Original article
Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure

https://doi.org/10.1016/j.jaad.2017.05.043Get rights and content

Background

Vitiligo is an autoimmune disease in which cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors.

Objective

To evaluate the efficacy of the JAK 1/3 inhibitor tofacitinib in the treatment of vitiligo.

Method

This is a retrospective case series of 10 consecutive patients with vitiligo treated with tofacitinib. Severity of disease was assessed by body surface area of depigmentation.

Results

Ten consecutive patients were treated with tofacitinib. Five patients achieved some repigmentation at sites of either sunlight exposure or low-dose narrowband ultraviolet B phototherapy. Suction blister sampling revealed that the autoimmune response was inhibited during treatment in both responding and nonresponding lesions, suggesting that light rather than immunosuppression was primarily required for melanocyte regeneration.

Limitations

Limitations include the small size of the study population, retrospective nature of the study, and lack of a control group.

Conclusion

Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low-level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration.

Section snippets

Methods

This study is a retrospective case series of 10 patients seen between July 2014 and January 2017. Medical records of patients with vitiligo, age 18 years and older, who were treated with tofacitinib for at least 3 months were reviewed. Clinical and demographic information, including biological sex, age, disease duration and course, medical history, family history, and prior treatments, were collected. Before initiation of tofacitinib therapy, all patients underwent baseline laboratory

Patient characteristics

All 10 patients in this case series were adults. Duration of disease ranged from 4 to 33 years (mean, 16.6; standard deviation, 8.8). Eight patients had generalized vitiligo and 2 patients had primarily acral involvement, with BSA 1% to 100%. Additional patient characteristics, together with previous treatments, are described in Table I.

Clinical response to treatment

Ten patients underwent treatment with tofacitinib, 5 to 10 mg daily or twice daily, for an average of 9.9 months (standard deviation, 4.1; range, 3-15). A mean

Discussion

The pathogenesis of vitiligo involves CD8+ T cell production of IFN-γ, which leads to CXCL9/CXCL10 expression by keratinocytes and further recruitment of CD8+ T cells, resulting in melanocyte destruction.7, 13, 14, 15, 16, 23 Originally, we hypothesized that inhibition of IFN-γ signaling using JAK inhibitors would lead to repigmentation, and the results in 2 patients19, 20 using 2 different oral JAK inhibitors, tofacitinib and ruxolitinib, supported this hypothesis. Recently, a case series

References (26)

  • B.G. Craiglow et al.

    Tofacitinib for the treatment of alopecia areata and variants in adolescents

    J Am Acad Dermatol

    (2017)
  • L.Y. Liu et al.

    Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients

    J Am Acad Dermatol

    (2017)
  • K. Bonotis et al.

    Investigation of factors associated with health-related quality of life and psychological distress in vitiligo

    J Dtsch Dermatol Ges

    (2016)
  • Cited by (0)

    Ms Liu and Mr Strassner contributed equally to this article.

    Supported by National Center for Advancing Translational Sciences grant UL1-TR001453. Dr Harris is supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases grant AR069114 and a Stiefel Scholar Award from the Dermatology Foundation. Dr King received funding support from The Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research.

    Disclosure: Dr King has served on advisory boards or is a consultant for Aclaris Therapeutics, Concert Pharmaceuticals, Eli Lilly and Company, Pfizer, Regeneron Pharmaceuticals, and Roivant Sciences Ltd. Dr Harris has served on advisory boards, as a consultant, or as principal investigator on research agreements with Pfizer, AbbVie, Genzyme/Sanofi, Concert Pharmaceuticals, Stiefel/GSK, Mitsubishi Tanabe Pharma, Novartis, Aclaris Therapeutics, The Expert Institute, Celgene, Biologics MD, and Dermira. Ms Liu and Mr Strassner and Dr Refat have no conflicts of interest to declare.

    Reprints not available from the authors.

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