PDE4 Inhibitors in Treatment of Plaque Psoriasis - Episode 1
Neal Bhatia, MD, provides an overview of treatment options for patients with chronic plaque psoriasis, focusing specifically on the use of topical agents.
Neal Bhatia, MD: We’re in a great time for treatment options for patients with plaque psoriasis, as well as psoriasis as a whole. We’ve seen the advancement of different topical, oral, and biologic therapies over the years, but now, with new topicals that are either with a cream vehicle that is much more tolerable, that don’t have any steroids in them, which we can use for a longer term, and even more so, that do something to the process and not just what we see in front of us. I think we have a lot of good opportunities to make psoriasis much more tolerable, easier to treat. Then of course, for the patient, we can improve quality of life as well as improve symptoms such as itching and dryness.
As far as some new categories of topical therapies, we’ve gone from calcipotriene and tazarotene as well as different steroids strengths, to now we have PD4 [phosphodiesterase-4] inhibitors, aryl hydrocarbon receptor inhibitors, and some other new inhibitors, as well as the Janus kinase inhibitors that are in the works for psoriasis. Even more so are the vehicles that are important for delivery into the scalp, intertriginous areas, as well as other surface areas on the body. Then of course, we have compatibility with oral therapies as well as biologic therapies. We have some new tyrosine kinase-2 inhibitors that are on the market as well as new biologics that approach not only IL-17 [interleukin-17] and IL-23 but are much more comprehensive in the process.
Many of us question who the ideal candidates for topical therapies are. For me, every single patient with psoriasis should have something topically to put on the affected area. Patients with psoriasis, as we’ve seen over the years, really like to have control over their disease. They like to put something on the affected area at least minimal, even if they’re on something systemic, to control the outcomes of what is going on from the top down. We talk a lot about breakthroughs. We talk a lot about areas that are more stubborn, like the scalp, the intertriginous areas, even the nails. Patients with psoriasis want to have control over their outcomes, and being prescribed something topically not only allows for control of that and the additional ability to do something about itch or something about dryness. But even more so it adds to the potency of the systemic therapies that they could be on as well as treating breakthrough.
We see patients who have concerns about the overuse of steroids. They have concerns about their long-term outcomes and safety with many of the topicals. There’s also a sense of fatigue, that if they’re not seeing results within a week or two, they want to give up and start something else. The expectations are there for a sprint effect; the safety is there for a marathon effect. But it’s the combination effect with topicals and systemic agents that will allow for the long run, even more so allowing for patients to maintain themselves on a topical agent that’s much safer than topical steroids and will be beneficial for all of us. In the end, I think we all need to be cognizant of how we treat from the top down as well as from the inside out.
There’s always a question of whether there is a cutoff of how much surface area there is when you switch from topicals to something oral or biologic, for example. Again, the average mild patient may come in with 3% body surface area, whether it be confined to the scalp, or the elbows and knees, or the inverse presentations and in the inguinal distribution. I think the key to the equation is even 1% body surface area needs to be treated topically because that patient really wants to control it from the top down. Even more so is the concept of what are we doing to the process of keeping those plaques under control and not just making them go away? For me, there’s really no cutoff of a body surface area percentage that says, “OK, we should switch from topicals to systemic agents.” We should keep patients on topicals no matter what and then add and subtract as we see fit. I think we’re living in a world now where patients are having concerns about what they read on the internet, and we have to be cognizant of what their information gathering will be as an obstacle for prescribing. I think the other part of the equation is reminding them that these newer agents that change the process of the disease and don’t just put out the fires like steroids do, will have long-term safety benefits as well as long-term tolerability.
Thinking about the cutoff of when to start a patient on biologic agents or systemic agents, obviously, we have new oral agents as well as a lot of tried-and-true biologic agents and some new biosimilars coming. I think the long story short of it is looking into the patient experience, what have they tried, what have they been on? I always upgrade scalp psoriasis to moderate because it’s a very difficult area to treat. There’s also thinking about areas on the back, which are very difficult to treat with topical therapies alone. Then of course, the nails. I think that’s also very important to think about because topicals may not deliver through the nail plate into the nail bed where the disease lies.
I think in the end, we have to think about whether this patient is willing to take shots. Is there a patient willing to take pills? Is there someone who just wants topicals, and is there someone who wants nothing? We have to work through all of those preferences. Patients who take shots, they may feel that they have control of their disease with the less frequent dosage of shots. On the flip side, there are patients who say, “Well, I don’t want to take shots because I feel like I’m sick.” They equate themselves to patients with diabetes or patients who take long-term infusions. There are patients who can’t take pills every day, they don’t have the time, they forget, they have very poor compliance. But there are others who feel like if they took a pill every day, they would have more control over the outcomes and they may see a more sprint effect. There are definitely benefits to both sides of the equation. But in the end, I think topical therapy still needs to be the mainstay and the building blocks of treating from the top down because there’s a lot of psoriasis that works that way, as well as the plaques that may be more difficult to respond with steroids and other agents, where we could see these newer molecules and formulations getting some better impact on them.
Transcript Edited for Clarity