Benjamin Lockshin, MD, FAAD

Expert dermatologists highlight the future of plaque psoriasis treatment, commenting on advances in therapy as well as increasing access to treatment.

The Future of Plaque Psoriasis Therapy

: Ben, what are some of the pipeline therapeutics, future developments that you’re excited about with regard to psoriasis?

If you look at this space in terms of the treatment options, you’d think that we’re close to the goal line using a football analogy or that we’re in the red zone. I think we’re somewhere between the 50-yard line and approaching the red zone in terms of therapeutics. We have high levels of clearance; we’ve got drugs that are well tolerated. Is there room for more agents in different MOAs [mechanisms of action]? I think absolutely yes. I’d love to see something that provides 1 shot and you’re clear for life—a cure for disease. I think that the small molecules that are targeting these interleukins, these small-molecule peptides that target IL-23, are going to be an exciting new endeavor. I’m very excited to see what future studies show with these, in addition, getting some data in terms of different patient populations that have response rates, being able to target these patients, identify what cytokines are overexpressed in each individual, and having more customized health care for them.

: Jennifer, how about you, in terms of developments on the horizon that really you think could bear fruit?

 I’m going to answer this question slightly differently. I’m going to say future developments focused on increasing access. I think we have really awesome treatments and some places where there are disparities in care and where some patients perhaps have a greater impact on their life. We’ve talked today about the impact on physical, psychosocial, and—I will even argue in some patients who don’t have access to care—even financial losses from psoriasis. I even had a patient who came to me, erythrodermic, and has never had been offered a systemic option. And in fact, year after year, he’s had so many flares and just been told to use topicals that he hasn’t been able to work, lost his job. And then his family divorced him because he was not able to provide for the family. How sad is that? And so, a kind of personal passion project of mine is really increasing access to care in these underserved communities where you see that skin conditions, chronic skin conditions like psoriasis have an even bigger impact on these patients’ lives. And so these new treatments that we have for psoriasis are just so amazing to me that that they both combine safety and efficacy. And so whatever way we can get more patients treated, that’s research that I would want to continue to be involved in.

: One avenue to doing that is biosimilars, which hopefully will reduce costs for some of the medications that are more mature because ultimately branded medications will become biosimilars. We’re seeing that right now. And that allows access at a lower cost for people like you’re describing. I just think that’s the cycle of innovation. We get new drugs, they’re branded, they’re necessarily expensive. But in the long run, they become Tylenol, where everyone can get Tylenol in their local drugstore. And they still call it Tylenol, but it’s just acetaminophen. And it’s like less than 0.5 cents per pill. So, you know, we know there’s a natural progression of innovation and maturation of drugs. And so I see the new biologics that we are talking about today as ultimately part of the pathway to access and affordability.

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Transcript is AI-generated and edited for clarity and readability.

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their experience with IL-23 inhibitors for the treatment of plaque psoriasis in clinical practice.

Using IL-23 Inhibitors in Clinical Practice for Plaque Psoriasis

: Ben, can you share with me an anecdotal case of success that involves an IL-23 inhibitor, one that really was impactful for you?

There’s a couple situations, and I think one of the most remarkable stories is the patient who’s failed a number of treatments and then finally goes on a [IL-]23 and they’re clear again. And that can be the most frustrating thing for a patient to cycle through medications and feel like you’re at the end of the line and that nothing else will work and if it does work, how long is it going to work? And to see a patient back in a year, 2 years, and they remain clear—it’s why I went into medicine. But I don’t reserve the IL-23s as second,

third, fourth line. I think it’s a great first-line consideration for all the reasons we talked about— the safety, the efficacy, the reliability of the dosing frequency—all of those things make it a clear choice for me to look at any patient who walks in my door and say, “You’re a great IL-23 candidate.”

: Jennifer, how about you—any typical patient who really is memorable?

