Upadacitinib Achieves Positive Phase 3 Results in Non-Segmental Vitiligo

AbbVie recently announced new positive topline results from 2 replicate phase 3 trials evaluating upadacitinib 15 mg (Rinvoq) in adult and adolescent patients with non-segmental vitiligo (NSV)—the most common subtype, affecting over 90% of individuals with vitiligo. These data mark an important step toward expanding systemic therapeutic options for this chronic autoimmune depigmenting disorder, which currently lacks any approved oral treatments targeting repigmentation.¹

"Vitiligo is a challenging disease because repigmentation is slow, relapse is common, and treatment options have been limited. Seeing 2 replicate phase 3 trials meet the co-primary end points of facial and total repigmentation at 48 weeks, with key ranked secondary end points also met, signals real progress for our vitiligo patients," said Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine in New Haven, Connecticut, and Dermatology Times' editor in chief, in an exclusive statement.

Study Design and Endpoints

The M19-044 program consisted of 2 replicate, double-blind, placebo-controlled studies (Study 1 and Study 2) conducted under a single protocol. A total of 614 patients (aged 12 years and older) with NSV eligible for systemic therapy were randomized 2:1 to receive upadacitinib 15 mg or placebo for 48 weeks (Period A), followed by a 112-week open-label extension (Period B) in which all participants received active treatment.

Co-primary end points included achievement of:

• T-VASI 50: ≥50% reduction from baseline in Total Vitiligo Area Scoring Index (T-VASI) at week 48
• F-VASI 75: ≥75% reduction in Facial Vitiligo Area Scoring Index (F-VASI) at week 48

Secondary end points included F-VASI 50 at week 48 and F-VASI 75 at week 24. The VASI metrics quantify depigmentation on the body and face, respectively, regions of particular psychosocial relevance to patients.

Efficacy Outcomes

Upadacitinib demonstrated statistically significant improvements over placebo across both phase 3 studies. In Study 1, 19.4% of patients treated with upadacitinib achieved T-VASI 50 at week 48 compared with 5.9% of those receiving placebo. Similarly, 25.2% of patients in the upadacitinib arm reached F-VASI 75 vs 5.9% in the placebo arm. For the F-VASI 50 end point, nearly half of patients on upadacitinib (48.1%) achieved at least a 50% reduction from baseline compared with 12.7% of those on placebo.

Results were consistent in Study 2, with 21.5% of patients receiving upadacitinib achieving T-VASI 50 compared with 5.9% in the placebo group. For F-VASI 75, 23.4% of patients in the upadacitinib arm met this end point versus 6.9% in the placebo arm. Additionally, 43.4% of patients receiving upadacitinib achieved F-VASI 50, compared with 12.9% of those on placebo.

Together, these data demonstrate that once-daily upadacitinib 15 mg significantly improved both total body and facial repigmentation compared with placebo after 48 weeks of treatment.

Vitiligo is more than a skin condition—it’s a chronic autoimmune disease that can deeply affect a person's confidence, identity and daily life,” said Kori Wallace, MD, PhD, vice president and global head of immunology clinical development at AbbVie, in the news release. “There are no approved systemic medical therapies for achieving re-pigmentation in vitiligo. These phase 3 results represent a significant milestone in AbbVie's commitment to supporting patients and expanding our immunology portfolio to deliver innovative solutions.”

Safety Profile

The safety findings were consistent with the previously established profile of upadacitinib across other indications. The most frequent treatment-emergent adverse events (TEAEs) included upper respiratory tract infection, acne, and nasopharyngitis. Serious adverse events occurred in ≤4% of both active and placebo groups. Importantly, no new safety signals were identified, and no major adverse cardiovascular events (MACE) or venous thromboembolic events (VTE) were observed.

Outlook

Although upadacitinib is not FDA-approved for NSV yet, these phase 3 data support JAK inhibition as a viable systemic pathway for vitiligo repigmentation, complementing recent topical advances, such as ruxolitinib cream (Opzelural; Incyte).2 Full results and long-term extension data will help clarify the durability of response and optimal patient selection for systemic therapy in vitiligo.

"Taken with positive phase 3 results in alopecia areata and the 9 indications already approved for upadacitinib across immune-mediated diseases, these findings underscore upadacitinib’s role as an anti-inflammatory drug that can reduce systemic inflammation in the skin and beyond," Bunick concluded.

References

1. AbbVie announces positive topline results from phase 3 pivotal studies evaluating upadacitinib (RINVOQ) in adults and adolescents with vitiligo. News release. AbbVie. October 29, 2025. Accessed October 29, 2025. https://news.abbvie.com/2025-10-29-AbbVie-Announces-Positive-Topline-Results-from-Phase-3-Pivotal-Studies-Evaluating-Upadacitinib-RINVOQ-R-in-Adults-and-Adolescents-with-Vitiligo
2. Cristallo M, Zaza I, Daddato MF, et al. Effectiveness and safety of ruxolitinib cream 15 mg/g in patients with non-segmental vitiligo: a real-life study. Int J Dermatol. 2025; doi:10.1111/ijd.70049