Advances in the Management of Atopic Dermatitis - Episode 13

Topical Calcineurin and PDE-4 Inhibitors in the Treatment of AD

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A review of topical therapies that have been long utilized for patients with atopic dermatitis.


Lawrence Eichenfield, MD: Let’s take a next step in discussion of our available standard medicines. We haven’t discussed topical calcineurin inhibitors or topical PDE-4s. Raj, do you want to give us a top line?

Raj Chovatiya, MD, PhD: Sure. We can take a little trip back in time here. Tacrolimus and pimecrolimus are 2 topical calcineurin inhibitors. They’re not new by any stretch. The FDA approved them about 20 years ago in 2000 or 2001. They’re approved for greater than 2 years of age. On the whole, tacrolimus, the higher concentration, is probably more potent than the lower concentration, pimecrolimus. There are mixed data in terms of head-to-head studies. It seems like the topical calcineurin inhibitors line up with lower potency steroids that can perform somewhat similarly. There’s limited potency when you compare it with more medium or higher potency. But on the whole, there are good data showing that topical calcineurin inhibitor use reduces flares, the time between flares, and overall topical corticosteroid use. Particularly with proactive use, it’s a really good option for sensitive skin sites, where we’re not looking to use that much in the way of topical corticosteroids.

There are a couple of aspects about safety that are worth noting. There’s a boxed warning about theoretical malignancy risk, which comes up a lot with patient discussions. But it’s really important to talk about what long-term data over the past 20 years have shown, which is probably evidence to the contrary that this isn’t something we’re worried about with this class of medications topically. And then the application site symptoms can range quite a bit among patients, but there’s a lot of stinging and burning with application, which can limit the use of this medication class.

Similarly, when you look at PDE-4 inhibitors, crisaborole is the one on the market. There are several others in various phases of development. This was approved not too long ago, in 2016, and it’s approvedfor 3-plus months of age, so you can use it in young children. It’s another nonsteroidal agent. The clinical trial data showed superiority to the vehicle [placebo], but it was only mildly better than the vehicle itself. But it’s a good nonsteroidal option for those sensitive sites.

Local reactions weren’t seen so much in the trials, but real-world data suggest that there’s probably a fair bit of application site pain in patients, along with stinging and burning. That’s something that limits its use. There have been a few network meta-analyses done in the literature trying to look at all these nonsteroidal agents, of which this group is going to grow. It seems like on the whole, crisaborole is probably comparable with tacrolimus when you’re looking at rates of clearance, superior to pimecrolimus, and superior to vehicle as well.

Lawrence Eichenfield, MD: That was a great rocket tour through those. It’s important to include them because we use them as alternatives to steroids, either on their own or in regimens of care.

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Transcript edited for clarity.