Latest Advances in the Management of Vitiligo

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EP: 1.Latest Advances in the Management of Vitiligo

Raj Chovatiya, MD, PhD: Vitiligo is a disease that we've seen in dermatology for years. It is historically well-documented going back thousands of years, but despite how much we know about it, the true burden it places on our patients, particularly that psychosocial aspect, there's very little we've actually been able to do about the 2o major problems in vitiligo. First, how do we start or rather stop the depigmentation process, but then how do we actually start repigmentation and acheive pigment back in the places where we've lost?

One of the most exciting things that's happened in vitiligo in the past decade, you could say century, is actually the approval of topical ruxolitinib repigmentation cream in vitiligo. Earlier this year we saw a brand-new indication for topical ruxolitinib cream for patients with vitiligo that did not have good responses to other treatments in the past. Much as we've learned about janus kinase [JAK] inhibition for atopic dermatitis and other diseases, the JAK-STAT pathway occupies a very key and central role for a lot of the chemokine and interferon-gamma signaling that's so important for the autoimmune-related destruction of the melanocytes that we think about in vitiligo. Ruxolitinib cream is very easy to use twice daily. The way they're studying the trials they are really taking a look at primarily facial vitiligo and finding improvement there, but also improvement in the body. Over the course of the long run, the medication was able to stop the depigmentation process and stimulate repigmentation.

I really want to set appropriate expectations for the time course of a disease like vitiligo, especially when you're dealing with hair follicular regions where there's stem cells and gliogenesis needs to happen very different than what we talk about as treatment responses in the case of something like atopic dermatitis where you're looking at very fast modification of itch. On some of the really cool data that you see with ruxolitinib, it's a case of slow and steady winning the race; if you keep patients on their therapy and keep them going, the cumulative additive effects get you to the point where you start to see some of these really big clinical outcomes.

Topical ruxolitinib has really changed the way I'm thinking about treatment for my patients with vitiligo and how I can intervene. Previously for the types of treatments we really were forced to use, like conventional topical corticosteroids and topical calcineurin inhibitors, phototherapy was a really important add-on, and even with primary therapy, particularly narrowband UVB phototherapy, it was often cumbersome because patients physically have to go to a phototherapy unit, which is also known for its slow responses and incomplete responses. Then the right patient type who is really thinking about oral immunosuppressive therapies, both in terms of the mini pulse dosing of steroids for people that have really rapidly progressing disease or when you're thinking about something like methotrexate for longer-term management.

In vitiligo, there's this phenomenon of segmental vs nonsegmental,l and that adds another wrinkle to this story. The nomenclature is a little unfortunate because segmental is the less common type where typically something is occurring in an isolated or geographically small area of the body, whereas non-segmental tends to be the predominant version of vitiligo where you're usually seeing some symmetry and more widespread involvement. Nonsegmental vitiligo is what we see a lot in clinic, and that's what was able to achieve the approval for topical ruxolitinib. With patients that are coming in that have perhaps used topical cortical steroids, they use topical calcineurin inhibitors and have not gotten to where they want to.

This is the place where I have that proactive discussion about topical ruxolitinib and in particular adding it to their current therapeutic regimen. While there isn't any data necessarily for combination therapy, even from a monotherapy standpoint, topical ruxolitinib can do a lot of the heavy lifting for our patients, in my opinion, perhaps even eliminate the need to think about some of those other bigger guns that were pretty broad acting and not as targeted as topical RUX is. Now, there probably is going to be a real important place for combination therapy in the real world, despite the fact that that isn't specifically studied in a course of the pivotal phase 3 trials and thus doesn't appear on the indication or prescribing information.

The big thing we're going to learn over the next year is people that are using topical ruxolitinib in combination with other therapeutic modalities, the one I'm thinking about most is phototherapy just given how important it is for vitiligo treatment and how often an adjunctive add-on therapy. It's going to be interesting if you're hitting the disease from 2 slightly different aspects if you're actually able to even boost efficacy and potentially even boost response to treatment because we all know that it is important to be that cheerleader for our patients, to keep them honest especially when something is going to take beyond 3 months to 6months, to really see some of those meaningful changes. Anything that can really help get us to that point or maybe even be an induction phase for treatment will be awesome. That's really where this idea of adherence comes in. What can we do to keep our patients using their therapy and not just saying, this isn't working, I'm going to stop? One big one is already in the name of the medication. It's comparable to ruxolitinib cream. It's easy to apply cream as opposed to a greasy sticky ointment, something that makes a big difference for patients. Then if we can figure out ways in the real world to combine this treatment with others or study it in a more direct clinical trial setting, we might be able to find ways to really boost treatment responses even higher.

This is the most exciting thing I've had the chance to experience in my practice in a long time for vitiligo, but there's a lot of other stuff on its way. Vitiligo research is not occurring in a vacuum, and, frankly, we're now starting to see maybe we're going to enter a golden age where there's a lot of interest in this disease. I'd say the 1 treatment that has a lot of promise that I'm really interested in over the coming year is ritlecitinib. An oral inhibitor of both JAK proteins and tyrosine kinase expressed in the hepatocellular carcinoma, another type of signaling molecule.

One is being studied for alopecia areata and vitiligo and has some very interesting data for more widespread vitiligo that individuals might have where topical therapy may not be the best choice. I think that the mechanism is allowing us to be specific again to vitiligo, but this will unlock even more doors for my patients that perhaps have wider spread disease beyond the 10% or 20% mark or for topicals that might be difficult for somebody to really hit with therapy. Finally, just given the fact that there's a lot happening in vitiligo and it's no longer the same old, same old, I really think that it's going to be on all of us to stay on top of these treatment updates. Really pay attention to the latest talk to what's happening in the field, tuning in to discussions like these or other similar activities where we get to hear some of the experts in the field talk about what's going on and really seeing what they do for this disease because when it comes to vitiligo prevalence; it's been a harder thing to study.

There's been some really nice studies over the past few years that have really uncovered the fact that it's more common than we think and as we get more treatments in this space, there are probably going to be even more diagnosis. Anything we can do to educate our peers, particularly those that see a lot of vitiligo or think about the disease, there's really going to be the way to unlock our potential to take treatment to the next level.

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