Nonsteroidal Topical Therapies for Psoriasis and Atopic Dermatitis

In this interview, Dr Linda Stein Gold discusses the shift from traditional therapies for psoriasis and atopic dermatitis (AD) to newer nonsteroidal options, focusing on their mechanisms of action, safety, and effectiveness.

The Dermatologist: Can you provide an overview of the current landscape of nonsteroidal topical therapies for psoriasis and AD, including highlighting any recent developments or emerging trends?

Dr Stein Gold: It is an exciting time for topical therapy for both psoriasis and AD, and we have a lot of new players that have made it to US Food and Drug Administration (FDA) approval. If we start with psoriasis, 2 new molecules have recently been FDA approved. We have tapinarof, which is an aryl hydrocarbon receptor agonist that is approved for adults with plaque psoriasis. And then we have roflumilast, which is a topical phosphodiesterase-4 (PDE4) inhibitor that is FDA approved down to age 6, also for plaque psoriasis. When we look at AD, we have the topical Janus kinase (JAK) inhibitor ruxolitinib that was recently approved. And then we have the other 2 molecules that I mentioned for plaque psoriasis that have finished phase 3 clinical trials and hopefully soon will be FDA approved for AD as well.

The Dermatologist: What factors should dermatologists consider when selecting nonsteroidal topical therapies for patients with psoriasis and AD?

Dr Stein Gold: We must remember that both psoriasis and AD are chronic diseases. They have exacerbations and they have remissions, but generally people are going to be treated for long periods of time, and that might mean many years. So, we must have a short-term game plan and a long-term treatment plan. Often, we might use a topical steroid up front to get the patient under control, but a long-term plan usually means that we must incorporate nonsteroidal options. Our new options can be used as monotherapy; however, in practice, we will often use them in combination with other agents. But when we look at a patient who has lesions that are on the face, or in sensitive areas, or maybe they have several different areas involved, I like to simplify the treatment regimen. We do not want to give our patients a lot of things to do because it can become too confusing. Patients will leave our office and they have no idea what we said, but if we can simplify the regimen and give them one thing they can use on multiple body surface areas, I think it will set our patients up for success.

The Dermatologist: In your experience, how effective are nonsteroidal topical therapies compared to traditional steroid-based treatments for managing psoriasis and AD?

Dr Stein Gold: The good news is that our nonsteroidal options are better than what we have had in the past, and a lot of them stack up nicely compared to a mid-potency topical steroid. We can expect to potentially use them as monotherapy and we can certainly use them on an ongoing basis, either on or off treatment. We have seen with tapinarof for psoriasis that patients can get to completely clear and then have the possibility of a drug holiday. We saw with roflumilast that when patients use the medication as needed in long-term treatment, they were able to gain control for longer periods of time. Ruxolitinib is recommend for short-term use, which means up to maybe about 8 weeks or so, and then it can be used for intermittent long-term use.

The Dermatologist: Could you discuss the mechanisms of action behind nonsteroidal topical agents used in the treatment of psoriasis and AD?

Dr Stein Gold: When we look at the mechanisms of action behind our new nonsteroidals, these are some new mechanisms that we have not seen before. Tapinarof is a small molecule that works inside the cell. It downregulates TH17 cytokines, which is why it is effective for psoriasis. It also downregulates TH2 cytokines and improves the skin barrier, which makes it very effective for AD. Roflumilast modulates the inflammatory milieu within the cell. It blocks the enzyme PDE4 and that stops the breakdown of cyclic adenosine monophosphate, which creates a more anti-inflammatory environment. And we have seen that this affects TH17, TH1, and TH2 cells. Ruxolitinib targets both JAK 1 and 2. And we know that the JAK-STAT pathway translates those extracellular signals into intracellular responses. It has been shown to downregulate a lot of the important cytokines that are necessary in the pathogenesis of AD.

The Dermatologist: What role does combination therapy play in the management of psoriasis and AD, especially when incorporating nonsteroidal topicals?

Dr Stein Gold: Combination therapy is something that we do quite commonly with our patients, especially when they have a long-term illness. Now, when we studied these new nonsteroidal options, we studied them as monotherapy. We had to show that each of these new drugs can stand by itself and get our patients to clear or almost clear skin. But in real life, we know that we often use combination therapy, and that means maybe using them with a topical steroid or maybe incorporating them with systemic or other agents. Most of our patients utilize topical therapy, and I think the nonsteroidal topicals fill an important void.

The Dermatologist: How do you approach the assessment of patient response to nonsteroidal topical therapies?

Dr Stein Gold: With our new agents, I think we have raised the bar on what we should expect and what our patients should expect in terms of getting their disease under control. I really want to see my patients getting to clear or almost clear skin. So, that is my bar. But often I will ask the patient, “How are you doing? How do you think your disease control is? How often are you thinking about your skin? How is your itching? How is your sleeping?” Each one is an individual evaluation. If the patient is heading in the right direction and they are happy, I will continue the treatment.

The Dermatologist: Given the paradigm shift in the use of nonsteroidal topicals, what challenges or barriers do you foresee in their widespread adoption, either from the clinician’s or patient’s perspective?

Dr Stein Gold: The main barrier we have is getting the appropriate treatment to the appropriate patient. Insurance coverage is always going to be our number one barrier. The other barrier falls on us to become educated and understand what these new drugs can do and how they will impact our patients’ lives. We need to understand which patients will benefit from which drug and know how to incorporate these new medications most effectively into our treatment armamentarium.

The Dermatologist: Can you share any insights or experiences related to long-term safety considerations associated with nonsteroid topical therapies for psoriasis and AD?

Dr Stein Gold: These nonsteroidal options are very safe, and we have studied them for long periods of time. There are some local skin reactions that we can see with each of the new agents. With tapinarof, we have seen some folliculitis and contact dermatitis, which tends to be mild or moderate. With roflumilast, we can see a little bit of systemic absorption. Patients might have some diarrhea, but that usually resolves fairly rapidly. Most patients continue the medication without having any problems. Ruxolitinib does have some restrictions on it. It should not be used for more than 20% body surface area, and it should not be used continuously for long periods of time. But the good news is that these drugs are well tolerated. In the past when we used a nonsteroidal agent, we had some stinging and burning, and we had to talk our patients through that. But with these 3 new agents, most patients tolerate them quite well. I am very comfortable using these medications for short-term as well as long-term therapy, either using the medication as needed or getting patients under control and then using it as needed.

The Dermatologist: As we continue to see advancements in dermatologic treatments, where do you see the future of nonsteroid topical therapies heading?

Dr Stein Gold: What I see now with our new nonsteroidal topicals is that we are changing the treatment paradigm. In the past, we have reached for our potent topical steroids or mid-potency topical steroids. But now we have agents that have shown that even as monotherapy, they can get our patients under control and keep them under control. I think in the future we are going to start thinking nonsteroidal first and using our steroidal options as backup therapy.

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