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Exploring Novel TYK2-Targeted Therapies for Plaque Psoriasis - Episode 8

Potential Uses for TYK2 Inhibitor Regiments in Plaque Psoriasis and Psoriatic Arthritis

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Linda Stein Gold, MD, and Bruce Strober, MD, PhD, discuss the potential use of TYK2 inhibitors in combination with other modalities.

Linda Stein Gold, MD: So we’ve gotten the patient the drug. We’ve gone through. We’ve done everything we need to. The patient’s on the drug. They have some breakthrough areas or maybe it’s the first 4 to 8 weeks where they’re seeing some clearing, but they’re not clear. Do you have any qualms in adding potentially a topical in addition to something like deucravacitinib? We know nowadays there are some drugs that suggest you do not use drugs in combination with other drugs that could potentially affect the immune system. Do you have any problems potentially with a topical?

Bruce Strober, MD, PhD: No because a topical therapy, no matter what its mechanism of action, even if it were immunosuppressive, it’s not going to systemically immunosuppress the patient when you’re just applying it to the small body surface area. In fact, almost all psoriasis patients should have a topical at hand to use for recurrences. That said, a lot of psoriasis patients don’t like using topicals. Once they’ve seen Shangri-La with a great oral or systemic biologic, they don’t want to go back to topicals. So I have to remind them at the visits when they have small recurrences, it’s OK to use the topical corticosteroid like clobetasol. Or I’ve added on much more frequently topical tapinarof, topical roflumilast, which I think are excellent add-on therapeutics. They’re a great addition that we’ve had this past year with regard to residual disease in people on systemic therapies.

Linda Stein Gold, MD: So given that, this is kind of an out of the box question. Would you consider using a TYK2 [tyrosine kinase 2] inhibitor with another systemic agent?

Bruce Strober, MD, PhD: I’m commonly doing so. Now, that’s off-label, and it’s important to note, not been studied. But I’ve been adding deucravacitinib to biologics, and particularly IL [interleukin]-23 and IL-17 inhibitors. Now, another category of patient I have found recently very benefiting greatly by deucravacitinib addition is people of inflammatory bowel disease who are on biologic for the inflammatory bowel disease like Crohn’s disease. And often these are younger people, and they get psoriasis form psoriasis-like dermatitis. And the addition of deucravacitinib has been clearing these patients quite rapidly. And so that combination I’m comfortable with. I’ve been combining systemics biologics for years, and from my point of view, it can be done safely in the patient who truly needs it. Another instance is a patient who has good clearance with psoriasis, but the psoriatic arthritis remains. Off-label, I feel that deucravacitinib has some benefit for psoriatic arthritis. There are phase 2 studies that demonstrate that. And so I add that on and you might get additional benefit.

Linda Stein Gold, MD: I was going to ask you about that because when the psoriasis patients come in the room, the first question, no matter what their body surface area is, really figuring out if they are showing signs or potential for psoriatic arthritis. You mentioned there’s some phase 2 data. Do you think that this would be a monotherapy drug for psoriatic arthritis in the future?

Bruce Strober, MD, PhD: Oh, it will be. To me, it’s an issue of what is its efficacy and do you feel it’s good as a monotherapy. I think that there’s gradations of efficacy amongst the systemics with regard to psoriatic arthritis, and actually the type of psoriatic arthritis, preaxial versus peripheral, etc. But I do believe deucravacitinib ultimately will be a PsA [psoriatic arthritis] drug. Like all of our systemics, they become PsA drugs eventually.

Linda Stein Gold, MD: And I think, we do our patients such a disservice, no matter how much body surface area they have, by not asking those critical questions. And we’re not rheumatologists. I am not a rheumatologist. I’ve thought somebody has psoriatic arthritis and it’s osteoarthritis. But I think asking those questions up front really, really is critical.

Bruce Strober, MD, PhD: Think of it this way. There’s a percentage of patients with psoriasis to go on to psoriatic arthritis. Is it 10% or is it 40%? It depends on the study. It depends on the severity of the psoriasis patient. But if you use a psoriasis therapeutic that covers the joints and the ligaments, you’re doing the right thing already. And I always screen for psoriatic arthritis. I have my 5 to 7 questions I ask. I think there’s pretty good sensitivity and specificity. And also, if I’m wrong, I’m wrong. I’m still clearing the psoriasis. If I’m right, I’ll see on follow up visits they feel better. And it’s common that patients say, “My achiness got lessened by this drug. I don’t have stiffness like I used to when I awaken in the morning.” And that to me tells me just empirically, I treated the psoriatic arthritis, and I didn’t need a referral to this rheumatologist.

Linda Stein Gold, MD: I agree with you. I think if we give a patient something that potentially covers both, it really sets the patient up for success and it kind of puts us at ease that we are taking care of the patient as a whole.

Transcript edited for clarity

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