Conference Coverage

Vitiligo: First-ever RCT is smashing success



Repigmentation in patients with vitiligo documented at 24 weeks continued to increase up to 1 year, in a randomized clinical trial of ruxolitinib cream for the treatment of vitiligo, Amit G. Pandya, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Dr. Amit G. Pandya, a dermatologist at the University of Texas Southwestern Medical Center, Dallas Bruce Jancin/MDedge News

Dr. Amit G. Pandya

“I have been waiting 30 years for the first clinical trial for vitiligo. I know many of you dermatologists have been waiting for something for vitiligo, so I’m happy to present the results of the first randomized, placebo-controlled, double-blind, prospective trial of a topical agent in history for vitiligo,” said Dr. Pandya, who was clearly overjoyed to present the final results of the 52-week trial.

Ruxolitinib is a Janus kinase (JAK) 1 and 2 inhibitor. Topical ruxolitinib is under study for vitiligo because this chronic autoimmune disease targeting melanocytes is now recognized as being driven by signaling through the JAK 1/2 pathways.

The interim 24-week results of the phase 2 trial, presented earlier in the year at the World Congress of Dermatology in Milan, showed significant repigmentation with ruxolitinib cream. Dr. Pandya’s key message at EADV 2019 was that continued treatment out to a year brought substantial further improvement, and with a benign safety profile indistinguishable from vehicle control.

Topical ruxolitinib looks good for facial vitiligo, in phase 2 study

“We see a tremendous difference between 6 months and 1 year,” said Dr. Pandya, professor of dermatology at the University of Texas, Dallas. “For the first time, we dare talk about F-VASI75 [Facial Vitiligo Area Scoring Index] and F-VASI90 responses. We don’t usually tell patients that they can get 75% or 90% of their color back, and yet the week-52 F-VASI75 rate was 51.5%, up from 30.3% at week 24. And the F-VASI90 response was 33.3%, versus 12.1% at week 24.”

F-VASI is measured using the patient’s hand, which is typically equivalent to about 1% of body surface area. The mean baseline F-VASI was 1.26% in this study of 157 mostly middle-aged adults with longstanding vitiligo of a mean 14-year duration. That’s fairly severe vitiligo, since the total face occupies only about 4% of total body surface area.

The primary study endpoint was achievement of greater than 50% repigmentation in the F-VASI, or an F-VASI50 response. Under double-blind conditions at 52 weeks in the group randomized to 1.5% ruxolitinib cream twice a day, the highest dose used in the trial, the F-VASI50 rate was 57.6%. That’s up from a week-24 F-VASI50 of 45.5%, and a week-34 response rate of 51.5%.

A key secondary endpoint was T-VASI50, reflecting the total body response.

“Patients don’t just want their face to be better, they want their chest, arms, elbows, knees, hands, and feet to be better,” the dermatologist commented.

The week-52 T-VASI50 rate was 36.4%, up substantially from 12.1% at week 24. And that week-52 T-VASI50 rate probably underestimates the full potential benefit. That’s because a safety-based study rule prohibited patients from applying the cream to more than 20% of their body surface area. Adverse effects reported for oral ruxolitinib, approved for treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease, include thrombocytopenia and anemia.

“In this early study we didn’t want to take a chance of systemic absorption with serum levels that would potentially affect the bone marrow,” Dr. Pandya explained.

He noted that 57 study participants had a baseline T-VASI greater than 20% of their body surface area and thus weren’t able to treat all of their disease. In the 100 patients with a vitiligo-involved total body surface area of 20% or less, however, the week-52 T-VASI50 reached 45%, compared with 20% at week 24.

Another prespecified secondary endpoint was the proportion of patients who received a facial physician’s global assessment of clear or almost clear. About 21% of patients in the highest-dose group achieved this milestone at 52 weeks.

A phase 3, randomized, controlled trial of ruxolitinib cream is ongoing and should be completed next year. Dr. Pandya reported receiving research funding from and serving as a consultant to Incyte, the study sponsor. He has similar financial relationships with Pfizer, Aclaris Therapeutics, and the Immune Tolerance Network.

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