A discussion on the benefits of combination drug therapy for adherence.
Casey Butrus, PharmD: Arash, I want to focus and transition into some of the newer approvals. I know we talked about some newer combination products, but also some new mechanisms of action. We have topical clascoterone, topical minocycline, and topical trifarotene. Could you go over their mechanisms of action and what populations that they’re indicated in?
Arash Mostaghimi, MD, MPH: Certainly. I’ll start with clascoterone. Clascoterone is a really exciting medication in that it’s the first drug in this category. When Steve was talking about the different causes of acne, he mentioned the idea that androgens are at the core. When you’re 8 years old, you have awesome skin. When you’re 12, your skin starts breaking out because you’re going through puberty. So the use of antiandrogenetic agents is common. Particularly for women; we use oral spironolactone as a common agent. We don’t have an equivalent in men because, as Hilary was saying, oral contraception or spironolactone can have unwanted adverse effects in men and an unknown safety profile. So the advancement of clascoterone doesn’t have exactly the same mechanism as spironolactone and, actually, the exact mechanism is a little bit debated and not as well understood. But we do know that it is antiandrogen, so it reduces androgen expression in the skin. And as a result, it reduces sebum, reduces bacterial overgrowth, reduces inflammation, and truly hits multiple causes. And the nice part about it is that it can be used not only in women, but also safely in men. So it’s a good treatment for mild to moderate acne. You can also use it in patients with more severe disease if they need it. And it has been shown to reduce inflammatory lesions quite markedly in some [patients]. If a hormonal driver is part of what’s driving the process for a patient, it’s nice to have that first option for men and a nonsystemic option for women, which I think is really exciting. It also has been studied on slightly larger surface areas, so you can use it on the chest or on the shoulder, which is a nice extension of some of the prior studies, which really were face only. As was mentioned before, truncal acne matters quite a bit, and it’s a nice way of approaching that. For minocycline, it was one of those old medications. How many years for minocycline?
Hilary Baldwin, MD: Fifty.
Arash Mostaghimi, MD: Fifty years. So it’s a half-century for minocycline. The use of tetracyclines from an antibiotic standpoint is one of the backbones of dermatologic care or dermatology care of acne. Over the years, we’ve tried to move away from more chronic antibiotic use as the impact not only as a sort of a population antibiotic stewardship sense is noted, but also on its impacts on an individual’s gut flora and other parts of their body. The hard part, though, is that doxycycline and minocycline had no topical version. From a drug delivery mechanism, it was hard to get there. Our only topical antibiotic was clindamycin. Benzoyl peroxide has some antibacterial activity but was not a traditional antibiotic. And then, dapsone, if you want to believe it’s more anti-inflammatory or antibacterial, you can put it in that category as well. And what this does is it takes minocycline and puts it in a topical form. It is shown that with the topical minocycline…you don’t get the photosensitivity that you get sometimes with oral tetracycline, you don’t get the gastrointestinal upset. And then although we don’t know 100% for sure, intellectually, it feels like your overall exposure to antibiotics is less. From a stewardship standpoint, it feels better. The one potential adverse effect of that medication is that it has a color to it that can sometimes stain clothing, fingers, things along those lines. These are little things that we have to consider in our treatments. Finally, trifarotene is the newest retinoid and certainly the first retinoid in probably more than 20 years to be approved. And as we discussed before, retinoids are the absolute bedrock. Vitamin A derivative retinoids, there are natural ones, and then over time, they’ve adjusted the molecules so there are first, second, and third generation. Some people consider this the first and the fourth generation. And there are different retinoid receptors in the skin that are targeted by these different medications. The RAR [retinoic acid receptor] γ is the one that is particularly affected by trifarotene, and the concept there is that you can get a lot of the antisebum, anti-inflammatory sort of turning over your skin, less reducing of the plugging that can cause acne with this, but reducing the irritation that can also come when you use retinoid. So that’s a major benefit there. The other advantage of this is that it has been studied quite extensively for truncal acne as well. And it seems to work quite well and to be well tolerated there. We have a new, first-in-class agent with clascoterone, a topical formulation of an old friend in minocycline, and then perhaps a newer, better, more tolerable version of a retinoid in trifarotene.
Transcript edited for clarity.