Advances & Unmet Needs in the Management of Plaque Psoriasis – Expert Advanced Practice Provider Perspectives - Episode 10
Jayme M. Heim, MSN, FNP-BC, reviews deucravacitinib as an oral treatment for moderate to severe plaque psoriasis, describing its unique mechanism of action.
Alexa Hetzel, MS, PA-C: Let’s jump into our second segment. We’re going to talk about recent advances and approvals in the management of plaque psoriasis. Recently, deucravacitinib, a first-in-class, oral, selective allosteric tyrosine kinase inhibitor was approved for the treatment of patients with moderate to severe plaque psoriasis. Jayme, can you describe what makes this mechanism of action and clinical profile of deucravacitinib unique? And how does it differ from the current existing options that we have?
Jayme M. Heim MSN, FNP-BC: Absolutely. It is very unique. It is considered a small molecule. We do have another medication on the market that is considered a small molecule also. However, its mechanism of action is very unique. When we talk about psoriasis itself, we talk about certain cytokines that are overexpressed within the psoriasis. We talk about TNF [tumor necrosis factor], IL-23, and IL-17. Those we know are extremely critical. In fact, in large amounts, these are elevations within the body and these are proinflammatory markers that lead to the hyperkeratotic skin that’s being developed on top of the body—the plaques on the body. So that’s why a lot of our biologic medications are either TNF inhibitors or IL-17s, IL-23s.
Well, this particular small molecule actually is right in between the IL-23 and the IL-17. So this actually is a dimer. On one side you have the TYK2, and on the other side you have the JAK2. What happens is that the IL-23 goes onto the receptor site, it is activated, and it goes down the TYK2 side. When it goes down to the TYK2 side, it inhibits the TYK2 response on the other side, and by doing that, it also inhibits the downstream of the STATs [signal transducers and activators of transcription]. By doing so, it also inhibits the IL-17 so that it’s not able to produce those extra cells onto the body.
And so it’s actually in between the IL-23 and the IL-17, but IL-23 is needed to activate that receptor site of the TYK2. And so it really is a very unique way of even looking at psoriasis and a very unique way of explaining that to our patients when we talk about the mechanism of action in relationship to the pathophysiology of the disease. Also, this is very important because this follows the Th17 pathway and is critical for the Th17 pathway, which we know, is our pathway for psoriasis.
Alexa Hetzel, MS, PA-C: I love it. I think what’s so cool about it too is it’s so new and so novel that it does bind to that TYK2 site instead of the ATP active site. So it’s binding to that regulatory domain and only acting on TYK2. It doesn’t act on its paired dimer, which is so different than a lot of the other molecules that are in relation to it. It is awesome.
Jayme M. Heim MSN, FNP-BC: Yes it is. It’s different because it’s the only other small molecule we have too. We have a medication, and this is a medication also for 18 years and older. We also know that this particular medication is a 6-mg tablet taken once a day, so we don’t have to titrate up or down. We don’t see a lot of the other side effects that we see with the other small molecule, such as nausea, diarrhea, GI upset. This particular molecule is very well tolerated.
Transcript edited for clarity