Erin Boh, MD, PhD, FAAD

Let’s segue into our final section, looking at the future and at the psoriasis treatment landscape. George, how do you see it evolving? I want to go around the horn as we wrap everything up.

There’s a lot of great research. We already hit on comorbidities and how we’re able to impact that and the genetics. We have a better understanding of what underlies the development of psoriasis with the idea that that could lead us to a cure, potentially. We have a better understanding, perhaps the genesis. There’s other stuff, like biomarkers. How do we rationally select an appropriate treatment for the right patient? For some things, if you could take a noninvasive test or a biopsy and figure out why—“This patient’s specific immune profile favors treatment with this”—that would be a nice benefit.

Lastly, even though we’ve a lot of medicines, we all have patients who aren’t doing well who could use better treatments. We need more efficacious treatments. We talked a little about the new IL-17AF inhibitor. That’s on the horizon and has been a leader of the pack in efficacy numbers. That’s 1 thing we’re looking for. Regarding oral medicines, Dr Bhatia mentioned the TYK2 [tyrosine kinase 2] inhibitor. That’s another thing we’re looking at in an oral medicine that has around a 60% PASI [Psoriasis Area and Severity Index] 75. There’s promise of a more efficacious oral treatment. We just need a better portfolio to be able to give our patients and be able to more selectively manage their disease process in an individualized pattern. That will be the promise going forward.

Neal, what are your observations and comments about the landscape for psoriatic disease, moving forward?

 George brought up the big 1: the role of tyrosine kinase 2 inhibition, and what we’ve explored, because there’s a big affinity for the processing of interleukin-12 and -23 through that pathway when combined with JAK2, for example. The other part of the equation is that we’re seeing safety signals we’re learning a lot from with 5-year data from the biologic set. Again, show us reliability. The tyrosine kinase pathway for psoriasis will be the big 1 that’s next. Obviously, bimekizumab is the other big biologic on the market in the future. We’ll see where and if that holds up, and then there are a couple of others in development. The future is bright if we decide to use these drugs.

 Dr Boh, your final comments. What do you think about the future for our patients with psoriasis? What about the treatment landscape?

What I would like to see is personalized treatment plans. We can achieve that 1 day by going to go back to genetics. It’s all in the genetics. If we can get biomarkers or get micro-assays that say, “This individual has a polymorphism in this gene, so most likely this drug will be your best bet,” then it will be very cost effective and patients will happy. It’s cost effective because we don’t go through 4 drugs to get the 1 that’s going to work for that patient. As we’ve developed, we’ve broken the human genome, and we should be able to figure out, on an individual basis, what that patient’s genetic makeup is in the sense of either messenger RNA sequencing or something where we can we say, “Here’s the defect. Give us the drug.” You’ll save a lot of money. You have a lot of issues solved in terms of expense and treatment. People will be happy. I’m going for personalized medicine, finding the genetic breakdown in each individual. From our great drugs, we can then pick because we have an array of drugs to choose from.

 There’s no question that we have a remarkable toolbox, and there’s more coming. I want to thank you all for this rich and informative discussion, and thank our viewers for watching this 

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Key opinion leaders conclude their discussion on plaque psoriasis by commenting on the potential for research into the genetic origin of disease, possible biomarkers, and treatment options with greater efficacy.   

Future Directions in the Treatment of Plaque Psoriasis

Neal, what are some of the unmet needs that we see with these patients with psoriatic disease?

 We talked about this before a little, and I’ll still divide it between the unmet needs of the patients and the unmet needs of the dermatologist. Because in the patients, we’re learning more about that in pediatrics now that a lot of pivotal trials are done, and we’re hearing about patients of color. Obviously, there are comorbidities that go along with skin and joints. We’re collaborating with rheumatologists. That’s still on the rise, and the unfortunate part of that is we’re heavily reliant on pharma dollars to bring us those data, which require our support, for not only participating but also supporting them in some of their endeavors and bringing that education to us. The bigger equation is that there are a lot of dermatologists who don’t feel as if they’re part of the biologics conversation. They feel like the immunology is above their head. They don’t write enough, nor do they want to. Their access to information is often limited to promotional programs from the industry or meetings that they don’t feel as if they’re a part of because they hear the same voices and see the same faces talking about biologics. They think there’s some club of which they are not a part. Something is going on with dermatologists, because these are some of the smartest people around, yet they’re the first ones putting their hands up and saying, “I don’t want to write these voices.”

