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



– Targeting the Janus kinase (JAK) 1 and 2 pathways in vitiligo resulted in significant reduction of facial depigmentation after 24 weeks of treatment, in a phase 2b trial of topical ruxolitinib cream.

Dr. David Rosmarin, a dermatologist at Tufts University, Boston. Kari Oakes/MDedge News

Dr. David Rosmarin

With all four doses of ruxolitinib in the cream formulation evaluated, significantly more patients with vitiligo had at least 50% facial repigmentation, compared with vehicle alone, said David Rosmarin, MD, speaking in a late-breaking abstracts session at the World Congress of Dermatology.

The highest response rate was seen with a higher dose: Among patients receiving ruxolitinib cream 1.5% once daily, 50% met the 50% clearing mark at 24 weeks, as did 45.5% of those with twice-daily 1.5% dosing of the 1.5% formulation. At 24 weeks, 3.1% of those receiving vehicle had 50% facial vitiligo resolution (P less than .0001, compared with vehicle for both doses).

Vitiligo affects about 3,000,000 people in the United States, and it is a plausible treatment target for the JAK inhibitor ruxolitinib, explained Dr. Rosmarin, a dermatologist at Tufts University, Boston. “Interferon-gamma, signaling through JAK1 and JAK2, is central to the pathogenesis of vitiligo,” he said. “Ruxolitinib is a potent inhibitor of JAK1 and JAK2, so it made sense to investigate it as a treatment for vitiligo.”

The 24-month randomized, double-blind, vehicle-controlled phase 2 study of ruxolitinib cream for vitiligo compared the vehicle to four different concentrations of ruxolitinib during the first phase of the study. For the first 24 weeks, patients were randomized to receive vehicle twice daily, or various doses of ruxolitinib ranging from 0.15% once daily to 1.5% twice daily.

At this point, the study’s primary endpoint was assessed, with investigators comparing the proportion of patients treated with ruxolitinib who had at least 50% improvement in facial repigmentation from baseline on the Facial Vitiligo Area Scoring Index (F-VASI50) compared with those who received vehicle. A secondary endpoint, also assessed at week 24, was the proportion of patients who were clear, or almost clear, of facial vitiligo; safety and tolerability were also assessed.

In addition to the F-VASI50 measure, Dr. Rosmarin and his coinvestigators also tracked 75% facial clearing (F-VASI75). Here, the 1.5% twice daily regimen topped the others, with 30% of those receiving that dose achieving F-VASI75, compared with almost 10%-17% of those on other doses.

Using another measure, More than one-third of patients using ruxolitinib (35.3%) had clear (no signs of vitiligo) or almost clear (only specks of depigmentation) facial skin at week 24, according to a clinician assessment tool. No patients on placebo had clear or almost clear facial skin at that point. “It is my hope that with continued use beyond week 24, more patients will meet this very stringent endpoint,” Dr. Rosmarin said.

The safety profile was good, with no serious treatment-related adverse events, and no application site reactions that reached clinical significance, although numerically more patients reported acne with ruxolitinib than with vehicle alone.

In the trial, patients aged 18-75 years with vitiligo were eligible if they had facial depigmentation that constituted at least half of their body surface area (BSA), as well as depigmentation of at least 3% of BSA on nonfacial areas. Patients were excluded if they had another dermatologic disease, infection, prior JAK inhibitor therapy, or recent use of biologic or experimental drugs, laser or light-based treatments, or immunomodulators. Of the 157 patients who were randomized, 18 patients (11.5%) had discontinued treatment by week 24, with 3 patients stopping for adverse events, 3 for protocol deviation or noncompliance, and 10 withdrawals. Two patients were lost to follow-up; all patients were included in analysis of the primary and secondary endpoints.

In the second year of the study, investigators rerandomized patients who had been receiving vehicle to an active arm of the study, and patients who had less than 25% improvement on a facial vitiligo scoring scale were rerandomized to one of the different doses. Twenty-eight weeks after rerandomization, all participants were given the opportunity to participate in a year-long open-label extension, receiving 1.5% ruxolitinib cream twice daily. Phototherapy was allowed in the extension arm, but not in the first year of the study.

Data beyond 24 weeks have not yet been reported, and the 2-year study plan acknowledged that “repigmentation takes a while,” Dr. Rosmarin said. He added that patients were allowed to use the study drug on body vitiligo as well, and many saw improvement there, although these results weren’t tracked in the study. “This isn’t a drug that’s meant just for the face,” he said.

Dr. Rosmarin and his coauthors reported financial arrangements with several pharmaceutical companies, including Incyte, which funded the study. An oral formulation of ruxolitinib (Jakafi), marketed by Incyte, was approved by the Food and Drug Administration in 2011, for myelofibrosis, and was recently approved for steroid-refractory acute graft-versus-host disease in adults and children aged 12 years and older.

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