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Novel Therapy in Vitiligo: Topical JAK Inhibitors


Shared insight from dermatologists on novel topical JAK inhibitor therapy being investigated as an option for patients with vitiligo.


Seemal Desai, MD, FAAD: Of course, I’m really excited about the JAK inhibitors. You gave a great talk at the New England Dermatological Society on that. I want to ask you to give us your thoughts and excitement about the new JAK inhibitors, particularly ruxolitinib and maybe tofacitinib. Tell me how you use it, what you’re doing, I’d love to hear your pearls.

William Damsky, MD, PhD: Thanks. Just to set the background, JAK inhibitors are Janus kinase inhibitors, for those who may not be familiar. They are small-molecule kinase inhibitors that inhibit JAK proteins. And why JAK proteins are really important in inflammatory and autoimmune disorders is because they mediate signaling from cytokines. As you mentioned, IL [interleukin]-15 is a great example. Interferon-gamma is a great example. JAK inhibitors block the activity of those cytokines. As opposed to, for example, a monoclonal antibody blocking drug that just targets 1 cytokine, JAK inhibitors are interesting because they can simultaneously inhibit multiple cytokines, so they can fend off the immune attack on multiple fronts. What’s really exciting are the clinical trials using topical, mostly at this point, JAK inhibitors in vitiligo. Probably the medication that’s the farthest along is ruxolitinib, which is a JAK1/2 inhibitor, 1.5% cream, and that’s been studied now in phase 2 and phase 3 trials. It really looks quite promising. I want to emphasize quickly the work that was done using preclinical models to identify the key cytokines, like IL-15 that’s so important, like interferon-gamma that are actually mediating melanocyte destruction in this disease, are so important in guiding the field toward these therapies.

In 2020, there was a landmark study that was published in The Lancet by [David] Rosmarin, [MD,] et al. This was a phase 2 multicenter study, dose-ranging, placebo-controlled, and blinded trial of ruxolitinib. There are a variety of dosing schedules and potencies of the cream used, but the highest was 1.5% ruxolitinib cream twice daily. A quick aside, ruxolitinib cream was just FDA approved for atopic dermatitis. A lot of folks may know that. So really, this is the same medication. The end point in that study was what’s called the F-VASI50 [Facial Vitiligo Area Scoring Index, 50% improvement]. F-VASI, the simplest way to think about it, is the percentage of your F, for face, that’s involved by vitiligo. The primary end point at 24 weeks was the number of patients who repigmented approximately 50% of their facial skin. They had 157 patients, and about 50% of the patients in the highest dosing group, using ruxolitinib cream 1.5% once or twice daily, achieved that F-VASI50. So, it’s really exciting stuff. It appeared safe, and I think this has really kickstarted this interest in JAK inhibitors and vitiligo into the next phase. There are preclinical data, some early clinical proof, and now there are really good clinical trial data. And as you’re well aware, this has moved into phase 3, and we already have some of that data available to us.

Seemal Desai, MD, FAAD: I’m excited to share with our listeners that we just presented the phase 3 data, as you said, on the ruxolitinib 1.5% cream at the EADV [European Academy of Dermatology and Venereology] meeting. It’s really exciting with those data out now and available, and the phase 3 data looks excellent. I’m really hopeful that we’ll have these [approved] very soon.

Transcript edited for clarity.

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