David Rosmarin, MD

: Heather, taking account of everything that we've been talking about? What advice do you have for dermatologists, and other physicians who are going to encounter vitiligo patients? What advice do you have for them in recognizing and treating vitiligo and counseling patients about this disease?

: I would say my biggest advice is to listen to your patients. That's my biggest advice. Don't make assumptions. Don't assume that it doesn't bother them or that it really bothers them. I also think another big take home is I do always offer my patients hope there are treatments. We have effective treatments, especially on sun-exposed areas. The most I think frustrating thing for vitiligo patients is when someone says, there's nothing we can do. And follow up as needed there's nothing we can do. I don't think that's accurate. The technologies and pharmaceuticals that are coming out right now and will be coming out in the upcoming years are exciting. They offer our vitiligo patients a lot of hope. That's another take home because I do think some people feel vitiligo is something that you just have to live with and you don't need to treat it. Another thing is offer your patients support groups, because it's a disease that people feel very isolated, and reaching out to a support group and participating in group processing meetings, or just even communicating online with people who have your condition, is very helpful for vitiligo patients. And we haven't touched so much on this, but don't forget that we can use camouflage makeup, tell your patients about that, including your male patients because for a lot of patients, it's a very effective way to live with vitiligo.

It's so important. You touch on so many important points, the concept that there's nothing that we can do. Well, first of all, there might be actually something that we can do to achieve repigmentation. But another thing that's been brought up repeatedly is what about halting further disease? Almost certainly we can do something for patients there. And it's not true that there's nothing that we can do. We can do something for the vitiligo that's there. We should be thinking about trying to halt further disease. And then beyond these things, there are masking techniques. And then there's just the community. And knowing that you're not the only person that's suffering from this disease, but there are other people, and it's always useful to know that we're not alone in the world suffering with whatever we're suffering from. And you just raise so many important points about the doctor-patient relationship and the different aspects of the visit and the different aspects of the disease to take time to cover with patients. Thank you so much for that.

: One thing I'd like to mention before Heather goes, if a physician is having difficulty getting coverage for in-office phototherapy or home phototherapy, the global vitiligo foundation website, globalvitiligofoundation.org has sample letters that you can use to get phototherapy coverage in your office, as well as a strong letter for home phototherapy, including references, showing that it works. And then finally an actual four-page handout that you give to the patient that walks them through how to give the treatment to themselves easily at home. I just wanted to mention that.

That's an important point. I want to thank you for watching this 

 Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters, to receive upcoming peer exchanges and other great content right in your inbox.

And lastly, I want to thank, David, Amit, and Heather, amazing and engaging experts, in vitiligo for their time and for sharing their experiences and expertise.

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Dr. Woolery-Lloyd shares her advice for vitiligo providers and tips for helpful communication with patients.

Advice for Providers Treating Vitiligo

Let's move on to segment 4, future directions. This is really an area of a lot of excitement, just because there's so much in development in the vitiligo. And Amit let's start with you. Can you tell us about the drugs that are in development?

