BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-γ transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA.
METHODS. We initiated an open-label clinical trial of 12 patients with moderate-to-severe AA, using oral ruxolitinib, 20 mg twice per day, for 3–6 months of treatment followed by 3 months follow-up off drug. The primary endpoint was the proportion of subjects with 50% or greater hair regrowth from baseline to end of treatment.
RESULTS. Nine of twelve patients (75%) demonstrated a remarkable response to treatment, with average hair regrowth of 92% at the end of treatment. Safety parameters remained largely within normal limits, and no serious adverse effects were reported. Gene expression profiling revealed treatment-related downregulation of inflammatory markers, including signatures for CTLs and IFN response genes and upregulation of hair-specific markers.
CONCLUSION. In this pilot study, 9 of 12 patients (75%) treated with ruxolitinib showed significant scalp hair regrowth and improvement of AA. Larger randomized controlled trials are needed to further assess the safety and efficacy of ruxolitinib in the treatment of AA.
FUNDING. Locks of Love Foundation, the Alopecia Areata Initiative, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the Irving Institute for Clinical and Translational Research/Columbia University Medical Center Clinical and Translational Science Award (CUMC CTSA).
Julian Mackay-Wiggan, Ali Jabbari, Nhan Nguyen, Jane E. Cerise, Charlotte Clark, Grace Ulerio, Megan Furniss, Roger Vaughan, Angela M. Christiano, Raphael Clynes
(A) Heatmap and clustering dendrogram of samples from patients at baseline (nresponders = 9, nnonresponders = 2) and week 12 of treatment (nresponders = 9, nnonresponders = 1) and healthy controls (n = 6) using differentially expressed genes between baseline responder and healthy control samples (Supplemental Table 2). Black, normal subjects; red, AA responder patient at baseline; purple, AA responder patient after 12 weeks treatment; yellow, AA nonresponder patient at baseline; blue, AA nonresponder patient after 12 weeks treatment. (B) Principal components plots of samples taken from subjects at 12 weeks after treatment and at baseline. Principal components are labeled PC1, PC2, and PC3. (C) Heatmap of AA disease activity index (ALADIN) genes. (D) Three-dimensional plot of ALADIN signatures. (E) ALADIN component signature scores. Left panel, cytotoxic T lymphocyte (CTL) signature scores; middle panel, IFN signature scores; right panel, hair keratin (KRT) signature scores. R, responders; NR, nonresponders; HC, healthy controls. *P < 0.05, **P < 0.01, ***P <0.001. Samples were compared using the Kruskal-Wallis test, followed by the Wilcoxon ranked-sum test. The Wilcoxon signed-rank test was used to compare week 0 and week 12 samples. (F) ALADIN component scores from skin samples of AA patients were determined at baseline, week 12, and, in some cases, intermediate or after treatment time points. Red, responder patients; blue, nonresponder patients; black, HC patients.