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Expert Perspectives on JAK Inhibitors in Dermatology Care - Episode 7

The Role of JAK Inhibitors in Treatment of Vitiligo and Alopecia Areata

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Dermatology experts discuss clinical specifics of JAK [Janus kinase] inhibitors and their impact on the treatment of patients with vitiligo and alopecia areata.

Jerry Bagel, MD, MS: Now we have a medication. Could you possibly explain what you think is the pathogenesis of vitiligo...and the role of the JAK inhibitor in that pathogenesis?

Brett King, MD, PhD: One of the fun things about JAK inhibitors in general is they have the potential to make clinically important immunology fun. None of us went into dermatology because we were immunologists, or necessarily interested in immunology, but nevertheless when we understand why we’re using a medicine in a disease, it’s certainly much more fun than if we’re just randomly writing prescriptions. In the case of vitiligo, we believe that interferon gamma or IL-15, we believe that these 2 important cytokines are driving that disease to happen. They’re part of what’s driving the interaction between T cells and keratinocytes that lead to T-cell destruction of melanocytes and eventually a white spot. Both interferon gamma and IL-15 signal throw the JAK stat pathway. JAK inhibitors were deliberately used in vitiligo based on the data that say that interferon gamma and IL-15 are important drivers of this disease. I gave a patient oral tofacitinib, going back 7 or 8 years now, because the science said that it might interrupt her disease, and it did. Then we…brought ruxolitinib cream to the disease, and here we are all these years later with a drug that works and it’s targeted therapy for this disease.

Jerry Bagel, MD, MS: With the development of treatment for patients with vitiligo, there’s obviously now a pipeline, ritlecitinib; how does that differ? How does that work? What expectations do you consider?

Brett King, MD, PhD: What’s really exciting...is ritlecitinib is in phase 3 clinical trials for moderate to severe alopecia areata. It’s in earlier stage clinical trials for vitiligo. Ritlecitinib is an oral JAK inhibitor. It’s a quite selective JAK-3 inhibitor, so getting back to the earlier part of our discussion about selectivity, again to the extent that selectivity is real when somebody actually puts one of these medicines in their body; it is a JAK-3 inhibitor. The data in alopecia areata are really promising and in vitiligo the data that we’ve seen to date are provocative. Not at the level of ruxolitinib cream, but I believe very much that that was clinical trial design and not a failure of the drug. In vitiligo, we need systemic therapy. It’s absolutely true; vitiligo is not a disease that always targets a patch of skin for which a topical can be used effectively. Patients with vitiligo often come in with generalized disease. We can’t prescribe enough cream, and nor do patients want to put cream necessarily all over their body and so we need an oral. We need a systemic therapy for vitiligo and I’m very hopeful that the next stage of clinical trials for ritlecitinib will bear out that that is a drug with really promising efficacy so that we have a second tool in our toolbox for this disease.

Transcript edited for clarity

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