 Oftentimes we think more injections, faster response, and I had a patient who was just at her wit’s end with scalp psoriasis so I decided to start an IL-23 and because she was just so miserable and kind of in tears that this was really bothering her and her psoriasis was starting to spread more to other areas of the body, I said, “OK, I’ll see you back out at 4 weeks” and that’s only after 1 injection. Usually I would wait at least 3 months to see the patient but after only 1 injection I was so surprised that her scalp was more than 50% better. It was the first time—just because I usually don’t see the patients that that early on—that I thought, wow, with even just 1 injection they can get a very early response. She also made an impression on me because at her follow-up visit my assistant told me, “Oh, she’s kind of upset” and I thought, great, that 1 injection didn’t really work; I’m going to have to add something else on top of this. She came in and she said: “Why has no one ever told me about this medicine before? Why are you the first dermatologist who’s offered a biologic to me?” And then I just [explained] that every dermatologist specializes in something different and I’m kind of strange; I like psoriasis. But I think it speaks to the fact that patients are really wanting treatment and that clear skin matters to them. Even though we may not think scalp psoriasis is maybe a big deal, because you can’t see it, like other areas of psoriasis, but this is how it was debilitating for this patient.

: You know, I would extend that. You get this kind of patient at all age groups. So college-aged, women of childbearing who are raising their families, men in their 50s, and then elderly patients, too, all of whom I've brought the… IL-23 inhibition and really effectively changed their lives and really the gratifying aspect of it doesn’t change no matter what kind of patient you’re taking care of. It really is an equal-opportunity disease, psoriasis, across age groups and both genders, of course. So it’s great that we can employ 1 mechanism of action to many different types of patients and achieve great success.

 I think what I’ve learned from my patients is that now that we have so many options, is that clear skin matters to them.

: Exactly. In fact, if you survey patients as opposed to surveying dermatologists, what rises to the top is clear skin. Of course, they want safe drugs, but they assume that you’re giving them a safe drug as opposed to dermatologists who put safety above clear skin, understandably, because that’s how we’re trained, to do no harm and make sure that first and foremost, we don’t hurt our patients. So again, we’re looking at a mechanism of action that serves the needs and the preferences of both the providers and the patients who receive the medications.

Benjamin Lockshin, MD, FAAD; and Jennifer Soung, MD, share their experience with IL-23 inhibitors for the treatment of plaque psoriasis in clinical practice.

Selecting IL-23 Inhibitors for Treating Plaque Psoriasis

: So, Ben, this is a tougher question. How do you go about selecting among the various IL-23 inhibitors we have at our disposal?

That’s a challenging question. I think we are fortunate to have 3 very good options. I think honestly to parse out the drugs, sometimes I choose dosing frequency. I think Q12 weeks vs Q8 weeks is sometimes a determining factor, especially if I’m bringing them into the office for their injections. And I personally think that the young male patient is the least [adherent]. I happen to live in that world. So many times, I’ll bring them in the office; 4 visits a year after the loading dose is nice. [I think about] tildrakizumab for patients that have Medicare, as that can be covered a little bit easier. But deciding between guselkumab and risankizumab is hard. And sometimes you’re a Coke [guy] and sometimes you’re a Pepsi guy, but I think that my ability to articulate the data from risankizumab and looking at head-to-head data against different MOAs [mechanisms of action] makes it an easier option for me to consider for my patients. And I always try to put myself in the patient’s shoes and say, “What would I go on if I were them?” And I would say 9 out of 10 times I am actually choosing risankizumab because of the dosing data, because of the other quality-of-life studies that we look at. Even that the most recent study looking against apremilast in terms of patient satisfaction surveys—which I think all of us know the patients are happier on a drug that is tolerated better that performs better—but having that data to draw on actually just allows me a little bit more information to push toward that patient to make them feel confident with that decision.

: You know I would just add that if you’re a provider using biologics in particular IL-23s no matter what your favorite one is, you’re really doing a good thing. So I have my preferences, and I’m sure Jennifer has her preferences but in the end if you’re using these drugs you’re already at the right level because it’s kind of a first-world problem: Which is the best of these drugs that blocks IL-23? Well, it’s amazing we even have drugs that block IL-23 and any of these drugs can potentially improve patients’ quality of life and actually normalize them to a large extent.

