Exploring Novel TYK2-Targeted Therapies for Plaque Psoriasis - Episode 9

Future Directions in the Use of TYK2 Inhibitors for the Treatment of Psoriasis

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Linda Stein Gold, MD, and Bruce Strober, MD, PhD, review the clinical and practical impact of TYK2 inhibition and its evolving role within the treatment landscape for psoriatic disease.

Linda Stein Gold, MD: I just want to touch on the fact that there are some other TYK2 [tyrosine kinase 2] inhibitors that are in clinical trials, not so far along, but can you comment on that?

Bruce Strober, MD, PhD: I actually think the approval of deucravacitinib has opened the door for this entire new class to be developed. I think this is not going to be our last TYK2 inhibitor. There are companies working on follow-on TYK2 inhibitors in phase 2 and entering into phase 3, that might actually be more efficacious than deucravacitinib. Yet maintain the comforting safety profile and lack of monitoring issues. So this is now the beginning of another revolution where we get oral therapeutics for psoriasis that might ultimately touch the efficacy of our modern biologic therapies. And so you might envision 10 years from now having a raft of oral therapies that are every bit as good as a biologic injectable, and it’s going to be a toss-up of which one you’re going to use.

Linda Stein Gold, MD: It’s really an exciting time. And I remember the beginning of my career, if a psoriasis patient came in, there’s just no way we were going to get this person to clear. That was just a dream, and today that’s really kind of the expectation is we have the tools necessary. Now, just to kind of conclude, our psoriasis patients are complex beings in that they have so many different comorbidities. Do you involve other physicians, or do you make sure the patient is involved? Potentially, do you ask about depression? Do you ask about cardiovascular risk factors? Because we know they are set up, especially those patients with moderate to severe disease to have other health issues. Do you have more of a holistic approach to the patient?

Bruce Strober, MD, PhD: You have to evaluate comorbidities in patients with psoriasis because they’re at risk for certain comorbidities more likely than the general population. For example, as you mentioned, they’re at risk for psoriatic arthritis. We have to cover that base. But the other issues are the features of the metabolic syndrome. Psoriasis patients are much more likely to be obese and therefore to have insulin resistance, hypertension, and dyslipidemia. My approach is tell the patient that you are at greater risk for these types of comorbidities through your lifetime. It might be actually programmed into your genetics that this is the case. Therefore, you need to see a PCP on an annual basis to manage these issues if they are present or they arise over time. And finally, the reason why we’re doing this is because we’re trying to prevent heart attacks and strokes. And that’s the hardest part for most patients to accept, because they have moderate to severe psoriasis, or psoriatic arthritis, they’re at a greater risk for having a heart attack or stroke early in life and later in life, to be honest. And that actually managing not only those comorbidities on their own, but managing the psoriasis, reducing systemic inflammation probably reduces their risks significantly, perhaps down to that of a person who doesn’t have psoriasis anymore. And that’s again, to conclude, why continuous control of psoriasis over a person’s lifetime has great impact, in my opinion, on their long-term health, comorbidities, and ultimately them being able to lead a normal healthy life with a normal lifespan.

Linda Stein Gold, MD: And just such a critical issue. I think that the burden of managing the patient’s entire health is too much for the dermatologist. And I agree with you that just making sure the patient has a primary care provider and letting them know, I know you feel like you just have to come to the dermatologist, but you need to have that primary care because you are at risk for these other issues. And we can’t forget depression, huge.

Bruce Strober, Md, PhD: There’s more depression in people with psoriasis. There is the concept that if you treat the psoriasis, you can treat the depression. But it might not be the case. So you do have to have your antenna up with regard to patients who might have depression or mood disorders that need additional assistance. Again, I turn to the PCP for the first gatekeeper for that issue. And I just make sure the patient is in touch with their primary care provider so that that particular comorbidity can be addressed if it’s present.

Linda Stein Gold, MD: Bottom line is it is a team approach. This patient, especially those with moderate to severe disease, is a complex being. They have their psoriasis, but there’s so much more to this person and we really want to treat the whole person, not just their skin.

Bruce Strober: Exactly.

Transcript edited for clarity