In this feature video, Dr Cathryn Sibbald shares the mechanism of action behind JAK inhibitors utilized to treat alopecia areata (AA), and how physicians can determine whether JAK inhibitors are the best treatment option for their patients with AA.

Cathryn Sibbald MD, MSc, FRCPC, DABD, is a board-certified dermatologist in Canada and the United States, and is currently practicing at SickKids Hospital in Toronto, ON.

Transcript:

Can you describe the mechanism of action behind JAK inhibitors utilized to treat alopecia areata (AA)?

Dr Cathryn Sibbald: JAK inhibitors basically block the cytokine signaling through the JAK/STAT pathway. And what we know about alopecia areata is that it's mediated by an immune attack on a hair follicle. And so in active disease, we see CD-8 positive T cells around the hair follicle, and those are rich in interferon gamma, which then stimulates IL-15 or interleukin-15 secretion. And those two cytokines, your interferon gamma and IL-15, really signal through that JAK/STAT pathway. So by inhibiting that pathway, that's thought to be one of the main mechanisms of their action.

What other options are available to treat AA? Can these be combined with JAK inhibitors?

Dr Cathryn Sibbald: So, there's many, many different treatments. Of course, not all are indicated. I think I'll start with the two that I will combine with JAK inhibitors. So first off is minoxidil. And I think probably the whole world, at this point, recognizes the many benefits and places that minoxidil can help. I use both systemic and topical in conjunction with a JAK inhibitor.

The other thing that I'll use is topical or intralesional steroids. And that's either at the onset, if there's specific patches that I want to sort of respond sooner, or I've had patients on JAK inhibitors who then develop small flares that respond very well to topical steroids.

The other two medications that I'll mention, so first off is dupilumab. The reason I don't combine this with JAK inhibitors is just because of an access issue. So I haven't had a single insurance company so far approve both concurrently, but dupilumab is especially helpful in those with an atopic history and high IgEs. And I've had at least two teenagers actually respond very nicely to dupilumab at regular doses, so q. two week dosing. So that is one agent I'll use. And then finally, I still use quite a bit of methotrexate. It's old, it's not indicated, but it's cheap. And I have had quite a bit of success with it.

How can physicians determine if JAK inhibitors are the best treatment option for patients with AA?

Dr Cathryn Sibbald: I think you can break it down into several different factors. So number one, who's going to respond to a JAK inhibitor? And I think almost anyone is likely to respond. The biggest factor that people think may be a negative is a longer history of disease. So those with maybe 10 years of alopecia totalis. But that's sort of the main thing when we're thinking about efficacy.

Next off, I think it's patient tolerance to risk factors and their susceptibility to side effects. So what we're talking about here is those who are at increased risk of all those black box warnings that are on it. Granted, we all know those are not in an alopecia areata population, but I think still definitely something we need to consider. So those who are at increased risk of clots, at increased risk of a malignancy, at increased risk of a heart event. That's usually in our older population, but I think really discussing those risks with the patient and coming to an agreement together is the most important thing there.

And then finally, obviously is access because these are expensive agents. It's definitely helpful that we now have FDA indications for two of them, at least. But I think that will be a barrier for some insurance companies.