Dermatologists Discuss the FDA Approval of Baricitinib for Alopecia Areata

On June 13, the US Food and Drug Administration (FDA) approved oral baricitinib (Olumiant) tablets for the treatment of severe alopecia areata in adults, which marked the first approval of a systemic treatment for the disorder.

The approval has excited patients and providers alike who struggled for decades to treat severe cases of this autoimmune disorder.

For this episode of DocTalk, several key opinion leaders in the dermatology field sound off on the implications of this decision, as well as the versatility of Janus kinase (JAK) inhibitors, and how this approval will aid providers in redefining alopecia areata as an autoimmune disorder rather than simply a cosmetic condition, which will help more patients receive proper care.

Joining us on the podcast and in written form are the following dermatologists:

• Brett King, MD, PhD, Yale School of Medicine, New Haven
• Lisa Arkin, MD, member of the Society for Pediatric Dermatology, University of Wisconsin School of Medicine & Public Health / American Family Children's Hospital.
• Karan Lal, DO, MS, FAAD, Schweiger Dermatology Group and member of The Society for Pediatric Dermatology
• Brittany Craiglow, MD, Yale School of Medicine, New Haven

Brett King, MD, PhD:

“Eight years ago, when my wife (pediatric dermatologist Brittany Craiglow), when she and I published this first case report of a patient treated with the JAK inhibitor tofacitinib, it made international headlines, truly, within hours of a press release regarding that case report- a single case report, imagine that, making international headlines, I think because the photographs were so striking.

Alopecia areata wasn't even on our radar. It was something that happened rarely, and I don't think very many people saw many of these patients with severe disease. All of a sudden there was all of this interest and patients coming from all over the world seeking care, and it became clear, like, ‘oh, this is real, this is relatively common, and, and whoa, we might have a medicine or a class of medicines that fixes this disease when it's severe.’

One case report turned into an open label clinical trial, (which) turned into a large retrospective study of 90 patients. Other people started publishing reports in small series, and the evidence accumulated wrapped rapidly. This is real, it works, and all of a sudden the pharmaceutical industry was interested.

So, that case report was in June of 2014, there was one JAK inhibitor that was FDA approved- tofacitinib- for rheumatoid arthritis. But the class (of drug) was brand new, and tofacitinib was only born in late 2012, approved at that time for rheumatoid arthritis. So it was a new class that medicine was beginning to explore, and the rest is history.

Eight years later there are multiple indications for different JAK inhibitors and diseases ranging from oncology. I mean, imagine a drug class that is effective for certain hematologic malignancies, also rheumatoid arthritis, also ulcerative colitis, also eczema and alopecia areata. I mean, that's crazy. The broad reach of this class is amazing.

We are coming from a time when there was really nothing for these patients with severe disease. For the majority of patients who have limited disease, meaning spots, we inject those spots with steroid intralesional triamcinolone, most commonly, and they regrow hair.

But when the severity gets to a point where people are missing 50%, 80%, 100% of their scalp hair, and not only that, but they've got an eyebrow missing, they got eyelashes missing, beard loss in men; the therapies that we've used in the past, which are just brought immune suppressants, so cyclosporine, methotrexate, prednisone, the usual cast of characters that we throw at everything that for which we don't have treatment, those things don't work.

So, this is a breakthrough, not only because it's the first FDA approved therapy for severe alopecia, but it's a breakthrough because we don't have anything else. These patients, they see doctors and they're told “get a wig, get a good therapist, you look great in that scarf.” Nobody went to see the dermatologist to find out that they've got a nice-shaved head. Nobody goes to the dermatologist for fashion advice. They go for answers, because they want a health problem resolved or remitted.

Now, for the first time in history, we're going to be able to offer people something, (and) we're going to be able to write a prescription- and I'm sure with some argument with payers, but much less of an argument than in the last 8 years. We're going to be able to get people the medicine that they need.”

Lisa Arkin, MD:

“This is an autoimmune disease that we happen to see in the skin, and we see it particularly in the hair follicle. People with alopecia areata, dermatologists and other physicians have been looking forward to this day for as long as we have known about the data that resulted in the FDA approval, because it's such a disabling disease for the patients who are really severely affected, and we've had no good treatment options until this point.

This really reflects a translational revolution, and the ability to say, “take a disease, let's look at the pathways that are driving it and think about how to leverage that pathway through targeted therapies”.

So, this is just a total celebration from our community. It's not just that (alopecia areata is) socially stigmatizing, it's that it represents ongoing active autoimmunity in the skin. Now we have a targetable agent that's FDA approved, and it validates the fact that we haven’t had good treatments that have worked very effectively for this subset of patients who have really severe disease.

