Upadacitinib Phase 3 Vitiligo (Viti-Up): Week 48 T-VASI50 21.5%, F-VASI75 25.2% — First Oral Systemic Vitiligo Therapy Filed with FDA
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Upadacitinib Phase 3 Vitiligo (Viti-Up): Week 48 T-VASI50 21.5%, F-VASI75 25.2% — First Oral Systemic Vitiligo Therapy Filed with FDA

By Léa · · AAD 2026 Late-Breaking
KO | EN

Late-breaking phase 3 data from the Viti-Up-1 and Viti-Up-2 trials presented at the American Academy of Dermatology 2026 Annual Meeting showed JAK1 inhibitor upadacitinib (RINVOQ) met both co-primary endpoints — T-VASI50 and F-VASI75 — at week 48 in nonsegmental vitiligo. FDA and EMA filings followed. If approved, upadacitinib would become the first oral systemic therapy for vitiligo.

The Data

Thierry Passeron, MD, PhD (University of Nice) presented the global phase 3 results in adolescents and adults aged 12+ with nonsegmental vitiligo. Patients were randomized to upadacitinib 15 mg once daily versus placebo across 48 weeks.

Co-primary endpoints at week 48:

  • T-VASI50 (≥50% total body repigmentation)
    • Viti-Up-1: upadacitinib 19.4% vs placebo 5.9%
    • Viti-Up-2: upadacitinib 21.5% vs placebo 5.9%
  • F-VASI75 (≥75% facial repigmentation)
    • Viti-Up-1: upadacitinib 25.2% vs placebo 5.9%
    • Viti-Up-2: upadacitinib 23.4% vs placebo 6.9%

Secondary endpoints met across F-VASI50 (24, 48 weeks) and F-VASI90 (48 weeks). Treatment effect deepened over time — week 48 response rates exceeded week 24, indicating cumulative benefit. No new safety signals or major adverse cardiovascular events were reported.

Vitiligo Is Immune-Mediated Melanocyte Destruction

Nonsegmental vitiligo is a chronic autoimmune disease in which melanocytes are destroyed. It affects 0.5-2% of the global population. White patches form in exposed areas — face, hands, feet, genital regions — and progressively expand.

The immunologic cascade runs IFN-γ → CXCL9/10/11 → CD8+ T cell recruitment → melanocyte cytotoxicity. JAK1/JAK2 signaling sits at the center of IFN-γ effector function.

Upadacitinib selectively inhibits JAK1, blocking IFN-γ effector signals and halting melanocyte destruction. This permits melanocyte regeneration from hair follicle stem cells. The drug is already approved for rheumatoid arthritis, atopic dermatitis, ankylosing spondylitis, and ulcerative colitis.

What the Existing Treatment Landscape Lacks

Vitiligo treatment has been constrained:

  • Topical corticosteroids + calcineurin inhibitors: useful only in small facial areas, with long-term side effect concerns
  • Phototherapy (NB-UVB): requires 2-3 sessions weekly for 1+ year. Time and access burden
  • Topical ruxolitinib: FDA-approved 2022. Restricted to face and limited surface area
  • Surgical melanocyte transplant: only in stable disease, large surface burden

Upadacitinib offers once-daily oral systemic access for whole-body vitiligo. Hands, feet, and limbs — areas where phototherapy and topicals struggle — become reachable.

Why 21-25% Response Rates Are Clinically Meaningful

A 21-25% response rate may appear modest. In the vitiligo treatment landscape, it is significant:

  • Spontaneous repigmentation rates run under 5-10%
  • Roughly 4x placebo response across both trials
  • 25% F-VASI75 in the face — the area with the highest psychosocial impact
  • Treatment effect is still rising at week 48; 60-week and 72-week extensions in progress

Beyond binary response, sub-50% responders frequently achieve 25-49% repigmentation. Disease stabilization with partial repigmentation has significant psychosocial value given vitiligo’s social impact.

Clinical Application

  • Likely indication: nonsegmental vitiligo, age 12+, in patients refractory to or unable to use phototherapy/topicals
  • Dose: upadacitinib 15 mg once daily oral
  • Time to effect: meaningful change at week 24, cumulative response at week 48, continued improvement to week 72
  • Monitoring: liver function, lipids, neutrophils/lymphocytes, hemoglobin; tuberculosis and hepatitis B screening prerequisite
  • Contraindications: active tuberculosis, hepatitis B, pregnancy
  • Side effects: upper respiratory infections, acneiform eruption, herpes reactivation. MACE signal not observed in phase 3
  • Combination therapy: phototherapy or topical calcineurin inhibitors may complement; trial data still needed
  • Patient selection: progressive vitiligo, phototherapy non-responders, body surface area >10%
  • Cosmetic vs medical: insurance coverage will follow medical necessity criteria