Experts in dermatology review the mechanism of action and clinical trials of topical ruxolitinib for repigmenting the skin in vitiligo.
Seemal Desai, MD: We know that we are for the first time ever, in the history of this disease, just 8 months ago, have the first-ever FDA-approved therapy to repigment vitiligo. We’ve never had any therapy to make this disease better. Ironically, the fun fact for any residents—and I love doing this, giving a true or false. There’s never been any treatment for vitiligo ever FDA-approved, and the answer is false because monobenzyl ether of hydroquinone was approved many, many years ago to depigment the disease.
Heather Woolery-Lloyd, MD: That’s right.
Seemal Desai, MD: But now we finally have something to make it better. So Heather, talk to me about the mechanism of ruxolitinib. How does it work? How do you explain it to your patients? What do you tell them?
Heather Woolery-Lloyd, MD: What I tell my patients is very straightforward. The treatment we have is topical ruxolitinib. And it is FDA-approved for, and I tell my patients this because they need to know. I have all ages. I see primarily adults, but I have younger patients too. So, it’s FDA-approved for adults and pediatric patients 12 years of age and older. First, when I go into discussing vitiligo with my patients, I explain it’s an autoimmune disease and that their immune cells got confused and started to attack the melanocytes and I just explain basically that it stops that process. So that’s how I explain it to my patients. We know it’s a JAK [Janus kinase] inhibitor. It’s not a biologic, so it works on the inside of the cell, and it basically stops the signal transduction of the production of these chemokines, these inflammatory chemokines that we know drive the destruction of melanocytes. So that’s how it works. And I’ve had great results and we talked about the face. I’m lucky that I live in this very sunny climate, so I have a lot of light helping me along. I can say with confidence we can repigment your face. It just feels so good to be able to say that with confidence.
Seemal Desai, MD: Absolutely.
Heather Woolery-Lloyd, MD: And that’s how I discuss it with my patients.
Seemal Desai, MD: I think some of you have heard me say this, and I know my residents at Southwestern hear me say this all the time, that if someone comes in with vitiligo on the face, I always say the face is fabulous. And these patients look at me like I’m nuts that I’m so excited they have facial vitiligo. I’m excited because that’s the one area I know I can probably get you better and get you better pretty quickly.
Heather Woolery-Lloyd, MD: Exactly. Yes.
Seemal Desai, MD: So, speaking of ruxolitinib trials, Nada, you do a lot of clinical research. So, when we talk about any of these studies there’s always a study design with inclusion and exclusion criteria. Can you talk to us just a little bit and set up for us the landscape of the pivotal ruxolitinib trials and how they were done?
Nada Elbuluk, MD: Yes. So, the trial was basically only for individuals 12 years of age or older, which is why, as to Heather’s point, we can only use it in kids that are 12 and up, but hopefully in the future, with more studies, be able to use it on younger individuals. It was also for people with non-segmental vitiligo. We talked early about the subtypes. So, these individuals had to have non-segmental vitiligo and a body surface area of 10% or less. With that inclusion criteria they basically divided the patients into 2:1 ratio, into individuals using the 1.5% ruxolitinib cream versus the vehicle or placebo for 24 weeks, and it was twice-a-day application. After the 24 weeks, everybody could then switch to using it. The 1.5% cream twice a day on all the affected areas up to 52 weeks. So that was essentially the setup for the study and the data that we currently have.
Seemal Desai, MD: That’s perfect. And Ted, do you want to comment on the results? Because I know you were actively involved.
Ted Lain, MD: Yes.
Seemal Desai, MD: And talk to us a little bit about what was seen at that primary efficacy end point, and perhaps some of the secondary efficacy end points.
Ted Lain, MD: I just want to reiterate that this is monotherapy. We’ve talked about how vitiligo is a—I call it a kitchen-sink disease, which is something that you throw the kitchen sink at, much like alopecia areata, for example. So, monotherapy, the ruxolitinib cream 1.5% applied BID [twice a day]. F-VASI [facial Vitiligo Area Scoring Index] 75 means a 75% reduction in the F-VASI, the Facial Vitiligo Area Scoring Index. That was a primary efficacy end point measured at week 24. And it was about 30% in the ruxolitinib cream and 7.4% in the vehicle group, and that was replicated between the 2 identical pivotal trials, TRuE-V1 and TRuE-V2. When you see that the data is replicable like that, it gives you confidence between the 2 pivotal trials, and that’s why it’s so important for us to have 2. In TRuE-V1 and TRuE-V2, half the patients who applied the ruxolitinib cream from day 1, had at least 75% facial repigmentation and 50% total body repigmentation, so an F-VASI 75 and a T [total]-VASI 50. So, 50% of the patients achieved both of those end points. It wasn’t a composite end point score, that’s just giving an idea that that 50% of patients were able to see results on both the face and the body. As expected, the body should not respond as well as the face based on the density of the hair follicles as I mentioned before. And then in terms of 52 weeks, because there was an open-label extension, excuse me, a long-term extension, where those who were in placebo at week 24 were randomized again into the active group. So, for those who were randomized from placebo back into the active group, they had results that were similar to the results that we saw at week 24 in the active group anyway. So, they performed much like they would have, had they been from week 0 to week 24. So again, that’s important because we see a catch-up there. So those are the results. Again, the thing to remember in my mind, week 24, about 30% of patients saw at least a 75% improvement in the F-VASI and that continued to improve, I think we talked about this, continued to improve through week 52 in the long-term extension.
Seemal Desai, MD: And I’m so glad that you’ve started your comments by saying that the study was monotherapy, because you’re absolutely right that, and I have to admit, I was an investigator in this study. I’m very proud of this study. This paper was just recently accepted to the New England Journal [of Medicine], so this is the first time there’s been a topical paper that’s published in the New England Journal of Medicine. This is landmark stuff. But it was monotherapy, and these patients did get better. It was hard as an investigator to remain blinded because it was very clear who was going to be on the active. But keep in mind in real life, all of us probably combine therapies even though that’s not per package insert. But in the study, you use monotherapy. These patients got better, and that’s why this ultimately got FDA-approved.
Ted Lain, MD: Exactly.
Seemal Desai, MD: I think our colleagues need to understand that even if you’re not comfortable taking a combination approach, you now have a therapy that actually tells you to not take a combination approach. And that you can take a monotherapy approach. So, I’m glad you teed it up that way. That was great.
Transcript edited for clarity