The Use of Janus Kinase Inhibitors in Alopecia Areata: A Review of the Literature

Abstract

Alopecia areata (AA) is a chronic, immune-mediated disorder that targets hair follicle epithelium, thereby restricting hair growth in localized patches. Although several therapies for AA have been tested, responses with traditional therapies have been limited. In recent years, numerous reports have been published of patients with AA responding to Janus kinase (JAK) inhibitors. This literature review aims to describe AA pathophysiology, explore how and why JAK inhibitors can be used for AA treatment, and review published case reports, case series, and open-label studies published to date. Pathogenesis of AA includes interactions between genetic, environmental, and immune factors and is mediated by the cytokines interferon-γ and interleukin (IL)-15. JAK inhibition resulting in hair regrowth in some cases supports that AA is associated with the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. The emergence of JAK inhibitors for AA therapy is changing the way health care providers think about and treat AA. A mixture of animal model studies and human case studies have reported the use of baricitinib (JAK 1/2), ruxolitinib (JAK 1/2), and tofacitinib (JAK 1/3) for the management of AA. JAK inhibition has shown potential as an effective AA therapy when used in case studies, case series, and open-label trials. Formal clinical trials are ongoing and will yield more definitive conclusions about the safety and efficacy of JAK inhibitors.

Evaluation of the level of serum Interleukins (IL-2, IL-4, IL-15 andIL-17) and its relationship with disease severity in patients with alopecia areata

“… 7 Case reports, case series, and open-label studies on the use of Tofacitinib, a Janus kinase (JAK) 1 and 3 inhibitors, have been published in recent years. 8 Previous studies showed that interleukins especially IL-2, IL-4, and IL-15 may have a role in the pathogenesis of AA. Current studies also mention IL-17 as a potential pro-inflammatory cytokine having a role in the disease mechanism.…”

TYK 2 inhibitors for the treatment of dermatologic conditions: the evolution of JAK inhibitors

“…[33][34][35][36] This has made JAK inhibition a favorable treatment option with its clinical utility documented in numerous case reports and clinical trials. 8…”

“…3-7 JAK-STAT signaling is critical for many of the cytokines involved in inflammatory dermatological diseases, and therefore, inhibition of this signaling has been pursued therapeutically. 8 JAK kinases are also involved in critical functions such as hematopoiesis and immune response, and the first generation of JAK inhibitors demonstrated some predictable AEs that were felt to be secondary to the broad inhibition of these critical functions. Most notably, JAK2 inhibition has been associated with dose-dependent cytopenias (e.g., anemia and neutropenia) due to reliance of erythropoietin (EPO) and thrombopoietin (TPO) signaling through JAK2 [9][10][11] and JAK3 inhibition with increased infections due to depletion of T, B, and natural killer (NK) cells.…”

The Role of Type III Interferons in Human Disease

“…The up-regulation of the JAK-STAT pathway has been identified in AA scalp lesion biopsies [71], and IFN signature gene expression was also increased [72]. Moreover, JAK inhibition has shown potential as an effective treatment in selected cases of AA and it seems effective as a topical treatment in vitiligo as well [73]. Despite these reports, type III IFN involvement has not yet been studied in these chronic skin diseases.…”