Ruxolitinib, Povorcitinib Effective in Treating Vitiligo, According to Posters

Nonsegmental vitiligo could be effectively treated by using either ruxolitinib or povorcitinib, according to posters published during Fall Clinical Dermatology 2023, held in Las Vegas. Both treatments were well tolerated in their respective cohorts.

Vitiligo is an autoimmune disorder that affects the pigmentation of skin due to the destruction of melanocyte cells. Effective treatment regulates the interferon-g activation of the Janus kinase (JAK) signaling pathway. Ruxolitinib has been approved by the United States and the United Kingdom for topical treatment of nonsegmental vitiligo whereas povorcitinib has been found to be effective after 24 weeks in a phase 2b trial.

The objective of the first poster¹ was to evaluate the efficacy and safety data of ruxolitinib through 104 weeks of the TRuE-V long term extension (LTE) study. All patients who had complete the TRuE-V1 and TRuE-V2 studies, where all patients applied 1.5% ruxolitinib cream between 28 and 52 weeks twice daily, could be included in the TRuE-V LTE study. Patients were randomized 1:1 to either 1.5% ruxolitinib cream group or the vehicle group if they had achieved facial Vitiligo Area Scoring Index 90% improvement (F-VASI90). All patients who did not achieve F-VASI90 continued with 1.5% ruxolitinib cream through to week 104. The primary end point was the proportion of patients who achieved 75% or more improvement from baseline in facial VASI and 50% or more improvement in total-VASI (T-VASI50).

There were 342 patients included in this study, of whom 224 were randomized into the ruxolitinib cream cohort and 118 changed to ruxolitinib cream after 24 weeks in the parent studies. The mean (SD) age of the patients was 39.4 (15.8) years and patients were enrolled as young as 12 years.

Two hands affected by vitiligo - autoimmune skin disorder put together on a wooden table | Image credit: Liga Cerina - stock.adobe.com

F-VASI75 was achieved by 66.1% of patients who applied ruxolitinib from the beginning of the trial and 47.3% of patients who started ruxolitinib after 24 weeks. T-VASI50 responses were achieved in 63.8% of patients who applied the cream from the start and 54.8% of the patients who started using the cream after week 24. Although similar patterns of response were found in patients who started ruxolitinib later, their response rates were generally lower compared with those who started day 1.

Adverse events during treatment occurred in 50.6% of patients in this study. Treatment-related adverse events were reported in 5.8% of patients, all classified as moderate or mild. The rates of adverse events were similar regardless of start time of ruxolitinib cream.

The researchers concluded that adolescents and adults who had nonsegmental vitiligo achieved F-VASI75 and T-VASI50 responses after 104 weeks when applying ruxolitinib cream 1.5% in the TRuE-V LTE study, regardless of their demographics and clinical characteristics.

The second poster² described the results of a study that had a primary objective of evaluating how safe and effective povorcitinib was for patients who had nonsegmental vitiligo after being treated for 52 weeks. The durability of the treatment was also tested for 24 weeks after the initial treatment.

The phase 2b study was randomized, placebo-controlled, and dose ranging. The participants were all adults aged 18 to 75 years who had a clinical diagnosis of nonsegmental vitiligo. Patients needed to have depigmented areas of 0.5% or more on the face and 8% or more on the total body surface. Randomization into 4 groups to receive 1 of 3 doses of povorcitinib (15, 45, or 75 mg) or a placebo was done in a 1:1:1:1 ratio. After 24 weeks had been completed, patients entered into an extension period where they were given either 45 mg if they were randomized into povorcitinib 45 mg or 75 mg if they had been initially randomized into 1 of the other 3 groups. This treatment lasted for 28 weeks and had a 24-week follow-up period.

The percentage change of T-VASI and F-VASI from baseline was the primary end point. The secondary end points included the percentage of participants who achieved T-VASI50 and a reduction of 50% or more in F-VASI50/F-VASI75 from baseline.

There were 171 patients included in this study, of whom 54.4% were female and 66.7% had Fitzpatrick skin types I through III. A total of 80.7% of the patients entered the extension period to receive povorcitinib 45 or 75 mg, with 86.2% of that cohort completing the additional treatment. A total of 32 patients completed the follow-up.

The researchers found that there was a statistically superior improvement in T-VASI in patients who were treated with povorcitinib compared with placebo after 24 and 52 weeks. More patients were able to achieve T-VASI50 compared with placebo at week 24 with continued improvement into week 52. F-VASI also significantly improved after 24 weeks with continued improvement through to 52 weeks, with more patients achieving F-VASI50 and F-VASI75.

Although the sample size was small, there was maintenance of T-VASI scores through to week 76. The median percentage of improvement in the score of T-VASI was –18.0% after excluding 1 outlier from week 52 to week 76. F-VASI scores also showed durability with the median improvement from week 52 to 76 in the povorcitinib 75 mg group being 13.3% after excluding 2 outliers.

Treatment-emergent adverse events occurred in 89.2% of patients with grade 3 or higher occurring in 16.9%; serious adverse events occurred in 2.4% of patients. However, none of these adverse events were considered to be related to the treatment.

The researchers concluded that oral povorcitinib was associated with substantial facial and total body repigmentation through 52 weeks of treatment. The durability of the response was also shown in the posttreatment period of 24 weeks, although the sample size was small. The treatment was deemed safe and well tolerated.

In these 2 studies, both ruxolitinib and povorcitinib appear to be effective treatments for vitiligo, indicating their potential to help patients with the condition.

Reference

1. Seneschal J, Wolkerstorfer A, Ezzedine K, et al. Efficacy and safety of ruxolitinib cream through week 104 in patients with vitiligo: subgroup analysis of the TRuE-V long-term extension phase 3 study. Presented at: Fall Clinical Dermatology 2023; October 19-22, 2023; Las Vegas, NV.
2. Pandya AG, Ezzedine K, Passeron T, et al. Efficacy and safety of povorcitinib for extensive vitiligo: 52-week results from a double-blinded, placebo-controlled, dose-ranging phase 2b study. Presented at: Fall Clinical Dermatology 2023; October 19-22, 2023; Las Vegas, NV.