Upadacitinib Shows Biomarker-Driven Efficacy in Nonsegmental Vitiligo

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At the 2025 American Academy of Dermatology (AAD) Annual Meeting, AbbVie presented new findings on upadacitinib’s effects in nonsegmental vitiligo through a biomarker-driven approach.¹

The abstract, "Upadacitinib Reduces Type 1 Inflammation and Increases Melanocyte-Associated Biomarkers to Drive Response in Vitiligo," highlighted insights from a phase 2 clinical trial that explored how upadacitinib impacts disease pathology at a molecular level.

Key Findings from the Phase 2 Study

The study leveraged proteomic profiling of plasma samples from patients with nonsegmental vitiligo who were treated with upadacitinib to assess changes in inflammatory and melanocyte-associated biomarkers.

At baseline, patients had significantly elevated levels of CXCL9 and CXCL10—chemokines associated with type 1 inflammation—compared to healthy controls. Conversely, levels of melanocyte-associated proteins such as Kit and Rab27b were significantly lower.

Furthermore, baseline Kit levels correlated with depigmentation severity as measured by the Vitiligo Area Scoring Index (VASI).

Following treatment with upadacitinib, CXCL9 and CXCL10 levels rapidly declined, reaching levels comparable to healthy volunteers within 4 weeks and remaining suppressed through week 24.

Simultaneously, melanocyte-associated markers increased, with Kit levels at week 24 showing a strong correlation with VASI scores, suggesting a direct link between biomarker restoration and repigmentation. By week 24, CXCL9 and CXCL10 levels no longer correlated with VASI scores, reinforcing the hypothesis that melanocyte-associated proteins serve as a better indicator of disease activity.

Clinical Implications

According to authors of the abstract, these findings suggest that circulating melanocyte biomarkers could offer a quantitative means to assess vitiligo progression and treatment response.

Additionally, the study highlights the role of systemic inflammation in vitiligo pathology and how targeted JAK1 inhibition with upadacitinib can modulate these pathways to support repigmentation.

Reference

1. Harris JE, Janarthanam R, Bi Y,et al. Upadacitinib reduces type 1 inflammation and increases melanocyte-associated biomarkers to drive response in vitiligo. Presented at: American Academy of Dermatology Annual Meeting; March 7-11, 2025; Orlando, FL.