Research Summary

Upadacitinib Improves Facial, Total-Body Repigmentation in Nonsegmental Vitiligo

Edited by:
Ashton L. Stahl

Key Highlights

  • Upadacitinib 15 mg significantly increased T-VASI 50 and F-VASI 75 response rates versus placebo at week 48 in both phase 3 Viti-Up trials.
  • At week 48, T-VASI 50 responses ranged from 19% to 21% with upadacitinib versus 6% with placebo, while F-VASI 75 responses ranged from 23% to 25% versus 6% to 7%, respectively.
  • Treatment-emergent adverse events were more frequent with upadacitinib than placebo, but investigators reported no new safety signals during the 48-week double-blind period.
  • The investigators said upadacitinib could represent a systemic treatment option for adults and adolescents with nonsegmental vitiligo.

Once-daily upadacitinib 15 mg significantly improved facial and total-body repigmentation compared with placebo among adults and adolescents with nonsegmental vitiligo in 2 phase 3 randomized controlled trials published in The Lancet. The Viti-Up-1 and Viti-Up-2 studies met both coprimary efficacy end points at 48 weeks, with no new safety signals identified.

The global, multicenter, randomized, double-blind, placebo-controlled studies enrolled patients aged 12 years or older with nonsegmental vitiligo affecting the face and body. Participants had an F-VASI score of at least 0.5 and a T-VASI score of 5 to less than 50 and were randomly assigned 2:1 to oral upadacitinib 15 mg once daily or placebo. The coprimary end points were T-VASI 50, defined as a ≥50% reduction from baseline in T-VASI, and F-VASI 75, defined as a ≥75% reduction from baseline in F-VASI, at week 48.

Study Findings

A total of 308 participants were randomized in Viti-Up-1 and 306 in Viti-Up-2. At week 48, T-VASI 50 was achieved by 19% of patients receiving upadacitinib versus 6% receiving placebo in Viti-Up-1 and by 21% versus 6%, respectively, in Viti-Up-2 (both P<.001). F-VASI 75 was achieved by 25% versus 6% in Viti-Up-1 and 23% versus 7% in Viti-Up-2 (both P<.001).

Upadacitinib also significantly improved several secondary outcomes. At week 48, F-VASI 50 was achieved by 48% versus 13% of patients in Viti-Up-1 and 43% versus 13% in Viti-Up-2 (both P<.001). F-VASI 90 responses were 16% versus 2% and 12% versus 3%, respectively. However, the difference between upadacitinib and placebo for T-VASI 75 at week 48 was not statistically significant in either trial.

Treatment-emergent adverse events occurred in 81% and 70% of upadacitinib-treated participants in Viti-Up-1 and Viti-Up-2, respectively, compared with 60% and 62% receiving placebo. Common events included upper respiratory tract infection, acne, nasopharyngitis, and headache. No adjudicated major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforations, active tuberculosis, lymphoma, or nonmelanoma skin cancer were reported.

Clinical Implications

According to the study authors, the findings demonstrate that upadacitinib can provide clinically meaningful facial and total-body repigmentation and may offer a systemic treatment option for adults and adolescents with nonsegmental vitiligo. The authors also reported that responses continued to improve through week 48 and that upadacitinib could potentially stabilize disease extent among patients with active vitiligo.

The authors noted that the study population might not reflect the full range of patients with nonsegmental vitiligo seen in real-world practice. They also noted that upadacitinib was evaluated as monotherapy, that patients with higher Fitzpatrick skin types were underrepresented, and that longer follow-up is needed because repigmentation had not plateaued by week 48.

The study was funded by AbbVie, which provided the study design, study conduct, financial support, and study drugs; performed the data analyses and interpretation; and participated in manuscript writing, review, and approval.

Expert Commentary

“Upadacitinib might offer a new and effective systemic therapy option for adults and adolescents with non-segmental vitiligo,” the researchers concluded.

Reference

Passeron T, Prajapati VH, Sivamani RK, et al. Efficacy and safety of upadacitinib in adults and adolescents for treatment of non-segmental vitiligo (Viti-Up): results of two phase 3 randomised controlled studies. Lancet. Published online August 15, 2026. doi:10.1016/S0140-6736(26)00896-2.