JAK Inhibitor Results in Skin Repigmentation in Patients With Vitiligo

David Rosmarin, MD, vice chair of education and research, assistant professor, Tufts Medical Center, walks through findings from TRuE-V, a phase 3 program designed to investigate ruxolitinib's efficacy and safety in patients with vitiligo. 

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Welcome back to PopHealth Perspectives, a conversation with the Population Health Learning Network where we combine expert commentary and exclusive insight into key issues in population health management and more.

Hello, my name is David Rosmarin, and I'm a dermatologist at Tufts Medical Center in Boston, Massachusetts. I'm also the vice chair of education and research and help direct our clinical trials unit.

What existing data led to the phase 3 TRuE-V study?

We know that vitiligo is fundamentally a Th1 disease where there are high levels of interferon gamma which signal through the JAK-STAT pathway. So it makes sense to think about using a JAK inhibitor, like ruxolitinib, which is a JAK1/2 inhibitor, to treat vitiligo. After an investigator-initiated study and a phase 2 program, we showed really promising results in being able to repigment both the face and body with ruxolitinib premonotherapy. This led to the phase 3 study.

And can you tell us about the design and participants in the study?

The TruE-V1, TRuE-V2 phase 3 vitiligo program included both adolescents, as well as adults, and patients were randomized in a 2:1 ratio to either ruxolitinib 1.5% cream used twice a day or vehicle for 24 weeks. The primary endpoint at that 24-week mark was repigmentation as measured by 75% or more in the facial Vitiligo Area Scoring Index (VASI) score. Other key secondary endpoints include total body repigmentation improvement with a Total VASI (T-VASI) score, and “a lot less noticeable” or “no longer noticeable” scores on the Vitiligo Noticeability Scale.

After the primary endpoint at 24 weeks, all patients in the vehicle arm were given active medication. Patients were allowed to enroll in the study if they had a half a hand or more of vitiligo on their face, and at least 3% of vitiligo on their whole body. There was also a washout period for other commonly used vitiligo treatments before enrolling in the trial.

What are the key findings from the study, and were you surprised by any of them?

For the phase 3 program, the primary and all key secondary endpoints were met. So 30% of patients achieved Facial VASI (F-VASI) 75% at week 24, and patients continue to improve with continued use of ruxolitinib cream, so that about 50% of patients who used the medication achieved that endpoint at the year mark. Additionally, about 20% to 25% of patients achieved a T-VASI 50% or 50% improvement in total body repigmentation in week 24, and that improved to about half of the participants at week 52. Furthermore, about 30% to 40% of patients described their vitiligo as a lot less noticeable or no longer noticeable at the year mark. 

All of these are key findings and meaningful for our patients. What's remarkable to me is how consistent the results were from the phase 2 study—very reproducible.

In terms of safety and tolerability, the medication performs quite well. The medicine doesn't seem to burn or sting. There is about a 6% application site acne rate. Labs were checked throughout the study, and luckily, there weren't any clinically meaningful changes in lab values. So, a very promising treatment from the phase 3 program.

How do you think these data will impact clinical practice or payer decision-making?

A key part of the use of this treatment is that it was studied as monotherapy. Even on its own, patients are able to achieve significant repigmentation, should they desire.

Do you and your coinvestigators intend to expand upon this research in the future?

There are several key things that we still need to find out. One is we're seeing great results through week 52, but with continued use of the medicine, will we continue to see more improvement? That was a finding that we saw from the phase 2 study, where patients have not yet plateaued at the 1-year mark. With more use of the medicine, we expect patients to continue to benefit. Additionally, the phase 3 program looked at ruxolitinib cream as monotherapy, but what happens if we combine ruxolitinib cream with light treatment? We may see a synergistic and more rapid effect.

And finally, we also want to know about maintenance of treatment. So, once patients repigment successfully and attain their goals, how long will they maintain those results for? Will they need to use some degree of the cream to maintain those results? Still more to come.

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This transcript has been edited for clarity.