Bruce Strober, MD, PhD

 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?

 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.

 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?

 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.

 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.

 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.

 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.

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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.

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

 So we’ve gotten the patient the drug. We’ve gone through. We’ve done everything we need to. The patient’s on the drug. They have some breakthrough areas or maybe it’s the first 4 to 8 weeks where they’re seeing some clearing, but they’re not clear. Do you have any qualms in adding potentially a topical in addition to something like deucravacitinib? We know nowadays there are some drugs that suggest you do not use drugs in combination with other drugs that could potentially affect the immune system. Do you have any problems potentially with a topical?

 No because a topical therapy, no matter what its mechanism of action, even if it were immunosuppressive, it’s not going to systemically immunosuppress the patient when you’re just applying it to the small body surface area. In fact, almost all psoriasis patients should have a topical at hand to use for recurrences. That said, a lot of psoriasis patients don’t like using topicals. Once they’ve seen Shangri-La with a great oral or systemic biologic, they don’t want to go back to topicals. So I have to remind them at the visits when they have small recurrences, it’s OK to use the topical corticosteroid like clobetasol. Or I’ve added on much more frequently topical tapinarof, topical roflumilast, which I think are excellent add-on therapeutics. They’re a great addition that we’ve had this past year with regard to residual disease in people on systemic therapies.

 So given that, this is kind of an out of the box question. Would you consider using a TYK2 [tyrosine kinase 2] inhibitor with another systemic agent?

 I’m commonly doing so. Now, that’s off-label, and it’s important to note, not been studied. But I’ve been adding deucravacitinib to biologics, and particularly IL [interleukin]-23 and IL-17 inhibitors. Now, another category of patient I have found recently very benefiting greatly by deucravacitinib addition is people of inflammatory bowel disease who are on biologic for the inflammatory bowel disease like Crohn’s disease. And often these are younger people, and they get psoriasis form psoriasis-like dermatitis. And the addition of deucravacitinib has been clearing these patients quite rapidly. And so that combination I’m comfortable with. I’ve been combining systemics biologics for years, and from my point of view, it can be done safely in the patient who truly needs it. Another instance is a patient who has good clearance with psoriasis, but the psoriatic arthritis remains. Off-label, I feel that deucravacitinib has some benefit for psoriatic arthritis. There are phase 2 studies that demonstrate that. And so I add that on and you might get additional benefit.

I was going to ask you about that because when the psoriasis patients come in the room, the first question, no matter what their body surface area is, really figuring out if they are showing signs or potential for psoriatic arthritis. You mentioned there’s some phase 2 data. Do you think that this would be a monotherapy drug for psoriatic arthritis in the future?

 Oh, it will be. To me, it’s an issue of what is its efficacy and do you feel it’s good as a monotherapy. I think that there’s gradations of efficacy amongst the systemics with regard to psoriatic arthritis, and actually the type of psoriatic arthritis, preaxial versus peripheral, etc. But I do believe deucravacitinib ultimately will be a PsA [psoriatic arthritis] drug. Like all of our systemics, they become PsA drugs eventually.

 And I think, we do our patients such a disservice, no matter how much body surface area they have, by not asking those critical questions. And we’re not rheumatologists. I am not a rheumatologist. I’ve thought somebody has psoriatic arthritis and it’s osteoarthritis. But I think asking those questions up front really, really is critical.

 Think of it this way. There’s a percentage of patients with psoriasis to go on to psoriatic arthritis. Is it 10% or is it 40%? It depends on the study. It depends on the severity of the psoriasis patient. But if you use a psoriasis therapeutic that covers the joints and the ligaments, you’re doing the right thing already. And I always screen for psoriatic arthritis. I have my 5 to 7 questions I ask. I think there’s pretty good sensitivity and specificity. And also, if I’m wrong, I’m wrong. I’m still clearing the psoriasis. If I’m right, I’ll see on follow up visits they feel better. And it’s common that patients say, “My achiness got lessened by this drug. I don’t have stiffness like I used to when I awaken in the morning.” And that to me tells me just empirically, I treated the psoriatic arthritis, and I didn’t need a referral to this rheumatologist.

