JAK Inhibitors' Applications Continue to Expand

While JAK inhibitors have become widely popular for several common skin diseases, their potential for other indications remains vast, and Ruth Ann Vleugels, MD, MPA, MPH, FAAD, highlighted some of these in “JAK Inhibitors for Lupus, Dermatomyositis, and SAVI” at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida.

With dermatomyositis, Dr. Vleugels noted that if the capillaries are still active, the disease is still active, so continuing treatment is necessary.

“We still need to be pushing the envelope in terms of therapeutics,” she said. “So, I’m super excited because the first randomized, controlled trial for JAK inhibitors [for dermatomyositis], oral brepocitinib, a JAK1/TYK2 inhibitor, actually completed enrollment with over 240 patients—which is phenomenal in dermatomyositis—this past summer, and we should have the results of this global phase 3 study this summer. So, ideally, we could have our first FDA-approved JAK inhibitor for dermatomyositis in the next year to year and a half. Fingers crossed.”

The data on JAK inhibitors for cutaneous lupus had been less clear. Dr. Vleugels noted that research had indicated “sort of a moderate response” for lupus in patients treated primarily for alopecia areata. Other research has indicated no improvement in CLASI scores, but improvement in the joints, which Dr. Vleugels said can make it worthwhile.

“What I would argue is: Our thinking about this is evolving,” she said.

Meanwhile anifrilumab has been shown in studies of systemic lupus to improve mild skin lupus, so Dr. Vleugels tried that drug for some of her cutaneous lupus patients.

“It is like nothing I have seen in my career, other than with lenalidomide or thalidomide,” she said.

Dr. Vleugels eventually published the first cohort of skin lupus patients treated with anifrilumab.

“The mean decrease in CLASI activity, or that validated skin score, was 17—when, again, meaningful reduction is 4 to 5,” she said. “So, just substantial improvement, and this was after only two doses.”

The area that is evolving most in the rheumatology-dermatology clinic in terms of JAK inhibition, meanwhile, is sclerosing disease, Dr. Vleugels said.

“Keep in mind, sclerosing diseases are slowest to respond—you’ve sort of got to hang out—but, again, we are using JAK inhibition more and more in sclerosing disease,” she said.

Dr. Vleugels also discussed STING-associated vasculopathy with onset in infancy (SAVI).

“What we are learning, since the description of this condition in 2014, is that children with milder phenotypes are diagnosed later,” she said. “So, what does this mutation do? It actually causes constitutive activation of interferon beta. [Similar to dermatomyositis], these kids present with interstitial lung disease, vasculopathy, systemic inflammation—a very similar phenotype. So, what are we going to give these kids? We’re going to give them JAK inhibition, of course.”

In conclusion, Dr. Vleugels speculated that still more conditions will prove to be strong fits for JAK inhibition.

 “We have had JAK inhibitors since 2012,” she said. “There is really excellent long-term safety data in skin. And we are going to use these in a wider array of skin diseases, including in our pediatric patients.”