I don’t understand what it’s going to take to open some eyes and say, “I understand what’s going on. We’re treating the big picture for these patients.” One of the biggest unmet needs is for dermatologists to drop their guard, get involved a little more, and understand. George and I were part of an initiative that took on the question and reversed the script that said, why are dermatologists not writing biologics? What are the fears? What are the misconceptions? What are the obstacles? We hear so much about why you should you write X biologic for whatever reason. We don’t have enough conversations about why you’re not writing biologics. If you see what it’s doing to the patients who don’t get access to the drugs because we’re not putting pen to paper—not because insurance companies aren’t paying for them but for whatever reason—that’s probably the biggest unmet need: getting dermatologists out of their own way and starting to understand the process of what’s best for the patients in the long run.

Erin, do you see other unmet needs in the setting of psoriatic disease?

Yes, there are a few, 1 of which is something that I’d like to see explored: what do we do with our patients who have a malignancy or who have had a malignancy? All the studies that we have that get these drugs to market involve excluding patients with a history of any malignancy for 5 years. They’re over it, but you have a patient on a biologic, and they’re going to get a malignancy—maybe it’s age related, or maybe it’s gender related, like prostate or breast cancer, or maybe it’s not related to the fact that they are on a biologic. What do we do with those patients? Nobody will do those studies because they don’t want to go there. I don’t know how we would obtain those data, but it would be interesting to find out what we can use in terms of patients who’ve had a malignancy and if it gets treated. Can you put them back on a biologic?

The other unmet need is similar but not malignant: pregnancy. Patients get pregnant and have terrible arthritis along with their psoriasis. Heretofore, we’re supposed to stop the biologic for the whole time that they’re pregnant. Well, untreated psoriasis is a much worse comorbidity for a pregnant woman than being on a biologic because that degree of systemic inflammation causes small birth-size babies and other problems with pregnancy, but we don’t have good data on that. We have 1 anti–TNF [tumor necrosis factor] that looks at it in vitro for the most part. We rely on registry data, mainly from GI [gastrointestinal] medicine and other fields like rheumatology, to say what may or may not be safe. Those are areas where I’d like to have answers to questions because I don’t know what to do. I’m winging it, and it’s a big area because people are older and people get this disease and malignancies in particular. What can we say about them?

 Our oncology partners don’t necessarily have a lot to say either, and they’re pretty much in the dark as well.

They don’t even know the name of the drug, let alone what the adverse-effect profiles are.

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A group of specialists discusses unmet needs in psoriatic disease including physician education about biologics and research about treatment options for pediatric patients, patients with malignancies, and patients who are pregnant.

Unmet Needs in the Treatment of Psoriatic Disease

Speaking of treatments and treatment challenges, let’s talk about such challenges that we may have regarding patient selection and drug selection. What about unmet needs? What are some of the challenges that you’re facing when we manage psoriasis or psoriatic disease? As 1 question, what can be done to help patients to overcome the psychological components of this disease? Erin, why don’t you chime in first?

To answer the last question, something we all can do is educate. If patients understand the disease, if they understand the natural course and the responses that we have, they’ll be better prepared. That’s a big hurdle right there. It’s very important to reiterate to your patients details about the disease and about the safety of the medicines. We should make sure that everybody is onboard. Then I talk to people about watching for triggers and understanding that the disease is forever and that these drugs don’t cure it. They only control it, so everybody has to be onboard. Education—for the drugs and the disease itself—is very useful in getting people onboard for managing and understanding when things don’t go exactly as they’re supposed to.

It seems that that plays into adherence and compliance as well. Education is power. Do you find that patients with psoriasis have some challenges with adherence?

No. If the drug works in the beginning, you cannot get them off it. It’s on us to make sure that we get them the right drug. If you keep giving them topicals, they’ll get deeper and deeper in the hole because it’s frustrating. They don’t want to hear that. They’ve done it for years, and so if you’re going to have a patient be compliant, you have to make it easy to comply. The biologics, as a group, do that. They don’t have to frequently come in. You must get them to that point. Listening, looking, and educating are the 3 big things that will go a long way in compliance.

I love that. I have to write that down. George, what about typical triggers for flare-ups in these patients? How do we manage the flares in conjunction with these triggers?