 I agree with you. I think if we give a patient something that potentially covers both, it really sets the patient up for success and it kind of puts us at ease that we are taking care of the patient as a whole.

Linda Stein Gold, MD, and Bruce Strober, MD, PhD, discuss the potential use of TYK2 inhibitors in combination with other modalities. 

Potential Uses for TYK2 Inhibitor Regiments in Plaque Psoriasis and Psoriatic Arthritis

 Now that we’ve talked about the efficacy, the safety, do you have any tips in terms of getting patients the medication, including deucravacitinib, that you want them to have? Because this is such a challenging area and it’s so frustrating for the patients, and frustrating for the physicians. What do you do?

 Well, the first point I like to make is if a patient has commercial insurance, private commercial insurance, they can get the drug because the manufacturers of deucravacitinib and of the other drugs too, like biologics, have what’s called bridging programs. If patients are denied therapy by their insurance, so there’s a delay in the approval process, they will be given free drug. At least that’s what’s occurring now in the United States and should be occurring into the indefinite future. Patients with commercial insurance get the drug. The challenging patients are people on government supported health care, for example, Medicare and Medicaid. And Medicaid of course is state by state. But Medicare in general is a challenge because expensive medications, the full bill is not flipped by the government. There’s only a portion of it. Unless there is a patient assistance program that can fill the gap and pay up the difference that’s due to the patient. Medicare is my greatest challenge, honestly. Obviously, uninsured patients are challenging too, because it’ll be very hard to deliver the drug. Though, again, patient assistance programs and low-income patients can get a drug free from the manufacturers as well.

Linda Stein Gold, MD, and Bruce Strober, MD, PhD, share considerations for ensuring that patients on Medicare and Medicaid receive the appropriate medication.

Navigating Treatment Access Challenges in Patients With Plaque Psoriasis 

 This sounds like a really great new tool in our treatment armamentarium. But when we have those patients who come in now with moderate to severe scalp psoriasis or psoriasis in a sensitive area, we have so many tools. When would you think about using an oral agent like deucravacitinib? If a patient walks in and says, “I’ve used topical therapy. I have maybe 15% body surface area. Maybe I have a little bit on my scalp. Maybe it kind of comes down onto my forehead. I’m kind of on the cusp. I’ve used some topicals. It’s OK. I feel like my life is consumed by trying to make sure I get my creams on, trying to make sure the flakes aren’t on my clothing.” When that patient walks in, I haven’t used anything systemic yet. What’s your thought process?

 You’ve defined a patient who needs to be on a systemic therapy because they failed topicals and their quality-of-life stinks. And in that instance, I generally choose between biologic therapies and oral therapies, all of which I’ve mentioned. Now, the good thing about deucravacitinib is it has very good efficacy for an oral therapy, requires little monitoring, and you can use it in men and women. You can go down to the age of 18. All of that gives it simplicity. So the patient who wants to be on an oral therapy that’s simple, they will get deucravacitinib. If I feel the patient needs more robust efficacy right now, and is comfortable with injectable medications, I use a biologic therapy for these same patients. So it comes really down to patient preference. And by the way, if a patient says, “I don’t want to do injections right now, I’m not comfortable with that.” I say, “You can have deucravacitinib. Let’s give it a 3-month trial,” which is about what it needs. And if it doesn’t work, then we’ll turn to a biologic therapy. We’ve made a deal, so to speak. And the patients usually agree to that deal.

 That makes sense. And I want to just ask you again, because we often talk about the mild, the moderate, and the severe patient, and I know you do not like that classification. Can you explain what your thought process is there?

 There are only 2 types of patients in psoriasis. Those you can manage on topicals and those you can manage on either systemic therapies or phototherapy, which are more or less one and the same. A person who is managed on topicals, you keep them on topicals. But if they’re not managed on topicals, you go to a systemic. Let’s say they have special areas—hands, feet, devastatingly affected, bad scalp, intractable facial, and intractable genital psoriasis, intergluteal, terrible quality of life—you got to go to systemics as a trial. Let’s say they’re greater than 10%. They walk through the door just covered in psoriasis. They don’t have to fail a topical. They go right to a systemic or phototherapy. So, for me, there’s 3 types: 10% or more, special areas of involvement, and failed topicals. That patient goes on a systemic. I don’t care about mild, moderate, and severe. I care about what the patient needs. This way I never undertreat the patient based on strict BSA [body surface area] cutoffs that are part and parcel of the mild, moderate, severe definitions.