I think these newer medications are almost pushing me out of job security because I thought for a long time there was a true art to choosing what the appropriate medication is but these newer-generation biologics from the IL-17s to the IL-23s do provide such high levels of skin clearance—reliable skin clearance with good safety profiles—that you can almost pick into a bag and choose a good medication.

: Well, you’re going to have a job then because they’ll tell you a lot of people a lot of patients are still amazed that you prescribe them risankizumab. All you might think is, well I learned how to use risankizumab and you’re a patient who should get risankizumab and that’s not any brilliant concept; it’s just that it is available and we use it. Nevertheless you have to be a provider who chooses to use these medicines and use them, as we said earlier, confidently and with an outlook that’s optimistic. So when you walk into the clinic room and you see that patient, you’re smiling and you don’t have this kind of pessimistic viewpoint on what the future is for them. It’s the opposite. You’re [able to say,] “I’m going to make you better.” And I think that’s what patients come to doctors to hear. [These patients are] obviously miserable with their psoriasis. So if you just use these medicines, you’re an important part of the process, even though it might seem so simple to you right now. And one thing I would add is I like to make this point. If you use drugs like risankizumab, you have really easy follow-up visits, right? So all of us are busy. We see large numbers of patients every day. And some of those patients are hard and challenging. But definitely the risankizumab follow-up visit is not one of them. And it’s kind of a built-in break in the action that allows us to quickly move forward with our day and feel good about ourselves. Let’s be frank. We went into medicine to help people. And if you can help a person, you definitely come out of the room feeling really positive about yourself. Do you have anything to add, Jennifer, to this conversation?

 I think the follow-up is easy. And it’s to the point where my patients forget, and they’ll see me just once a year. And I’m totally fine with once a year as long as they come to that once-a-year [appointment]. And other times I leave it flexible to the patient because I don’t feel like there’s a lot I really truly need to monitor. But we do need to touch base that one time in there in case there are any changes in medication. I want to make sure they’ve seen their primary care doctor if any other new medications or comorbidities come up. And I love how you mentioned the integrative approach. I talk about it and emphasize it a lot because truly it is a systemic disease or can be a systemic disease and we want to treat the patient as a whole. I want them to be healthy in every aspect.

: So that’s another great point. If you have a clear patient, they come back clear 6 months later or a year later, it’s still an opportunity because you have a little time to talk about, “Are you seeing your primary care physician? Are you having your overall health measured with blood work and counseling?” And then you can even mention how people with psoriasis are at increased risk for things like obesity, hypertension, dyslipidemia, diabetes, and those need to be managed, too, in order for them to lead a normal life span. And a lot of that information is very shocking to patients that they are at increased risk for some of these other comorbidities. But to me, that follow-up visit, which is easy on the skin side, is now dedicated to the overall health and especially young patients. They don’t have such a frequency of touch point with their PCPs [primary care providers], so you’re actually reinforcing things they need to hear going forward. So the ease of the follow-up visit still has benefits going beyond dermatology if you’re doing it right, and you’re not slowing your day down because it’s only another 25 seconds to bring up these issues.

Benjamin Lockshin, MD, FAAD, comments on the higher efficacy and reliability of recent IL-17 and IL-23 inhibitors and how these factors into treatment selection for patients with plaque psoriasis.

Expert dermatologists discuss the paradigm shift occurring in the management of plaque psoriasis as a result of the expanded array of treatment options.

Shifting the Paradigm for Plaque Psoriasis Therapy

 Jennifer, is there a paradigm shift occurring right now that you can foresee that defines how we approach psoriasis in 2023 moving into 2024 or from the way we did in 2015 to [20]18?

 I always tell my residents I don’t use biologics in the order that they were FDA approved. We see a lot of times [that] step therapy will tell us to use [biologics] in that order, and so our newer biologics, [such as] the [IL-]23s, are my first line. Earlier, I talked about when a bio[logic]-naive patient comes to me and says, “I don’t know; I’m hesitant [about biologics]”. I think the [IL-]23s are such an easy way to ease them into the idea of a subcutaneous injection. A lot of patients still have some hesitation around that because they’re not used to it. But as there are more and more therapies outside of dermatology that are injectables, for example, this class of semaglutides that everybody wants to take, patients are now more open to the idea of injectables. Whereas I have some patients [with] psoriasis who have been on [IL-]23s and find [them] so convenient [that] they even ask me, “Don’t you have an injectable for acne?”

