In this feature video, Dr Amy McMichael shares what will be presented during her session, “JAK Inhibitors in Alopecia Areata: How to Use in Varied Clinical Scenarios,” held at the 2023 Fall Clinical Dermatology Conference.

Amy McMichael, MD, is a professor in the department of dermatology at Wake Forest Baptist Health in Winston-Salem, NC.

Transcript:

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

Dr Amy McMichael: So, the mechanism of action in JAK inhibitors is really quite astounding because this was actually figured out a long time ago. So, years ago, Dr Lloyd King and another researcher who is actually a veterinarian researcher found that this pathway was actually active in the mouse model of Alopecia areata. But at the time, the JAKs stat pathway hadn't been discovered. So they didn't have a name for it. It was only through amazing work of Dr Angela Christiano at Columbia University that we were able to sort collect the information needed, inform and connected so that we could understand that the JAK-stat pathway is so important in the alopecia area pathway. So exactly what is going on, we still don't know, but what we do know is that IL-15 is important and necessary for Alopecia areata to happen. And we also know that interferon gamma is very integral in the process.

So, interferon gamma stimulates both the white blood cell and the hair follicle and just keeps the process going where the JAK/STAT pathway is activated. And so what we know that there's first some sort of change in the immune privilege of the hair follicle. Once that happens, and that's probably a genetic process, then the JAK/STAT pathway becomes active, and this sort of interferon gamma and process continues to make chemokines get excited and they call more white blood cells up to the surface of the hair follicle. And then the process just keeps on going until either there is a stop to the JAK/STAT pathway with the new JAK inhibitors or there's just a remission in the disease process.

And we still don't quite understand the sort of remissions that come on just naturally, but that's really essentially it. So it's this JAK/STAT pathway activation with the interferon gamma sort of calling the shots on both the hair follicle and the white blood cell.

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

Dr Amy McMichael: So now that we have JAK inhibitors available to treat Alopecia areata, we actually have two FDA-approved JAK inhibitors. We're really in a very good place. We're in a better place than we've ever been because we didn't have even one medication that was FDA approved for this disease in the previous time before these FDA approvals. Well, now the question is, okay, we know what these two drugs can do. We have seen the either phase three studies or the phase 2B, 3A studies and we know that they can work. And we know that they don't work in every single person. So the question is, how can we even increase the likelihood that our patients are going to grow hair with the JAK inhibitors on board?

And one way to approach that is to use oral minoxidil. Now of course, this is off, off the approved method of using minoxidil. Minoxidil is, of course, a blood pressure medication, but when used in low doses, we found that it can be effective in a lot of different forms of hair loss with Alopecia areata being one of them. So you can combine this drug along with JAK inhibitors to get a little bit better outcome. Now, there's only a bit of data published yet about this. I think we're going to see this more and more, but there are some folks who are in the hair research world who literally start both of them at the same time. There are people who add the low-dose oral minodixil in later. There's certainly potential complications and side effects, but really ultimately, we haven't been seeing a lot of potential. A lot of these potential side effects actually happening in real life with the low-dose minoxidil.

So, hypertrichosis, lower extremity edema, of course, the most common, but there are several very, very few reports in the literature about more worrisome things, pericardial effusion, those sorts of things. But again, very limited likelihood of that happening. So I think that's probably the number one option. Now in children where you might not wish to use an oral minoxidil, we still do topical minoxidil. We've done topical minoxidil for years and years. And the thought behind these sort of use of minoxidil is that we're promoting antigen. So maybe we're not changing the inflammatory process with this, the JAK inhibitors do that, but maybe we're adding to the prolongation of antigen and those hairs that want to go back into a falling out stage with the Alopecia reata ADA process. So we don't know exactly what's happening, but those two drugs seem to work well together.

Now, there are probably those out there who've used methotrexate in the past, and methotrexate can certainly be used with JAK inhibitors. I don't think that there's any data to support that yet. And if you have two things that suppress the immune system, perhaps that might be a little bit more risky. So I think that probably minoxidil is a better option. And then you can always use intralesional corticosteroids when people come in and they've done well with the JAK inhibitors, but still have patchy alopecia, we certainly will use both topical corticosteroids and intralesional corticosteroids to keep us on track in terms of getting those hairs to regrow.

There's nothing out there yet that's a miracle. There's nothing that's going to be 100% effective in every single patient. So we still do need to use our adjunctive measures to help people with Alopecia reata get as much hair regrowth as possible.