Mona Shahriari, MD: We’ve beat around the bush enough. Why don’t we talk about these newer agents that have hit the space? Which one do you want to start with?

Alexandra K. Golant, MD: We were creating a bit of a teaser for the audience. We can start with roflumilast. Roflumilast is one of the 2 newer agents that we have. We know it’s a PDE4, a phosphodiesterase-4 inhibiting topical. It’s not a new target in dermatology. As we know, we’ve had prior topicals that target PDE4 and also a systemic agent and oral agent for psoriasis that target PDE4. Roflumilast does it a bit differently. We know that by inhibiting PDE4 we have modifications of cyclic AMP [adenosine monophosphate] levels, and downstream that leads to an inhibition of proinflammatory cytokines. [This includes] some of the ones that you mentioned at the beginning, our key players IL-17, IL-23, TNF-α. What has made roflumilast different and novel in the space is the excellent delivery mechanism that this molecule contains. And there is a lot of high science these days in terms of vehicle and delivery, in terms of making vehicles that are so elegant and deliver the medication without taking anything away. But, in part, this is due to the hydro arc technology that this vehicle has. It’s pH balanced, it has a long half-life, so it’s a once-daily dosing. And from a tolerability perspective, [it’s better than] the nonsteroidal topicals, which have a history of poor tolerability, or calcineurin inhibitors, which burn and sting. There is some local irritation from our other nonsteroidal options, such as vitamin D analogues. So [it’s great] to have a nonsteroidal topical that is once-daily dosing, that is so tolerable. But with local tolerability, no cutaneous absorption or low cutaneous absorption, and no adverse events, [no] box warnings with either of these 2 agents, [they are] so easy to use.

Mona Shahriari, MD: Yes. I feel like this is not your grandmother’s PDE4 inhibitor. I like to think of it as PDE4 inhibition 2.0. Because, as you said, the high affinity that it has for the PDE4 molecule, the fluorination that you see in the molecule itself. That hydro arc technology allows for the vehicle to spread nicely on the skin, get absorbed quickly, and then the medicine gets through the skin barrier without disrupting it—these are all key features that we want to see in a topical agent for our patients. And, of course, the efficacy is a huge bonus right there.

Alexandra K. Golant, MD: Absolutely. It’s the icing on the cake, with both of these agents. Do you want to take tapinarof?

Mona Shahriari, MD: Yes. Tapinarof does represent a novel mechanism of action. It’s an aryl hydrocarbon [AHR] receptor agonist, which…based on what’s bound to it, modulates the transcription of different genes. So when tapinarof binds to AHR, we get impacts on different molecules that affect the level of the skin in particular…. And this molecule very similarly to roflumilast has been elegant on the skin and does a nice job of calming down the signs and symptoms of psoriasis on the skin. It also has that once-a-day dosing regimen, which is nice for our patients.

Alexandra K. Golant, MD: What excites me so much about tapinarof, it’s so great to have a truly new mechanism of action in the space. And we talk a lot about that in dermatology, when we treat inflammatory skin disease with things that decrease inflammation, and tapinarof has that…. But we know, too, that it increases, it normalizes things like skin barrier proteins. So there are many ways to explain the efficacy that we see with these 2 agents. And what makes them different than things that we’ve had before [is their] excellent safety. What excites me about the data for both of them is the excellent itch data that we see. Itch is not always something that we ask enough about in our patients with psoriasis. We ask about it all the time in our patients with atopic dermatitis, but we sometimes forget to ask our psoriasis patients about itch, and we know that so many of them come in with significant baseline itch burden.

Transcript edited for clarity.