Safety of Topical Medications in Pediatric Atopic Dermatitis

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In this exclusive interview with The Dermatologist, Dr Peter Lio discusses how new topical agents have been developed for the treatment of atopic dermatitis (AD) in children following his study, “Safety of Topical Medications in the Management of Pediatric Atopic Dermatitis.”

The Dermatologist: What new topical agents are available for AD and how do they impact pediatric patients?

Dr Lio: This is an incredibly exciting time for AD, and I think we really lean on our topical therapies. They are so important because, especially for kids, we are trying to minimize the exposure to systemic agents whenever we can. We cannot always do that, of course, and so we need good systemics too, but I think there is a real impetus or pressure to try to avoid them when possible or minimize them.

Of course, our topical corticosteroids were released and developed in the ’50s, which became popular in the ’60s, ’70s, and beyond. They have been very helpful, but they have a whole bunch of potential issues, and we really are trying to constantly minimize their use or avoid them when we can.

The next big breakthrough was around the year 2000 when we had tacrolimus, and then about a year later, pimecrolimus, our topical calcineurin inhibitors. They were great and saw a huge heyday in those fi rst few years. But then there was quite a chilling effect in March 2005 when the US Food and Drug Administration put a black box warning on them, which changed things. Then there was this long dearth of any innovation until 2016 when we got crisaborole, which is like an anti-inflammatory molecule that works by inhibiting phosphodiesterase-4 (PDE4). It is a small molecule, it is well absorbed through the skin, and now it is approved down to 3 months of age, which is exciting. It is one of the lowest [age group] levels that we have in dermatology.

Then very recently we got our newest addition, topical ruxolitinib, which is one of the Janus kinase inhibitors. That is exciting because topical ruxolitinib is well-penetrating into the skin at a great speed. This rapidity of effect is robust, in my opinion, and I feel that it is on par with a mid-potency topical steroid. It is the first nonsteroidal agent that can play with the big guys, so to speak. Now, unfortunately, it is only approved right now down to age 12 years. So, for the younger patients, it is not much of an option, and it has several warnings, including some scary black box warnings that can be a real issue for patients and families. They start looking at [the warning] and it says things about major adverse cardiovascular events and more mortality. But overall, it has been good.

We have 2 new topicals that have recently been released for psoriasis and completed their studies where we have seen the top line data for AD. These are tapinarof, which is an aryl hydrocarbon receptor modulator, and rofl umilast, which is another PDE4 inhibitor, kind of like crisaborole, but different. To me, these are extremely exciting, and I am hopeful that these are going to make their way to pediatric AD soon.

The Dermatologist: How do topical calcineurin inhibitors compare with topical corticosteroids when it comes to managing pediatric AD?
Dr Lio: We know that our topical corticosteroids, in some ways, are hard to beat because they are incredibly reliable. They help almost every single patient who we put them on. Additionally, they are generally accessible and inexpensive. They are also safe when used correctly. Again, we have decades—we are talking almost 70 years—of experience with them. Even though there are risks, it is nice to have something that we have seen literally generations of people use.

The calcineurin inhibitors are fantastic because they are nonsteroidal, and they are different in that they do not have a lot of the same side effect issues. They do not thin the skin, as topical steroids do. They cannot cause stretch marks or stria. They also do not seem to have the same kind of a rebound effect. Part of it is that topical steroids are vasoconstrictive, so when you stop using them, you can get flushing. Sometimes I find that the dermatitis we are treating can become worse.

I think the calcineurin inhibitors are less likely to do that, and, of course, they do not affect the blood vessels in the same way. What is the trade-off ? Well, the trade-off is twofold. In general, they are less reliable and I have some patients for whom they just do not do enough. Overall, they are less powerful. Then the third piece is they have different adverse effects, like stinging and burning. There are some patients who cannot tolerate them, although it is rare. I like to use a topical corticosteroid to cool things down, then use a nonsteroidal agent because it is treating less severe effects, so it makes more sense, and it is much less likely to cause stinging and burning. However, there are some limitations.

Lastly, it comes down to accessibility. Both tacrolimus and pimecrolimus are very expensive, costing hundreds of dollars, even though they have been generic for years now. Sometimes patients just cannot get them through insurance, and they are too expensive to pay for out of pocket.

The Dermatologist: Do you have any tips or insights for your colleagues regarding topical medications in the management of pediatric AD?
Dr Lio: I think the secret is, if you can, use them together in a harmonious way. I like to think about painting a picture or putting together an orchestra using different instruments. I really like the idea that we could use some topical corticosteroids, even though there are a lot of concerns about them. I am very cautious about them, but I still think they can play an important role when using them carefully in a targeted way for a short period of time, and then switching to some of our nonsteroidals.

Most importantly, write out an action plan, which is empowering the patient, and frequently follow up by asking, “How did we do? How much time did you use [the topical]? Did you have trouble? Did it sting? Did it burn?” I think those pieces to refine the therapy are critical.

Some patients can get better with topical therapy alone, but the truth is, if we do not try our best, then it is hard to know if we skipped over something or moved on in a way that we did not need to. I do think that we must be willing to go to the systemics when it is warranted because I do not want people to suffer.

Reference
Zhao S, Hwang A, Miller C, Lio P. Safety of topical medications in the management of paediatric atopic dermatitis: an updated systematic review. Br J Clin Pharmacol. 2023;89(7):2039-2065. doi:10.1111/bcp.15751