Hair's What We Know! Inside the Treatment Revolution for Alopecia Areata

JAK inhibitors are "game changers" in the management of alopecia areata, says Susan C. Taylor, MD, faculty for the DEF Essential Resource Meeting (DERM). She provides an update on the diagnosis and treatment of this impactful disease. Plus, Alexa Hetzel, MS, PA-C gives tips for optimizing vitiligo treatment, and Joe Gorelick, MSN, FNP-C shares strategies for documenting disease severity and progression or improvement in the busy clinic. 

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Transcript

This transcript is provided as a courtesy and has not been edited for accuracy.

Welcome to The Dermalorian(TM) Podcast from the Dermatology Education Foundation. The Dermalorian Podcast is an independent program made possible with support from UCB. The emergence of JAK inhibitor therapies has changed the way that dermatology approaches many inflammatory skin diseases, including alopecia areata. In fact, for the first time, there are directed treatments specifically intended to treat this condition, which is known to have a significant psychosocial impact. "The two JAK inhibitors available in the US to treat alopecia areata are game changers," says dermatologist and derm faculty member, Dr. Susan Taylor. Plus there are other agents in the pipeline. She provided an update on the latest treatments and began with the case of a 65-year-old man with a seven-year history of alopecia areata.

Dr. Susan Taylor:

It involves the scalp and the beard. No involvement in the eyebrows or the eyelashes. No nail involvement. So the onset of this episode was sudden. He lost all of his hair about five years ago. During previous episodes of alopecia areata, he had small annular patches and the hair regrew spontaneously. Scalp biopsy revealed alopecia areata. Previous therapy, topical and oral corticosteroids, topical and oral minoxidil. Current medication is insulin. He has a history of type 1 diabetes. Father had hair loss in the male pattern, and a social history significant for the fact that the patient has lost interest in outside activities. He has significant hair loss involving about 84% of the hair, which is gone and therefore has a SALT score of 84. His eyebrows are intact, as are his eyelashes, and no loss of hair on other parts of his body.

So there are several clinical presentations of alopecia areata. Classically, we know the coin-shaped areas of complete hair loss. They can occur anywhere on the scalp as well as the rest of the body. There's a type where there's overall generalized thinning of the scalp hair. There's an ophiasis type that presents in a band-like distribution in the anterior scalp or the posterior scalp. There's inverse ophiasis that you have a patch in the vertex and mid-scalp. Alopecia totalis, no scalp hair at all, and alopecia universalis, loss of hair over the entire body.

Now, the severity of alopecia is very important to quantify and that's going to impact your treatment, particularly our newer treatments. So mild alopecia areata is 20% or less scalp hair loss. Moderate, between 21 and 49%, and severe alopecia areata, where you have 50% or greater loss of scalp hair. There are nail findings in alopecia areata. There's pitting or ridging of the nail, and also there's trachyonychia, where you have roughness in the nails. Eyebrows can be involved. Eyelashes can be involved.

Pathogenic factors, there's a genetic susceptibility in patients with HLA gene, BQ8103, and there are other biologic markers. There are autoimmune comorbidities, type 1 diabetes, rheumatoid arthritis, vitiligo. Our patient had type 1 diabetes. Infections as well as drugs and vaccines. You may have had a variety of patients who received the COVID vaccine and then developed alopecia areata. Drug induced alopecia areata can indeed occur. A recent systematic review of 102 patients revealed 30 medications that are associated with alopecia areata, 70% of which are monoclonal antibodies. Of those patients with drug induced alopecia, over half of them were female. Average age of onset of alopecia areata, after the medication, was about 11 months. About 70% of those had patchy alopecia and about 15% had biopsy proven. So it was a clinical diagnosis.

Alopecia areata affects the quality of life of our patients. They experience loss of self-esteem, emotional distress, mood disturbances, disrupted relationships at work, and school, and in their personal life. It can impact their basic activities of daily living, and many of them have poor performance at school or work. Histologically, if you do perform a biopsy, because in most cases alopecia areata can be made clinically, you do see a swarm of bees and that represents your lymphocytic inflammatory infiltrate around an antigen follicle, and that infiltrate is composed of CD8 lymphocytes.

