another fair way to use these molecules.

What about monitoring? How do we monitor patients going on nonsteroidals or topicals in general? Broadly speaking, how do you assess efficacy, safety, and adherence?

 The wonderful news is that they don’t need close monitoring. There are no boxed warnings with these new medications, and there’s no blood monitoring. We know that these drugs have been studied on and off for an entire year. If we give patients a prescription and a refill and don’t hear from them, that’s probably a good thing. So I’m not worried about it. If my patient isn’t doing well or is having a reaction, they’re going to call me in a minute or send me a message on their Epic software. The good news is that these drugs are relatively safe and can be used. It’s not as if I gave them clobetasol propionate and I’m worried they’ve been using it on their eyelids and they’ve gone rogue—they feel they can use it wherever they want to. There’s a good safety factor here. I’m usually prescribing with confidence.

You know I asked this question because we have a topical Janus kinase inhibitor. Every once in a while, when I have the opportunity to speak about this product, someone will ask me, “Are you checking labs for your patients on topical ruxolitinib?” Of course, the answer is no. Mona, what are your comments on any monitoring, whether it’s adherence, because these are once-daily therapies. What are just some general thoughts as we close.

I agree with Linda. This has made my life much easier. I can give them an effective medicine that doesn’t need high levels of monitoring. But if a patient calls me with concerns about adverse effects—like irritation, contact dermatitis, or anything that’s off—I ask them about how they’re using the medication. I found our patients are used to using medicines twice a day, so they may be using this 1 twice a day and not reading the directions on the label. We all know if you overuse a product, there’s a chance for irritation. I definitely double check that piece.

Expert dermatologists comment on the use of nonsteroidal topical therapies in the treatment of plaque psoriasis and how it has affected clinical practice.

The Impact of Non-Steroidal Topical Agents in Plaque Psoriasis

Mona, talk to me about roflumilast. It’s a newer version of a topical PDE4 inhibitor. We’ve had 1 before. Tell us a little about roflumilast. I’d like you to segue from that into telling us about those DERMIS trials that led to the approval of roflumilast for plaque psoriasis.

I like to call roflumilast a PDE4 2.0 because we’ve had PDE4s in this space before, and there were tolerability and efficacy issues with them. This is a medication that’s once a day and highly efficacious. That safety and tolerability profile is much better than what we’ve seen with other agents on the market when it comes to the high-level of adherence it has to PDE4 molecules. All of those are starkly different from what we’ve had in previous generations. The DERMIS trials highlighted the efficacy and safety of roflumilast. We took patients who were ages 2 and above and we randomized them to either receive roflumilast once a day or vehicle. The 8-week mark was the end point that we looked at. We looked at a similar end point—clear or almost clear—with at least a 2-grade improvement. In this trial, our patients had a BSA [body surface area] of 2% all the way up to 20%. These are individuals that don’t have insignificant psoriasis involvement. We had 4 of 10 patients get to that primary end point. As early as 4 weeks, we saw that separation from placebo that was statistically significant.

The thing about trials with roflumilast is that they specifically looked at intertriginous areas, which is something we haven’t seen in the topical space. The majority of patients were able to get to almost clear in the intertriginous zone, which is important to our patients who have psoriasis in areas they don’t want to tell us about but want us to know about. To have that high-level of safety and tolerability in those intertriginous sites was another piece that we found very important in that trial.

Linda, do you have additions to those comments?

 I agree. This is 1 of the medications I consider a “yes” medication. Can I use it on my face? Yes. Can I use it near my eyes? Yes. Can I use it anywhere? Can I use it in my private areas? Yes. Can I use it alone? Yes. Is it once a day? Yes. It helps to simplify and set those patients up for success. Individuals might think, “It’s a PDE4 inhibitor. I’ve seen that before.” But we have to take a step back and say that just because a medication is within the same class doesn’t mean it’s the same medication. Think about topical steroids, clobetasol vs hydrocortisone. They’re vastly different. Roflumilast has a potency that’s much more potent than the other PDE4s in the same dermatologic space. These new medications are a much-needed addition to our treatment armamentarium.