 Now, if somebody has come in and say they’ve been on another oral therapy, maybe apremilast or maybe they’ve been on methotrexate, is there a reason to believe that another oral such as deucravacitinib would not work in that patient and you need to go to a different category of drugs like a biologic agent?

 No. No reason. In fact, I have a first principle of treating patients with psoriasis. One drug may fail, any of the others might succeed, and it doesn’t even matter what class they’re in. So failure of one doesn’t have any meaning to me regarding success of the next. Though there are certain circumstances where I’m biased towards certain classes and types based on how they responded initially. And that’s for another discussion.

 So Bruce, you mentioned needle phobia. People talk about needle phobia. I always thought that’s not a real thing. I have had patients who are needle phobic. Do you? Is that really something that you see?

 The initial impression from a lot of people is I don’t want to be injected with anything. Sometimes you just have to teach them, and they’ll get over it, or you do it for them. Some of the injectable biologics are so infrequent, you just have them come in for a nursing visit and they get an injection. They’re very happy with that. And they learn the injections are nothing. They’re just like mild vaccination type sensations, in the worst instances a little injection site pain. So, most patients can get over the needle phobia that they have. That said, if you were to ask 100 patients, what do you prefer, a pill or an injection, 70 to 80 will say, I’d much rather have the pill, even if it’s of a lower efficacy than the injection. And the truth is, most of us in our lifetime have been taking pills since like age 6, depending on the child. But my children learned early. If you’ve been taking pills all your life, taking a pill for psoriasis is the no-brainer. And nobody gets injections for medication really, until they first encounter a biologic therapy for psoriasis, so if they have psoriasis. It’s really an easy question as to what your average patient would prefer.

 Absolutely. And say you’re going away for the summer, you take your pills and you kind of throw them in your suitcase, as opposed to thinking about your injections, your refrigeration and things like that. I used to think, no, I could tell anybody, I think an injection is for you and they’d be fine with it. I’ve subsequently learned there’s absolutely a population of patients, if you have a safe and effective alternative that’s a pill, that’s what they would prefer.

 My only concern is do daily pills lead to poorer adherence. So do people actually take every dose every day. And I’m doubtful they do. But I also know people don’t take injections on schedule. About a third of my patients don’t even have a calendar. I asked them, I said, “Why don’t you just put it in your calendar every 8 weeks?”

 And they’re like, I don’t have a calendar. So I said, they just lead life kind of randomly and therefore there’s no way they’re doing their injections on time.

 So that leads me to a really important issue. In terms of patient compliance, we know with the traditional JAKs [Janus kinase inhibitors] that if you go off of therapy, your results will start to diminish very rapidly. For some patients, within even a day or 2, they start to notice that their disease is starting to recur. With deucravacitinib, which works by a different mechanism of action, targets different pathways. What do we see, say I got on the airplane and I forgot my pills at home and I’m going to be gone for 2 weeks?

 So the good thing about the mechanism of action of deucravacitinib is it inhibits IL [interleukin]-23, which we think from the biologics that inhibit IL-23 is somewhat of a remitive mechanism of action. In others, you give a dose and you can induce clearance, and then the patient can maintain that response for many months not taking the medicine. That’s actually why you could have long intervals between the IL-23 inhibitor injections. Deucravacitinib having a similar MOA [mechanism of action], probably has the same behavior and its clinical trials show that, that when you take people off drug, who’ve done well, they maintain their response for quite a long time. So the consequence of missed doses or holidays or vacation trips without meds because they forgot to pack it, are much less severe. And it’s really a unique feature of an oral medication that, in my experience, I haven’t seen in previous medications that are oral for psoriasis.

 I find that critical, really critical, and such an important feature of the medication.

Linda Stein Gold, MD, and Bruce Strober, MD, PhD, discuss the nuances of treatment selection for patients with moderate to severe plaque psoriasis.

Bruce Strober, MD, PhD

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