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Mechanism of Action of Tapinarof in Plaque Psoriasis


Experts discuss the unique mechanism of action of tapinarof and its use in the treatment of plaque psoriasis.

James Q. Del Rosso, DO: I have a couple of other questions about the mechanism of action. Does it mean anything to you that it’s a new mechanism of action that hasn’t been talked about before? It’s the first therapy that has a certain mechanism of action. Brad?

Brad Glick, DO, FAOCD: Novel is great. Patients who have been suffering from psoriasis for 20 years keep getting their 1-pound jar of triamcinolone. I’m like the cortisone guy on the panel evidently. But I believe in the possibility of paradigm shifts. We’ve been prescribing mostly corticosteroids and rotating in other nonsteroidals, and we’ll shift to some of the other agents we discussed when we’re trying to take a break from the corticosteroids. Our patients want to know that there’s something new.... I’ll explain that this is something that works differently. It’s only once a day. They’ll say, “That’s great because with the medicine you’ve been giving me, you told me to use it twice a day, but I don’t use it twice a day.” It makes it a lot easier for us.

I like the idea of treat to complete. I tell patients about that: treat to complete. You can use this. With other drugs I’d say to you take a break with corticosteroids—2 weeks on, 1 week off, 2 weeks on, 2 weeks off. We can use this continuously. Something novel is great. Then we combine something that’s unique, particularly tapinarof, which is unique not only for us as clinicians but also for my patients. I’d also say, perhaps even beyond the scope of this discussion, that what’s unique about tapinarof is it isn’t doing something just to reduce inflammation. It impacts the barrier and has some antioxidant properties. That’s something novel. It’s going to work fairly well in another disease state as a topical therapy.

James Q. Del Rosso, DO: You said, “It looks like I’m the corticosteroid guy on the panel.” Would there be patients for whom you’d say, “I’m going to give this a try as a monotherapy so that you can get a sense of how well it’s working”? Otherwise, you’re never going to know.

Brad Glick, DO, FAOCD: I’ve done it already.

James Q. Del Rosso, DO: In the clinical trials?

Brad Glick, DO, FAOCD: No, I’ve done it in clinical practice already. If a patient has reasonably limited disease, mild to moderate disease, we’re doing them a service by not putting them in that on and off therapy, that soft-tooth pattern. The condition is a soft-tooth pattern in and of itself, and we can have something that’s more of a straight line. I don’t have to tell them to disrupt the therapy barring any consequences. These new agents, like tapinarof, have a limited scope of adverse effects.

James Q. Del Rosso, DO: The interesting part in the phase 3 trials is that even when they cleared, they were told to continue applying it to the normal-appearing skin because there’s no concern about what adverse effects you’re going to get. That’s pretty novel in and of itself. Nick, let’s come back to you. You’re the young guy who’s learning from your experiences, from your trainers. How are you seeing the therapies being used where you are at Temple University Hospital?

Nicholas Brownstone, MD: I’m in an interesting situation. We’re a safety net hospital, so a lot of patients can’t get access to these therapies. It’s a difficult situation, but every once in a while we get a patient who has access to it. That’s very exciting. My favorite way to treat psoriasis is to calm things down with a topical steroid and then go to a maintenance therapy. But it’s exciting to see therapies you can give them from day 1, have them treat, get them clear, and then stay that way. That’s been exciting to see.

Dawn L. Sammons, DO, FAOCD, FAAD: We’ve alluded to the fact that patients can use them virtually anywhere on the body. They can use them in the body folds, eyelids, elbows, and knees, and it’s nice for our patients not to worry about burning or stinging. We don’t have to worry about skin thinning or safety adverse effects. But there are also the tolerability pieces.

James Q. Del Rosso, DO: And vehicle cream is cosmetic.

Dawn L. Sammons, DO, FAOCD, FAAD: Sure. Patients like it.

James Q. Del Rosso, DO: We haven’t talked about how some of the corticosteroids are in greasy vehicles. Some are in very nice vehicles. But some are in vehicles that they’re not using because they don’t like the way greasy-type ointments feel on their skin.

Benjamin Lockshin, MD, FAAD: One thing that surprised me the most, making that transition from the clinical trial space to the commercially available product, is that I’m seeing far less folliculitis than I expected in the real world with tapinarof. It’s because we’re using it in conjunction with some steroids at times. Either patients are using it on their own because they have it in their medicine cabinet, or they’re not applying it as religiously as they would have in the clinical trial space. For that reason, there’s greater patient satisfaction. The phone calls I’m getting related to the adverse events, which I expect in clinical trials, are far less.

James Q. Del Rosso, DO: The fact that they have it in the medicine cabinet means they weren’t compliant with it when you prescribed it to them, right? They weren’t necessarily using it. Any other thoughts on tolerability or adverse effects?

Nicholas Brownstone, MD: Folliculitis was the biggest thing that was seen, and that’s a great adverse effect. Way better than atrophy, striae, steroid acne, and everything else. We treat folliculitis all day, so that’s a fine adverse event. We can totally deal with that, and it won’t bother the patient much.

James Q. Del Rosso, DO: We had 1 patient in practice who had the psoriasis clear completely. They were thrilled, but they had milia or keratosis pilaris [KP] on the legs, which eventually resolved. But their psoriasis had cleared. It was the only case that we had.

Benjamin Lockshin, MD, FAAD: The few episodes I’ve seen have been more of a KP-like appearance, loosely called folliculitis in my eyes.

James Q. Del Rosso, DO: Folliculitis was a general term for bumps in a follicle. It wasn’t necessarily bacterial or viral.

Brad Glick, DO, FAOCD: I did the trials, so I have the same experience as Ben in that I saw it in the clinical trials. It was more milia form or KP-like. But after the launch, I haven’t seen the folliculitis. I’d probably interject that I’ve seen a little keratin contact dermatitis, which has been manageable. Patients want to go back on therapy because they see clearance. I had 1 patient in particular who used it, and he stopped it a little too soon. It’s sitting on the shelf. As opposed to some of our trial patients who know they have to use it every day. We’ve counseled them to use it every day. We try the same way in the clinic, but it doesn’t always happen that way. With this therapy, we’ve seen such remarkable clearance that, in this patient, he had some residual plaque and improved so much that he took a bit of an early break. He went back to therapy a bit of an irritant reaction. He took a break, went away, did some emollients, and we put him right back on therapy.

James Q. Del Rosso, DO: It’s also important that if they stop it and they go back to it, it’s going to work. It’s not going to stop working. There was no evidence of tachyphylaxis, so the dependability is there. That’s pretty consistent with the newer topical nonsteroidal that we have.

Transcript edited for clarity

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