Dr Brett King: The Algorithm of Treating Vitiligo Is Not Straightforward

The complicated nature of vitiligo, and the different ways it may present on patients, means treatment decisions will vary from patient to patient, explained Brett King, MD, PhD, associate professor of dermatology, Yale School of Medicine.

In an interview with The American Journal of Managed Care^® (AJMC^®), King also discussed the treatment response based on location of vitiligo, the length of time it takes to repigment skin, and the importance of educating dermatologists on the pathogenesis of the disease.

Check out part 1, which includes a discussion on the challenge of how long treatment can take at a time when treatments for other conditions show improvements much faster.

AJMC^®: When determining how to treat patients, what factors drive treatment decisions, and how does the length of treatment impact that economic burden?

King: Thinking about non-segmental vitiligo: We have the patient; we have repigmentation that we want to achieve. For the patient with progressive disease, we want to halt progression. Depending on the patient, we're going to think about these 2 things, and we're going to think about them differently. If I've got a spot here, and a spot on my hand, and a spot on my knee, and a spot on my back, and a month ago I only had 2 of those spots, well, that's somebody for whom topicals are not going to work because I can't get topicals all over my body, and I don't know where the next spot is going to appear. That's a patient who might need systemic corticosteroids to try to halt progression. That's a patient that may need phototherapy, because phototherapy can be administered to the entire body surface area. That's the way that we're going to try to address that patient.

Then there's repigmentation, as well. What are the areas that are of great concern? Is most of your disease on your face? A topical? Perfect. We know ruxolitinib 1.5% cream works well on the face. Topical calcineurin inhibitors work well on the face. That's how we're going to address your disease. We have to recognize that this takes time, and we have to do some counseling and set expectations. That really is important to that sub question: how does the length of treatment impact the burden? It takes time, and along the way, that means, perhaps, more copays. It might mean more copays for phototherapy. Then we begin to think about for the patient undergoing phototherapy, maybe at some point it makes more sense to write for a home phototherapy unit and try to get insurance to cover that, as opposed to them coming into the office 2 or 3 times a week for the next year.

Different considerations around that progressive patient versus the stable patient. Can we address the disease with topicals, because we're really chasing after small areas or limited surface area involvement or is it a patient with disease everywhere and they want it all better, in which case topicals are not going to work, and we need to be chasing with phototherapy, or we need to think about a systemic, an oral Janus kinase (JAK) inhibitor, which would be off-label—important to note in this discussion. There's an oral JAK inhibitor in clinical trials for vitiligo called ritlecitinib.

It's a complicated disease. The algorithm is not totally straightforward, because there are so many factors to consider. But with this new awareness of disease and new treatments being brought to bear on disease, we're going to be able to address the multitude of considerations in the future.

AJMC^®: How does the location of vitiligo impact the response to treatment? And why can it take so long to re-pigment and treat?

King: This is possibly the most important question, and the answer to it is probably the most important to communicate to dermatologists. We've not done a good job of educating ourselves and educating the newer generations of dermatologists regarding pathogenesis and how to make disease better. There is a distinct difference in vitiligo that affects the face versus the body versus the hands and feet. One of the things that's really important for us to understand is that when we have depigmentation—loss of the melanocytes in the skin, which leads to a white spot—the way to get pigment back is we have to take melanocytes precursors or melanocyte stem cells, there needs to be a reservoir to go into that affected area that white spot.

The melanocytes reservoir is in hair follicles. Areas of the body in which there are no hair follicles, we almost cannot re-pigment. Fingertips: you've never seen somebody with hair on their fingertips. That person doesn't exist. You've never seen somebody with hairy wrists. You've never seen somebody with hairy lips. These are areas that almost cannot be re-pigmented when patients come to us and their areas of their involvement are mainly their fingertips, the conversation with them—this is the complexity of what we're trying to communicate—that patient's goal is probably to not develop more vitiligo on their hands, because vitiligo on the hands almost doesn't get better. Only rarely will it get a little bit better and almost never can it get all the way better. We're talking about repigmentation, yet the goal for the patient with hand involvement or feet involvement or lips involvement is no further progression, not repigmentation.

The fundamental answer to this question is site location of the vitiligo is really important to the entire discussion around treatment. What treatment success means—simply halting the progression or getting repigmentation. Face repigments very well probably related to the density of hair follicles—again, the melanocytes reservoir is in the hair follicle. A part of the body where we have dense hair follicles, such as the face, tends to re-pigment very well. Another consideration with the face is that no matter whether you live—Alaska or Texas—we all get some amount of sunlight on our faces every day. Probably light is an important stimulator of melanogenesis or contributes to melanogenesis. Face does very well. Hands, feet, wrists, and lips do very poorly in terms of repigmentation. The body responds not as well to treatment as the face, but it can, and we can sometimes actually achieve great success when we combine treatment such as ruxolitinib 1.5% cream or topical calcineurin inhibitors with narrowband, ultraviolet B (UVB) phototherapy. I think in those cases, we can actually achieve exceptional results on the body. But there's an access issue and whether or not the dermatologist has phototherapy, whether they offer phototherapy, whether they'll tell you where you can get phototherapy. Those are the issues.

Again, the reason it takes a while to re-pigment is because there is no pigment, and then we have to stimulate melanogenesis. We're not making red skin go away like in dermatitis or psoriasis. We're literally putting pigment back in the skin. That cannot happen today. It cannot happen tomorrow, next week, or in a month. It takes time for melanogenesis to happen and to happen completely.

AJMC^®: What are you working on vitiligo that you were excited to share?

King: I'm a really big believer that we need to optimize every opportunity we have. We need to optimize the rapidity of response and just optimize response in general. I really believe that that's done with combination therapy: topical or oral plus narrowband UVB phototherapy. Every patient who comes to me hears, “If, over the next 6 months, we want to optimize your chances of success, you're going to do both.” And I get it, narrowband phototherapy, is a pain. It's time-consuming. You have to find an office that does it. Three times a week, you're going to drive 30 minutes, take off your clothes, get in the booth, get dressed, drive 30 minutes back to work. It's a commitment. For me, what we want is for everybody to get better as quickly as possible. For me, combination treatment is really key, and I'm big on promoting it.

The things that I think are really exciting that are happening is that, 8 years ago vitiligo wasn't one anybody's radar in the pharmaceutical industry. Now it is. We have our first approved agent; we have clinical trials happening with an oral JAK inhibitor. The National Institutes of Health is doing a clinical trial with an IL-15 antibody to try to remit vitiligo. There are other companies getting interested and involved in this space. What's really cool is something that—I believe this is not far from the truth—nobody cared about vitiligo in terms of the pharmaceutical industry, and maybe not even so much in dermatology, a decade ago, where now have several things happening, which is just so cool for patients.