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Steven R. Feldman, MD, PhD: Welcome to Medscape InDiscussion: Psoriasis. I'm your host, Dr Steve Feldman. This is the third episode of our second season. Today, we'll focus on the important problem of treating limited psoriasis. Most people with psoriasis have only a few spots, yet they may be very bothered by the lesions. We have a lot of treatment options. To discuss them, we have an internationally renowned clinical dermatology researcher and author of over 200 publications — many in The New England Journal of Medicine and the Journal of the American Medical Association. He's an adjunct professor of medicine and dermatology at the University of Toronto School of Medicine and a private practitioner in Waterloo, Ontario, Canada. It's my pleasure to welcome Dr Kim Papp. Welcome, Kim.
Kim A. Papp, MD, PhD: Steve, thank you very much. It's indeed a real pleasure and a privilege to be with you today. I agree with you that this is a very vexing problem for many patients, and it can be a major issue for clinicians, as well.
Feldman: Before we get started on psoriasis, I understand you were an astrophysicist first before dermatology. There's something I've always wondered about, and maybe you have the answer for me. Does heavy metal abundance affect galaxy development and the frequency of formation of planetary nebulae?
Papp: Interesting question. I would have to go back into the far recesses of the distant past — almost the prehistoric past — but I think the short answer is probably not. As you may know, heavy elements are the result of a supernova. The heavy elements get dispersed throughout the galaxy, and this really doesn't affect much. The galaxy is already well formed by the time the heavy elements have occurred. So, if anything, the heavy elements are more of a marker of the age of the universe or how quickly the galaxy is going to be burning out.
Feldman: I wonder about the Webb telescope. Do you wish you were back in astrophysics looking at these types of things?
Papp: You know what? I keep my little pinky finger dabbling in astrophysics, but for the most part, I'm buried in clinical medicine.
Feldman: I'm not surprised that you're so focused on clinical medicine because your clinical research efforts have been extraordinarily successful. Do you have a secret to having accomplished so much?
Papp: One: luck. Two: luck. Three: When an opportunity presents itself, take advantage of it. Then the fourth — something that hopefully will give me legs — is maintaining or expanding your experience. So, there are many different facets to everything we do, whether it's in clinical medicine or in clinical research. The better one manages each of those various facets and the better one understands each of those facets — whether it's pharmacology, immunology, or diagnostic medicine and outcome measures, it doesn't really matter. It just creates more opportunities.
Feldman: I think of psoriasis as two different conditions — a limited form we can treat with topicals and an extensive resistant form that needs more than topicals. Let's focus on the treatment with topicals. Does this seem like a reasonable way to divide the psoriasis patients?
Papp: I agree with you 100%. When a patient comes through the door, we already have a pretty good idea of what the likelihood of success is going to be using a topical agent. I agree that it's for patients who have more limited disease. Whether it's 1% confined to one area or a few areas, if patients have 1% of their body covered, but it's in small spots — little papules or little plaques scattered all over the place — you're never going to be successful with the topical. So, you always must look at the clinical presentation. It's not just the one parameter. Body surface area or Psoriasis Area and Severity Index score are not going to tell you whether a topical or systemic therapy is best. You look at the patient and you know which treatment is most likely to succeed.
Feldman: Let's say we have a patient, and we and the patient agree that they can put topicals on all the spots. We've got a bunch of options. What are some of them, and how do you determine which one to use in a particular patient?
Papp: The issue with topicals is partly that we must look at managing the drug and the patient or where their psoriasis happens to be. There is a great deal of steroid phobia — not only on the patient's part but also on the part of the pharmacist, those who are around them, and to some extent, even clinicians. As dermatologists, we see the problems that are associated with chronic steroid use. We're always trying to modulate the adverse effects of whatever we're prescribing with the effectiveness, and this is a perennial problem. Patients are not adherent to therapies they don't think work. In large part, it's because psoriasis is a chronic disease for most patients, and they've been told you cannot use this recurrently — you must take a break or interrupt therapies. So, there's not one step. I think it's still a problem as to how best to approach this whole therapeutic option. We still have corticosteroids, which are the least expensive and most readily available treatment. We've had them for the longest time. We also have our calcium analogs. The problem with calcium analogs is that alone, they're probably not terribly effective. They can be somewhat useful, but they're not super effective, and patients who use them are also prone to some degree of irritation. The retinoids are similar. We have combination products, and now we have some new products that are challenging the old paradigm.
Feldman: You said calcium. Those are the vitamin D analogs that might affect calcium, right?
Papp: You're right. My apologies. I'm getting ahead of myself.
Feldman: So, topical steroids are vitamin D and vitamin A analogs. We also have tar. Then you say we have some new products as well.
