Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy

Importance  Vitiligo is a common condition that is often emotionally devastating for patients. At present, no reliably effective treatments are available.

Observations  Recent advances in the understanding of the pathogenesis of vitiligo suggest that Janus kinase inhibitors may be a therapeutic option. We report a case of generalized vitiligo for which treatment with tofacitinib citrate, an oral Janus kinase 1/3 inhibitor, resulted in significant repigmentation.

Conclusions and Relevance  The results suggest that tofacitinib and other Janus kinase inhibitors may be effective in the treatment of vitiligo. Additional studies will be needed to confirm their efficacy and to explore their safety.

Vitiligo is a condition that often causes significant psychological distress for patients. Treatment options are limited and often inadequate. Recent progress in the scientific understanding of vitiligo suggests that Janus kinase (JAK) inhibitors may be an effective therapy. We report a case of vitiligo treated with the JAK 1/3 inhibitor tofacitinib citrate.

A woman in her 50s presented for evaluation and management of vitiligo, which had been widespread and progressive for approximately the past 1 year. Increasing involvement of the face and hands was causing the patient significant concern. She had used triamcinolone ointment, 0.1% (owing to the need for a large amount of topical medication in the setting of generalized involvement), and tacrolimus ointment, 0.1%, without effect. Treatment with narrowband UV-B phototherapy had recently been initiated; however, after 3 treatments, the patient continued to note progression of the vitiligo and therefore sought a second opinion regarding treatment. She was otherwise healthy and denied a family history of vitiligo or other autoimmune conditions. Complete review of systems was negative. Physical examination revealed innumerable white macules and patches involving the forehead (Figure 1A), trunk, and extremities (Figure 2A) involving approximately 10% of body surface area, which highlighted with Wood’s lamp.

The possibility of continuing phototherapy was discussed, including the typically months-long duration of treatment that is required to achieve repigmentation, which is usually incomplete.¹ Given the progressive, generalized nature of the vitiligo, the limited and often inadequate treatment options, and the patient’s associated concern, we decided to pursue a therapeutic trial of an agent that, based on recent advances in the understanding of vitiligo,² might yield faster and more complete repigmentation.

Treatment with oral tofacitinib citrate (Xeljanz) was initiated at a dosage of 5 mg every other day. After 3 weeks, the dosage was increased to 5 mg/d (half the approved dosage for rheumatoid arthritis, which is 5 mg twice daily). After 2 months of therapy, partial repigmentation of the face and upper extremities was evident. After 5 months, repigmentation of the forehead (Figure 1B) and hands (Figure 2B) was nearly complete, and the remaining involved areas demonstrated partial repigmentation. Approximately 5% of the total body surface area remained depigmented. The patient tolerated tofacitinib without adverse effects, and results of laboratory monitoring revealed no abnormalities in complete blood cell count, serum creatinine, hepatic function, or lipids during the course of treatment.

Tofacitinib is a JAK 1/3 inhibitor that was approved by the US Food and Drug Administration in 2012 for the treatment of moderate to severe rheumatoid arthritis. Within dermatology, oral and topical formulations of tofacitinib have been demonstrated to be safe and effective for the treatment of plaque psoriasis,^3-7 and we have recently described the success of oral tofacitinib in treating alopecia universalis.⁸ Clinical trials evaluating tofacitinib treatment of several disorders are presently under way.

Alopecia areata and vitiligo share genetic risk factors and can co-occur within families and individual patients, suggesting a common pathogenesis.⁹ As such, it is not surprising that a medication that has been shown to be effective in treating alopecia areata⁸ may also be effective in treating vitiligo. Moreover, recent advances in the scientific understanding of vitiligo support the use of JAK inhibitors for this condition. Interferon-gamma–induced expression of C-X-C motif chemokine 10 (CXCL10) in keratinocytes is an important mediator of depigmentation in vitiligo.² Antibody neutralization of interferon gamma or CXCL10 reverses depigmentation.¹⁰ We propose that because interferon gamma signal transduction occurs through JAK 1/2,¹¹ the use of the JAK 1/3 inhibitor tofacitinib effectively leads to blockade of interferon gamma signaling and downstream CXCL10 expression, thus giving rise to repigmentation in vitiligo.

To our knowledge, this report is the first to demonstrate effective pathogenesis-based therapy for a patient with vitiligo. The fairly rapid response and the repigmentation of the hands, which are often resistant to therapy, are noteworthy. Further investigation of the efficacy and safety of tofacitinib in the treatment of patients with vitiligo, including those for whom the condition has been more long-standing, will be important. Although uncommon, serious adverse effects, including malignant disease, have been reported in patients taking tofacitinib; therefore, investigation of the efficacy of a topical formulation for the treatment of localized vitiligo would be useful.

This case exemplifies the ways by which advances in basic science can guide treatment decisions and ultimately benefit patients. As we better understand the pathomechanisms of different diseases, targeted therapy becomes possible, and existing medications can be repurposed and/or new medications created for diseases with limited, if any, treatment options.

Accepted for Publication: April 21, 2015.

Corresponding Author: Brett A. King, MD, PhD, Department of Dermatology, Yale University School of Medicine, PO Box 208059, New Haven, CT 06520 (brett.king@yale.edu).

Published Online: June 24, 2015. doi:10.1001/jamadermatol.2015.1520.

Author Contributions: Drs Craiglow and King had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: King.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Study supervision: King.

Conflict of Interest Disclosures: None reported.