Ruxolitinib Cream Improves Pigmentation in Vitiligo

Ruxolitinib cream was associated with greater repigmentation of vitiligo lesions compared with control, however, ruxolitinib also caused acne and pruritus at the application site. These findings, from 2 phase 3 trials, were published in The New England Journal of Medicine.

Patients (N=673) aged 12 years of age and older with nonsegmental vitiligo affecting 10% or less of the total body-surface area (BSA) with 0.5% or greater of BSA on the face and 3% or greater BSA on nonfacial areas were recruited for these phase 3, double-blind, vehicle-controlled trials (TRuE-V1 and TRuE-V2) at 101 sites in North America and Europe from 2019 to 2021. Patients were randomly assigned in a 2:1 ratio to receive 1.5% ruxolitinib (n=449) or vehicle (n=224) twice daily to lesions for 24 weeks. All patients were eligible to continue or switch to ruxolitinib for a 28-week open-label extension. The primary endpoint was 75% or greater improvement in Facial Vitiligo Area Scoring Index (F-VASI).

In the TRuE-V1 (n=330) and TRuE-V2 (n=343) trials, the patients had mean ages of 40.2±15.9 and 38.9±14.3 years, 56.4% and 50.1% were women or girls, 83.6% and 80.2% were White, 40.0% and 39.1% had Fitzpatrick skin type III, 74.2% and 74.1% had stable disease, 58.2% and 63.8% had received previous therapy, and they had F-VASI scores of 0.95±0.59 and 0.88±0.52 points, respectively.

In TRuE-V1, at week 24, 29.8% of ruxolitinib recipients achieved 75% or greater F-VASI improvement (F-VASI75) compared with 7.4% of vehicle recipients (relative risk [RR], 4.0; 95% CI, 1.9-8.4; P <.001). Ruxolitinib was also associated with a greater likelihood of achieving 50% or greater improvement of F-VASI (RR, 3.0; P <.001), 90% or greater improvement in F-VASI (RR, 7.3; P =.004), 50% or greater response in Total Vitiligo Area Scoring Index (RR, 4.1; P =.002), and a greater improvement in Vitiligo Noticeability Scale (RR, 7.5; P <.001) compared with vehicle.

Similar findings were observed in TRuE-V2, with 30.9% of the ruxolitinib and 11.4% of the vehicle groups achieving F-VASI75 (RR, 2.7; 95% CI, 1.5-4.9; P <.001).

Adverse events were reported by 45.7% to 50.0% of ruxolitinib recipients and 33.9%-38.5% of vehicle recipients. The most common adverse events included COVID-19, nasopharyngitis, headache, application-site acne, application-site pruritus, application-site dermatitis, and application-site rash. From 3.6% to 17.2% of the participant cohort experienced drug-related adverse events, in which application-site acne, pruritus, and exfoliation were most common. In all, 4 participants withdrew from the study due to adverse events of fatigue (n=1), application-site rash (n=1), and application-site eczema (n=1) for ruxolitinib recipients and nausea and headache for a vehicle recipient (n=1).

Plasma concentrations of ruxolitinib were consistent throughout the studies. The average steady-state concentrations at weeks 4 and 24 were 55.8±56.7 nM in TRuE-V1 and 58.0±68.1 nM in TRuE-V2.

The major limitation of this study was that few study participants had Fitzpatrick skin types IV (14.8%-23.3%), V (5.5%-7.9%), or VI (1.2%-2.9%).

These data indicated to researchers that “application of ruxolitinib cream resulted in greater repigmentation of vitiligo lesions than vehicle control through 52 weeks,” however, some patients experienced application-site reactions, such as acne, pruritis, dermatitis, and rash.

Disclosure: Several authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.