Alopecia Areata Clinical Case Review

Britt Craiglow, MD, an Associate Professor Adjunct of Dermatology at Yale Medical School, discusses the treatment options for the case:

"So, when we think about treatment in a patient there really isn’t any one size fits all. There are lots of things that we have to consider, including the age of the patient. Obviously, a 2-year-old we’re going to treat differently from a 20-year-old. How severe is their disease? How long have they had it? We’re learning more that the duration of one’s current episode of severe alopecia areata — meaning how long it’s been since they’ve had any meaningful scalp hair — can really impact response to treatment. So, in patients in whom that’s longer than, say, 4 or 5 years, a chance of regrowing even with really reliably effective drugs starts to decrease. And then — really important — is how is the person doing with it? The psychosocial impact of this disease, I think, is really often what primarily guides our treatment, and I think for most patients, it’s a really big deal. And also I like to say, just because somebody’s coping doesn’t mean that we should withhold treatment, right? I think most patients, if you gave them the opportunity, they would like to have their hair back if possible. And then, of course, how motivated is the patient? How much does it mean to them? How risk-averse or not are they?

There are lots of things to consider. But fortunately, we have options for people now. Historically we really didn’t have a lot of options. It was kind of corticosteroids or bust. Most patients, even patients with really severe disease, were still being treated with intralesional corticosteroids, which really isn’t practical or effective, especially in patients with severe hair loss. Now, if you have mild disease, maybe 10% to 15% scalp involvement, then for sure, intralesional corticosteroids are still something that really is kind of the mainstay of treatment for those patients. Sometimes, topical irritants or immunotherapy, things like anthralin [or] DPCP are used. The idea behind those is to kind of create irritation with the idea being that you bring in a sort of different arm of the immune system to get rid of the part that’s causing the problem. These are really labor-intensive. They can be uncomfortable, time consuming. I think now that we have better options, these are really falling out of favor, but nevertheless, [they’re] something that we’ve used. Minoxidil is something that we’re using a lot more in dermatology for hair loss, I would say primarily for pattern alopecia, but for sure there’s a role for it in alopecia areata. Even by itself, monotherapy can actually be useful in some patients, so [that’s] definitely something to keep in mind. We used to think about it as a drug that was really like a fertilizer for hair, so if there was hair there, it would help it grow faster and thicker, but actually in some patients with AA, even alone, it can make a difference. So definitely that is an option that we still are using. Traditional systemic immunomodulators — things like methotrexate, mycophenolate — these have been used and unfortunately they don’t tend to be very effective and oftentimes, in order for them to be effective, we have to combine them with prednisone, which obviously is not something that’s safe to do long-term. So fortunately, in the past year-plus, we have seen two oral [Janus kinase (JAK)] inhibitors be approved for alopecia areata, and these medicines are really pathogenesis-directed treatment, so they are very effective for many patients and are really kind of becoming standard of care for patients with severe disease.

So, for this patient with really extensive hair loss, corticosteroids are very unlikely to be helpful. Immunotherapy, irritant treatment, not something that we’re likely to get very far with, and again, those treatments take a lot of time, they’re labor-intensive, he’s in high school, this is something that’s probably not going to be something that he really wants to do. And he kind of needed his hair back yesterday, right? So, I think a lot of patients with severe hair loss, unfortunately, hair takes a long time to grow, so any treatment we do, they have to wait. But we want, especially in this case, for someone who’s having such an impact on his day-to-day, we want to do the thing that has the best chance of helping him move forward, and in this case that would be a JAK inhibitor.

So, we now have two FDA-approved JAK inhibitors for severe alopecia areata. Summer of 2022, we saw the approval of baricitinib, which is a JAK1/2 inhibitor for adults with severe alopecia areata. And then just in 2023, we saw the approval of ritlecitinib, which is very exciting. [It] was approved also for adolescents. So that has only been available for a few months and something that I would have used in this patient had I had that as an option, but we’ll be able to show before and afters of patients on ritlecitinib in the near future since some of them will have been on it long enough to see regrowth very soon.

So, I’m just going to show you the data really quickly for ritlecitinib and baricitinib. Before we do that, just a little refresher of the SALT score. So SALT is the Severity of Alopecia Tool, which is really just a measure of the percent of the scalp that’s involved in hair loss. So it’s a little bit counterintuitive, I think, in that a SALT 100 means 100% loss and a SALT zero is no hair loss, so the higher the number, the more severe the patient, and in clinical trials in general, SALT score had to be 50 or higher at baseline, and the goal or the primary endpoint is looking at how many patients or what percent of patients got to a SALT score of 20 or less at a certain time period. So obviously, our patient in question here had a SALT score of 100, and this is something I used to say it’s just a clinical trial measure, you’re probably not going to be asked to calculate it, but now that we do have approved treatment options, this is something that payers are going to want to know about your patient who you're maybe asking for one of these medicines for.

So, these are the phase 3 results for baricitinib. This was studied in two randomized double-blind placebo-controlled trials. A couple of sort of notable things about looking at clinical trials in alopecia areata, and one is looking at the placebo rate. So, you can see that placebo rates in patients with severe AA are very, very low. So this is really important because some people are kind of holding on to hope that maybe their hair will regrow spontaneously, and the chance isn't zero, but it’s very, very close, so most of these patients are not going to get better unless we actually treat them. So, you can see the placebo rates over the course of 9 months are very low. And so that’s the other thing, is looking at when the primary endpoint was looked at, in baricitinib, that was 36 weeks. So, we’re used to clinical trials in atopic dermatitis, psoriasis, where we see endpoints at maybe 12 weeks or 16 weeks. In alopecia areata, they’re farther out because hair takes a long time to grow. So, this is something we really have to keep in mind with treating patients, that this really is a marathon and not a sprint and we’re not going to expect to see regrowth at a month or even 2 months. Some people, you can see as early as 12 weeks are starting to meet that endpoint but really those curves kind of really start to creep up around the 16-week mark, and as you can see by the slope, if you look out farther, not surprisingly, many more patients actually meet the endpoint if you just give them time. So this is something we have to kind of prepare our patients for, but I will say that most of them are really just excited to have a treatment and even seeing a little bit of hair is really reassuring and exciting for them, and so I think you’ll find that adherence is really excellent in patients with severe AA. So you can see at the end of 36 weeks with the 4 mg dose, which is what’s recommended for patients with complete or near-complete hair loss, about 35% to 40% of patients were getting to a SALT score of 20 or less.

This is looking at ritlecitinib. [In] their phase 3 study their primary endpoint was actually at 24 weeks, so 6 months, so a little bit shorter. And [it’s] a little bit of a confusing, busy curve here, and that’s because this was a dose ranging study, so several different doses were studied, including some patients getting a loading dose. But the dose that was ultimately approved is a 50 mg daily dose, which you can see here in the purple. And you can see fairly similar to baricitinib, a little under 40% of patients meeting that endpoint, you can see halfway through here is the 6-month mark, and then this is looking out to 48 weeks. And so SALT score of 10 or less, obviously a little bit of a trickier endpoint to meet, but many patients are getting there if you give them enough time."