ruxolitinib for treatment of vitiligo

Vitiligo is a chronic autoimmune disorder characterized by the selective destruction of melanocytes, leading to depigmented patches of skin (1):

• onset of vitiligo is commonly associated with external oxidative stressors, including UV radiation, chemical exposure and trauma, which cause melanocytes to release reactive oxygen species, heat shock protein 70 (HSP70) and damage-associated molecular patterns
• accumulation of these molecules results in melanocyte dysfunction and increased antigen presentation, activating the innate immune system and initiating a cascade of downstream immune responses
• autoreactive CD8⁺ T cells become activated, producing IFNγ, a key regulator in vitiligo
• external triggers induce IFNγ signalling, activating the JAK–STAT pathway, and promoting melanocyte apoptosis
• IFNγ binds to its associated receptor, triggering the activation of JAK, a transmembrane protein kinase, which then undergoes auto-phosphorylation
  • leads to STAT phosphorylation and dimerization, activating the JAK–STAT pathway via JAK1 and JAK2
  • subsequent initiation of gene transcription drives an autoimmune response, leading to melanocyte apoptosis, cellular senescence and depigmentation

Ruxolitinib

• is a selective, competitive JAK1 and JAK2 inhibitor that disrupts vitiligo pathogenesis by blocking IFNγ signalling, inhibiting dendritic cell migration and dampening cytotoxic T cell activity, thereby promoting melanocyte recruitment and facilitating repigmentation (1)
• ruxolitinib cream is considered a safe treatment option for patients with vitiligo, as demonstrated in phase 2 and phase 3 trials (2)

NICE state (3):

Ruxolitinib cream can be used as an option to treat non-segmental vitiligo with facial involvement in people 12 years and over. Ruxolitinib cream can only be used if:

• topical first-line treatments have not worked or are not suitable

The NICE committee note that “…For this evaluation, the company asked for ruxolitinib cream to be considered only after topical first-line treatments. This is narrower than the marketing authorisation for ruxolitinib cream…Clinical trial evidence shows that ruxolitinib cream increases repigmentation and reduces how noticeable vitiligo patches are compared with a placebo cream. But results of an indirect comparison are too uncertain to show how well ruxolitinib cream works compared with phototherapy…”

Reference:

1. Monteiro E Silva G, Mohamed A, Ferreira C, Torres T. Treatment of vitiligo with topical ruxolitinib: a narrative review. Drugs Context. 2025 Sep 15;14:2025-5-2.
2. Seneschal J et al. Efficacy and Safety of Ruxolitinib Cream in Vitiligo by Patient Characteristic Subgroups: Descriptive Pooled Analysis From Two Phase 3 Studies. Dermatol Ther (Heidelb). 2025 May;15(5):1227-1238.
3. NICE (March 2026). Ruxolitinib cream for treating non-segmental vitiligo in people 12 years and over.