Heather Woolery-Lloyd, MD, and Ted Lain, MD, discuss the mechanism of action and efficacy of ruxolitinib cream in the treatment of vitiligo.
Heather Woolery-Lloyd, MD: Topical ruxolitinib cream is FDA-approved for nonsegmental vitiligo. How does the product work?
Ted Lain, MD: It is a topical JAK [Janus kinase] inhibitor. JAK inhibitors are intracellular small molecule medications. They work inside the cell to block the effects of interferon on the keratinocyte or on the melanocyte. By blocking the effects of the JAK, which is attached to the receptor on which the interferon binds, you can block the downstream effects, which stops the phosphorylation of the JAK, stops stack phosphorylation, and, therefore, blocks any kind of transcription of and the production of inflammatory cytokines. It binds to the JAK enzyme, which, at its core, stops the production of inflammatory cytokines and, therefore, destruction of the melanocytes is halted.
Heather Woolery-Lloyd, MD: It works inside of the cell and stops that signal to produce all of those inflammatory cytokines that are driving this disease. Based on the clinical trial findings, and in your experience and practice, how does the repigmentation with ruxolitinib cream compare to other treatments for vitiligo?
Ted Lain, MD: There are no head-to-head trials yet. In fact, there are very few trials for vitiligo since nothing is FDA-approved. We look at week 24 in terms of the primary efficacy outcome for the ruxolitinib trials against the 6-month end point. That compares very favorably to anything else we do where you only see results 3 to 6 months after you have initiated the therapy.
Heather Woolery-Lloyd, MD: Patience is key when it comes to vitiligo because it takes so long to repigment. If you are already using ruxolitinib in your practice, how do you choose the right patient? Do you do monotherapy or combination therapy? How do you approach a patient when you decide topical ruxolitinib is a good treatment option?
Ted Lain, MD: First, we look inside the patches of vitiligo and make sure that there are dark hairs there. Because if there is pure leukotrichia, which means only white hair, there is no target for the ruxolitinib. If the stem cells aren’t there, you are not going to get the pigmentation that you need. So, focusing on the hair in those hair-bearing areas is important. The other thing to think about is the difference in response across the body. Areas with a higher density in hair follicles have a higher target for that treatment to work on and will repigment faster. So, the face will repigment faster, for example, than the wrists, knees, or elbows.
You also have to think about areas of trauma, such as the hands, elbows, and knees. Unfortunately, trauma plays a part in vitiligo, so you also need to educate your patient in terms of where they have the vitiligo and how different areas may repigment at different rates.
In terms of my treatment options, I tend to prescribe polytherapy. I do not use monotherapy, as we do in the trials, because I want things to get better quickly, and I have different options. I use a lot of narrow-band [ultraviolet B phototherapy] and excimer with my vitiligo patients. Now with the ruxolitinib, I will combine those 2. I might cycle on and off, either systemically pulse methylprednisolone, for example or pulse strong steroids, depending on where it is on the body. It depends on the patient and the location of the vitiligo.
Heather Woolery-Lloyd, MD: Topical ruxolitinib is approved for up to 10% body surface area. What do you do in those patients who have more than 10% of their body surface area affected?
Ted Lain, MD: I can prescribe the ruxolitinib for those areas that are more cosmetically appropriate, where I want to try my very best to get the pigment to come back. So, the face, the neck, the décolleté area, and the hands. I can use topical calcineurin inhibitors, topical corticosteroids, or narrow-band phototherapy elsewhere. If it’s a lot of body surface area involved, I may try a systemic JAK inhibitor because none of those are available for atopic dermatitis. Many of them are in trials right now for vitiligo. And I feel comfortable with them based on my experience with A&D [acquisition and development] and based on my experience with clinical trials.
Heather Woolery-Lloyd, MD: I do the same thing in my practice. I focus on the areas that the patient’s most concerned about that we are most likely to get the best response, like the face, for example. I practice in a very sunny climate, so repigmentation is a little bit easier.
Transcript edited for clarity