Data Show Upadacitinib Repigments Skin in Nonsegmental Vitiligo

Nonsegmental vitiligo has never had an FDA-approved systemic treatment option. New phase 3 data published in The Lancet show that oral upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, drove statistically significant facial and total-body repigmentation through week 48 in 2 identically designed trials (NCT06118411), Viti-Up-1 and Viti-Up-2.¹

A Disease With No Systemic Option

Nonsegmental vitiligo is a chronic autoimmune disease in which the immune system destroys pigment-producing skin cells, leaving depigmented patches on the face and body. A systematic review and modeling study estimated the global lifetime prevalence of physician- or dermatologist-diagnosed vitiligo at 0.36% of the general population, or roughly 28.5 million people, rising to 0.67%, or about 37.1 million people, among adults alone.²

Despite that reach, treatment has long been limited to topical corticosteroids, topical calcineurin inhibitors, and phototherapy, none of which offers a systemic option for patients with more extensive disease. Viti-Up was designed to test whether a targeted oral therapy could fill that gap.¹

Two Replicate Global Phase 3 Trials

Viti-Up-1 and Viti-Up-2, the 2 replicate studies, were global, multicenter, randomized, double-blind, placebo-controlled trials conducted at institutions across Asia, Europe, North America, and South America. Eligible patients were 12 years or older with nonsegmental vitiligo affecting the face and body, a Facial Vitiligo Area Scoring Index (F-VASI) of at least 0.5, and a Total Vitiligo Area Scoring Index (T-VASI) of 5 to less than 50, and either had failed topical therapy, showed signs of actively progressing disease, or had a T-VASI of 10 or higher.³

Investigators randomized patients 2:1 to upadacitinib 15 mg once daily or placebo. Viti-Up-1 enrolled 308 patients (n = 206 upadacitinib; n = 102 placebo), and Viti-Up-2 enrolled 306 patients (n = 205 upadacitinib; n = 101 placebo), with a roughly even sex split in both. The coprimary end points were T-VASI50 (at least 50% reduction in T-VASI) and F-VASI75 (at least 75% reduction in F-VASI) at week 48.¹

Both trials met their coprimary end points (P < .001 for every comparison below). In Viti-Up-1, 19% of patients receiving upadacitinib achieved T-VASI50 at week 48 vs 6% on placebo, and 25% achieved F-VASI75 vs 6% with placebo. In Viti-Up-2, 21% of patients receiving upadacitinib reached T-VASI50 vs 6% with placebo, and 23% reached F-VASI75 vs 7% with placebo.

Secondary end points followed a similar pattern. F-VASI50 was reached by 48% of patients receiving upadacitinib in Viti-Up-1 and 43% in Viti-Up-2, compared with 13% on placebo in both trials, and F-VASI90 was reached by 16% in Viti-Up-1 and 12% in Viti-Up-2, vs 2% and 3% with placebo, respectively. T-VASI75, a higher bar for total-body clearance, did not separate from placebo in either trial, a sign that facial repigmentation outpaced trunk and limb repigmentation over the same 48 weeks.

“Upadacitinib 15 mg daily provides clinically meaningful repigmentation of both the face and total body for adults and adolescents with nonsegmental vitiligo, with no new safety signals identified,” the researchers wrote.

Safety Profile Consistent With Prior Upadacitinib Data

Treatment-emergent adverse events were more common with upadacitinib than placebo in both trials (81% vs 60% in Viti-Up-1 and 70% vs 62% in Viti-Up-2). Upper respiratory tract infection, acne, nasopharyngitis, and headache were the most frequently reported events in both arms.

Neither trial recorded an adjudicated major adverse cardiovascular event, venous thromboembolic event, gastrointestinal perforation, case of active tuberculosis, lymphoma, or nonmelanoma skin cancer during the 48-week double-blind period. Herpes zoster was the only opportunistic infection reported, occurring in about 2.0% of upadacitinib-treated patients in Viti-Up-1 and 1.5% in Viti-Up-2. Upadacitinib already carries FDA approvals in other immune-mediated skin diseases, including atopic dermatitis and alopecia areata, where a similar safety profile has been tracked over longer follow-up; the investigators characterized the Viti-Up safety data as consistent with that established profile.

Monotherapy-Only Data, Limited Skin-Type Diversity

The study authors noted several limitations. Both trials tested upadacitinib only as monotherapy, so the results do not address how the drug performs alongside phototherapy or other treatments already in common use. Patients with higher Fitzpatrick skin types were underrepresented, leaving open how generalizable the findings are to the patients in whom vitiligo's cosmetic and psychosocial impact is often most pronounced. Repigmentation had also not plateaued by week 48 in either trial, so longer follow-up is needed to determine how much further patients might improve.

For clinicians and payers, Viti-Up offers the first peer-reviewed, placebo-controlled evidence that a systemic drug can meaningfully repigment nonsegmental vitiligo, turning a disease with no systemic treatment lane at all into one with a late-stage, phase 3-backed candidate. That shift sets up a formulary and coverage conversation managed care has not previously had for this population, even as the monotherapy-only design and open follow-up window leave questions a regulatory review will still need to sort through.

References

1. 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. 2026;408(10555):636-648. doi:10.1016/S0140-6736(26)00896-2
2. Akl J, Lee S, Ju HJ, et al. Estimating the burden of vitiligo: a systematic review and modelling study. Lancet Public Health. 2024;9(6):e386-e396. doi:10.1016/S2468-2667(24)00026-4
3. A study to assess adverse events and effectiveness of upadacitinib oral tablets in adult and adolescent participants with vitiligo (Viti-Up). ClinicalTrials.gov identifier: NCT06118411. Updated June 9, 2026. Accessed October 8, 2026. https://clinicaltrials.gov/study/NCT06118411