With now more than 6 months of real-world use for baricitinib available, what challenges still remain for the alopecia areata treatment and what other agents are on the horizon?
Armed with the first approved systemic therapy for patients with alopecia areata, clinicians are now settling in and getting comfortable with baricitinib, the Janus kinase (JAK) inhibitor approved in June 2022. That includes analyzing the long-term safety and efficacy data, as well as navigating why some patients may respond better than others.
Raj Chovatiya, MD, PhD, assistant professor of dermatology, director of the Center for Eczema and Itch, and medical director of the Clinical Trials Unit at Northwestern University Feinberg School of Medicine, in Chicago, Illinois, as well as a Dermatology Times® editorial advisory board member, presented a talk on new JAK inhibitors for alopecia areata at Winter Clinical Miami, held February 17-20, 2023, in Miami, Florida.1
This transcript has been edited for clarity and length.
Dermatology Times: Why should clinicians care about alopecia areata?
Chovatiya: If you asked me this question 10 years ago, is alopecia areata important, you may hear that no, this isn't a disease that anyone cares about. It's largely cosmetic. But what we've learned over the past decade of research is that the psychosocial burden of this disease is huge. First and foremost, hair, eyebrows, eyelashes, scalp…such an important part of our personal identity, that we're talking about a disfiguring autoimmune condition. I think that alone is a reason why we need to care as dermatologists.
Dermatology Times: Can you talk a bit about the evolution of the treatment landscape for alopecia, up through the June 2022 approval of the JAK inhibitor baricitinib?
Chovatiya: For a long time, there really wasn't much progress in the way of treatment and we'd been using the same stuff over and over again—topical steroids, other topical anti-inflammatories, injectable steroids, oral steroids, and even oral immunosuppressive agents, all of which come with variable levels of efficacy. Maybe they work okay in mild alopecia areata, but not our moderate and severe or very severe forms. There really just wasn't much progress for a long time.
It's really until we started uncovering some of the basic science behind exactly what's happening, getting down to the follicle, understanding about CD8+ T-cell activity, the autoimmune nature of the disease, that this idea of targeting the JAK STAT signaling pathway really came in and, after a number of cases, showed immense regrowth of hair on people who had that pathway targeted. We ended up in development programs for multiple drugs. The first one to really come out is baricitinib in the past last year, a JAK1/2 inhibitor that is approved for alopecia areata.
Dermatology Times: What are you hearing from colleagues about baricitinib’s real-world use? What challenges still remain?
Chovatiya: On the plus side, I think what we're hearing is that efficacy in the real world is matching what we see in trials, which is exactly what we want to hear. Slow and steady wins the race when it comes to alopecia areata treatment and real-world experience is mirroring that. Access has also been less of an issue too because there were no treatments for this condition. Therefore, that should be the reason why we get people started.
In terms of challenges, it's the same challenges we've seen with a lot of oral JAK inhibitors—individuals maybe being a little less certain about safety, boxed warnings, how to use the medication, and really it's through educational programs and through listening to talks, reading, getting familiar with the data, that's going to get more people to want to dip their toe in the water and really understand the best way to use these medications.
Dermatology Times: What do we know about why certain patients may respond better to baricitnib than others?
Chovatiya: Based on data that we have so far, it looks like the best time to treat is when there's still some hair present. Once you have almost 95 to 99 or 100% hair loss, it becomes really hard to get the hair to regrow. Also, the longer somebody has alopecia areata, also much more difficult for the hair regrow as well. So what we really want to do is treat as early as possible with as much hair as possible.
Dermatology Times: How do the long-term safety data look?
Chovatiya: The great thing about the newest long-term safety cuts we've seen from baricitinib, they reflect the short-term data and largely reflect what we've seen from atopic dermatitis development programs where baricitinib has approved externally of the US as well. By and large, there really hasn't been much concern about infections, thrombotic events, major adverse cardiovascular events, or death, some of those things that are highlighted on that box warning label.
Dermatology Times: What else is in development or what other trials are underway for alopecia areata?
Chovatiya: There's a lot and probably too much for us to cover in our time together, but I would say the 2 I want people to be ready for that probably may be coming to a clinic near them…One is going to be ritlecitinib. This is a JAK3/TEC inhibitor that's in development currently. And then there's another medication, deuruxolitinib, which is a JAK1/2 inhibitor. These are both oral JAK inhibitors. In the case of ritlecitinib, potentially even more selective and targeting some different pathways, and I think these are going to be some of the first we have a chance to really try out in the clinic.
Chovatiya R. New JAK inhibitors for the treatment of alopecia areata. Presented at Winter Clinical Miami 2023; February 17-20, 2023; Miami, FL.