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"Speaking of Vitiligo..."

Vitiligo JAK Inhibitor Update

Thursday, December 29, 2016

Ever since the report from Yale published about a vitiligo patient who improved after using Xeljanz (tofacitinib) and then our report about Jakafi (ruxolitinib) in another patient, there has been a lot of buzz around the use of JAK inhibitors in vitiligo. Many have asked me for updates on these new drugs for vitiligo by commenting below the blog posts, or tweeting, or emailing me, or stopping me in the hall, pulling me aside at conferences, etc. There have been no published reports since these first two, and I have to be careful speaking publicly about ongoing studies, discussions with companies, etc. But I will do my best to update you on the potential for these drugs in vitiligo.

First, similar to vitiligo, there has also been a lot of interest in the use of JAK inhibitors in patients with alopecia areata, an autoimmune disease like vitiligo where patients lose their hair in spots on their scalp and other parts of their bodies. Four recent published studies tested the efficacy of Xeljanz (tofacitinib) or Jakafi (ruxolitinib) in small clinical studies for alopecia areata patients. While not controlled or blinded, they give some insight into the usefulness and safety of these drugs in alopecia areata patients. One study tested Xeljanz in 66 subjects and reported that 32% experienced at least 50% regrowth of their hair during the study period, while a second study in 12 subjects reported that 75% of those treated with Jakafi reached this benchmark. Most patients in both studies relapsed (saw the disease return) when the drug was discontinued, demonstrating that these responses are not permanent. Two other studies used Xeljanz, one in 13 adolescents and one in 90 adults, and both reported better results but with longer treatment courses and some with increased doses. Side effects in all studies were reportedly mild, including treatable infections, headache, fatigue, acne, GI upset, low blood count, mild liver changes, and a few others. But overall the treatments seemed well tolerated.

So what does that mean for vitiligo? Well, we’re learning a lot about using JAK inhibitors for inflammatory skin diseases from these studies, even if they’re not directly in vitiligo patients. First, the doses may need to be higher than what is typically recommended by the FDA for their approved diseases, particularly for Xeljanz. Often effective doses (10mg twice daily) are double that which is currently approved by the FDA (5mg twice daily). Second, topical treatments are being tested in alopecia areata and vitiligo – there is an ongoing small trial to test topical Jakafi for vitiligo patients in Boston, although the results aren’t public yet. I’ll be sure to let you know when they are. Third, so far the patients getting these treatments haven’t experienced severe side effects. BUT, that doesn’t mean these are perfectly safe. The reported efficacy and safety in these studies leave me cautiously optimistic about this strategy, but the emphasis on caution with our limited experience cannot be underestimated.

To highlight this, let’s look at a disease that represents the opposite of vitiligo – melanoma. Patients with melanoma don’t have a good enough immune response against cancerous melanocytes, whereas vitiligo patients have such a strong immune response that even normal melanocytes are killed. New melanoma treatments that increase immune responses to the tumor are exciting new treatment options for patients, resulting in 5-year survival in about a third of severe, late-stage patients (that’s a huge improvement, by-the-way). However 25% of those who initially get better then relapse within two years, suggesting that melanomas may develop mutations that allow them to escape immune attack during these new treatments. It turns out that some tumors escape the immune attack by turning off JAK signaling, which is similar to what the inhibitors are doing. Therefore, one concern will be that JAK inhibitors increase the risk of cancers as a possible side effect. So some respect for the role of JAK signaling in helping immune responses against tumors is important. Now chemical inhibitors won’t be as strong as actually mutating the JAKs to eliminate them as the tumor does, so they may still be relatively safe. But this is one of many reasons why my lab isn’t relying on JAK inhibitors for future treatments (i.e. put all of our eggs in the JAK basket), but we’re looking into many other options as well. In the end, we will use treatments that work the best in patients and have the best safety as well.

So there’s the update on what’s going on in the development of JAK inhibitors for vitiligo and other autoimmune diseases. The two vitiligo patients mentioned above seem to have improved significantly on JAK inhibitors. Hundreds more with alopecia areata have improved as well, and so far the drugs seem to be relatively safe. But our experience is still limited, and we should remain cautiously optimistic about their use. Many companies are developing new JAK inhibitors that may work better and be safer than what’s available today. Clinical trials are starting shortly for other autoimmune diseases, and trials for vitiligo shouldn’t be far behind. It simply depends on when the companies who make them decide to fund the trials, and you can help. Advocate for yourselves! Let them know how important it is to have better treatments for vitiligo. And remember if you’re interested in participating in future clinical trials for vitiligo, sign up for our newsletter here, which is where I will announce enrollment for these trials first.