Novel Topical Treatments in the Management of Plaque Psoriasis - Episode 3
Expert dermatologists provide an overview of the current topical, oral, and biologic medications available to treat plaque psoriasis.
Brad Glick, DO, MPH, FAAD: Let’s move on and talk about factors guiding treatment selection in our patients with plaque psoriasis. Now, I’m going to throw this out to both of you. Provide an overview of the different treatment options that we have for plaque psoriasis. This is a pretty big topic. Linda, I’ll jump to you first. Tell us a little bit about some of the topicals that we have and the mechanism of action. We’ll talk a little bit about orals and biologics too, but start with the topical therapies. What do we have and what are their MOA [mechanisms of action]?
Linda Stein Gold, MD: Well, I think it’s important to take a step back and look at our basket of psoriasis patients and understand that the vast majority of these patients actually have localized disease. That means that the vast majority of these patients can be treated with topical therapy alone, even for those patients who have moderate or severe, or more widespread disease, some patients are achieving a PASI [Psoriasis Area Severity Index] 100. Even our patients who have more widespread disease, who are on very effective systemic medications, still require topical therapy to get to that point of efficacy where they really desire. So, traditionally, we consider topical corticosteroids as the mainstay of therapy. Often, we must go to those more potent steroids in order to get control as quickly and as completely as possible. Though, I consider topical steroids to be a short-term solution to a long-term problem. We can’t use topical steroids indefinitely. Although they’re great in kicking in quickly, they actually don’t necessarily have the efficacy that we think that they have. They do well, but they don’t necessarily clear our patients completely. So, then we have to look to our nonsteroidal options.
We have 2 good options. We have a topical vitamin A derivative, like tazarotene. Tazarotene is great because it helps to counteract some of the negative effects of the topical steroids. It might help to diminish the atrophogenic effects and it works by a different mechanism of action. The steroid helps to calm down the irritation from the topical retinoid. We have topical vitamin D derivatives, also nonsteroidal, that work well. Especially in sensitive areas such as monotherapy. Generally, we utilize these nonsteroidals with combination therapy, which means we usually use them in combination with a topical steroid because they don’t tend to jump in that quickly. We have other agents that we use off label. Topical immunomodulators that we can use for the face or the sensitive areas. Overall, what we’ve been lacking is a medication that works well without a steroid that we can use for a long term, and something that I call one-stop shopping. I like to be able to have 1 agent, and the answer is always yes. Can I use it on my face? Yes. Can I use it on my elbows, knees, arms, legs, wherever, hands? Yes. Simplify the regimen. That’s really what we have been missing for a topical treatment of psoriasis.
Brad Glick, DO, MPH, FAAD: Michael, give us a brief overview of oral agents that we have in our toolbox for managing our patients with plaque psoriasis and tell us a little bit about their mechanism of action.
Michael Cameron, MD, FAAD: So, we’ve had for quite some time now apremilast, the brand name being Otezla, which is actually the number 1 prescribed systemic that many people don’t realize for psoriasis. A large part of it is just because it’s just so safe, right? We now have that across all the severities with psoriasis. So we have the mild indication as well for psoriasis for Otezla. That’s a PDE-4 [phosphodiesterase-4] inhibitor, as you know, so because of that I don’t like to think of it as an immunosuppressant. You know obviously immunosuppression exists on a spectrum and it’s just relative to other agents, but apremilast is just attenuating our immune response and our autoimmunity via PDE-4 inhibition. So it’s not going to put you at increased risk for tuberculosis or viral infections or bacterial infections, and it really is quite helpful for things like scalp psoriasis we’ve seen and palmar plantar psoriasis. I actually use it off-label for most psoriasis patients to stack with biologics.
