Exploring Novel TYK2-Targeted Therapies for Plaque Psoriasis - Episode 6
Linda Stein Gold, MD, and Bruce Strober, MD, PhD, discuss the nuances of treatment selection for patients with moderate to severe plaque psoriasis.
Linda Stein Gold, MD: This sounds like a really great new tool in our treatment armamentarium. But when we have those patients who come in now with moderate to severe scalp psoriasis or psoriasis in a sensitive area, we have so many tools. When would you think about using an oral agent like deucravacitinib? If a patient walks in and says, “I’ve used topical therapy. I have maybe 15% body surface area. Maybe I have a little bit on my scalp. Maybe it kind of comes down onto my forehead. I’m kind of on the cusp. I’ve used some topicals. It’s OK. I feel like my life is consumed by trying to make sure I get my creams on, trying to make sure the flakes aren’t on my clothing.” When that patient walks in, I haven’t used anything systemic yet. What’s your thought process?
Bruce Strober, MD, PhD: You’ve defined a patient who needs to be on a systemic therapy because they failed topicals and their quality-of-life stinks. And in that instance, I generally choose between biologic therapies and oral therapies, all of which I’ve mentioned. Now, the good thing about deucravacitinib is it has very good efficacy for an oral therapy, requires little monitoring, and you can use it in men and women. You can go down to the age of 18. All of that gives it simplicity. So the patient who wants to be on an oral therapy that’s simple, they will get deucravacitinib. If I feel the patient needs more robust efficacy right now, and is comfortable with injectable medications, I use a biologic therapy for these same patients. So it comes really down to patient preference. And by the way, if a patient says, “I don’t want to do injections right now, I’m not comfortable with that.” I say, “You can have deucravacitinib. Let’s give it a 3-month trial,” which is about what it needs. And if it doesn’t work, then we’ll turn to a biologic therapy. We’ve made a deal, so to speak. And the patients usually agree to that deal.
Linda Stein Gold, MD: That makes sense. And I want to just ask you again, because we often talk about the mild, the moderate, and the severe patient, and I know you do not like that classification. Can you explain what your thought process is there?
Bruce Strober, MD, PhD: There are only 2 types of patients in psoriasis. Those you can manage on topicals and those you can manage on either systemic therapies or phototherapy, which are more or less one and the same. A person who is managed on topicals, you keep them on topicals. But if they’re not managed on topicals, you go to a systemic. Let’s say they have special areas—hands, feet, devastatingly affected, bad scalp, intractable facial, and intractable genital psoriasis, intergluteal, terrible quality of life—you got to go to systemics as a trial. Let’s say they’re greater than 10%. They walk through the door just covered in psoriasis. They don’t have to fail a topical. They go right to a systemic or phototherapy. So, for me, there’s 3 types: 10% or more, special areas of involvement, and failed topicals. That patient goes on a systemic. I don’t care about mild, moderate, and severe. I care about what the patient needs. This way I never undertreat the patient based on strict BSA [body surface area] cutoffs that are part and parcel of the mild, moderate, severe definitions.
Linda Stein Gold, MD: Now, if somebody has come in and say they’ve been on another oral therapy, maybe apremilast or maybe they’ve been on methotrexate, is there a reason to believe that another oral such as deucravacitinib would not work in that patient and you need to go to a different category of drugs like a biologic agent?
Bruce Strober, MD, PhD: No. No reason. In fact, I have a first principle of treating patients with psoriasis. One drug may fail, any of the others might succeed, and it doesn’t even matter what class they’re in. So failure of one doesn’t have any meaning to me regarding success of the next. Though there are certain circumstances where I’m biased towards certain classes and types based on how they responded initially. And that’s for another discussion.
Linda Stein Gold, MD: So Bruce, you mentioned needle phobia. People talk about needle phobia. I always thought that’s not a real thing. I have had patients who are needle phobic. Do you? Is that really something that you see?
Bruce Strober, MD, PhD: The initial impression from a lot of people is I don’t want to be injected with anything. Sometimes you just have to teach them, and they’ll get over it, or you do it for them. Some of the injectable biologics are so infrequent, you just have them come in for a nursing visit and they get an injection. They’re very happy with that. And they learn the injections are nothing. They’re just like mild vaccination type sensations, in the worst instances a little injection site pain. So, most patients can get over the needle phobia that they have. That said, if you were to ask 100 patients, what do you prefer, a pill or an injection, 70 to 80 will say, I’d much rather have the pill, even if it’s of a lower efficacy than the injection. And the truth is, most of us in our lifetime have been taking pills since like age 6, depending on the child. But my children learned early. If you’ve been taking pills all your life, taking a pill for psoriasis is the no-brainer. And nobody gets injections for medication really, until they first encounter a biologic therapy for psoriasis, so if they have psoriasis. It’s really an easy question as to what your average patient would prefer.
Linda Stein Gold, MD: Absolutely. And say you’re going away for the summer, you take your pills and you kind of throw them in your suitcase, as opposed to thinking about your injections, your refrigeration and things like that. I used to think, no, I could tell anybody, I think an injection is for you and they’d be fine with it. I’ve subsequently learned there’s absolutely a population of patients, if you have a safe and effective alternative that’s a pill, that’s what they would prefer.
Bruce Strober, MD, PhD: My only concern is do daily pills lead to poorer adherence. So do people actually take every dose every day. And I’m doubtful they do. But I also know people don’t take injections on schedule. About a third of my patients don’t even have a calendar. I asked them, I said, “Why don’t you just put it in your calendar every 8 weeks?”
Linda Stein Gold, MD: What’s that?
Bruce Strober, MD, PhD: And they’re like, I don’t have a calendar. So I said, they just lead life kind of randomly and therefore there’s no way they’re doing their injections on time.
Linda Stein Gold, MD: So that leads me to a really important issue. In terms of patient compliance, we know with the traditional JAKs [Janus kinase inhibitors] that if you go off of therapy, your results will start to diminish very rapidly. For some patients, within even a day or 2, they start to notice that their disease is starting to recur. With deucravacitinib, which works by a different mechanism of action, targets different pathways. What do we see, say I got on the airplane and I forgot my pills at home and I’m going to be gone for 2 weeks?
Bruce Strober, MD, PhD: So the good thing about the mechanism of action of deucravacitinib is it inhibits IL [interleukin]-23, which we think from the biologics that inhibit IL-23 is somewhat of a remitive mechanism of action. In others, you give a dose and you can induce clearance, and then the patient can maintain that response for many months not taking the medicine. That’s actually why you could have long intervals between the IL-23 inhibitor injections. Deucravacitinib having a similar MOA [mechanism of action], probably has the same behavior and its clinical trials show that, that when you take people off drug, who’ve done well, they maintain their response for quite a long time. So the consequence of missed doses or holidays or vacation trips without meds because they forgot to pack it, are much less severe. And it’s really a unique feature of an oral medication that, in my experience, I haven’t seen in previous medications that are oral for psoriasis.
Linda Stein Gold, MD: I find that critical, really critical, and such an important feature of the medication.
Transcript edited for clarity