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Among patients being treated with JAK inhibitors for atopic dermatitis (AD), the risk for some adverse events increased relative to those taking placebo, but the risk of more serious events including malignancy and major cardiac events did not change.

That's according to a systematic review and meta-analysis appearing recently in the .

The risk of 11 adverse events was compared between AD patients taking JAK inhibitors and patients given placebo. Fourteen randomized controlled trials, published between 2019 and 2022, were analyzed as part of the review. JAK inhibitors included in the analysis were abrocitinib (Cibinqo), baricitinib (Olumiant), and upadacitinib (Rinvoq).

The analysis was conducted by a team of researchers from South Korea. The following study excerpts have been edited for length and clarity.

What was the impetus for this review?

JAK inhibitors have recently been approved for the treatment of AD by the FDA and are increasingly used to treat this condition. Despite not having received FDA approval, baricitinib has been approved and is currently being used as a therapeutic agent for AD in European countries, Japan, and Korea.

Recently, the FDA issued a boxed warning for JAK inhibitors for the treatment of arthritis and other inflammatory diseases as well as AD to include information about risk of major adverse cardiac events (MACE), venous thromboembolic events (VTE), and certain cancers.

Recently, several meta-analyses on the safety of JAK inhibitors have been published. However, some of the studies analyzed were small, with only a portion of the adverse events reported, among other limitations. Therefore, the research team sought to provide a more comprehensive safety picture of systemic JAK inhibitors in patients with AD.

What were the key findings?

The types of adverse events included serious infection, herpes zoster, non-melanoma skin cancer (NMSC), malignancies other than NMSC, MACE, venous thromboembolism (VTE), nasopharyngitis, acne, blood creatinine phosphokinase elevation, and nausea.

The relative risks of herpes zoster, headache, acne, blood creatinine phosphokinase elevation and nausea were increased for people taking JAK inhibitors compared with placebo at 1.97 (1.03-3.77), 1.43 (1.13-1.81), 4.97 (3.38-7.31), 1.82 (1.40-2.36), and 3.74 (2.07-6.78), respectively.

What about other adverse events?

The relative risks of serious infection, NMSC, malignancies other than NMSC, MACE, VTE and nasopharyngitis were 0.88 (0.44-1.77), 0.97 (0.25-3.81), 0.58 (0.14-2.33), 1.07 (0.11-10.17), 0.50 (0.05-4.76), and 1.15 (0.98-1.35), respectively.

Hence, the risk of serious infection, NMSC, malignancies other than NMSC, MACE, VTE, and nasopharyngitis was not increased.

Further, due to the wide spectrum of immunosuppressive effects of JAK inhibitors, concerns about the risk of malignancy and serious infection have arisen. The risk may be dose-dependent. Thus, researchers also analyzed the risks of adverse events according to the doses of JAK inhibitors: they did not observe a dose-dependent increase in the risks of malignancy and serious infection.

What else should dermatologists be aware of regarding this study and its findings?

Since the follow-up periods of the studies analyzed in this review were mostly limited to 16 weeks or less, comprehensive long-term observational studies are needed to determine any potential adverse events associated with MACE or malignancies.

Key points

• For patients with AD taking JAK inhibitors, adverse event risk increased for herpes zoster, headache, acne, blood creatinine phosphokinase elevation, and nausea.
• There was no increase in relative risk for serious infection, malignancies other than NMSC, MACE, VTE, or nasopharyngitis.
• No dose-dependent increase was observed in malignancy and serious infection risk.

Correction: The article has been updated to indicate that the brand name of abrocitinib is Cibinqo (not Dupixent).