<p>The number of systemic therapies with US Food and Drug Administration (FDA) approval for treating atopic dermatitis (AD) in adults has increased in recent years. The most important factors to consider when selecting systemic therapy for patients with AD are how severe and widespread a patient’s disease is, their comorbidities, and what they find most important.</p>

There are now a variety of FDA-approved therapeutics for AD. For example, the currently approved biologics are dupilumab, tralokinumab, lebrikizumab, and nemolizumab, and there are other agents that may gain approval in the future. Dupilumab, which inhibits IL-4 and IL-13 signaling, was the first FDA-approved biologic for AD, and it changed the treatment landscape. There is no regular laboratory monitoring requirement with this drug, and it is also approved for several common comorbidities. Tralokinumab, which inhibits IL-13, is also available, and, while this agent appears to have more modest initial activity, it does seem to catch up later. Dupilumab and tralokinumab are both given every 2 weeks, and, if the patient is doing better after a certain period, you can decrease the frequency to every 4 weeks.

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Lebrikizumab is a biologic that targets IL-13, which is important for both itch and inflammation. It has good efficacy, and there are data demonstrating that, after 16 weeks of giving therapy every 2 weeks, you can transition therapy to every 4 weeks. The most recently FDA-approved biologic for AD is nemolizumab, which targets IL-31, a cytokine that is thought to heavily contribute to itch. Nemolizumab works rather quickly to improve itch, with lesions improving and clearing over time. A small subset of patients can develop eczematous dermatitis or eczema-like reactions with nemolizumab therapy.

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The oral JAK inhibitors abrocitinib and upadacitinib are also FDA approved for AD. JAK inhibitors have an impact on the signaling of a broader number of cytokines compared with biologics. Patients with AD who are recalcitrant to biologics may respond better to a JAK inhibitor. In head-to-head trials, JAK inhibitors have shown a more rapid effect than biologics, but, as noted previously, biologics may catch up over time.

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There are FDA boxed warnings for serious heart-related events, blood clots, cancer, and death with oral JAK inhibitors based on a study of patients with rheumatoid arthritis and at least 1 cardiovascular risk factor. Although the AD population is much different from that, it is important to ask patients with AD if they have any cardiovascular contraindications. Infections are more common than the more serious adverse events; we vaccinate patients before their first dose of JAK inhibitor, time willing. We usually order a baseline tuberculosis test, and we may also test for hepatitis B and C. In addition, patients on JAK inhibitor therapy need routine laboratory monitoring, which may not be needed with biologic therapy. However, if you obtain those laboratory tests and appropriately counsel patients, it is very reasonable for these drugs to be a therapeutic option.