: It's a very exciting time for me. I've been practicing for 30 years, and this is the first time we've had medications that are about to be approved and are being studied for vitiligo up until now we didn't have anything that was approved for vitiligo. Ruxolitinib is the one that's closest to being approved. We've had the completion of the phase 2 in the phase 3 studies, and hopefully, we'll be having FDA approval soon. Ruxolitinib is already approved for atopic dermatitis. It is a JAK 1/2 inhibitor and is very effective in removing the T cells from the skin. In these studies, no phototherapy was given, these patients were simply asked to do their normal daily activities, including driving and walking, and the amount of sun exposure they were getting normally. And amazingly, after 52 weeks of treatment, they got 50 to 75% of the color back on their face. And that's called the FVASI, the facial vitiligo area scoring index. It was very exciting to see that result. It is a study ongoing in which we're going to be combining the topical ruxolitinib with phototherapy, and we expect to see even better results with that one. Ruxolitinib is an oral JAK 3 inhibitor and as a JAK 3 inhibitor, it would have less toxicity than oral JAK 2 inhibitors, which is exciting that has completed its phase 2 studies. And it did show response compared to placebo the response wasn't quite as good as what we saw with the topical ruxolitinib. But that might have had something to do with the type of patients that were enrolled patients with active disease and not patients with stable disease. We're going to have to see what further studies show with ruxolitinib, but that was the first oral JAK inhibitor study that completed the phase 2 study. Upadacitinib is ongoing. It's a JAK1 inhibitor. Again, we think that's going to be safer than other type of JAK inhibitors. And that is right now undergoing its phase 2 studies. We should have the results of that hopefully later this year or next year. And that's exciting to have an oral JAK inhibitor, something that can be ingested rather than something to apply topically. There are other oral JAK inhibitor studies going on, as well as a new pathway, which is the IL-15 pathway. And there's a study with AMD 714, which is a subcutaneous injection, which is given for a certain period in patients with vitiligo. And what it does is it blocks, IL-15 production in the skin, which we think is important for resident memory T cells. When vitiligo occurs and goes away when it comes back, it comes back in the same spot frequently. And that's because resident memory T cells are still there. This strategy by blocking IL-15, it gets rid of the resident memory T cells, we think which will give you a durable remission in that area. An exciting study that's being done, and then future studies are going to be done on IL-15 receptor antibodies. And finally, there's a study going on with a kit. And this kit allows you to isolate melanocytes from a skin sample from the patient's hip, and then apply those melanocytes in drop-like fashion onto an area that you've prepared with dermabrasion or laser, where you can expand the donor-recipient ratio a multiple fold. And that study is ongoing. It has finished enrollment and we should see the results of that later this year or next year. There are a lot of great studies going on with both topical and systemic therapy, and we're going to have a lot more in our armamentarium very soon.

It's exciting to think about the idea of we're going to have to become more sophisticated, practitioners, and think much more carefully in a world of multiple choices. David, how do you think about topical versus systemic therapy? What's your algorithm going to look like for that?

: Currently we don't have a single FDA-approved medication to repigment patients with vitiligo. We have a clear need for both topicals as well as systemics. For those patients who have more limited involvement, a body surface area of maybe of 10% or less will probably be thinking of using our topical options, such as ruxolitinib cream. And for patients who have very widespread disease who may have 30% of their body covered with vitiligo, the oral option may make more sense. Additionally, if a patient has progressive disease, if they're getting new lesions, it's hard to use a topical to chase after new lesions, whereas an oral or a systemic option makes a lot more sense. And a lot of the systemics that we decide and will depend on what is the data that comes out of those studies, the safety, the comorbidities of the patient. And it's certainly a bright future.

Amit as you pointed out this is like, just an unbelievably exciting time. Literally, we've gone from having topical corticosteroids, topical calcineurin inhibitors, and phototherapy to a conversation in which we're talking about new topicals that are targeted, new oral agents that are targeted, a subcutaneous treatment that might create a durable remission. It's an unbelievably exciting time. And putting this all together, David, what does the future look like for treating vitiligo?

: With the first medicines that'll be FDA approved, I'm first hoping that we'll get improved access and recognition from the insurance companies and the payers that this is truly a medical disease not just a cosmetic disease and that patients who want treatment are able to receive it. Furthermore, not all patients have access to phototherapy, or providers who are adept at providing that phototherapy. And being able to give patients topical options pills, whether or not in combination, I think is very promising and to tailor the options to the particular needs of the patient, I think provides us with a lot of hope.

I'm glad you brought up the points that you did. We really must and that's part of why we're all here doing this round table is it's really critical that we as providers recognize this disease and recognize that it is a medical disease and treat patients with the respect that they deserve and to try as much as they want to get better, try to make them better. We need to fight as providers for access. We can't just accept the denial. We have to appeal. We have to fight for our patients. And ultimately, in doing this, we can change this disease forever. But ultimately these new treatments coming along are going to create possibility that we've never had before and make the process so much more enjoyable for us as providers and for our patients who are going to get better with these new therapies.

Drs. Pandya, Rosmarin and King share their enthusiasm about emerging therapies and data that is available for ruxolitinib.

