Janus Kinase Inhibitors in Dermatology

In her session, “JAKs in Dermatology,“ presented at Fall Dermatology Week 2022, Ruth Ann Vleugels, MD, MPH, MBA, offered pearls for integrating Janus kinase (JAK) inhibitors into patient care.

Dr Vleugels reviewed 7 case studies, starting with her own 2016 study on successfully using tofacitinib to treat refractory cutaneous dermatomyositis. There was a mean decrease in the Cutaneous Dermatomyositis Disease Area and Severity Index score for all patients and decreased pruritus. She remarked, “Why did I start using JAK inhibition in dermatomyositis? We’ve known for many years that there is a strong type 1 interferon signature in dermatomyositis. This was first shown in the muscle, then in the blood, then in the skin. But we never really knew if this was driving skin disease. … What we found was that in patients with mild disease activity, they had a low interferon gene signature, and in patients with moderate to severe skin disease, they had a high interferon gene signature. … The JAK 1/tyrosine kinase 2 complex is induced by type 1 interferon. … So, I know that if I use a JAK inhibitor, I’m going to be able to help in diseases that are mediated by type 1 interferon.”

JAK inhibitors were first US Food and Drug Administration (FDA) approved for rheumatoid arthritis (RA). Dr Vleugels discussed why some physicians have concerns about using JAK inhibitors. Initially, tofacitinib had a black box warning for an increased risk of venous thromboembolism. More recent data have indicated that there is also an increased risk of major cardiovascular events and cancer. She posited, “The question is, will these same risks apply to nonRA populations, in particular because RA populations have an increased risk of these 3 entities at baseline?”

Throughout her presentation of the case studies, Dr Vleugels shared clinical pearls, such as when higher doses are warranted. Many diseases warrant a higher dose but consider adverse reactions and a clear signal for zoster. “When I’m considering a JAK inhibitor, I’m asking about a personal or family history of clotting, I’m thinking about reducing that patient’s cardiac risk factors, and I’m also thinking about whether they have a history of cancer or are at a current high risk for cancer,” she said.

Although the only currently FDA-approved dermatologic indication for JAK inhibitors is atopic dermatitis, they may prove useful in an even wider array of recalcitrant skin diseases in the future. Dr Vleugels concluded, “When you are considering a JAK inhibitor for a particular patient, recall if there is an increased signal for zoster, and then we have data from rheumatoid arthritis populations specifically to consider clotting risk, cardiac event risk, and cancer risk. Risk stratify your patient population based on thinking about this. It will take years to have this amount of data in other populations, such as a healthier dermatology population.”

Reference

Vleugels RA. JAKs in dermatology. Presented at: Dermatology Week 2022; September 14-17, 2022.