PDE4 Inhibitors in Treatment of Plaque Psoriasis - Episode 11
Neal Bhatia, MD, FAAD, reviews the clinical implications of roflumilast, a newly approved topical agent for chronic plaque psoriasis treatment.
Neal Bhatia, MD, FAAD: Looking at PDE4 [phosphodiesterase-4] inhibition as a target or a class of mechanism of action for these therapies, it’s much different from what we’re seeing with the tried-and-true topical steroids, which work more cellularly, or some of the calcineurin inhibitors, which have a different approach than steroids and might be more specific. Calcipotriene has some impact on differentiation as well as an inflammatory aspect. Tazarotene, which is a retinoid, is also anti-inflammatory and has a strong impact on epidermal hyperplasia. The newer agents such as tapinarof, roflumilast, and these others that are all in clinical research have very exciting end points as well as some of the opportunities for use in areas such as intertriginous, scalp, and even on the face, where consequences from steroids might be limiting. I think what we’re seeing with the use of PDE4 inhibition is that we can slow down the progression of those cytokines which, once they’re activated by phosphorylation, will continue to propagate the inflammatory cascade, and we can slow that down without risk of steroid atrophy, tachyphylaxis, calcium abnormalities, or any other consequence of long-term therapy.
Now that the approval has been obtained by Arcutis Biotherapeutics and the FDA has brought the drug to market, we’re now seeing that the cream base is lending itself to where we once thought ointments, foams, or other vehicles might be necessary. We’re also seeing the opportunity to treat intertriginous areas, to treat the scalp with a cream, to treat surface area because of the spreadability of the vehicle. We have the trial data that shows we can obtain some success. I think we can modulate patient expectations and say this may not work immediately or in the first 2 days, but we need to go into the marathon of treating through the disease as well as having some good exceptions of what they’ll see in 2 months. We’ve seen time and time again where patients who are on topical therapies will give up or they won’t see the results they want in a week, and it really takes that extra counseling to say, “This is a therapy that we’re not only going to use to try to make things go away, but we’re going to try to keep things away as much as we can based on the efficacy of the trial as well as the safety of being able to use these drugs for the long run.”
Aside from plaque psoriasis, we were participants in trials both for atopic dermatitis and for seborrheic dermatitis, sponsored with the same drug, with roflumilast cream, and we found some exciting clearance of seborrheic dermatitis, especially around the face, eyebrows, scalp, and behind the ears. The safety of the cream lends itself to good application in the head and neck areas, as well as in areas of the chest or intertriginous areas where seborrheic dermatitis might be more common. Even more so is the potential use in atopic dermatitis because of the broad-brush nature of the inhibition of phosphodiesterase-4, which we’ve seen with both apremilast and crisaborole in clinical practice. The infinity of the roflumilast molecule to do that job and do it more potently is an exciting opportunity to put it into other disease states.
Transcript edited for clarity