Emerging Therapies in Vitiligo

Let's think about maintenance therapy. We talked about treatment of acute rapidly evolving disease. We talked about treatment of a stable disease and making that better. Now we have a patient that is better or has reached a plateau in their repigmentation. Now, how are we going to think about maintenance therapy in these patients? Are we going to suggest that they, again, if they're doing phototherapy, are we going to continue that infrequently? Are we going to have patients continue to apply topical Calcineurin inhibitors to areas of repigmentation perhaps on a decreased frequency? What do you all think about this? How do you counsel your patients starting with you Amit?

: I agree with David. That one study out of France, which showed that once your vitiligo lesion is gone, it tends to come back in the same spot later. One way that you can prevent the vitiligo from coming back again is to apply, for example, tacrolimus twice a week, and probably corticosteroids would work in the same way, twice a week show was shown to reduce the frequency of recurrence in the same area. You can do the same in areas that are not completely repigmented, but you reached a plateau. And at this point, you can also apply it perhaps twice a week to keep it from getting worse. When it comes to phototherapy, there haven't been good studies in looking at maintenance. However, we did assemble the consensus of approximately 15 to 20 centers across the world. And we published this a few years ago, which are called the consensus guidelines for phototherapy for vitiligo. And what we recommend is once the patient has hit a plateau to reduce phototherapy from 3 times a week, to twice a week for 1 month and see if the vitiligo comes back, if it doesn't, we reduce it to once a week for a month and see if it comes back. If it doesn't, we reduce it to once every other week for 2 months and see if it comes back. If it doesn't come back, then we stop. And the reason we don't go to every 3 weeks or every 4 weeks is because the skin doesn't have a memory beyond 2 weeks of the previous UVB treatment. I don't see a point in treating patients every 3 weeks or every 4 weeks. Now, as Heather mentioned earlier, there's such a burden of phototherapy that home phototherapy, is an ideal option. It's been shown to be just as safe. and just as efficacious as in-office phototherapy, I have over 600 patients with home phototherapy, and this is something that helps them to do maintenance phototherapy, and it helps them restart treatment when they notice a new lesion which can happen in many patients. I believe that about 60 to 70% of patients will have a new lesion if they stop therapy completely at some point, within the next few years after stopping.

David, what do you tell patients about maintenance?

: Like Amit, I will also offer the option of tacrolimus twice a week. If patients prefer to use topical corticosteroids will just counsel about them being careful about corticosteroid atrophy, and there's not quite the same amount of data, but it likely works. I also will do phototherapy for patients at a lower frequency oftentimes at around, once a week, for patients. And again, there's some flexibility there depending on the patient and how they're doing, and there's an art there for, if a patient starts to do worse, you can always increase the frequency if they're not doing as well. If they are doing really well, then you can also try to stop it and see if they'll maintain that response.

Vitiligo clinical experts discuss the role of maintenance therapy in preventing recurrence of vitiligo.

Place of Maintenance Therapy in Vitiligo

Wrapping up this section, a couple of important points everybody has said at one point or another, this takes time. We've talked about counseling patients, this is going to take time. How much time, and here Heather, what do you tell patients to create reasonable expectations? We know if we tell a patient, go home, and use this and we don't tell them this is going to take months, it makes sense. They're going to stop in 6 weeks and go find another dermatologist. And so how do we need to have this conversation with patients? What do we need to tell them to expect over time?

: This is such a good point because we really need to set realistic expectations when it comes to vitiligo improvement. I am very honest with my patients. I feel like the face as we've discussed is the easiest to repigment. I tell my patients, you should see significant improvement at around 4 months. You should definitely start to repigment and a lot of patients do quite well. I do think that I am lucky as to where I practice where we just get a tremendous amount of ultraviolet light. But, in addition to the patients who are doing UV treatments in the office, but I say months and months and months. For the face, I say at least 4 months for you to see results that you will feel like this is really working. Now for the other parts of the body so we've talked about the more challenging areas, the hands particularly the tips of the fingers that can take much longer, a year. And we must be honest with our patients. I think that's very, very, very important to say, this can take 6, 8, 12 months to treat these areas. And you may not see improvement in the most challenging areas, like the tips of the fingers. I set the expectations early and I tell them for the face I'm confident. It's important to give vitiligo patients hope. I do emphasize on the positive. Most patients that I see present with some facial involvement. And I say with a lot of confidence, your face is going to do really great. And in around 4 months you should see some significant improvement. And then I temper that with the realistic expectations for the body, which we all know covered areas, genitals, chest underarms are hard to treat. I set those expectations to be months and some areas are very, very challenging to repigment and we may not see pigmentation in those areas.

