Investigators have revealed that U.S. Food and Drug Administration (FDA) Black Box warnings included with most Janus kinase (JAK) inhibitors were established through a rheumatoid arthritis (ORAL Surveillance) study involving patients with cardiovascular risk factors and may be misleading for those with dermatologic conditions, according to a report from Medscape summarizing findings presented by King et al at the 2023 AAD Annual Meeting. The investigators indicated that the original study only assessed one JAK inhibitor, tofacitinib, which has been shown to cause different side effects and carry different risks from those of other JAK inhibitors. They detailed that the FDA Black Box warnings specify that all JAK inhibitors—including topical ruxolitinib but excluding the newly approved deucravacitinib—may cause major adverse cardiac events and are nearly identical on all labels. The investigators explained that in the ORAL Surveillance study—published by Ytterberg et al in The New England Journal of Medicine—researchers concluded that the incidences of major adverse cardiac events, thromboembolic events, and cancer were more prevalent among patients who received tofacitinib compared with those who received a tumor necrosis factor inhibitor. However, the investigators noted that the characteristics—including age and preexisting cardiovascular risk factors—of patients involved in the ORAL Surveillance study did not align with those of the overall population of patients with dermatologic conditions who may require treatment with JAK inhibitors. Additionally, a previous study has shown that patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis may have been more susceptible to severe infections, major adverse cardiac events, and venous thromboembolisms after taking upadacitinib than those with atopic dermatitis.
Other experts not involved in the new study voiced support and agreed that studies assessing a nonselective JAK inhibitor should not be compared to those examining selective JAK inhibitors in younger patients. However, some experts stressed that while patients with dermatologic conditions tend to take lower doses of JAK inhibitors than those with rheumatologic conditions, there may not be enough data on the risks of long-term usage to determine whether patients with skin conditions face the same adverse events over time.