Prolonged Ruxolitinib Cream Effective for Vitiligo in Early Non-Responders

Individuals with vitiligo exhibiting minimal 6-month response to ruxolitinib cream may still attain substantial repigmentation with prolonged treatment extending to 2 years, new findings suggest.1

These findings resulted from an analysis assessing the long-term efficacy and safety of continuous treatment with ruxolitinib cream through 104 weeks in participants with vitiligo who had shown little or no clinical response by 24 weeks in the TRuE-V1 and TRuE-V2 trials.2 Investigators such as Albert Wolkerstorfer, MD, PhD, of Amsterdam University Medical Center authored these data.

Wolkerstorfer and coauthors described the aims of the TRuE-V1 and V2 trials as determining whether those who initially responded poorly to the medication could still see meaningful repigmentation with extended use of this therapy.

“Here, efficacy and safety of continuous ruxolitinib cream treatment over 104 weeks were evaluated among patients who had no or limited response to treatment at Week 24 in TRuE-V1/TRuE-V2,” Wolkerstorfer and colleagues wrote.1

TRuE-V1 and TRuE-V2 Details

In the original studies, those involved were randomized in a 2:1 ratio to be treated either with 1.5% ruxolitinib cream twice daily or a vehicle control for the initial 24 weeks. Following this double-blind period, all trial subjects entered a 28-week open-label extension in which they used ruxolitinib twice each day. Those who had not attained a 90% improvement in their facial Vitiligo Area Scoring Index (F-VASI90) at minimum by Week 52 continued therapy with ruxolitinib cream twice daily for an additional 52 weeks.

Wolkerstorfer et al’s current analysis was aimed specifically at participants who had originally been assigned to ruxolitinib cream but demonstrated less than a 25% improvement from the point of baseline in either the facial or total Vitiligo Area Scoring Index (F-VASI or T-VASI) at the 24-week mark. To be included, patients also needed to have available VASI assessments at the 52, 80, and 104-week marks.

Investigators evaluated shifts in F-VASI and T-VASI scores among those with either no repigmentation or worsening depigmentation (defined as ≤0% improvement) as well as those with limited improvement (>0% to <25%) at Week 24. Among the 443 individuals in the efficacy-evaluable population who were initially randomized to ruxolitinib cream, the mean baseline F-VASI score was 0.92 (SD, 0.55), while the mean baseline T-VASI score was 6.64 (SD, 2.04).

Of these individuals, 127 had shown either no facial repigmentation or only minimal improvement by the 24-week mark. Continued use of ruxolitinib cream was linked with progressively increased facial repigmentation rates over time.1 At the 52-week mark, 71.7% of these patients (n = 113) had achieved some level of improvement in F-VASI. This proportion was shown by the investigators to have risen to 87.5% at Week 80 (n = 80) and attained 90.1% by the 104-week mark (n = 71).1

When stratified by Week-24 response status, improvement by the 104-week mark was seen in 97.1% of those who had no repigmentation at Week 24 and in 83.3% of subjects with limited early improvement.1 The investigators also found the proportion of patients attaining at least a 75% reduction in F-VASI from baseline rose steadily during follow-up. Specifically, F-VASI75 was reached by 13.3% of patients at 52 weeks, 38.8% at 80 weeks, and 54.9% by 104 weeks.

A similar pattern was observed for total body repigmentation outcomes. Among 193 patients who had demonstrated no or minimal improvement in T-VASI at Week 24, the percentage showing subsequent improvement increased over time.1 By Week 52, 68.8% (n = 173) had experienced some degree of improvement in T-VASI. This rose to 81.4% at Week 80 (n = 118) and 84.9% at Week 104 (n = 106).

In their subgroup analyses, Wolkerstorfer and coauthors found improvement at Week 104 took place in 93.3% of individuals who initially had no total body repigmentation and in 81.6% of those showing a limited level of improvement at Week 24.1 T-VASI50 attainment, defined as at least a 50% reduction in T-VASI from baseline, also rose throughout the study period. The investigators noted the proportion of patients reaching this endpoint was 23.1% at Week 52, 42.4% at Week 80, and 50.0% at Week 104.

“In conclusion, >80% of patients with no or limited repigmentation at 6 months who continued to apply ruxolitinib cream over an additional 18 months achieved F-VASI or T-VASI improvements,” the investigative team concluded.1 “Half of the patients achieved clinically meaningful F-VASI75 or T-VASI50 at 2 years.”

References

1. Wolkerstorfer A, Gooderham M, Sebastian M, Harris JE, et al. Prolonged ruxolitinib cream treatment for vitiligo among patients with no or limited response in the first 6 months. J Eur Acad Dermatol Venereol. https://doi.org/10.1111/jdv.70402.

2. Rosmarin D, Passeron T, Ezzedine K et al. Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo. N Engl J Med. 2022 Oct 20;387(16):1445-1455. doi: 10.1056/NEJMoa2118828. PMID: 36260792.