That’s the 1 oral agent we’ve had for quite some time, and then more recently we’ve gotten deucravacitinib, which has a moderate-to-severe indication for psoriasis, and that’s been really exciting. What’s interesting is it’s actually not a JAK [Janus kinase] inhibitor. If you read the label, the FDA was very explicit about this. It’s a TYK2 [tyrosine kinase 2] inhibitor, and so why is that? There’s a few reasons why I think the agency felt comfortable not calling it a JAK inhibitor. One, is that TYK2 is actually only present in a couple receptor pairs, unlike JAK1 and JAK2, which are affecting myriad cytokines. Number 2, it’s actually an allosteric inhibitor of the regulatory domain of the JAK proteins. Every other JAK inhibitor we’ve had in hem [hematology]-onc [oncology] or dermatology or rheum [rheumatology], those have all been ATP [Adenosine triphosphate] reuptake competitive inhibitors.
Now, we’re really getting into the weeds here, Dr Glick. But essentially, long story short, this is a very elegant mechanism of action that, because of it being a regulatory domain inhibitor, it doesn’t affect the other JAK isoforms at all. Thus, we’re seeing no lab changes. We’re seeing really no signs of immunosuppression besides for a slight shingles risk because of interferon inhibition. The FDA was like, let’s not give this a black box warning. Let’s call this a TYK2 inhibitor, and my patients are really loving it. I think we finally have an oral option that has biologic-like efficacy. I’m using it for my more mild-to-moderate patients more and more now, which frankly most psoriasis patients are. And then for all my moderate-to-severe patients, I’m letting them choose between an injectable and Sotyktu because I think given the safety profile, patients have that right to know about the different modes of delivery.
Brad Glick, DO, MPH, FAAD: Wonderful answer about oral therapies in the toolbox. What I find interesting, coming from a young physician like yourself as opposed to an older gentleman like me, we don’t even necessarily bring up the subject of some of the traditional oral systemic therapies like methotrexate and acitretin and cyclosporine. I personally use them sometimes, to your point, we have these unique and novel mechanisms of actions and these therapies that work quite well. An agent like apremilast, we don’t have to really do any drug monitoring. I think that that is quite helpful. So great responses. Mona, talk to us about biologic therapies for the management of patients with plaque psoriasis.
Mona Shahriari, MD, FAAD: Biologics have really been a welcome addition to our psoriasis toolbox, and they’ve revolutionized how we treat this disease. When they hit this space back in the early 2000s, the TNF [tumor necrosis factor] inhibitors were first-generation biologics. They were the next best thing since sliced spread, and they really did offer our patients a chance at a meaningful clearance. In the year 2023 though, they don’t have as much of a role as they had say 10-plus years ago. One is because there are concerns about immune suppression. We also do need to be cognizant of the risk of nonmelanoma skin cancer in some of our patients that are on these agents.
Thankfully, since then, we’ve had the development of newer generations of biologics. The next 1 was the IL [interleukin]-17 inhibitors, which either target the cytokines or they target the receptor themselves. The fact that these drugs were more efficacious than the TNF inhibitors, but also, they offered a more favorable safety profile than our TNF inhibitors, made them a great addition to our toolbox. Their claim to fame was that speed of efficacy, which we saw that clearly stated in a couple of head-to-head trials that we had with the 17s going up against some of our TNF inhibitors. We also do have some concerns we need to keep in mind with that class. Higher risk of fungal infections as well as potential unmasking of inflammatory bowel disease. This is true because, as we know, inflammatory bowel disease is a comorbidity in our patients with psoriasis. So, you do need to keep that in mind when you’re starting a psoriasis patient on an agent from this class.
Finally, our most recently approved biologics, those IL-23 inhibitors, have really raised the bar in terms of the efficacy that we can expect from biologics in the year 2023. They offer a very low burden of injections, whether it’s every 8 weeks or every 12 weeks, and they have a safety profile to be reckoned with. So, we’ve really, with the advent of these biologics, given our patients a chance to live healthy, normal lives free from that constant reminder of their psoriasis.
Transcript edited for clarity