Experts in dermatology describe the topical treatment landscape of atopic dermatitis: corticosteroids, calcineurin inhibitors, crisaborole, and upcoming topical JAK inhibitors.
Margaret Bobonich, DNP, FNP-C, DCNP, FAANP: We have a lot of things that we have used traditionally as well as new pharmacologic therapies that are in the pipeline. So Doug, let’s start with some of the topical therapies.
Douglas DiRuggiero, DMSc, PA-C: Yeah, I think – I just want to mention. The real question I get from folks who refer to me is how do you decide or when I have residents or students rotating with me, how do you decide if you're just going to use topicals or just going to try to use some of the new systemics. And I think that’s kind of an underlying question. If you're going to put people – I think basically with atopic dermatitis treatments, you're looking at two boxes you're going to put folks in. Those that you feel like that are mild that can be treated alone with topicals. Maybe some of these newer ones coming out may even say mild to moderate you may be able to treat with topicals and those that you feel like that are moderate to severe that may need to be systemics. The choice to put someone on a systemic is basically this. Have they failed topicals? There’s no lab work you're going to check, there’s no great algorithm that’s out there right now that says this is when you're going to put someone on a systemic versus not. It’s just basically their severity, their presentation, what they failed in the past, make sure you know why they failed in the past, was it lack of compliance, in order to make that decision. Let’s just stick on that mild to moderate patient where we’re going to use topicals. I’ll start off with talking about what we already have. I kind of think of topicals in four categories. What’s in our back pocket, what’s been around the longest. And that’s our topical corticosteroids. The first one came out topically in 1952. It’s the first trial to really change the whole direction of dermatology having topical corticosteroids. And so, we’ve been using them since that time. They still are the mainstay of treatment in dermatology and in primary care. But you know those are not meant to be long-term because of skin thinning and hypopigmentation, atrophy triad that can happen. We know that calming down flares is important, but they're not good for maintenance therapy. If we move into the next tier, what’s in our front pocket in terms of what’s a little more new. What do we have in hand? Now first of all it’d be the topical calcineurin inhibitors, protopic and elidel. We had a good study come out last year of long-term safety looking at kids over ten years, looking at incidence of potential cancer and this study showed that based on lack of seeing any cancer signals that these medications do not have any significant increased risk of cancer according to this trial, even though there is some black box warnings in using them under the age of two. The other side of non-steroidal topicals is crisaborole. And crisaborole came out a few years ago. It’s a PDE4 inhibitor. We have some new PDE4 inhibitors coming out soon that may have a higher binding effect and rate of clearance. But crisaborole is awesome in that category. We’ve got topical steroids as the old traditional. Then we move into some things that have come out more recently that are things that can be moved towards maintenance therapy or maybe even initial therapy, crisaborole and then your two topical calcineurin inhibitors.
And then we move into what I consider the new kids on the block, ones that we are about to get into our hands; ones that are going to come to us this year or early part of next year. And when we move into those, we’re talking about topical JAK inhibitors. And I’ll just go ahead and give it some special mention. The topical JAK that’s going to come out I think soon to get into our hands first is ruxolitinib. And this ruxolitinib is a JAK1, JAK2 inhibitor. We can talk about that class in a second just to describe what JAKs are. But this cream has great excitement around it simply because of its EASI scores and EASI is this test where this indicator, this subjective market that we use to look at severity and how much the severity improves. It’s a severity index. Eczema area severity index. And they have EASI scores of 62 percent of patients seeing an EASI 75. That means they get 75 percent improvement. So you're looking at greater than six out of ten are getting a 75 percent improvement with a topical alone. And then they have an EASI 90. I mean that’s 90 percent improvement. Almost 41 percent of those patients are doing that. And they’ve run some trials too looking at head-to-head against a.1 percent triamcinolone and saw that that versus.1 percent triamcinolone with a BID application over eight weeks, how it’s typically studied and how it’ll probably come out. We’ll wait to see what the FDA says on that. But even it was as strong as or maybe even a little better than our triamcinolone without the side effects that we see with topical steroids. This is kind of our exciting new topical JAK that we feel is going to be in our hands very, very soon. Delgocitinib I think is the other one that’s far in the horizon. It’s approved already for atopic dermatitis in Japan, but it looks like they’re only going to go for an indication of hand dermatitis in the United States, and not even an indication for atopic dermatitis. So that’s a second topical JAK that is further down the road but may not even have an impact on our AD population in terms of FDA indication.
Margaret Bobonich, DNP, FNP-C, DCNP, FAANP: I’m glad you mentioned that Douglas. It’s exciting to have all of these new agents. And the truth is when you have patients who have moderate AD and understanding this is – this last year, this is relapsing. Applying topicals over and over and over is difficult for parents. When they start off with the topical steroid and then they switch over because alternating or rotating is often very helpful and helps eliminate some of those side effects and risks. The problem is is that some of the calcineurin inhibitors or the PDE inhibitors, PDE4 inhibitors can cause a lot of stinging. I find my parents want to keep going back to that topical steroid with those side effects. I really welcome the new topicals that will hopefully provide this new option for our patients that give them both control with less side effects.
Douglas DiRuggiero, DMSc, PA-C: Yeah, it’s going to be great. And it looks like these new topicals, particularly this new topical JAK, ruxolitinib is going to have far less stinging and greater tolerability than the others. We also have a new PDE4, roflumilast that will probably come to market soon as well. It seems to have a higher binding affinity than the original PDE4, crisaborole so its EASI scores are likely going to be higher. And there’s one called tapinarof, which should be coming out. Again, these are things that are an arm’s length away from us right now, not quite imminent but coming soon. That’s a whole new compound, what’s called an aryl hydrocarbon blocker. It’s going to be interesting to see if that AhR. I don’t have any data on it at all to say. But lastly too, which I think is definitely going to come in with high tolerability and maybe even be attractive to our patients who want to use natural products is that we mentioned the skin bio earlier. And this dysbiosis or the shift in different populations from a good mixture, a good diversity of the microbial atmosphere on our skin versus when one particular group overtakes, like staphorias. And using these new topical treatments that are in Phase II and entering Phase III trials, looking at the Roseomonas mucosa and also the staph hominis.
These are “good” bacteria so to speak that when you apply to the skin in the form of a spray or a mist into the antecubital fossa, into the back of the knees, if you look at these trial designs and it shows tremendous improvement, decreasing itch, improvement in skin barrier function as well. We’ve got a lot of exciting things approaching the microbiome side of skin, approaching the intercellular blockade with JAK inhibitors and PDE4 inhibitors, things that will give us better options than just using the traditional topical steroids.
Margaret Bobonich, DNP, FNP-C, DCNP, FAANP: Thank you for watching HCP Live® Peers and Perspectives. If you’ve enjoyed this content please subscribe to our newsletters to receive the upcoming programs and great content right in your inbox. So thank you everyone. Be safe and live well.
Transcript Edited for Clarity