From my recollection in the tapinarof trials, PSOARING 1 and PSOARING 2, and throughout the long-term extension, we assessed tolerability as the investigator, but our patients well too. That drug was perceived by our patients and by the investigator as well. It’s highly tolerable, particularly in challenging areas and folds. The drug wasn’t specifically studied in the folds, as roflumilast was, but what’s unique for our patients is the concerns we have about some of the agents. Linda, you referenced trying to use a retinoid in the fold, and you couldn’t do that. Even topical calcium calcipotriene and the topical calcium urine inhibitors are inherently irritating. What I don’t hear from either of you is the irritancy factor. Thinking of what we have with crisaborole and some of the irritancy, using this in the fold is remarkable. Mona, what about adverse effects from roflumilast? What are our concerns? What do we have to talk to our patients about with roflumilast?

The typical adverse events that we worry about with PDE4 inhibitors—headache, loss of appetite, weight loss, diarrhea—came up in the clinical trials, so that’s something to keep in mind. I’ll be honest: using it in the real world, I haven’t seen much of it. Obviously, it’s a numbers game. The more prescriptions you write, the more you’ll see. But overall, I counsel my patients on it because I want to make sure they call me if anything like that does come up.

 No. This is a drug that’s already FDA approved in the oral formulation for COPD [chronic obstructive pulmonary disease]. We’re not worried about systemic manifestations. We know this drug is safe. We know that this drug is exceptionally well tolerated when applied to the skin, even in sensitive areas. This is a drug that makes it very easy to use.

I agree completely. I’ve been excited using it in clinical practice in the last several months. I haven’t seen irritancy, which would have been an inherent concern from our prior experience from using a topical PDE4 inhibitor.

Experts discuss the DERMIS clinical trials of roflumilast in the treatment of plaque psoriasis, highlighting its efficacy in the intertriginous areas.

Clinical Trials of Roflumilast in Plaque Psoriasis

Mona, what has your experience been? Give me your perspective, not only the long-term extension PSOARING 3 but also what you’ve seen in clinical practice. Comment as well on the very few adverse effects in the tapinarof trials, particularly highlighting folliculitis and contact dermatitis.

Linda did an incredible job summarizing the PSOARING 3 open-label extension. It was a unique trial design. During that 40 week-period, we had patients coming on and off drug the entire time. But when you looked at their response, we saw this durable disease control. This pointed to the drug working over time, but we also didn’t see tachyphylaxis, which is something that we’ve historically been concerned about with our topical corticosteroids. When it comes to using this drug in the real world and the safety signals, I’ve written quite a few prescriptions since this drug has launched. The safety profile has been consistent with what we saw in the clinical trial. I’ve seen folliculitis, contact dermatitis, and nasopharyngitis, but nothing was different from what we had seen in the clinical trials. When it comes to the folliculitis piece, for the majority of my patients, we treat through it because they’re happy with the results and it goes away on its own. That’s very powerful as well. That might be 1 of the reasons we didn’t see high treatment discontinuation rates within the clinical trial.

Linda, postapproval, is that your experience as well?

 It’s very similar. What I love about being a medical dermatologist who sees a lot of patients but also does clinical trials is that we get a unique perspective. We get to see a drug as it’s being born and raised, FDA approved, and then when it’s launched. Sometimes, clinical trial results don’t mirror what we see in actual practice, and we find that very frustrating. But I’ve had an experience similar to Mona’s in that it’s worked the same way in my practice—with patients who have comorbidities and might be using other medications—as what we saw in clinical trials.

In my experience, 1 year postapproval, is that I’ve seen folliculitis, but I’m not seeing it at the same rate that we saw in the trials. Linda, to your point that it’s not always the same, 1 good thing is that we’re not seeing any new safety signals that I’ve seen at least in the trenches.

Mona Shahriari, MD, and Linda Stein Gold, MD, review the long-term safety and efficacy data of tapinarof as well as its use in clinical practice for the management of plaque psoriasis.

Brad Glick, DO, MPH

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