Topical treatment for atopic dermatitis (AD) has expanded beyond corticosteroids and calcineurin inhibitors to include the PDE4 inhibitors crisaborole and roflumilast, the JAK inhibitor ruxolitinib, and the aryl hydrocarbon receptor (AhR) agonist tapinarof. These newer agents offer the possibility of a reduced reliance on topical corticosteroids for the acute and long-term management of AD. This update reviews the current clinical considerations for today’s topical treatment landscape.

For many years, the topical treatment of AD consisted of only topical corticosteroids. In the early 2000s, however, topical calcineurin inhibitors were approved by the US Food and Drug Administration (FDA). For the longest time, we relied on those 2 options (ie, either topical corticosteroids or topical calcineurin inhibitors), and there is still a big place for them. In fact, there are multiple trials showing that they work, they are safe, and most of them are covered by health insurance.

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While these topical therapies are great for controlling flares quickly, one of the issues with long-term topical corticosteroid use is that they tend to cause skin atrophy, discoloration, and stretch marks when used for longer periods. The topical calcineurin inhibitors pimecrolimus and tacrolimus offer an alternative to topical corticosteroids, which is important in the pediatric population, as we try to avoid the widespread use of corticosteroids in patients who are very young. Sometimes we cannot avoid using them in this population, but if we can, we will try. Pimecrolimus tends to be used in patients with milder disease, whereas tacrolimus can be used for moderate or severe AD. One of the main issues with topical calcineurin inhibitor use is that they may cause burning and irritation, which in some cases may be transient but in other cases can continue to happen, thus rendering them intolerable.

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Until recently, we lacked other options for treating AD. However, since then, we have seen an influx of topical agents with good clinical efficacy and favorable safety profiles. For example, we have the topical PDE4 inhibitor crisaborole and the topical JAK inhibitor ruxolitinib. More recently, another PDE4 inhibitor (ie, roflumilast) and an AhR agonist (ie, tapinarof) received FDA approval for the treatment of AD. Some of these new agents have indications for very young patients (eg, the indication for crisaborole is down to 3 months of age), making them a reasonable treatment option for pediatric patients.

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Prior studies have also demonstrated that calcineurin inhibitors and topical corticosteroids may be used proactively for the treatment of AD. This approach consists of the application of a topical agent 1 to 2 times per week to previously affected areas to prevent AD from recurring in these areas. More data are needed on the use of this approach with newer topical agents for AD.

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Overall, as a group, the newer topical therapies for AD tend to be well tolerated, but, with crisaborole, sometimes we might run into stinging and irritation that may limit its use. If a patient applies a topical, say, 1, 2, 3, or, at most, 4 times and just cannot tolerate it, it is likely that they will not continue with this said therapy. Clinical trial data have shown that newer drugs such as ruxolitinib, tapinarof, and roflumilast are well tolerated, with low rates of treatment discontinuation due to tolerability issues. Personally, I have not really seen ruxolitinib, tapinarof, or roflumilast cause stinging and burning in my patients, and patients can also use these in sensitive areas of the body.

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Based on my experience, and depending on the patient being evaluated, my first choice for treatment will probably be a medium- to high-potency topical corticosteroid to calm things down quickly if the patient is experiencing an “acute” flare. Then, long-term, I will transition the patient to something else because I do not want them to stay on a topical corticosteroid forever, if possible. I tend to gravitate toward ruxolitinib, but it does have the FDA boxed warning about major adverse cardiovascular events, serious infections, thrombosis, malignancy, and mortality, even though it is a topical agent. And let us not forget that, for whatever reason, topical calcineurin inhibitors also have boxed warnings about the risks of serious infections and malignancies.

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It is important to take the time to counsel patients about these risks and about how these risks apply to them, as this could have an impact on treatment adherence. Still, the improved tolerability that these new agents offer may be a game changer for some patients with AD. I think that if you can get the patient to apply a medication and tolerate it well, they are more likely to stay on the treatment, which, in turn, could result in better disease control.