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Mechanism of Action

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IFN-ɣ driven Inflammation in Vitiligo is JAK-mediated⁵

IFN-γ mediated JAK-STAT signaling is thought to drive an inflammatory cycle, creating a hostile environment in which CD8+ T-cells target and destroy melanocytes.⁵ Autoimmune IFN-γ producing cytotoxic T lymphocytes are thought to be directly responsible for melanocyte destruction in human vitiligo.⁶

Adapted from ref. 5

The Role of the JAK-STAT Pathway in Vitiligo⁵

Intrinsic and/or extrinsic factors induce the cellular stress response in melanocytes, which then activates innate immunity within the skin to trigger the initial inflammation that leads to autoimmunity.⁵

IFN-γ secreted by CD8+T cells.⁵

Under IFN-γ activation, JAK-STAT pathway triggers chemokines CXCL9 and CXCL10 in keratinocytes.⁵

Chemokines attract more CD8+T cells, which destroy melanocytes and lead to depigmentation.⁵

Lumirix® (ruxolitinib 15mg/g) cream is a Janus Kinase (JAK) Inhibitor.³

Ruxolitinib cream has been found to have physicochemical properties suitable for topical delivery through the skin of patients with inflammatory skin diseases.⁷

Adapted from ref. 8

Lumirix® (ruxolitinib 15mg/g) cream can be a promising treatment for vitiligo.5

In addition to Ruxolitinib’s anti-IFN-γ effect, it also seems to activate the hair follicle melanocyte stem cell.⁹

CD: Cluster of Differentiation; CXCL: C-X-C motif chemokine ligand; IFN-ɣ: Interferon gamma; JAK: Janus kinase; STAT: Signal Transducer and Activator of Transcription.

References

  1. Lumirix® Prescribing Information for Hong Kong.
  1. Howell MD, Kuo FI, Smith PA. Targeting the Janus kinase family in autoimmune skin diseases. Front Immunol. 2019; 10: 2342 [Internet]. 2019.
  2. Frisoli ML, Essien K, Harris JE. Vitiligo: mechanisms of pathogenesis and treatment. Annual review of immunology. 2020;38(1):621-48.
  3. Smith P, Yao W, Shepard S, Covington M, Lee J, Lofland J, Naim A, Sheth T, Parikh B, Yeleswaram S. Developing a JAK inhibitor for targeted local delivery: ruxolitinib cream. Pharmaceutics. 2021;13(7):1044.
  4. Utama A, Wijesinghe R, Thng S. Janus kinase inhibitors and the changing landscape of vitiligo management: a scoping review. International Journal of Dermatology. 2024 Apr 12.
  5. Birlea SA, Goldstein NB, Norris DA. Repigmentation through Melanocyte Regeneration in Vitiligo. Dermatol Clin. 2017 Apr;35(2):205-218.​