Ruxolitinib cream, a cream formulation of the JAK 1/JAK2 inhibitor was first approved for use in vitiligo by the FDA in July 2022 and is the only topical treatment approved for repigmentation. We were delighted to speak to Dr. Amit G. Pandya (Palo Alto Foundation Medical Group, Sunnyvale, CA, USA) around the rationale and adverse events associated with the use of JAK inhibitors in vitiligo, the impact ruxolitinib cream has had on the treatment paradigm since its approval and the other JAK inhibitors in development in this indication.
The abstract ‘Treatment-Emergent Adverse Events of Interest for Janus Kinase Inhibitors: Pooled Analysis of the 52-Week TRuE-V Phase 3 Studies of Ruxolitinib Cream Treatment for Vitiligo.’ (Poster ID: 43978) was presented at AAD 2023, 17-21 March, 2023.
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- What is the rationale for the use of JAK inhibitors in the treatment of vitiligo and what adverse effects are associated with JAK inhibition? (0:21)
- What has been the clinical impact of ruxolitinib cream in this indication since its approval? (1:57)
- What other JAK inhibitors are in the pipeline for vitiligo? (3:13)
Disclosures: Amit G. Pandya discloses consulting for: Abbvie, Arcutis, Avita, Chromaderm, Incyte, Pfizer, Viela Bio, Villaris, Immune Tolerance Network, Thalocan, Trifecta, TWi, and Vyne; receiving grant/ research support from: Incyte and stock options with Tara Medical and Zerigo Health.
Support: Interview and filming supported by Touch Medical Media Ltd. Interview conducted by Victoria Jones.
Filmed in coverage of the 2023 AAD Annual Meeting.
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What is the rationale for the use of JAK inhibitors in the treatment of vitiligo and what adverse effects are associated with JAK inhibition? (0:21)
JAK inhibitors are used in vitiligo because they block the signalling from skin cells that attract pathogenic T cells to the skin. In vitiligo interferon gamma is involved in the pathogenesis. What happens is T cells migrate to the skin and kill melanocytes and they’re attracted to the skin by a signal that’s produced by keratinocytes or skin cells and signals CXCL9 and CXCL10. JAK inhibitors reduce the signal production. So that the pathogenic T cells disperse and then vitiligo can improve.
JAK inhibitors are associated with several adverse effects. The older JAK inhibitors had more of a toxicity on the bone marrow, and so there were issues of bone marrow suppression, opportunistic infections and even cardiovascular events, especially in people who are over the age of 50 and had a history of cardiovascular disease or cardiovascular risk factors. There was also an elevated incidence of certain malignancies in these patients, but the newer JAK inhibitors are more specific. They target just JAK1 or JAK3, and so far in studies of topical and oral use, we are not seeing any real significant or serious adverse effects.
What has been the clinical impact of ruxolitinib cream in this indication since its approval? (1:57)
Well, ruxolitinib cream was approved last summer and since then I certainly have been using it in a lot of my vitiligo patients. I have a practice exclusively of pigmentary disorders and I see hundreds of patients with vitiligo. And so, what I have found is that the topical ruxolitinib definitely helps re-pigment vitiligo when it’s combined with light, either sunlight or phototherapy. It’s also been very well tolerated by patients. It’s not a steroid, so patients apply it on their eyelids, around their mouth on any parts of their body without any risk of thinning of the skin or other steroid related side effects. The cream also is very moisturizing, and patients seem to like it. So it’s been really well accepted. Fortunately, we’re able to get insurance coverage and the vast majority of our patients, so they’re able to use it. And I’ve been pleased with the results. I can’t tell you how it’s been accepted nationwide, but I have spoken to many dermatologists who are using it for vitiligo and eczema, which are the two conditions for which it is approved.
What other JAK inhibitors are in the pipeline for vitiligo? (3:13)
Well, there are three oral JAK inhibitors that are in the pipeline right now. They’ve completed their phase 2 studies and they’ve launched or about to launch their phase 3 studies. Ritlecitinib is a JAK3 inhibitor and it shows some promise in oral form in patients with vitiligo, especially when it was given for 52 weeks. There are two JAK1 inhibitors, upadacitinib and abrocitinib, which have completed their phase 2 studies and the results also look encouraging for both of them. And so phase 3 trials, we hope, will be coming up later this year or next year. And hopefully we will have an oral JAK inhibitor soon for vitiligo.
Subtitles and transcript are autogenerated.
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