Papp: Yes. We have topical roflumilast, which has been demonstrated as a competent treatment for psoriasis and probably also for atopic dermatitis. Its advantage is that it doesn't have any of the steroid-associated adverse effects either locally or systemically. It's a wonderful product. Then we have our other scavenger protein looking at aryl hydrocarbon agonists.
Feldman: We'll go back to the point where we were finishing up with the steroids, vitamin D, and vitamin A. Let's talk about those for a moment. The steroids have the overuse phobia and possibly some skin thinning. Maybe we don't want to use steroids that are too strong around the eyes because of the cataracts and glaucoma issues.
Papp: The face and skin folds are more vulnerable, and partly it's related to what you just described. Patients may also get a steroid effect where the skin becomes "addicted." To try to stop these therapies, patients can go through a difficult rebound, which can be very problematic. And of course, the risk for striae in folds is relatively high.
Feldman: So, for those sensitive areas like the face and the folds, we have vitamin D analogs such as calcipotriol and calcitriol. We also could use a topical calcineurin inhibitor — topical tacrolimus or topical pimecrolimus.
Papp: True, but they're not as effective for sensitive areas. The problem with our vitamin D analogs is that they also tend to irritate or can irritate the skin, and they have a modest effect. So at least until recently, we didn't have any perfect one-size-fits-all or all-areas treatment.
Feldman: I get the sense that having patients use a topical steroid with a vitamin D analog is great because you get the vitamin D reducing how much steroid you need and the steroid reducing the irritation you mentioned from the vitamin D product.
Papp: Yes, there is a notion that they are synergistic. I'm not so sure they are truly synergistic, but there certainly appears to be added benefit.
Feldman: An astrophysicist uses the word synergistic correctly.
Papp: Well, maybe a little less loosely than some.
Feldman: So, you have a typical patient. They've got scalp involvement, maybe some elbow and knee involvement, and a little psoriasis in the body folds. That would be a typical patient, and it gets complicated quickly. There are different steroids you can use. How would you treat somebody like that?
Papp: We'd have several different agents for each region, which is another thing that leads to lack of adherence. Put yourself in the patient's situation. Are you going to use three different agents — one for your face, one for your groin, and one for your elbows and knees? What happens if you forget or mix them up? It's going to take you so much time. And the cosmesis part of it becomes a nightmare. I can understand why some patients are not very motivated to maintain therapy. In fact, I just had a patient come in this morning who said, "You know what? This stuff worked well when I first used it, but it doesn't work so well anymore." I asked, "When was the last time you used it?" And they said, "Oh, maybe 3 months ago." And I said, "How long did it work when it first worked"? They replied, "It was really good for the first month." Now I didn't say this, but in my mind, I looked back, and the last time I saw the patient was a little over 3 months ago. That means they used it for 1 month and they got results, but they didn't want to start it again because it's a nuisance. I understood, so I said we needed to find something that would be more effective for their psoriasis. This happens, I think, not infrequently. At least this patient was open enough to give me a reasonable timeline so I could piece it together. That's the reality. There is no magic recipe because we don't have any magic ingredients.
Feldman: In medical school, they told me people don't take their pills very well. And I'm sure they rub ointments on a lot less well than they take their pills. I used to say ridiculous things like, "Let's use these two for your scalp, these two for the thick lesions, and these two for the body folds." I would write six prescriptions for people, and now I'm thinking, that's just insane. Are these new topicals that are becoming available going to make it easier for us and our patients?
Papp: Yes. I think they will. I think that two new topicals are going to bring a lot to the treatment of psoriasis because we don't have any of the concerns we had with topical corticosteroids. We certainly don't see the same degree of irritation or effects associated with a topical application as we do with the other drugs we have — whether they're retinoids or vitamin D analogs.
When we look at the Arcutis product — the topical roflumilast — although systemic absorption is seen in a few patients, for the most part, it's doesn't get to levels that are likely to cause systemic effects of any kind. It appears to be extremely well tolerated. I can say that because I've had dozens of patients on it as well, and we were specifically making sure we captured any kind of irritation — either perceived by the patient or something that we may have observed following application of the drug. It's a wonderful product that can be used in any area of the body.
We also have tapinarof, which has a totally different mechanism of action. It also appears to be extremely well tolerated, and it works very well. The only issue with tapinarof is this funny folliculitis that develops in some patients. It's more like keratosis pilaris. In cases that are very mild, I would say it's typical of keratosis pilaris, but you do get some of these less common but quite fulminant eruptions that are very inflammatory. There are very few patients, however, who either discontinued tapinarof or requested a switch to something else simply because of this follicular eruption. It does occur, but for the most part, it's just a nuisance. Rarely, it's a little bit more dramatic and does appear to be self-limiting.
