by Aunna Pourang, MD

There are several challenges faced by patients with vitiligo:

• Unpredictable nature of the disease
• Few treatment options are available with limited efficacy
• No FDA approved treatments are available
• Depending on the type of treatment, relapse rates of treated areas can occur in up to 40% of individuals

Several pathophysiologic mechanisms contribute to vitiligo, which include, but are not limited to:

• Intrinsic abnormalities of melanocytes and vitiligo epidermal keratinocytes
• Increased oxidative stress within the microenvironment of melanocytes and keratinocytes
• Autoimmune mediated destruction of melanocytes via CD8+ T cells, which are recruited indirectly by interferon-gamma (INF-γ)

Many therapies are used in conjunction to target the various pathways involved, including:

• Reducing oxidative stress with antioxidants such as oral vitamin E, alpha lipoic acid, Gingko biloba and Polypodium leucotomos
• Narrow band UVB to recruit melanoblasts from the stem cell niche to the interfollicular epidermis
• Melanocyte-keratinocyte transplantation procedures, also known as non-cultured epidermal suspension transplantation
• Downregulation of the autoimmune response by inhibiting the INF-γ pathway using JAK1/2 inhibitors or by inhibiting Signal Transducers and Activators of Transcription (STAT)

There are a few ongoing trials for Janus Kinase (JAK) inhibitors for the treatment of vitiligo:

• The open label extension of the phase 2 randomized controlled trial of topical ruxolitinib for vitiligo (Incyte)
• Initial results of the double blind randomized portion of this study showed that 45% of patients achieved FVASI50 after 24 weeks compared to 3% in the placebo group (p<0.0001)
• This topical JAK inhibitor may be the first FDA approved treatment for vitiligo
• Phase 2b trial for 2 oral JAK inhibitors (Pfizer)
• Novel JAK 3 inhibitor and a JAK1/Tyrosine Kinase(TYK2) inhibitor
• More long term data on JAK inhibitors for the treatment of vitiligo is needed

Other treatment considerations:

• Anti-inflammatory agents and immune modulators are necessary to prevent the progression of vitiligo
• Equally as important is the regeneration, recruitment and maintenance of melanocytes
• This may be achieved by migratory factors such as the α- melanocyte-stimulating hormone analog, afamelanotide

The future of vitiligo treatment will likely include:

• An approach which can induce and maintain pigmentation with decreased side effects, while meeting different needs for the patient (ie. disease extent, access to care)
• JAK inhibitors, NBUVB and oral antioxidants may be the mainstays of treatment
• Surgery can be an option with select patients as can oral corticosteroids in patients with severely unstable disease
• Overall, the rapid advancements that are being made in the treatment of vitiligo will not only continue to reverse disease burden in patients but also improve their quality of life.

 

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References

1. Abdel-Malek ZA, Jordan C, Ho T, Upadhyay PR, Fleischer A, Hamzavi I. The enigma and challenges of vitiligo pathophysiology and treatment. Pigment Cell Melanoma Res 2020.
2. Cavalie M, Ezzedine K, Fontas E, Montaudie H, Castela E, Bahadoran P et al. Maintenance therapy of adult vitiligo with 0.1% tacrolimus ointment: a randomized, double blind, placebo-controlled study. J Invest Dermatol 2015;135:970-4.
3. Nicolaidou E, Antoniou C, Stratigos AJ, Stefanaki C, Katsambas AD. Efficacy, predictors of response, and long-term follow-up in patients with vitiligo treated with narrowband UVB phototherapy. J Am Acad Dermatol 2007;56:274-8.
4. Rosmarin D, Pandya AG, Lebwohl M, Grimes P, Hamzavi I, Gottlieb AB et al. Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. Lancet 2020;396:110-20.