The role of JAC inhibitors in the treatment of vitiligo

David Rosemary, MD: Our JAK inhibitors have shown the best results. Ruxolitinib 1.5% cream twice a day went through two phase studies 3. PDUFA [Prescription Drug User Fee Act] The date is July 18, 2022. Studies show that about half of patients per year will get 75% or more of the dye on the face, and about half of the patients per year will get 50% or more of the dye back on the whole body. This is what the data for ruxolitinib cream show. In terms of safety, it looks promising. It’s already approved for the treatment of atopic dermatitis as of September 2021. We see an average of 6% acne and 6% application site reaction, itchiness, or redness, but it generally doesn’t burn or sting. This is a very promising treatment for vitiligo patients.

When we look at the subgroup analysis, we see that it does not matter whether the patients have had vitiligo for more than 50 years or for a short time. It works across age, gender, and ethnicity. We see fairly similar responses across all of those different subgroups. This is also what we see from the data from ruxolitinib cream. When we look at the anatomical regions, we find that the head and neck are in the best condition, the trunk and extremities next, and the unstable locations are the least responsive. However, we still saw a significant benefit to the hands and feet with ruxolitinib cream compared to vehicle.

Regarding some other JAK inhibitors in development, ritlecitinib, a JAK3 inhibitor from Pfizer, completed a phase II trial. This study was designed slightly differently. Only patients with progressive active vitiligo were included. About 12% of patients achieved 75% or more of repigmentation at the 6-month mark on the highest dose of the drug. We view both oral and topical as essential because oral may be better for patients who have a large area of ​​the body. ruxolitinib cream has limited body surface area to 10% or less. With patients naturally aging and getting new places, it’s hard to keep chasing that with the cream. An oral agent would make more sense, just like using light therapy. This is how we see it. There is room for both topical and oral JAK inhibitors, and both will be important for helping patients out.

Brett King, MD, PhD: One thing we left out in the conversation is that it’s no coincidence that we’re talking about JAK inhibitors. This is very intentional with JAK inhibitors, autoimmunity [system]The mechanism of the disease, the mechanism by which T cells or immune cells attack and destroy melanocytes, or melanocytes, in the skin, appears to be mediated to a large extent by the body’s cytokine or chemical messenger, from which messages are sent that can be disrupted with a JAK inhibitor. . It is important for everyone to know that this is not another case of just dumping a JAK inhibitor into an autoimmune problem. We have a lot of data to support that this is the right course for this disease.

David Rosemary, MD: It has a great mechanical meaning. Our typical immunosuppressants do not work well on a particular arm of the immune system that is very active in treating vitiligo. JAK inhibitors work, which is why it is appropriate to use these medications for vitiligo patients. It targets the specific aspect that is problematic for vitiligo patients.

David Epstein, MD, MBA: I heard data from Phase II that only 12% of patients achieved it.

David Rosemary, MD: That was for ritlicitinib at the highest dose at 6 months. 12 percent of patients received F-VASI [Face Vitiligo Area Scoring Index] 75 in that study, with the caveat that it was not designed quite like the ruxolitinib cream study done by Incyte.

Text has been edited for clarity.