Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata

Abstract

IntroductionAlopecia areata (AA) is a major medical problem and is among the most prevalent autoimmune disease in the US, with a lifetime risk of 1.7% (1). AA affects both sexes across all ethnicities and represents the second most common form of human hair loss, second only to androgenetic alopecia (2). AA usually presents with patchy hair loss. One-third of these patients will experience spontaneous remissions within the first year. However, many patients' disease will progress to alopecia totalis (AT, total scalp hair loss) or alopecia universalis (AU, loss of all body hair). Persistent moderate-to-severe AA causes significant disfigurement and psychological distress in affected individuals (3). In clinical practice, there are no evidence-based treatments for AA (4), yet various treatments are offered, most commonly topical and intralesional steroids, which have limited efficacy.Our recent mechanistic studies demonstrated a dominant role for type I cellular immunity in AA pathogenesis, mediated by IFN-γ-producing NKG2D-bearing CD8 + cytotoxic T lymphocytes (CTLs) (5). The central role of type I cellular immunity is also reflected in the transcriptional landscape of AA lesional skin in humans and mice, which is dominated by IFN response genes and a CTL signature. These findings provided 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.

Complete Regrowth of Beard Hair with Ruxolitinib in an Alopecia Universalis Patient

“…Several studies have shown its effectiveness in the treatment of AA, and it was also found to be beneficial for the more severe types, AT and AU [17,18,19]. The current report further highlights the effectiveness of the JAK inhibitors to treat AA, also in recalcitrant and chronic cases.…”

Alopecia areata

“…Several case series and individual reports have documented regrowth of hair in patients with different forms of alopecia areata, including alopecia universalis, following treatment with oral JAK inhibitor drugs. Three JAK inhibitors have been used: tofacitinib 194–198 , ruxolitinib 2,199,200 , and baricitinib (JAK 1/2 inhibitor) 201 . Hair regrowth has also been observed when treating human patients with JAK inhibitors for other diseases who have concurrent alopecia areata.…”

“…Although the number of reports is small, and no randomized, placebo-controlled studies have yet been performed, the response in patients with severe alopecia (in which spontaneous remission is rare) strongly suggests a therapeutic effect. Not surprisingly, there have been several reports of relapse following initial improvement in patients treated with ruxolitinib and tofacitinib 196,197,200,202 , suggesting that an eventual therapeutic regimen may need to include long-term maintenance therapy. The overall positive results in these early clinical studies are supported by the results of JAK inhibition in a mouse model of alopecia areata and by an improved understanding of the pathogenesis of the disease.…”

Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata

“…ruxolitinib-treated patients (5) and in Mackay-Wiggan et al (16), adequately predicted patient response to ruxolitinib, and it was not able to stratify SRs from NRs to tofacitinib. This is not surprising, as the target specificity of the drugs differs and because there was a predominance of AT and AU patients in this study, rather than patch-stage AA in the ruxolitinib trial, or, alternatively, because our study analyzed patients at 2 months after treatment with tofacitinib, which may not represent a complete response or reversion of gene expression signatures.…”