Incorporating JAK Inhibitors into Clinical Practice for the Treatment of Atopic Dermatitis—Safety Considerations

J Clin Aesthet Dermatol 2023;16(2 Suppl 1):14

An interview with Nicole Keeter

Ms. Keeter is a certified physician assistant in dermatology who practices in Fort Mill, South Carolina.

It’s an exciting time in the atopic dermatitis field. We have new topical and systemic options for treatment—Janus kinase inhibitors or JAK inhibitors. Topical and oral JAK inhibitor formulations have been FDA–approved, and we are beginning to incorporate these therapeutic options into clinical practice for the treatment of atopic dermatitis, as well as other inflammatory conditions, such as psoriasis and alopecia areata, in patients 12 years of age and older. Here, I review safety considerations and offer suggestions on patient counseling when prescribing JAK inhibitors for the treatment of atopic dermatitis. 

For patients who have atopic dermatitis on a body surface area greater than 20 percent or have moderate-to-severe atopic dermatitis, RINVOQ® (upadacitinib, Abbvie,  North Chicago, Illinois) and CIBINQO™ (abrocitinib, Pfizer, Inc., Mission, Kansas), which were FDA-approved for atopic dermatitis in 2022,  are oral JAK inhibitors that have both demonstrated effectiveness in improving pruritus, similar to topical corticosteroids, without the concern of atrophy or stria. RINVOQ is approved for use in patients 12 years of age or older, while CIBINQO is approved for patients 18 years of age or older. Both therapies are efficacious and provide a rapid decrease in symptoms, particularly pruritus, which is one of the most significant symptoms for our patients with atopic dermatitis. 

Opzelura® (ruxolitinib, InCyte, Wilmington, Deleware) is a topical JAK inhibitor approved by the FDA in 2021 for the treatment of mild-to-moderate atopic dermatitis in patients who are 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. Opzelura is safe for use on a body surface area of 20 percent or less, and on special sites, including eyelids and skin folds. Historically, we’ve treated these special sites with topical immunomodulators or cautiously with corticosteroids. Opzelura provides rapid improvement similar to that of steroids, with excellent tolerability and safety. No screening is required for Opzelura, and I look forward to Opzelura’s label extension in the future to include our younger patient population.

Oral JAK inhibitors come with a black box warning due to association with thrombotic events, myocardial infarction, stroke, immunosuppression, skin cancer, and infections. Topical JAK inhibitors also carry a black box warning. These black box warnings are based on data extrapolated from studies evaluating tofacitinib, a systemic JAK inhibitor used to treat rheumatoid arthritis. It’s important to note that the patient population in the tofacitinib studies were considered to be at higher risk for adverse events due to being older than 50 years of age, having at least one cardiovascular risk factor, and having inflammatory arthritis. However, because of this black box warning and, with it, the potential for significant adverse events, some clinicians may not feel comfortable prescribing oral JAK inhibitors for a disease process historically treated with topical agents. However, keep in mind that as dermatology clinicians, we frequently counsel and manage patients on other systemic agents that have significant safety concerns, such as isotretinoin, methotrexate, cyclosporine, and prednisone. We have experience in evaluating and screening patients for candidacy for these medications, including taking a thorough history of patient risk factors and monitoring patients with serology. The same approach is used when prescribing JAK inhibitors.

After familiarizing yourself with the clinical data on JAK inhibitors, formulate your patient education conversation. This discussion with the patient should include the black box warning for the potential of the thrombotic events, malignancy, and infection that was observed in tofacitinib studies. However, increased risk of major adverse cardiovascular and thrombotic events have not been observed in RINVOQ or CIBINQO thus far, and the class effect association found in the oral therapies has not been observed in the topical formulations—this should also be discussed with your patients. All the same, these risks should be thoroughly reviewed with your patients, who should be involved in the treatment decision-making process, similar to your clinician-patient discussions regarding other systemic medications routinely prescribed in dermatology. 

When prescribing oral or topical JAK inhibitors, rely on your experience counseling patients on similar safety signals we’ve seen with TNF inhibitors. As derm clinicians, we have experience with this; we’ve counseled our patients on black box warnings before with the use of other topical immunomodulators. Let your experience guide you through the process of prescribing JAK inhibitors to your patients with atopic dermatitis.