Oral upadacitinib delivers meaningful repigmentation in non-segmental vitiligo

The selective Janus kinase 1 (JAK1) inhibitor upadacitinib produced significantly greater facial and total repigmentation than placebo in adolescents and adults with non-segmental vitiligo across 2 replicate phase 3 trials. Notably, responses continued to deepen through week 48, with no apparent plateau.

Non-segmental vitiligo remains a challenging condition to manage, with treatment largely confined to topical agents and phototherapy. Against this background, the Viti-Up-1 and Viti-Up-2 programme (NCT06118411) evaluated oral upadacitinib as monotherapy in patients with both facial and body involvement, recruited from 18 countries [1]. A previous phase 2 study had already demonstrated the efficacy of this agent in vitiligo [2].

The 2 identically designed trials randomised a combined 614 participants aged ≥12 years (Viti-Up-1, n=308; Viti-Up-2, n=306) in a 2:1 ratio to upadacitinib 15 mg once daily or placebo. Eligibility required a baseline Facial-Vitiligo Area Scoring Index (F-VASI) of ≥0.5 and a Total-Vitiligo Area Scoring Index (T-VASI ) of ≥5. The mean age was around 45 years, and the time since diagnosis ranged from 15.6 to 16.7 years. Around 60% of participants had active disease at baseline, and more than three-quarters had >10% body surface area involvement. Most participants had Fitzpatrick skin types II–IV, and 53–63% had previously received topical therapy. As Prof. Thierry Passeron (Centre Hospitalier Universitaire de Nice, France) noted during the presentation, all the patients were instructed to get photoprotection and did not receive phototherapy or any other concomitant treatments. Following the 48-week double-blind phase, all participants entered a 112-week open-label extension on upadacitinib 15 mg.

Both co-primary endpoints were met. In Viti-Up-1, 19.4% of patients receiving upadacitinib achieved T-VASI 50 at week 48, compared with 5.9% in the placebo group. Additionally, 25% achieved F-VASI 75 (compared with 5.9% in the placebo group). Viti-Up-2 showed similar results, with T-VASI 50 achieved in 21.5% versus 5.9%, and F-VASI 75 in 23.4% versus 6.9%. Response curves showed continued improvement through week 48 without a plateau.

Patient-perceived cosmetic benefit also favoured upadacitinib: on the Vitiligo Noticeability Scale, scores of 4 or 5 (“a lot less noticeable” or “no longer noticeable”) were achieved by 12.6% versus 2.0% in Viti-Up-1, and by 14.6% versus 1.0% in Viti-Up-2. Multiple secondary dermatological endpoints, including F-VASI 50 and F-VASI 90 at week 48, F-VASI 75 at week 24, and both physician- and patient-reported global impressions of “much better” change, were statistically significant (P<0.001 for all). T-VASI 75 at week 48 was not significant.

Safety findings were consistent with the established profile of upadacitinib, with no new signals identified. The most common treatment-emergent adverse events (≥5%) were upper respiratory tract infection, acne, nasopharyngitis, and headache. Four serious infections occurred in the upadacitinib arm of Viti-Up-1 (bronchitis and influenza in 1 patient, complicated appendicitis and parainfluenza in others), none of which led to treatment discontinuation.

In summary, oral upadacitinib 15 mg has the potential to serve as a systemic monotherapy in non-segmental vitiligo, delivering clinically meaningful facial and total repigmentation, with a safety profile consistent with prior experience in other indications.

Passeron T. Efficacy and Safety of Upadacitinib in Adolescents and Adults for Treatment of Non-Segmental Vitiligo: Results of Two Phase 3 Studies (Viti-Up). S023: Late-Breaking Research: Session 1. AAD 2026, 27–31, March, Denver, CO, USA.
Passeron T. EClinicalMedicine 2024:73:102635.