Systemic therapy with JAK inhibitors may be future of alopecia areata treatment

Brett Andrew King

NEW YORK — Systemically administered Janus kinase inhibitors hold potential for the treatment of alopecia areata and vitiligo, a presenter said here.

“I hope I can persuade you that JAK inhibitors for alopecia areata and vitiligo are a really valuable class of medicines,” Brett Andrew King, MD, PhD, FAAD, said at the American Academy of Dermatology Summer Meeting. “We don’t yet have one in dermatology, but we will soon. This is really just the beginning.”

Clinicians do not often think about targeting cytokines when they treat diseases, King said.

“When we use systemic agents and biologics, we are indeed modulating cytokine signaling. Cytokines prominently mediate many of the diseases we treat, and they circulate through tissue or blood, and inside the cell there’s a signaling event which is mediated through the JAK pathway,” he said. “These enzymes activate downstream events that lead to translocation in the nucleus, where gene transcription and disease happens.”

The idea is that cytokine signaling is often mediated by the JAK/STAT pathway. The cytokine signaling cascade is blocked via the small molecule inhibitor of the JAK enzymes with a JAK inhibitor.

“It will be particularly interesting in a couple years to see what the side effects profile looks like when JAK inhibitors are applied in dermatology, as current side effect profiles are from patients in rheumatoid arthritis clinical trials,” he said.

There are no reliable, effective therapies for severe disease in alopecia areata.

Five years ago, King had a patient in his 20s who was diagnosed with refractory psoriasis and alopecia universalis. King recommended treatment with tofacitinib, as it was helpful in a mouse model with alopecia. In 8 months, the patient had complete regrowth in scalp hair, eyebrows and eyelashes.

In an open-label clinical trial across 3 months in 66 patients, about one-third of patients had more than 50% scalp regrowth.

In another study on ruxolitinib, nine of 12 patients experienced complete scalp hair regrowth over 6 months, he said.

The disease often strikes in adolescents or even younger patients.

After living with no scalp hair for 10 years or more, the ability for hair regrowth with a JAK inhibitor decreases, King added. “Patients need treatment sooner rather than later. They lose the ability to get their hair back.”

Topical treatment with JAK inhibitors does not show the same efficacy, he said. – by Abigail Sutton

Reference:

King BA. Treating alopecia areata and vitiligo with JAK inhibitors, a new frontier in dermatology. Presented at: American Academy of Dermatology Summer Meeting; July 25-28, 2019; New York.

Disclosure: King reports he is a consultant, speaker or advisor for Concert Pharmaceuticals, Eli Lilly and Company, Pfizer and Regeneron.