Neal Bhatia, MD, provides an overview of the spectrum of disease, topical choices, and transitioning to oral medications for the treatment of plaque psoriasis.
Brad Glick, DO, AOCD: Neal, what I want you to do is talk about the spectrum of disease; mild, moderate, severe. Who is the mild patient? Who is the moderate patient, the moderate to severe patient? What are our choices? Talk a little bit about the topicals that we’ve been using, kind of transitioning into those oral systemics. We have older drugs now. Apremilast has now been around pushing 9 years in the space of skin and joint disease. Methotrexate, we’ve used for a number of years. Put all that into perspective and tell us where these agents play a role in your practice on a day-to-day basis. I’ll expand that even to your opinion on [whether we have] been over-relying on topical therapy. That’s a big question right there, but see if you can handle that.
Neal Bhatia, MD: That’s a little bit loaded, but it’s also a little bit thought-provoking because the concept of just working from the top down we now know is not complete. Again, we used to think about vehicles delivering to the scene of the crime of where psoriasis pathogenesis starts, but we now know it’s not a sandwich of epidermal hyperplasia and inflammation, it’s all swimming in one. We’ve gone from those days of treating top-down and using methotrexate to stop the immune response to now thinking about, let’s look at surface area, let’s look at scalp, let’s look at nails and upgrade a little bit, let’s throw in skin of color. Then we say this violaceous erythema may actually still be activity. Even more so, let’s think about what happens when you walk in the door and in the first 10 seconds is your physician’s global assessment. All of those are wrapped into one and thinking in terms of what’s your approach.
We’ll be talking to patients about what they’ve been on. We’ll talk about the keratolytics they’ve tried over the counter, probably some formulation of topical steroids from classes 1 to 4. We’ll think about the additives that we’ve seen now; calcipotriol and tazarotene are mainstays in combination with steroids. Now we have tapinarof, we have roflumilast, we have new things coming down the pipeline, which is great. But again, top-down therapy is now, for me, more for breakthrough from what we’re using systemically, whether it be oral or biologic. I’m thinking in terms of let’s put out the fire topically, let’s get the drug covered, let’s get them on autopilot. I think that’s probably the approach that makes the most impact on keeping retention but also keeping expectations.
George said things in terms of having a real good perspective of optimizing mechanism, optimizing opportunity. I look at the flip side, then I look at the dermatologist and I think, “What are you afraid of?” What are you afraid of in terms of treating this patient aggressively? Why are we giving up our scope to rheumatologists, to nonphysicians, to influencers, who come back and say, “You should be on these biologics, these are great.” But the dermatologists say, “No, these drugs aren’t for us,” like George has said about these commercials. What is it about dermatologists who are so afraid of treating aggressively and thinking in terms of what we are doing for the next month, the next 6 months, and the long term? We have 5-year data for IL-23s that says it’s consequence-free for the vast majority of these patients. We have 5-year data for other therapies that are working anywhere systemically.
Then, of course, the JAK inhibitors, where everyone is afraid of the big black box warning. The black box warning is not going to get you arrested or deported, it’s meant to say, use these as guidelines for past experience of what to watch out for. It is the same thing with the biologics; these come with warnings because we want to be careful. But methotrexate has, I think…17 black box warnings, and we don’t even blink when we use it, right?
So, I think the long-term approach has to be [to figure out] what is going to slow down the process. As George pointed out too, think about what else is under the hood. One thing about IL-17, it is is elevated in patients with depression. IL-17 is a very strong cytokine that has neurovascular impact, like George said about cardiovascular impact. So slow down the process that makes IL-17 signal through the JAK step pathway, whether you’re using deucravacitinib or using IL-23 blockers. You can slow down that effect [to keep] cytokines from doing their job. As you mentioned both about the tumor necrosis factor inhibitors, they’re still there. They’d be pulled from the market if we didn’t have safety or efficacy data, but we still use them. I think the key is just to get on the bandwagon saying this is how you look at psoriasis from the top down as well as inside out.
TRANSCRIPT EDITED FOR CLARITY