New Vitiligo Therapy: Topical JAK Inhibitors

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Seemal Desai, MD, FAAD: Of course, I am really excited about the JAK inhibitors. You gave an excellent lecture at the New England Dermatological Society on this subject. I want to ask you to share your thoughts and excitement with us about the newer JAK inhibitors, especially ruxolitinib and possibly tofacitinib. Tell me how you use it, what you do, I would love to hear your pearls.

William Damsky, MD, PhD: Thank you. Just for context, JAK inhibitors are Janus kinase inhibitors, for those who may not be familiar. These 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 cytokine signaling. As you mentioned, IL [interleukin]-15 is a great example. Interferon-gamma is a prime example. JAK inhibitors block the activity of these cytokines. Unlike, for example, a monoclonal antibody blocker drug that targets only one cytokine, JAK inhibitors are interesting because they can simultaneously inhibit multiple cytokines, so they can repel immune attack on multiple fronts. What’s really exciting are the clinical trials using topical JAK inhibitors, mainly at this stage in vitiligo. Probably the most advanced drug is ruxolitinib, which is an inhibitor of JAK1 / 2, a 1.5% cream, and which is currently being studied in phase 2 and phase 3 trials. It really looks very promising. I want to quickly highlight the work that has been done using preclinical models to identify key cytokines, like the IL-15 which is so important, like interferon-gamma which actually mediates the destruction of melanocytes in this disease, are so important in guiding the field towards these therapies.

In 2020, a landmark study was published in The Lancet through [David] Rosemary, [MD,] et al. This was a multicenter, phase 2, dosing, placebo-controlled, blinded study of ruxolitinib. There are a variety of dosage regimens and strengths of the cream used, but the highest was 1.5% ruxolitinib cream twice daily. As an aside, ruxolitinib cream has just been approved by the FDA for atopic dermatitis. Many people may know this. So really, it’s the same drug. The end point of this study was the so called 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 the face, that is involved in vitiligo. The primary endpoint at 24 weeks was the number of patients who repigmented approximately 50% of the skin on their face. They had 157 patients, and about 50% of the patients in the highest dose group, using ruxolitinib 1.5% cream once or twice a day, achieved this F-VASI50. So, this is really exciting. It sounded safe, and I think it really took that interest in JAK inhibitors and vitiligo into the next phase. There is preclinical data, early clinical evidence, and now there is very good clinical trial data. And as you well know, that moved into phase 3, and we already have some of this data at our disposal.

Seemal Desai, MD, FAAD: I am delighted to share with our listeners that we just presented the phase 3 data, as you said, on Ruxolitinib 1.5% Cream at EADV [European Academy of Dermatology and Venereology] Encounter. It’s really exciting with this data now available and available, and the data from phase 3 looks great. I really hope we get these [approved] very soon.

Transcription edited for clarity.


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