Tofacitinib for Treatment of Severe Alopecia Areata

Alopecia areata (AA) and its variants have an estimated lifetime risk of 1.7% in children and adults. However, current medical therapies are not reliably effective, particularly for severe disease.

In a murine model of AA, natural killer gene 2D-expressing CD8+ T cells were shown to be central, causing up-regulation of interleukin-15 in hair follicles and production of interferon-y, targeting the follicle for attack.

Janus Kinase (JAK) inhibitors have shown, as downstream regulators of interferon-y and interleukin-15, to eliminate the interferon signature and reverse disease.

A 2017 study in the Journal of the American Academy of Dermatology (JAAD) sought to evaluate the safety and efficacy of the JAK 1/3 inhibitor, tofacitinib, in AA, alopecia totalis (AT), or alopecia universalis (AU) patients over an extended period.

“Several recent case reports have demonstrated efficacy of JAK inhibitors for the treatment of AA, including ruxolitnib (JAK 1/2) in both oral and topical formulations, tofacitinib (JAK 1/3), and baricitnib (JAK 1/2),” write the study authors, but the long-term benefits of tofacitinib have not been evaluated.

In the study, 90 patients, 18-years and older, received 5 mg of tofacitinib twice daily for the first two to three months of treatment. After that time, and based on the presence or absence of regrowth, standard monotherapy continued, or adjuvant therapy began.

“Adjuvant therapy included either tofacitinib 5 mg twice daily plus prednisone or higher-dose tofacitinib up to 10 mg twice daily with or without prednisone; when used, the dose of prednisone was 300 mg once monthly for 3 doses (pulsed prednisone) except in a single patient taking prednisone 10 mg daily for arthropathy (started prior to tofacitinib),” write the study authors.

Three of the 90 patients did not receive the standard monotherapy for the first three months and were instead treated with 5 mg of tofacitinib twice daily, along with pulsed prednisone.

Treatment efficacy was evaluated using a tool that quantifies the percent of scalp hair loss, called the SALT score. A SALT score of zero indicated no hair loss while a score of 100 indicated a complete absence of hair.

Patient treatment responses were assessed based on complete response (>90% change in latest SALT Score), intermediate response (51%-90% change), moderate response (6%-50% change), and nonresponse (≤5% change).

Of the patients included, 77% achieved a clinical response, with 58% achieving greater than 50% change in SALT score over four to 18 months of treatment.

AA patients experienced a higher percent change in SALT scores compared to AT and AU (81.9% vs 59.0%) and no serious adverse events were observed over a median duration of 12 months.

Study authors conclude that long-term use of tofacitinib is an effective and well-tolerated treatment for severe AA, AT and AU, but more studies are needed to further examine the treatment.

Reference:

Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. Journal of the American Academy of Dermatology. 2017;76(1):22-28.