Alopecia areata (AA) affects 1 to 2% of the population and has a markedly negative impact on health-related quality-of-life (HRQoL). Approximately, 25% of patients suffer from generalized anxiety and major depressive disorder. Unfortunately, there is no reliable effective therapy, especially for patients suffering from severe disease.

As oral tofacitinib is approved for use for plaque psoriasis, one patient who suffered from both alopecia universalis and plaque psoriasis was treated with daily tofacitinib. Initial hair growth was seen at 2 months, complete scalp coverage was seen at 5 months, and a full head of hair was present by 8 months.¹ Regrowth of eyebrows and eyelashes also occurred.

AA is caused by cytotoxic T lymphocytes. It begins with the secretion of IL-15 in the follicular epithelial cells which, in turn, recruits and activates cytotoxic T cells. The cytotoxic T cells secrete IFN-gamma, which returns to the follicular epithelial cell, binds to the receptor, and leads to more secretion of IL-15. This cyclical action leads to inflammation and subsequent hair loss.² This theory was published shortly after the results of a mouse study and sample AA patient became available. In the study, the mice and patient were treated with ruxolitinib, both of which demonstrated hair regrowth within 12 weeks.³

Currently, there are three JAK inhibitors available for use: Table.

• An open-label, 2 center trial was conducted for AA patients with >50% scalp hair loss for at least 6 months without evidence of hair regrowth.⁴ A total of 66 patients were enrolled in this study and treated with oral tofacitinib 5 mg twice daily for 3 months. The Severity of Alopecia Tool (SALT) score was used to assess the percent change in treatment response (100 = no scalp hair; 0 = no hair loss). Over the course of 3 months, 1/3 of patients had >50% improvement from baseline, 1/3 had 5 to 50% of hair regrowth, and the remaining 1/3 were unresponsive to treatment. It was interesting to note that patients that had hair loss for >10 years had a poor response rate, suggesting that time is an important factor for response.
• In a small open-label trial with 12 AA patients, oral ruxolitinib 20 mg twice daily was given for 3 to 6 months and treatment response was assessed by change in SALT score.⁵ All patients recruited had AA with >30% and <95% scalp hair loss for at least 3 months without evidence of hair regrowth. A total of 9 out of 12 patients regrew hair over 6 months. When therapy was concluded, hair loss was reinitiated.
• As AA is a considerable issue in adolescents, a retrospective study of 13 AA patients, aged 12-17, with >20% scalp hair loss, alopecia totalis (AT) or alopecia universalis (AU), stable or worsening for 6 months or longer was performed.⁶ Patients were treated with tofacitinib for 2 to 16 months and assessed by the latest percent change in SALT score (initial visit prior to treatment and most recent visit while taking tofacitinib). There were a total of 9 responders. Responders had complete or near complete scalp hair regrowth. Topical tofacitinib had minimal results and may only be useful for mild cases or for eyelashes, eyebrows, and facial hair.⁷

Vitiligo affects approximately 1% of the population and has a significant negative impact on quality-of-life. There are limited treatment options for vitiligo. Topical steroids, calcineurin inhibitors, and phototherapy are sometimes effective. The only FDA-approved treatment is monobenzone, which is specific for depigmentation (not repigmentation).

It is theorized that T cells interact with keratinocytes which subsequently secretes IFN-gamma.⁸ The IFN-gamma stimulates the keratinocytes to secrete CXCL 9 and 10, which recruits and activates more T cells.⁸ The T cells accumulate and destroy melanocytes leading to white patches in the skin.⁸

• In a pathogenesis-directed therapy study, one patient was treated with tofacitinib citrate (5 mg QD 5 months) and regained full pigmentation of the face, arms, and a majority of the hands.⁹
• A patient with coexistent vitiligo and AA was treated with oral ruxolitnib and had 51% repigmentation on the face at 20 weeks. ¹⁰ The patient lost his pigmentation within 12 weeks of study discontinuation. Accompanying CXCL 10 levels dropped during treatment suggesting the model for pathogenesis is correct.¹⁰
• Topical ruxolitinib demonstrated a 76% improvement in facial vitiligo.¹¹ However, truncal and acral involvement did not show significant improvement. This finding suggests that concomitant light therapy may be required. To test that theory, a retrospective study of 10 patients was undertaken.¹² Skin samples were taken of sun exposed vs non-sun exposed skin after treatment with tofacitinib. In responsive skin, CD 8 cells, CXCL 9/10 trend toward 0 after treatment.¹² This finding suggests that a JAK inhibitor is required to inhibit T cell destruction of the melanocyte, but that light is required to stimulate melanogenesis and repigmentation of the interfollicular epidermis.
• In a study treating vitiligo patients with tofacitinib followed by concurrent ultraviolet light therapy, patients’ head and neck repigment by 3 months with complete repigmentation by 6 months. Hands repigmented slower with partial repigmentation at 6 months and almost complete repigmentation by 9 months.