Achieving Victory Over Vitiligo: JAK Inhibitor Promotes Repigmentation

Vitiligo is a chronic condition characterized by a loss of pigmentation to patches of skin. The pathophysiology is multifaceted, and involves genetic factors, oxidative stress, and the immune system. With respect to the latter, immune activation—primarily through cytotoxic T cells—destroys melanocytes, which are responsible for the normal pigmentation of the skin. 

Isolated patches can be treated with topical administration of immunosuppressants like tacrolimus and corticosteroids. For more diffuse disease, systemic therapy is needed, which often involves systemic glucocorticoids. These drugs are often limited by unacceptable long-term toxicities. 

Recently, several new targeted immunotherapies have been investigated for the treatment of vitiligo. In this commentary, we explore a new study evaluating the safety and efficacy of ritlecitinib for the treatment of nonsegmental vitiligo.  

Point 1: The JAK Pathway Is Where It’s At

JAK inhibitors represent a novel class of targeted immunotherapy with demonstrated efficacy in immune-mediated diseases, including dermatologic conditions. Ritlecitinib is an oral treatment that inhibits JAK3 and the tyrosine kinases expressed in the hepatocellular carcinoma kinase family. Ritlecitinib is highly selective for JAK3 over JAK1/JAK2/TYK2, which may be central to the ongoing immune destruction of melanocytes. 

In this new phase 2b study, patients were randomized to either ritlecitinib once daily or placebo for an initial 24-week dose finding period, followed by a 24-week extension period. Over the 48-month treatment period, significant improvements in the Facial-Vitiligo Area Scoring Index were noted in the 364 patients who received ritlecitinib. 

These findings were accelerated in the 24-week extension period, and continuous repigmentation with no plateau was observed up to week 48. These results were achieved without any serious treatment-related side effects over the 48 week follow-up period. 

Point 2: Promising, but More Data Is Needed

These results are impressive, but it is important to remember that this is only a phase 2 study, and larger phase 3 studies are required to confirm these preliminary findings. Additionally, this study only included patients with stable vitiligo, although data from other studies suggest ritlecitinib promotes repigmentation in stable lesions as well. Of note, most patients in this paper were White, which is important to mention as higher baseline pigmentation could impact self-reported assessments and physician scoring.

Reference:
Ezzedine K, Peeva E, Yamaguchi Y, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: A randomized phase 2b clinical trial. J Am Acad Dermatol. 2023;88(2):395-403. doi:10.1016/j.jaad.2022.11.005