Selectivity of Deucravacitinib in Plaque Psoriasis

Lauren Miller, MPAS, PA-C: As we’ve already discussed, the FDA approved deucravacitinib last year, in 2022, for the treatment of adults with moderate to severe plaque psoriasis. It is a selective TYK2 (tyrosine kinase 2) inhibitor. What are your thoughts on how selective this molecule is, and how does that selectivity play into its safety and efficacy in your mind and where you put it in your toolbox?

Jayme Heim, MSN, FNP-BC: I think that knowledge is huge. So, what is a TYK2, right? And it’s an allosteric [inhibitor]. It…specifically binds at a specific site. The one thing is that it’s a member of the JAK family, [or] Janus kinase family. However, when you look at the in vivo studies and you look at the assays associated with that, you see that it does not go ahead and have that effect on the JAK 1, 2, and 3. It does specifically go to the TYK2 binding site. So…when we talk about the JAKs, we also get the heaviness that is associated with the JAKs.

Lauren Miller, MPAS, PA-C: [The]elephant in the room.

Jayme Heim, MSN, FNP-BC: The elephant in the room. That’s right. And we talk about patients over the age of 50, patients with heart disease, [or] thrombotic events. We really need to understand that mechanism of action. We also need to understand that it’s really important because [of] the role it plays with IL13, right in between where it is located, where the TYK2 is located, and that it is specific. So when we look at that and we look at that particular mechanism of action, it is important. Do we [completely] know how that mechanism of action works, why it works the way it does? No, we don’t. But what we do know tells us it is specific.

Lauren Miller, MPAS, PA-C: It’s interesting because we can’t really speak to the specificity and…why possibly it’s more tolerable than other therapies or why it might be more efficacious than other therapies. But it definitely leads you to think that. And as science has evolved, you think about the anti-TNFs [tumor necrosis factors], and then we had IL12/23 and then the [IL]17s. And every time science seems to advance and we get new molecules, they become a little bit more specific, and safety tends to be a little different. Efficacy seems to be a little bit better. So it does lead you to think that the specificity is a big deal.

Transcript is AI-generated and edited for clarity and readability.