This is a pathway that turns out to be incredibly relevant for not just alopecia, but for many of the other dermatologic disorders we take care of which are also driven by ongoing autoimmunity or just site-specific immunity.

The thing about this class of drugs is that they turn out to be effective not just for alopecia areata, but lots of ways for atopic dermatitis, they may become the targeted treatment of choice for dermatomyositis (and) potentially for vitiligo. There's an ever-expanding series of indications to which this drug could be applied. But it's going to be really important as we learn more about how the drugs work in real life over real time that we're using them in the right patient population, because these are not drugs without risk.

We know that not from the dermatologic literature, but from the RA treated population, where it took about a decade to see a safety signal. And it was seen in the patients who were JAK treated with RA, and not seen in the patients with RA who were treated with TNF inhibitors. But there are a lot of questions that remain: was it the population studied, was it something about RA in particular, was it something about the fact that most of the patients with RA who received this drug were quite elderly? All of those things make it difficult to generalize to the dermatology population. So, we just want to make sure that we're really reaching for this drug in the scenarios where it's most indicated, and that, of course, is patients who have severe disease (who are) followed closely and appropriately, because this is an immune-suppressing agent.

Amidst the COVID-19 era, that becomes a bigger conversation because this pathway is critical in containing the severe manifestations of COVID-19. So, I think as a field we're going to be learning about these agents in real time and just wanting to make sure that patients are followed closely and managed appropriately. But it offers a whole new world of opportunity for all these disorders that had very limited treatment options until this came along.

Just having an FDA approval will expand our ability to get this covered by insurance for the patients who are most severe and really need it, because we already have a lot of literature supporting that in this patient population treated over a relatively short period of time, we think it's really safe.

The insurance barrier is huge because people will say it's just hair- it's not hair. This affects every possible aspect of a child and an adult's life. It's all encompassing, and it's autoimmune. This is the immunologic signature of autoimmunity, and that's what we're targeting. And the data is amazing.

Karan Lal, DO, MS, FAAD:

Alopecia areata is a very distressing disease; all dermatologists know that, all patients know that- it's not fun for anyone in the room when we don't have a solution. Alopecia areata is an autoimmune mediated disorder that involves CD8+ T cells, and we know has involvement of the JAK-STAT pathway, as do many diseases. Many diseases have downstream have effects with the JAK-STAT pathway.

So, this all started when, a few years ago, we had seen reports of patients being treated with Xeljanz, which is a pen JAK inhibitor, and is approved for RA and psoriatic arthritis with alopecia areata, and patients had regrowth. This is what many of us that felt comfortable doing in the meantime, because we were all hoping that something would come of this given the positive response to Xeljanz or tofacitinib.

However, tofacitinib has a blackbox warning, as do many JAK inhibitors for major adverse cardiac events as well as blood clots and cancer and infections. Baricitinib, which has just been approved by the FDA, is a JAK 1 and 2 inhibitor. So, it's a little bit more specific and in theory that should reduce the amount of side effects.

This approval came after these two big studies called BRAVE-1 and BRAVE-2; they were multinational studies that enrolled about 1200 patients, and were patients with a solid score of at least 50 who were followed over 36 weeks, and were randomized to receive 2 milligrams or 4 milligrams of baricitinib, or placebo. They found a significant improvement in patients who receive baricitinib 2 milligrams and 4 milligrams compared to placebo. Patients who had 4 milligrams had 16% ,on average, greater hair growth in the baricitinib 2 milligram group. Both groups had side effects, (and) many of these were mild, including acne, increases in cholesterol increase in muscle enzymes, but none of the major serious side effects.

However, this was only for 36 weeks. Long term data efficacy will come out as these patients will continue therapy. But this is very exciting, because we know that patients with alopecia areata are often very difficult to manage, and it's really a disease that affects not just the skin, but I also the immune system and the mind. This is a disease where that affects a part of us that really helps identify people, and for many people, men or women, it's extremely serious.

Now, up until now, we've had a lot of treatments that were not even necessarily FDA approved that we were using. We were using prednisone, subjecting people to multiple injections at every visit with tears (resulting at the end of) the visit. So, this is going to be a big game changer for patients; now ,for patients who have 50% or more hair loss on their scalp, I have an option for them.

The way that this medicine is going to be successful is that it's really going to help prevent really bad disease, because I think people are going to start getting treated early. I don't think a great medication for all patients, because we know that local disease with a few patches here and there respond well to local therapy. But I have to say there's a ton of patients that have either alopecia totalis or universals are progressing in that direction. And this is going to help us stop that from happening, and hopefully patients will get treatment earlier and will know and learn more about the disease itself.