Clinical Trials of Roflumilast in Plaque Psoriasis

Brad Glick, DO, MPH: 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.

Mona Shahriari, MD, FAAD: 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.

Brad Glick, DO, MPH: Linda, do you have additions to those comments?

Linda Stein Gold, MD: 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.

Brad Glick, DO, MPH: 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?

Mona Shahriari, MD, FAAD: 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.

Brad Glick, DO, MPH: Linda, any addition to those comments?

Linda Stein Gold, MD: 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.

Brad Glick, DO, MPH: 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.

Transcript edited for clarity