There are dermatoscopic findings and you will find, using your dermatoscope as a tool is great for diagnosing this disorder. Often you will see yellow dots and those represent follicles, dilated, intact follicles that are filled with sebum. There're black dots. Black dots simply represent hair shafts that have broken off. Exclamation mark hairs, and exclamation hairs are nothing but short broken hairs that are tapered. SALT score. Now your SALT score is critically important and it's pretty easy to use. We divide the head into four different areas and then you're going to characterize the sum of the hair loss in each area, times the surface area of the scalp. And that will help you arrive at the SALT score. And you need to know the SALT score, so if you're going to use our newer agents like our JAK inhibitors, you need a SALT score of 50 or higher. So that's going to represent about 50% of their hair being lost.

Now, what about prognosis? Now, spontaneous regrowth, as we all know, can be very common. About 50% of patients with the patchy pattern of hair loss will recover within a year, but about 10% were going to go on to alopecia totalis or universalis. Now, risk factors associated with poor prognosis, onset during childhood, alopecia totalis or universalis, the ophiasis pattern, nail disease, atopy, or a family history of alopecia areata. Basically, the pathogenesis is a collapse of the immune privilege and that allows the T cells to go in and destroy the hair bulb. There are cytokines, specifically IL-2, 4 and 15, and also there's increased production of interferon gamma.

Now, our JAK inhibitors, new guys on the block, very effective. So what they are is they're intracellular tyrosine kinase that signals cytokines as well as growth factor receptors. And you see they're downstream regulators of interferon gamma and IL-15. For treating alopecia areata, for local involvement, you can use topical corticosteroids. We use intralesional corticosteroids. There's immunotherapy that's been used for many, many years, but again, for those individuals who have involvement of 50% or more of their scalp, JAK inhibitors are appropriate.

So let's talk about some of them. Well, the first is ritlecitinib and the ALLEGRO study. It's a phase II/III trial, randomized-controlled, double-blinded, placebo-controlled. It enrolled individuals aged 12 and older with alopecia areata, 50% or more scalp hair loss, no evidence of regrowth within six months of both the screening and baseline visits. The total duration for the alopecia areata was 10 years or less. They tried various dosages of ritlecitinib versus placebo for 24 weeks. That was the endpoint, and the endpoint involved a SALT of 20. So we're going from 50 or more down to 20. Prior to starting therapy, baseline labs, CPC and diff, LFTs, lipids, hepatitis B, QuantiFERON Gold for TB. In terms of immunizations, they're fine as long as they're not live vaccines, and they're also, JAK inhibitors are contraindicated in patients with active or serious opportunistic infections. You're going to avoid using JAK inhibitors in patients with low neutrophil count, low lymphocyte count, a low hemoglobin, or severe hepatic or renal impairment.

So here are some of the results. At the 24-week primary endpoint, compared to placebo there was a significant improvement in the SALT score, down to 20 in those patients who received 50 milligrams of ritlecitinib. The efficacy continued through 48 weeks. So they did better the longer they were on ritlecitinib. Here we see, at baseline, at the top, an individual with a SALT score of 100, no hair at all, eyebrows and eyelashes. Regrowth has been noted of those areas with ritlecitinib. In terms of safety, very good safety as well as tolerability. Some of the more common side effects are things like headache, pharyngitis, respiratory tract infection. So there were no major adverse cardiovascular events, no deaths, no opportunistic infections that were reported. There was one case of a patient on 50 milligrams of ritlecitinib who had a pulmonary embolism.

Speaker 1:

Dr. Taylor talks more about the safety of JAK inhibitors and the data for another agent in the second half of this episode. But first, we pause for this episode's Dermalorian Clinical Clip. JAKs are also changing the approach to vitiligo. Speaking after this month's DEF Biologic & Small Molecule CME Bootcamp, bootcamp faculty member and DEF Advisory Council member, dermatology physician assistant Alexa Hetzel recapped some tips for getting the best results for patients with vitiligo.

Alexa Hetzel:

I think what's little extra pearls that we can take back with us and really implement into our daily clinical practice are very simple. Adding ritlecitinib b.i.d. is such a fantastic option, but don't forget that patients with vitiligo take a lot of time. So we want to make sure we're counseling them. It could not just be three months, it's a year and two years. So hold their hand, make sure that you're telling them, "We will try to get there, but we will get there." The other thing is there's so much exciting things that are coming, we just don't have them yet, so make sure that we're keeping up with our data, follow along with our podcasts, with all of our webinars, follow along with the blogs for what's new and what's coming up within the DEF.