Hearing you say that reminded me of what Amit said earlier about photography and the value of photography in the vitiligo patient encounter. Because the worst is when somebody comes back and they're living in their skin. And they're not necessarily seeing the dramatic change because it's happening day after day. And they get used to it and they fail to remember what they look like 4 months ago or 6 months ago. And a photograph is critically important in helping them understand, whoa, whoa, whoa, look how far we've come or look that we've made even a little bit of progress. But again, if you establish, early in the relationship with patients that this is going to take a lot of time, even seeing a little bit of improvement, it helps to reinforce, look, I said that this is going to take time, but look, you're making progress. And let's keep going if that's what you want to do.

: Yes. And the other thing I want to bring up is that we also should never make assumptions on what a patient thinks improvement is. Sometimes a patient might follow up and they might just be when you look at the photographs a little bit better, but they get excited because they do see some change and some improvement. Other patients can totally repigment except for a few little areas and be very disappointed because those few little areas didn't repigment. It requires a lot of discussion setting expectations and also discussing with the patient realistically, what results would you be happy with. Once you set those expectations at the beginning, it's a much easier management– once you set those expectations with the patient, it's much easier to manage vitiligo as a team. The dermatologist and the vitiligo patient together are on the same team. We know what our expectations are and what we're both actively working to achieve.

: I'd like to answer their question of why it takes so long to see repigmentation. I'm amazed that when I see a patient with guttate psoriasis, I can give them 12 phototherapy treatments. And when they come back after just 12 treatments, they are substantially better or clear. Why is that? In psoriasis the phototherapy is getting rid of a band of T cells in the dermis and the neutrophils in the epidermis. And once those are gone, everything just comes back to normal. But in vitiligo, the phototherapy, and the creams and such, you're applying first it has to get the epidermal keratinocytes and dendritic cells to make less CXCL9 and CXCL10. And then the T cells that are attacking the melanocytes have to disappear from the epidermis. And then the helper T cells have to disappear from the dermis. And then the melanocytes that are at the edges, who are in a state of shock must recover from the killing. And then the melanocytes at the base of the hair, which is one centimeter or half a centimeter way below the epidermis must be stimulated to start replicating and migrating. And you're asking cells to migrate up the outer roots sheath and then fill in the skin and the ones from the side to move in. This helps explain why psoriasis and vitiligo are so different in terms of response. And the studies have shown that in the average improvement with everything we've talked about is 25% improvement in 3 months, 50% improvement in 6 months, and 75% improvement in nine months. And then it plateaus. Now, like Heather said, the face will do more than 25%. The hands will do less than 25%, but on the mean improvement is 25, 50, and 75. I explain that to every single patient. They know that they're going to be my friend for at least 9 months, and I'm going to be walking this path with them, and we're going to be seeing that percentage improvement.

Again, the conversation with patients and helping them understand the process, and love that. For the patient who wants more information, helping them understand that is critical, but, I also think Amit, it's really important that all of us, that providers understand that process. Because again we have this idea from psoriasis biologics, why can't we make everything go away, and get improvement in three months? It's because we're talking about melanocyte destruction and melanocyte revival. And that fundamentally is not like making red skin go away, as is often true in other inflammatory diseases that we're accustomed to treating. And it's helpful for us as providers to understand that process and to understand why it's so slow, but also to communicate that with patients, so that they get early buy-in to the amount of time this is going to take.

Drs. Woolery-Lloyd, King and Pandya discuss time to re-pigmentation of different areas in vitiligo.

David Rosmarin, MD

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