Reviewing the Safety Profile of Deucravacitnib

Linda Stein Gold, MD: You talked to us about the mechanism of action and what we should expect, blocking TYK2 should not have the downstream effect on hematopoiesis or other metabolic…. In the clinical trials, did that hold true?

Bruce Strober, MD, PhD: Yes. The issues you are concerned with when you use what’s called a JAK inhibitor, which TYK2 is a JAK kinase inhibitor, are major adverse cardiovascular events [MACE], thromboembolic events, cancer, herpes zoster, serious infections. These issues pop up rarely with the traditional JAK inhibitors, but nevertheless, we need to be more conscious of them. They were followed specifically with the deucravacitinib studies in phase 3 for psoriasis. Essentially, when you compare deucravacitinib to apremilast and placebo, the rates of these events—MACE, DVT [deep vein thrombosis], pulmonary embolism—are extraordinarily low to nonexistent, and very comparable to apremilast and very comparable to placebo. I would call out zoster because zoster is something that we definitely associate with traditional JAK inhibitors. And the rates for deucravacitinib are very similar, again to placebo and apremilast, and totally in line with other biologics that we know have low rates of zoster to nonexistent, not more than background. So from my point of view, there is no zoster signal based on these studies, there’s no DVT signal, and no MACE signal. All of the issues specific to JAK kinase inhibition, traditional JAK kinase inhibition, are not there with deucravacitinib.

Linda Stein Gold, MD: I think that’s such an imperative issue, and I really appreciate the fact that they looked individually at each one of the issues because there is no boxed warning with deucravacitinib. That’s what you were making reference to; there is a boxed warning with the traditional JAK1, 2, 3 inhibitors with the downstream effects you just mentioned. There’s not a boxed warning with deucravacitinib. And they looked at, as you mentioned, each one of those potential adverse effects listed in the boxed warning. It’s fortunate that we not only have the placebo, but we have apremilast. I think it gives us great comfort that when you look at each one of these, as you mentioned, it’s not much different than apremilast, and not much different from placebo. That gives us all a good feeling of comfort. Then in terms of the blood abnormalities that were seen in the clinical trials, the FDA, we all know is fairly conservative, which they should be.

Bruce Strober, MD, PhD: They should be.

Linda Stein Gold, MD: And based on the data from the clinical trials, they did not mandate blood monitoring in terms of ongoing.

Bruce Strober, MD, PhD: Right, like I said, there were some excursions of triglycerides upward in people getting deucravacitinib. It’s about 10 mg/dL, which if you think about what your average person sits at with regard to fasting triglycerides, it’s somewhere between 125 and 225 mg/dL, depending on the individual. So going up by 10 mg/dL in a large population is a very small excursion. There are a few people who have elevations in CPK [creatine phosphokinase] and a very rare individual who has an elevation in their liver function test. But like you said, the FDA looked at these data and only made suggestions surrounding triglycerides and monitoring of the liver in people with baseline significant hepatic disease.

Linda Stein Gold, MD: In terms of the general adverse effects we’re seeing, we understand with apremilast there are some adverse effects that tend to be seen more commonly, such as the GI [gastrointestinal] adverse effects, maybe some headache. Is there a category of adverse effects that are seen more frequently with deucravacitinib?

Bruce Strober, MD, PhD: Yes, and it’s very well spelled out by the clinical trials. While all of these adverse effects were low in percentage, low in rate, we want to look out for herpes simplex, acne, folliculitis, oral ulcers, and upper respiratory tract infection. If you cover those bases with your patient at the beginning of therapy, you discuss the possibility of those, you are explaining the possible negative effects that can exist with people taking deucravacitinib. That said, like I told you, most of those instances, most of those adverse events, are rare. For example, acne happens with about 2% of patients and folliculitis is 1%. Herpes might be in the low percentage rate, and that’s a person who’s had herpes in the past. I always ask, “Hey, have you had herpes, either genital or oral, or cold sores frequently?” If they say yes, which is not common, I say, “There is a possibility deucravacitinib could worsen that situation. You might get more instances of herpes outbreak, and then we’ll just treat it.” We’ll treat it as it comes along with typical antiviral therapy.

Linda Stein Gold, MD: What is your thought on offering patients a zoster vaccine before going on therapy?

Bruce Strober, MD, PhD: It’s a little tough with this particular medication because zoster is not an adverse event specific to deucravacitinib. On the other hand, it’s not bad medicine, and I always do recommend to patients, “Why don’t you go get the zoster vaccine?” It’s the 2-dose dead, inactivated zoster vaccine, that’s modern. You get it week zero, and then 2 to 6 months thereafter. You can go to your local drugstore, and they’ll offer it to you. It’s generally covered by your insurance, particularly if you’re on a drug that modulates the immune system, it can go down to age 18. It’s just not a bad idea for everyone to get that vaccine because it’s an effective vaccine. And if there were a risk, you would be preventing the issue outright when you do this. So it’s a suggestion I make to all my patients going onto deucravacitinib.

Linda Stein Gold, MD: You also mentioned an important thing. As opposed to the kind of old-fashioned zoster vaccine, which was a live vaccine, this is not. And that’s important because we don’t want to use live vaccines.

Bruce Strober, MD, PhD: Correct.

Linda Stein Gold, MD: There are not that many live vaccines that people would have, but….

Bruce Strober, MD, PhD: There’s smallpox, MMR [measles, mumps, and rubella], and yellow fever.

Linda Stein Gold, MD: If somebody’s traveling.

Bruce Strober, MD, PhD: There are a few out there we need to think about.

Transcript edited for clarity