Both roflumilast and tapinarof are great products because they work very well, and we're not concerned about the effects of a steroid. Both products also appear to be very well tolerated in terms of irritation.
Feldman: You've seen a lot of efficacy with these. Is that in clinical trials, in clinical practice, or in both?
Papp: It's entirely through clinical trials at this time because neither have yet been approved in Canada. Typically, we're about 1-2 years behind the United States in approvals, with a few exceptions in which we're ahead or comparable. But at this point, we're still awaiting the drugs to be approved.
Feldman: I hope that in clinical practice, they prove to be as effective as they are in the trials. In real-life practice, drugs don't seem to work as well as they do in the trials.
Papp: I think the difference there also relates, in large part, to two things. The first is how we educate the patient and the second is adherence. Patients who are in trials are very motivated and adherence is very high. There are two reasons for adherence. One is that we see the patients who are in trials more frequently. When you're in the real world, you're seeing someone every few months — maybe once a year in some cases or possibly even less. And there's a lot of what I call mental attrition that occurs over a period of even a few months. You can imagine it is information overload. There are a lot of things that happen during people's lives. The advantage of a clinical trial and one of the better ways to maintain adherence is simply routine follow-up. This could even be a 1-minute contact with a patient on systemic therapies whom I'm concerned about. I might give them a call once a month, but it's going to be a short call. That's just so they follow the drill — they don't forget their labs and take their pills appropriately. With patients on topicals, it probably doesn't make much sense to be that aggressive. But I think these points of contact will help maintain adherence, which is why I believe this is the primary reason we see a drop in adherence in the real world compared with clinical trials. There's absolutely no reason that with the drugs, when they're applied properly and when they're utilized properly — which is the intent of a clinical trial — you wouldn't see a certain level of response. Why would you expect, in a population that's very similar just outside of the clinical trial, to see such a difference? Adherence, adherence, adherence, adherence and, to a lesser extent, it's the instructions.
Feldman: What's one thing you want our physician listeners to do differently after hearing our podcast today?
Papp: Be more comfortable with the new agents because they pose a big opportunity for us as clinicians and for patients by removing the steroid phobia that's pervasive in our society right now. If you're dealing with children or adolescents, parents are going crazy over it. Many clinicians are concerned because we have seen side effects. We know they're not that common when a drug is used properly. But then when we say, "used properly," we're talking about intermittent use, and allowing a patient to use a drug whenever they need it is very liberating. That gives patients ownership and the ability to manage the disease in a way that reflects what's happening with them. When you have products that are effective and well tolerated, you've already increased their motivation and the likelihood of success. The takeaway should absolutely be to look at the new products. The challenge is going to be the price point. Sometimes we're going to have to revert to our old standbys that are less expensive. But having said that, the next thing is adherence. You want to make the process as simple as possible for the patient, so you can maintain their ability to take control of their disease.
Feldman: We do think alike. To summarize, most people with psoriasis have very limited disease, and we should be able to control their disease with topical treatments. We've got older agents that work well. They have their issues, but if we can get patients to use them, they're very inexpensive and effective treatments. We have new agents now available in the United States that can simplify the treatment and don't have steroid side effects. Some patients may prefer that approach. Okay, Kim, thank you so much for your time today. I really appreciate it.
Papp: Thank you very much. It's been a real pleasure, and it's wonderful hearing your voice again.
Feldman: Let me just say to our listeners, I hope you've enjoyed our discussion on limited psoriasis with our guest, Dr Kim Papp. Be sure to check out the Medscape app and share, save, and subscribe if you enjoyed this episode. In our next episode, we'll begin to focus on what to do with psoriasis so severe that topicals alone are not the solution. We'll be discussing advantages and disadvantages of oral agents with dermatology nurse practitioner Lakshi Aldredge. I am Dr Steve Feldman for Medscape InDiscussion. Thank you for listening.
Listen to additional seasons of this podcast.
Resources
Medscape: Body Surface Area–Based Dosing
The Benefits and Limitations of the PASI Score
Mechanisms of Action of Topical Corticosteroids in Psoriasis
Use of Topical Coal Tar Foam for the Treatment of Psoriasis in Difficult-to-Treat Areas
Trial of Roflumilast Cream for Chronic Plaque Psoriasis
Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis
Psoriasis in Special Localizations
Vitamin D Analogs in the Treatment of Psoriasis: Where Are We Standing and Where Will We Be Going?
Tacrolimus for the Management of Psoriasis: Clinical Utility and Place in Therapy
Zoryve™ Prescribing Information
Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis
Tapinarof-Induced Folliculitis: The Paradigm of Activation of the Aryl Hydrocarbon Signaling Pathway
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Cite this: Surfacing Synergistic Solutions for Limited Psoriasis - Medscape - May 25, 2023.
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