Phase 3 Data Show Upadacitinib Drives Progressive Repigmentation in Non-Segmental Vitiligo

At the 2026 American Academy of Dermatology (AAD) Annual Meeting in Denver, Colorado, new data on upadacitinib (Rinvoq; AbbVie) for non-segmental vitiligo (NSV) from the phase 3 Viti-Up-1 and Viti-Up-2 trials were presented during the first late-breaking session. Study authors Passeron et al noted that despite its substantial impact on quality of life, no systemic therapies have been approved for NSV, a gap that the Viti-Up program was designed to address.¹

Viti-Up-1 and Viti-Up-2 (NCT06118411) evaluated upadacitinib 15 mg, a selective, once-daily JAK1 inhibitor, in 614 adults and adolescents aged 12 years and older across 134 sites in 18 countries. Patients were randomized 2:1 to receive upadacitinib 15 mg or placebo for a 48-week double-blind period, followed by a 112-week open-label extension.^1,2

Co-Primary End Points Met Across Both Studies

The trials' co-primary end points—a 50% reduction in total body depigmentation (T-VASI 50) and a 75% reduction in facial depigmentation (F-VASI 75) at week 48—were met with statistical significance in both studies.

In Viti-Up-1, T-VASI 50 was achieved by 19.4% of patients treated with upadacitinib vs 5.9% on placebo (P ≤0.001), and F-VASI 75 by 25.2% of patients treated with upadacitinib vs 5.9% (P≤0.001). Viti-Up-2 produced nearly identical results, with T-VASI 50 in 21.5% of patients treated with upadacitinib vs 5.9% and F-VASI 75 in 23.4% of patients treated with upadacitinib vs 6.9% (both p≤0.001).

Notably, responses continued to build throughout the observation period with no sign of leveling off, a finding the investigators highlighted as clinically meaningful in a disease that often requires prolonged management. Secondary end points further reinforced the positive results: F-VASI 50 at week 48 was achieved by approximately 48% of patients treated with upadacitinib across both trials, and roughly 12% to 15% achieved the more stringent F-VASI 90 threshold.

Stabilization of Active Disease

Among patients with actively progressing vitiligo at baseline, defined by confetti-like depigmentation, koebnerization, or trichrome vitiligo, upadacitinib also demonstrated a meaningful ability to halt further spread. Approximately 76% of patients treated with upadacitinib in this subgroup showed no increase in T-VASI at weeks 8 and 12, compared with roughly 61% on placebo (p=0.025 in Viti-Up-1; p=0.042 in Viti-Up-2).

A Favorable Safety Profile

Safety findings through 48 weeks were consistent with the established profile for upadacitinib across its other dermatologic and rheumatologic indications. The most commonly reported treatment-emergent adverse events included upper respiratory tract infection, acne, nasopharyngitis, and headache. Importantly, there were no cases of adjudicated major adverse cardiovascular events (MACE), venous thromboembolic events (VTE), gastrointestinal perforation, active tuberculosis, lymphoma, or non-melanoma skin cancer in either study. Herpes zoster was reported in a small number of patients treated with upadacitinib across both trials (2.0% and 1.5%, respectively).

Clinical Implications

The Viti-Up results offer the first robust phase 3 evidence for a systemic oral therapy in NSV. The data suggest that JAK1 inhibition with upadacitinib can meaningfully reverse depigmentation, particularly on the face, while also stabilizing active disease spread. According to the study authors, the absence of a response plateau at 48 weeks points to potential for continued benefit with longer-term therapy, a question the ongoing open-label extension period is designed to answer.

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References

1. Passeron T, Prajapati V, Sivamani R, et al. Efficacy and safety of upadacitinib in adolescents and adults for treatment of non-segmental vitiligo: results of two phase 3 studies (Viti-Up). Presented at: 2026 American Academy of Dermatology Annual Meeting; March 27-31, 2026; Denver, CO.
2. A study to assess adverse events and effectiveness of upadacitinib oral tablets in adult and adolescent participants with vitiligo (Viti-Up). Clinicaltrials.gov. Updated November 2025. Accessed April 10, 2026. https://clinicaltrials.gov/study/NCT06118411