Outside of just doing topical therapy for prescriptive strengths and actually repigmenting the skin, making sure we're educating patients on sun exposure is huge. Those patients do not have enough of melanocytes to repigment on their own, so they're much more likely to burn, and when they burn on that skin, they can still get skin cancer, so we want to make sure we're protecting them. So sunscreen and SPF is important. You can also combine phototherapy with our topical creams, whether you're using excimer laser in the small body surface area or using full body UVB. If they have a large surface area, you can combine them together and see even more improved efficacy.

Speaker 1:

You're listening to The Dermalorian Podcast from the Dermatology Education Foundation. This independent program is made possible with support from UCB. Let's rejoin Dr. Taylor as she addresses trial results for the second available JAK inhibitor for alopecia, baricitinib.

Dr. Susan Taylor:

We're going to review the BRAVE-AA1 and BRAVE-AA2, randomized-controlled, placebo-controlled phase III trial. Again, this required a SALT score of 50% or higher. In this particular case, the age was 18 years or older. In the other study it was 12 years or older. Their episode had to be greater than six months, but less than eight years, the other study, it was 10 years, without spontaneous improvement in the previous six months. There were two dosages. There was four milligrams and two milligrams of baricitinib that was compared to placebo. This particular endpoint was 36 weeks and a SALT score of 20 or less. And what they found was that at 36 weeks and continuing through 52 weeks, the percent of patients who achieved that SALT score of 20 was superior to the placebo in both the BRAVE-AA1 and the BRAVE-AA2.

With baricitinib, the two milligram, about 20% of those individuals responded with their SALT score down to 20. And 34% of those on that higher four milligram per day dosage responded with a decrease in their SALT score down to 20. Improvement as well, with both two and four milligrams, in the eyebrows and the eyelashes, with regrowth. Safety profile, very good for both groups. The most frequent adverse event was upper respiratory tract infections, headaches, nasopharyngitis, acne, urinary tract infection, increase CPK. There are several different trajectories of regrowth. There are early responders, gradual responder, this is someone who at 12 weeks really didn't have much hair. 36 weeks, SALT score of 20, and then at 52 weeks, SALT score of 0. And then there are late responders. So this basically says, "You really shouldn't give up on it."

Couple of learnings, number one, in these studies, the four milligram dosage, the patients responded better than the two milligram dosage. Patients who had very severe alopecia areata, that's a SALT score of 95 to 100, did not respond as well. And overall responders, early to late, were more frequent in patients with short episodes of hair loss, those whose alopecia areata was of four years or less. Up-titration is something that you can do, going from two milligrams to four milligrams, and you can get better results. They went on and looked at patients beyond 52 weeks, and basically the findings were if your patient didn't respond up to that time and then they continued, you could get additional response.

We all want to know if JAK inhibitors are safe. Well, we went over some of the more common side effects, but in regard to the black box warning, that includes risk of infections, heart-related events, malignancy, blood clots, and death. And there was a systematic review of 35 randomized clinical trials of patients with various conditions on JAK inhibitors. And they found that basically they didn't show a difference in terms of JAK inhibitors versus placebos or comparators, on major cardiovascular events, all-cause mortality or venous thromboembolism. So we all will see that JAK inhibitors, in particular, really provide an important therapy in our armamentarium for alopecia areata.

Speaker 1:

Now it's time for the Dermalorian Derm Decoder. Are you familiar with the AD Control Tool and its potential applications in clinical practice? DEF president, nurse practitioner Joe Gorelick explains.

Joe Gorelick:

This is a really easy six-question questionnaire that can be answered by patients. It's a validated, super easy and easy to score, and it asks about sleep. And so I wanted to point that out. The question about sleep is number four, talks about sleep, gives it a number. If these patients are scoring seven or greater, what you're discovering is that the patients are not adequately controlled. But I like the diversity of questions here because it really asks some probing questions and if you don't use these particular tools, there can be a question or two that you pull off of these tools and then you can actually put into the charts to help you ask that same question again, so that you can determine if patients are improving based on these parameters.

Speaker 1:

That's it for this edition of The Dermalorian Podcast. If you like what you've heard, check out past episodes wherever you stream audio and share the podcast with a colleague. Thanks for joining us.