Regarding flare-ups, there’s some seasonality psoriasis, and the stressors we were talking about throughout the pandemic caused some people to be getting bad flares. There would be anxiety because of vaccines or other reasons. Especially for the patients on biologics—I agree with Dr Boh—we’d like to save it for them as much as we can. Meaning if they get a little breakthrough flare, we can manage it with a topical. There are actual data on that looking at newer agents like betamethasone calcipotriol foam. There are data looking at adjunctive treatment. Not only does that help maintain them, but patients may get back to a level of clearance. They can stay on that medicine, so it’s a known entity. We know they’re responsive. We know they’re not reacting to it negatively. That’s definitely helpful. Other than that, life happens. One of the things we must do is assess for compliance. That’s 1 of the things that’s a great unknown.

Back in medical school, 1 of our preceptors told us about how they found their patient in the parking lot scribbling down their glucose diary and basically—almost like Christmas—treeing it, writing what they really wanted. It happens. Having that open relationship with your patient and saying, “We don’t want to necessarily search you, but let us know if you missed a dose or you’re behind on something. Stuff happens.” All those are things we need to keep in mind. The more stability, the better. That helps with all those other aspects: keeping patients on a stable regimen, making sure they know what to expect. When the psoriasis comes back, after you’ve cleared and it’s coming back, that psychological impact is different from the patient who just had that amount of psoriasis to begin with. It’s probably worse because they remember how bad it was. It’s important not to overreact in that sense too.

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A panel of experts builds a lively discussion on the evolving treatment landscape in plaque psoriasis and highlights the emergence of IL-23 inhibitors as a new class of biologic agents. 

Treatment Challenges in Plaque Psoriasis 

Neal, what’s been your experience with interleukin-23 blockers?

 I brought up who my preferred populations are. There’s a downside of 23s. They may not provide rapid response to some degree; they may be a bit of a slow starter in comparison with 17s. You don’t have the frequency of doses like with anti TNFs [tumor necrosis factors]. There may be a little of that, but to be honest, I don’t think it’s much. The patients who receive them see results pretty quickly, sometimes even after just 1 or 2 doses. There’s some strong encouragement from what we’ve been seeing with this class of drugs in terms of getting patients better, not just quickly but, as Erin was just saying, staying better. Recapture data are huge. It’s a matter of saying, “This could be the 1 thing that keeps you out of your own jail if we do this right.” I’ve found this to be the class of drugs—especially when thinking about the process—that I turn to more exclusively. I’m not a huge biologics writer by any means. We run more of a trials-based practice than an outpatient practice, but for the few outpatient-practice patients we see, this is the class of drugs we primarily turn to. We’re fortunate because in California the coverage of this class of drugs is also favorable.

I’d like to point out—I don’t know if you’ve all seen this; I write a ton of these drugs, so I can tell you. The arthritis response, I find in my experience, is a little slower. I talk to patients. If they have a component of arthritis, a TNF is not on board for them. If they have extensive skin disease, then the TNFs often fall short. I caution patients because I don’t see the brisk response to this arthritis that you’d see with the TNFs, but many of the patients on the IL-23s do catch up in terms of response to their arthritis amphicytes. It takes several months. I like to tell people that so they don’t jump ship too early. Sometimes I’ll use it in combination with a low dose of methotrexate. I know that’s off-label for some things. I’ll even use some of the small molecular weights while I’m waiting for the effect to kick in with the arthritis. I’d be interested to hear your thoughts on that.

The methotrexate was used across the board in all the psoriatic arthritis trials, even in KEEPsAKE 1 and KEEPsAKE2, and some of the other trials that haven’t been completed. Obviously, we have 1 of the interleukin-23 blockers approved for psoriatic arthritis. George, what about your comments? We’re segueing from what Erin just said, which included some great comments.

I agree completely. Where I might pause a little in thinking about reaching for an IL-23 first is in that patient with severe joint disease. A couple things. We just haven’t had as much time and experience with these. That means something when you’re dealing with a destructive arthropathy, rather than something we can see a little more clearly. More than that, there was a phase 2 trial of risankizumab on actionable disease that was quite a miss. We’ve had this concept with certain IL-23 inhibitors for some reason, and it’s not well explained. Guselkumab does have some data looking at patient-reported outcomes in actual disease that seemed to imply that there’s some efficacy. That’s 1 area in which I’m looking for more data: actual disease. There’s also heavy-duty psoriatic arthritis. For most patients, those who have some vague joint pains or those you’re starting to see with 1 or 2 joints affected, I wouldn’t hesitate to reach for this. I’d tell them to wait a little longer to see the efficacy, but it's a very well-rounded class of medicines that have been pretty easy to give, stomach, and accept.

George, in keeping with that, in your experience, have you switched within the class of interleukin-23s? Have you had to do that?

