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Systemic Treatment for Atopic Dermatitis
Updated AAD Guidance on Systemic Treatment for Atopic Dermatitis

Released: July 18, 2024

Expiration: July 17, 2025

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Key Takeaways
  • Systemic corticosteroids are no longer recommended for treatment of moderate to severe atopic dermatitis (AD) due to the risk of adverse events and severe rebound flares.
  • Dupilumab and tralokinumab are biologic therapies with demonstrated efficacy and a proven track record of safety, making them attractive options for first-line therapy.
  • JAK inhibitors, including abrocitinib, upadacitinib, and baricitinib, are also recommended for moderate to severe AD in patients who cannot take or do not respond to biologic therapies.

Atopic dermatitis (AD) impacts up to 7% of adults in the United States, with almost 40% experiencing moderate to severe disease. People with moderate to severe AD are generally undertreated, with more than 55% of individuals reporting inadequate disease control. In light of these statistics, the new updates to the American Academy of Dermatology (AAD) AD guidelines, the first since 2014, emphasize the importance of appropriate systemic therapy for this population. Read on for insights into these updates from Dr Benjamin Ungar, Assistant Professor of Dermatology at the Icahn School of Medicine at Mount Sinai.

Rethinking Systemic Corticosteroids for AD
Once the clinical assessment is made and healthcare professionals (HCPs) determine that patients are in the moderate to severe range of AD, these patients will generally warrant some form of systemic treatment. The updated guideline reaffirmed the recommendation provided by the authors in 2014 that systemic corticosteroid therapy, although used historically, should be avoided in AD management due to an unfavorable adverse event profile. Although people can have some clinical response to initial treatment with systemic corticosteroids, there is a very high risk of a severe rebound flare that will complicate the clinical course. Ultimately, the risk outweighs the potential benefit with this therapy.

Fortunately, there are other options for patients with moderate to severe AD, including phototherapy and other systemic options. Typically speaking, most patients with uncontrolled moderate to severe AD will require treatment with either a biologic or an oral small molecule.

Biologic Therapies
Biologic therapies, also known as monoclonal antibodies, are among the newer treatment options for AD. Dupilumab was the first new FDA-approved systemic therapy for the treatment of moderate to severe AD. I think for many people, dupilumab remains a first-line and mainstay treatment. It has a strong track record of safety and efficacy, having been approved in the US for 7 years. It also is approved for pediatric patients all the way down to the age of 6 months, which further serves to highlight the excellent safety profile of this medication.

Tralokinumab is a newer biologic that was originally approved in 2021 for adults with AD and was recently approved for pediatric patients 12 to 17 years of age in 2023. The mechanisms of dupilumab and tralokinumab are related but different, which suggests that although people may respond to both, there are going to be some patients who respond to one and not the other. In particular, dupilumab blocks the interleukin (IL)-4 alpha receptor subunit, therefore blocking IL-4 and IL-13, while tralokinumab blocks the IL-13 cytokine directly. In all, both drugs have similar mechanisms, but are distinct enough that even if one is insufficiently effective, the other one may be considered. No head-to-head trials have been published comparing the 2 agents, and there are currently no formal guideline recommendations recommending one agent over the other. It has been suggested that the evidence for benefits may be stronger for dupilumab compared with tralokinumab based on their respective mechanisms of action.

I think it is important to keep in mind that both dupilumab and tralokinumab require no laboratory monitoring, perhaps making this an easy way to treat patients effectively and appropriately. For many people, these are excellent options as first-line treatments to treat moderate to severe AD.

JAK Inhibitors
In addition to biologics, the guidelines mention 3 Janus kinase (JAK) inhibitors, which are oral small molecules that relieve AD symptoms by reducing inflammation. Two JAK inhibitors, abrocitinib and upadacitinib, are approved to treat moderate to severe AD in the US and can be considered a first-line treatment in some patients or a second-line treatment as well. The third, baricitinib, demonstrated efficacy in clinical trials for eczema and is approved in the United Kingdom, but is only FDA approved in the United States for treatment of severe alopecia areata.

When comparing the overall efficacy of JAK inhibitors to biologics, particularly at the higher doses, both FDA-approved JAK inhibitors, upadacitinib and abrocitinib, have higher potential ranges of efficacy at earlier time points. Furthermore, these drugs work through different mechanisms than the biologics, so it is possible that patients who did not respond to treatment with biologics could respond to JAK inhibitors. Therefore, these can be promising options for people who have insufficient responses to either dupilumab or tralokinumab.

Upadacitinib and abrocitinib also have 2 different approved doses. This means that there is the potential to titrate the dose to an individual patient’s needs. For example, some people may respond very well to the lower dose, which is 15 mg of upadacitinib or 100 mg of abrocitinib. But if they are not fully responding, the dose can be increased to 200 mg for abrocitinib and 30 mg for upadacitinib. JAK inhibitors tend to work relatively quickly, so HCPs can assess the response in just a few weeks to see whether a dose titration may be necessary.In contrast to the biologics, treatment with JAK inhibitors requires lab monitoring. Bloodwork needs to be done prior to initiating treatment and patients must undergo routine monitoring while on therapy. The FDA has not given specific guidelines as to what routine monitoring may entail, but for most people this includes obtaining a complete blood count, comprehensive metabolic panel/liver enzymes, and lipids every few months. After treatment is initiated, if patients are on a stable, well-tolerated dose, I think monitoring bloodwork may be extended a little beyond the 3-month timeline.

Considerations for Treatment
Lastly, I will say that it is important to note that people with moderate to severe AD and inadequate treatment really need and deserve better treatments. Although they may not respond to dupilumab or tralokinumab, there is often the possibility to treat them with oral JAK inhibitors. The fact that the FDA issued boxed warnings for the oral JAK inhibitors and the fact that there are safety considerations should certainly be acknowledged and factored into treatment decisions, but if patients do not have clear contraindications to treatment, there is no reason why HCPs should shy away from using them. It is important to keep in mind that they can often be effective and have a very dramatic positive impact on patients’ quality of life.

Your Thoughts?
How will the new guideline updates affect which treatments you recommend to your patients with AD? Leave a comment to join the discussion!

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Which of the following systemic therapies recommended in the AAD guidelines have you used in your patients with moderate to severe AD? [select all that apply]

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