 We wish [we did and] with the same level of efficacy. These are great points. What you’re pointing to is we’re intervening earlier with a mode of administration, subcutaneous injection, at an earlier time point. Maybe 7 to 10 years ago, there was greater fear of quickly going to the injectable. The specialty is more comfortable with it, and as you’re pointing out, maybe patients are more comfortable with it. Anything to add to this, Ben? This change in paradigm?

At least in my practice, [we] have had utilization creep, where I’m treating patients with [less] body surface area because there’s less concern about safety signals. In addition, we have mounting legacy data with multiple different MOAs [mechanisms of action] that are providing us tremendous reassurance that the overall health benefit outweighs any of the risk that we see attributed to it. I always tell the patient that there’s a risk of doing and there’s a risk of not doing. Patients with psoriatic disease who are not being treated effectively are putting themselves at more risk than [with] the medications we’re giving them. And what you and Jen said earlier in terms of the understanding of an injectable [is important], because individuals now are familiar with the terms, see the ads, have friends that are on these medications, and we can articulate it better describing this as a large molecule that’s not absorbed through the gut and that’s why it’s administered that way, rather than their preconceived notion that this is taking the treatment to the next level, that it’s more severe than an oral, which [it] is not, as we all know.

 I’ll go further. As a specialty, we are more aware of psoriatic arthritis [PSA]. We query our patients about signs and symptoms of PSA, and we appropriately incorporate the presentation of PSA into our treatment decisions. As a specialty, even 7 or 8 years ago, we were a little less sophisticated about psoriatic arthritis. Now that most of our therapeutics have FDA approval for the [management] of active psoriatic arthritis, we have greater confidence thinking about the disease, talking about it with patients, understanding what might indicate the presence of psoriatic arthritis, and how to follow patients over time for adequate [management] and control of their psoriatic arthritis. We’re at a different level with regard to how psoriasis affects patients holistically, and I didn’t even get into the comorbidities beyond psoriatic arthritis and how we understand psoriasis presents cardiovascular risk [and] requires regular visits to the provider for issues that create cardiovascular risk, diabetes, dyslipidemia, hypertension, [and] obesity. We know how to talk about these things better, and then we cartridge in our therapies in that conversation.

 I’m going to add 1 more thing, Bruce. I’m so happy you brought up psoriatic arthritis because I don’t think we can make our treatment decision until we screen our patient for psoriatic arthritis, and that’s really been the biggest change. When I started as a dermatologist, I never thought I would be looking at joints, screening for joint involvement, or able to identify a sausage digit. But as dermatologists, because we have such amazing tools, we are in that key position where we can help those patients make that connection and [we can] say, “Patients with psoriasis can develop arthritis,” and patients often are surprised. [We are in] that position to help them identify earlier. For example, [we can] ask about back pain that wakes them up in the middle of the night or morning stiffness. If we wanted to make it easy and efficient, I like using the PEST [Psoriasis Epidemiology Screening Tool] questionnaire in my practice. It has a high positive predictive value and makes it easy in terms of patient flow. You’re not spending a lot of time [as] a rheumatologist would but identifying those patients who are at higher risk so you can make your next treatment decision.

 Absolutely. I agree with you regarding the PEST questionnaire. I do a miniature PEST questionnaire in my head when I talk to patients with psoriasis whom I first meet. [As] you said, [I ask about] morning stiffness, being awakened in the middle of the night by joint pain, low back pain, stiffness, neck pain, ligament tissues [such as] carpal tunnel [syndrome], plantar fasciitis, Achilles tendonitis, and family history of psoriatic arthritis. One rheumatologist taught me one of the best questions you can ask your patients is, “Has a [physician] ever told you [that] you had psoriatic arthritis?” That will point you in the right direction.

Transcript is AI generated and edited for clarity and readability.

Benjamin Lockshin, MD, FAAD

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