AbbVie Files for Vitiligo Indication, Putting Systemic Therapy Under Regulatory Review

Non-segmental vitiligo (NSV) remains one of the more challenging autoimmune skin diseases to manage in daily practice. Despite advances in understanding immune pathways involved in melanocyte destruction, treatment options have historically been limited, particularly for patients with widespread or progressive disease.¹ In an effort to provide patients with further therapeutic options, AbbVie has announced regulatory submissions to both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) seeking approval of upadacitinib 15 mg once daily for adult and adolescent patients with NSV. The applications are supported by data from the phase 3 Viti-Up clinical studies.²

"It is an exciting day for vitiligo patients and the dermatology field to learn that upadacitinib is taking the next regulatory steps with the FDA and EMA to become the first approved systemic therapy for adolescents and adults experiencing vitiligo,” Christopher Bunick, MD, PhD, Dermatology Times editor-in-chief and associate professor of dermatology at Yale School of Medicine, said in an exclusive statement. “Effective treatments for vitiligo are major unmet need in dermatology, yet upadacitinib's phase 3 trial data for F-VASI and T-VASI response at 48 weeks gives vitiligo patients hope that meaningful improvement is coming soon. Adding to the growing list of anti-inflammatory indications throughout medicine, upadacitinib continues to demonstrate that optimized chemistry matters, driving structure-function activity and translating into elevations of the standards of care for dermatology patients."

Targeting JAK Signaling

Interferon-γ–driven immune pathways and downstream JAK-STAT signaling have been implicated in melanocyte destruction in vitiligo. This mechanistic understanding has driven interest in JAK inhibitors as potential disease-modifying agents. Upadacitinib is an oral JAK inhibitor with greater inhibitory potency for JAK-1 relative to JAK-2, JAK-3, and TYK-2 based on enzymatic and cellular assays. However, the clinical significance of selective JAK inhibition with respect to efficacy and safety remains an area of active investigation.

Upadacitinib is already approved for multiple immune-mediated inflammatory diseases and is being studied across a range of dermatologic and systemic autoimmune conditions, including alopecia areata and hidradenitis suppurativa. Its evaluation in vitiligo represents a logical extension of this development strategy.

Viti-Up Phase 3 Program

The regulatory submissions are supported by the Viti-Up clinical studies (NCT06118411), which comprised 2 replicate phase 3 trials conducted under a single protocol. Each study maintained independent randomization, investigative sites, data collection, and statistical analyses, strengthening the robustness of the findings.

A total of 614 patients aged 12 years and older with NSV were enrolled across 90 global sites. All participants were considered candidates for systemic therapy. During period A, patients were randomized in a 2:1 ratio to receive either upadacitinib 15 mg once daily or placebo for 48 weeks. Those completing period A were eligible to enter period B, a 112-week open-label extension in which all participants received upadacitinib. Combined, the studies allow for evaluation over a total of 160 weeks.

Clinically Relevant Endpoints

The co-primary endpoints were selected to reflect meaningful clinical improvement. These included achievement of at least a 50% reduction from baseline in Total Vitiligo Area Scoring Index (T-VASI 50) and at least a 75% reduction in Facial Vitiligo Area Scoring Index (F-VASI 75) at week 48. Facial involvement is of particular interest given its disproportionate impact on quality of life and patient-reported outcomes.

Secondary endpoints evaluated both the magnitude and timing of facial re-pigmentation, including F-VASI 50 at week 48 and F-VASI 75 as early as week 24. These measures provide insight into how quickly visible improvement may occur and whether early responses are achievable with systemic therapy.

Moving Forward

AbbVie has reported that the Viti-Up studies met key efficacy objectives, forming the basis for regulatory review. However, full peer-reviewed publication of efficacy and safety data will be essential for clinicians to assess the durability of re-pigmentation, long-term safety, and real-world applicability. As with other JAK inhibitors, safety considerations—including infection risk and long-term immunologic effects—will be central to regulatory and clinical decision-making.

The submission itself marks an important inflection point in vitiligo drug development. For clinicians, it signals the possibility that systemic therapy may soon become part of the therapeutic armamentarium for NSV, particularly for patients with widespread, progressive, or treatment-refractory disease. Whether upadacitinib ultimately alters standard practice will depend on regulatory outcomes and careful integration of emerging data into patient-centered care.

References

1. Feng Y, Lu Y. Advances in vitiligo: Update on therapeutic targets. Front Immunol. 2022;13:986918. Published 2022 Aug 31. doi:10.3389/fimmu.2022.986918
2. AbbVie submits regulatory applications to FDA and EMA for upadacitinib (RINVOQ®) in adults and adolescents with vitiligo.