I’ll put out the caveat that we don’t know why, necessarily, patients fail on a certain biologic. That’s an area we’re very interested in. There’s a lot of active research going on, and I’m involved in some of it. That’s exciting because traditionally, what we think about is antibody formation, and we think about mechanisms that we can explain well. In some cases, it probably is that way. There’s some correlation between antibody and reduction of response, but I have these patients who get better on any biologic. And after 6 months to a year and a half, they start having the psoriasis come back in a very real way. You start to wonder what immunological escape mechanism they have, or you wonder about the lack of propensity. You might have an antibody response. It’s hard to explain. I’d like to see more data. I can’t think of anybody who I switched from a 23 to another 23. We do have data from the NAVIGATE trial, in which we look at switches from ustekinumab, a 23 inhibitor, to guselkumab. You do see that you can pick up some of the nonresponders or partial responders with that mechanism, so there’s probably some element of strength to that medication. To that end, you might reach for 1 of the medicines that has a higher, PASI [Psoriasis Area and Severity Index] 100 range if you’re looking to switch. I find, more often, I’m switching from an IL-23 class, because the patients have some breakthrough joint pain or something else where you have more of a clear route toward TNF or IL-17 inhibition.

I’ve switched. I do class switching sometimes. I don’t particularly like to, but in some cases I’m forced to. Sometimes, the insurance coverage says, “This is the IL-23 du jour, and you must do it.” Otherwise it’s not covered. I’ve had some patients who’ve failed to respond or maintain that 8-week or even 12-week response, so they’re going at every 6 weeks. I’ve switched them, and I find that, like the TNFs, you can switch classes and sometimes gain a response where you couldn’t before. Why? I don’t know. George, your speculation is as good as any. It’s going to come back to the genetics—maybe there’s a bit of nuance in the genes that are overexpressed, and there’s not just 1 IL-23 gene. These particular drugs will target certain IL-23 molecules and maybe a patient has a different 1, but I’ve been successful in switching out classes. In general, like George, if I find that they’re not going long enough or keeping their response, or they develop arthritis, I’m going back to something else, or I’ll add a small molecular weight that I can get covered.

In the past year, I’ve done a lot with the JAK inhibitors with the IL-23s, and that combination is a knockout. It does very well when you can’t get a full response with the IL-23. It’s not going to be covered easily, I can tell you, but we’ve worked it where we can cover some of it. If it’s not covered for arthritis, I can get the small molecular weight JAK inhibitor for the arthritis and use the IL-23 for the skin because the JAKs aren’t quite as good for extensive psoriasis. I think you can switch in the class. I don’t like to because the more you switch, inherently, you do lose efficacy. But I’d like to see, like George, why some patients lose efficacy with every drug they’re on, regardless of the class. I can’t explain it. I have no clue.

Neal, what’s your barometer for shifting from 1 class to another? How long do you wait?

 All 3 of you brought up good points about when you switch, when you want to do that, and when you see the breakthrough of first-line things going sideways. Let’s be honest too: not every biologic is going to meet the trial end point for clearance. You’re going to get people who fail. I like Erin’s idea with the JAK inhibitors. I think of those as the sprint for some of these patients, to get them clear after what we’re seeing some of the tyrosine kinase do, molecule with some of the others. If we have patients on autopilot with 1 of the 23s and they start to breakthrough, we may switch them over to 1 of the JAK inhibitors. We can put out the fire and then reestablish biologics for the next set of years. There could be a different rotation of therapies that we could find that would affect both parts of the equation if we are talking about skin and joints, especially in terms of the comorbidities. We’re at least encompassing the entire process and not what’s outside. There are a lot of ways to spin it, but you want to be safe and get the right labs—for TB [tuberculosis test], of course—and everything else that goes with safety. Obviously, it must be tangible, but we’re learning new ways to make that work. There are a lot of ways to make that happen.

One thing to remember is not to give it up too soon because patients will flare regardless. Before I switch out drugs, I search for triggers: a concomitant infection, a flare of a comorbidity, a contact dermatitis or any kind of trigger that will flare the psoriasis. I try to salvage the drug first and then switch if I really need to.

 That happened to me with 1 patient. We were doing great, and suddenly she started taking beta-blockers for anxiety. I said, “Wait a minute. We didn’t talk about this.” Suddenly, there you go. Sometimes that’s all it takes.

Thought leaders in the management of plaque psoriasis share personal insights into factors to consider when treating patients with IL-23 inhibitors, including when to switch biologic agents.

Erin Boh, MD, PhD, FAAD

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