Safety of Deucravacitinib in Plaque Psoriasis

Alexa Hetzel, MS, PA-C: So, Andrea, how does the safety of deucravacitinib compare to the JAK inhibitor class of treatment?

Andrea Nguyen, PA-C, MS: Even though deucravacitinib is considered, technically, since it’s a Tyk2 inhibitor, part of the JAK family, we don’t see a lot of the behavior of Tyk2 being similar to that of JAK1, JAK2, or JAK3. The processes that you’re involved with inside of the body, you have a little bit different effects when you have inhibition of JAK1, JAK2, JAK3, versus when you have inhibition of Tyk2. So, the safety signals that we’ve seen, or lack thereof, in the clinical trials from POETYK- [PSO-]1, POETYK- [PSO-]2, and the long-term safety extension, is really reflective of the difference of Tyk2 inhibition versus other traditional inhibitors. The way that deucravacitinib works, how it inhibits allosterically, is the regulatory site also increases that selectivity for Tyk2 because you’re not activating or inhibiting the active ATP binding site, which is a little bit more commonly shared across the JAK family. So, when you’re very selective for Tyk2, we don’t really see things like significant hematological shifts or other sorts of safety signals that we see with inhibition of the other JAK family members. That’s in large part due to just being selective for Tyk2. The selectivity is looked at in cell-based assays, which can have some variability, but the overall sentiment is that it’s very selective for Tyk2.

Alexa Hetzel, MS, PA-C: Are there any types of adverse events that patients should be monitored for?

Andrea Nguyen, PA-C, MS: Deucravacitinib, as a Tyk2 inhibitor, because of the safety that they saw in the clinical trials and sort of the favorable safety monitoring that they saw, the FDA did not mandate the same box warning on deucravacitinib as some of the other families of medications inhibiting the other JAK family members, such as JAK1, JAK3, JAK2. So, we don’t necessarily have the same kind of box warning for mortality, … the things that we have to monitor very closely with some of the other JAK inhibitors. That doesn’t mean that we don’t monitor our patients at all, it just means that there are certain things that we would selectively look for more frequently using some other agents.

With deucravacitinib, in general, especially for patients who have a primary care physician, we want to take a look at some lipids. If you have patients with certain comorbidities, you may want to keep a closer eye on them, but in the long-term trial, after 60 weeks, and some of the other data that we saw, we don’t really see a lot of changes in their CBC [complete blood count], neutropenia, and things like that. So, these are kind of general screening measures, but not necessarily something that we would anticipate to have significant abnormalities in. I think at baseline, all of us are used to screening for tuberculosis just because that’s something that has been inherent with treating patients with psoriasis and using systemic therapy. Obviously, if a patient develops an infection on any therapy, whether it’s deucravacitinib or something else, we would interrupt treatment and make sure that the patient gets treatment for their infection. That’s the goal.

Alexa Hetzel, MS, PA-C: So, you brought up the black box warning that the other JAK inhibitors have. In your experience, is this still a concern for APPs [advance practice practitioners] although it’s not a JAK inhibitor? I feel there’s been a lot of mumbling around that they didn’t get it, but they’re still kind of related. Do you find that a concern for you, in your clinical experience?

Andrea Nguyen, PA-C, MS: I think that, as clinicians, all of us want to do the best for our patients. The sentiment, in general, is that we don’t want to inflict harm. We want to provide value and better clinical outcomes. I concerned myself personally as a clinician. My threshold for concern for deucravacitinib, particularly, versus potentially using another type of JAK inhibitor, is not going to be the same level of concern when I’m monitoring my patient due to the selectivity of the pathway because Tyk2 is not involved in a lot of the processes that we see with the other JAKs in the family. However, I think that, in general, when something is new, clinicians may want to screen still. They still might want to check. I don’t necessarily think there’s anything wrong with that, especially because that might be their comfort level.

What I would say, though, is look at the long-term outcomes, look at the long-term safety, and so far things like lipid abnormalities are not really something that we see that’s clinically significant in their long-term extension, as well as any sort of changes in their CBCs and other things that we monitor for. So, understanding that deucravacitinib is a Tyk2 inhibitor and that we, in general, want to be mindful of patients if they have active malignancy or active infection, but outside of that, the long-term safety looks, so far, to be very favorable.

Transcript edited for clarity