Topical Therapies

What is the connection between phosphodiesterase 4, Janus kinase, and aryl hydrocarbon receptors? April Armstrong, MD, MPH, cites evidence for emerging eczema topical therapies. Dr Armstrong is professor of dermatology and associate dean of clinical research at Keck School of Medicine of University of Southern California in Los Angeles.

Transcript
Dr Armstrong:  For topical therapies for patients with atopic dermatitis, that landscape also looks very exciting. We are at a time point we're currently looking at three different mechanism actions. One is a topical PDE-4 inhibitor. Then in addition to that, JAK inhibition is another mechanism of action. Then finally, we are also looking at modulating the aryl hydrocarbon receptor. I'm going to talk about those three different classes and the different molecules that are being developed under those different three classes.

First, when we are looking at PDE-4 inhibitor in terms of a topical version, we are talking about roflumilast. In its phase 2 study, what was shown was that with the 0.15% cream formulation, there was about 72% EASI improvement and also greater than 50% of the patients achieving clear almost clear for roflumilast when they are looking at the time point of 4 weeks.

This is quite promising for our patients with atopic dermatitis to know that there are now several nonsteroidal options that are available for them. Roflumilast is certainly something to watch out for.

Another class, as I mentioned before, are the topical JAK inhibitors. And when we're thinking about the topical JAK inhibitors for atopic dermatitis, we're looking at ruxolitinib and delgocitinib.

Ruxolitinib is a JAK1 and JAK2 inhibitor. In its studies, it looked at the 0.75% formulation, as well as the 1.5% formulation. What was found was that in the 0.75% formulation, 45% of the patients achieved clear or almost clear, and in the 1.5% formulation, 53% of patients achieved clear or almost clear. This is important because what we saw was very good efficacy with ruxolitinib in patients who are age 12 and above with mild to moderate atopic dermatitis. Overall importantly, it's very well tolerated. What was noted was at the rates of, for example, application site reaction was actually lower than that of the placebo group.

The last class of innovative therapy in terms of topical therapies for atopic dermatitis that I want to talk about is tapinarof. Tapinarof is a topical aryl hydrocarbon receptor agonist. It has a role in terms of limiting the dysregulated T_H2 pathway that we see in patients with atopic dermatitis. Specifically, it can inhibit the IL-4, STAT6 pathway. In addition to that, it can increase the level of filaggrin, which as we know is typically impaired in patients with atopic dermatitis.

In the dose-ranging study, what was found was that around 55% of patients on tapinarof 1% applied BID achieved clear almost clear by week 12. When they looked at another dose of QD application, what they found was that 45% of them achieved clear or almost clear. This was all compared to about around 25% response in the vehicle group by week 12. Overall, tapinarof was well tolerated. About 5% to 7% of the patients experienced folliculitis. However, this was mild, generally, and resolved with or without treatment. It's important to know that tapinarof is another option that will be very important to our patients with atopic dermatitis.

At this time, I will say it's very exciting that we have various emerging therapies for patients with atopic dermatitis in the topical realm. I think they're very important because our patients are oftentimes more and more, even I will say more so in the past decade, asking for nonsteroidal options. While we've had good nonsteroidal options, such as our topical calcineurin inhibitors or crisaborole, but the advent of these emerging therapies will add to our toolbox in terms of what we can offer to our patients.