A Comprehensive Literature Review of JAK Inhibitors in Treatment of Alopecia Areata

Abstract

Alopecia areata (AA) is a chronic, immune-mediated form of nonscarring alopecia that is multifactorial and results in localized patches. It is often described as a self-limiting condition that results in the spontaneous regrowth of hair in most cases. However, this regrowth may take several months or years to occur in some patients, leading to the development of psychoemotional trauma in those that are affected. Although several therapies for AA have been developed and tested, there is no specific treatment that has been approved, leading to the availability of many off-label conventional treatment options, with very limited responses. More recently, with the advancement of pre-clinical and genetic studies, a greater understanding of the pathomechanisms involved in the development of AA has been uncovered. This has resulted in the introduction of targeted therapies that use small molecules to block specific pathways involved in AA pathophysiology. As such, the use of janus kinase (JAK) inhibitors for treatment of AA has emerged. JAK inhibitors block the T-cell mediated inflammatory response thought to be the driving factor behind AA pathogenesis, by inhibiting the janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway, leading to a reversal of hair loss in AA patients. Thus, in an effort to demonstrate the efficacy of JAK inhibitors in the treatment of AA, several studies have been published within recent years. However, the question remains, “Are JAK inhibitors effective and safe in the management of Alopecia Areata?”. This review aims to provide a comprehensive report on the role, efficacy, and outcomes of using JAK inhibitors in the treatment of AA. To competently answer the research question highlighted, the most recent, quality articles published over a 10–15-year period were sourced using PubMed, NCBI, Research gate, Medline, Cochrane Central Register of Controlled Trials, EMBASE and Google scholar. The literature search was primarily focused on randomized controlled trials (RCTs); however, in the absence of such, only the most recently published case reports, case series, clinical trials and open-label studies published to date were included.

Case Report: Successful Treatment of Alopecia Universalis With Tofacitinib and Increased Cytokine Levels: Normal Therapeutic Reaction or Danger Signal?

“…Tofacitinib, a JAK inhibitor, mainly acts on JAK 1 and 3 and has been previously investigated in AA treatment. These studies show that it is well-tolerated and effective for severe and recalcitrant cases without any reported serious adverse effects, although tofacitinib is unable to maintain a durable response when treatment is stopped ( 10 ). After tofacitinib treatment, our patient’s hair regrew gradually, and the SALT and AA-IGA™ scores decreased significantly ( Figure 2 ).…”

“…Serum Th1 cytokines, including IFN-γ, TNF-α, and IL-12p70, and serum Th2 cytokines IL-4, IL-6, IL-10, and Th17 cytokines IL-17 participated in the progression of AU. Tofacitinib can inhibit cytokines in hair follicles of AA patients, including IL-2, IL-4, IL-7, IL-15, IL-21, and IFN-γ, by blocking the STAT phosphorylation and disrupting the signaling pathway of JAK 1/3 ( 10 ). However, studies on peripheral blood cytokine changes after tofacitinib treatment are still lacking.…”

Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice

“…However, JAKis increase sensitivity to infection and cancer by nonspecific suppression of immune cell activation. Also, human patients invariably relapse upon treatment cessation, indicating that its therapeutic effect is transient (8)(9)(10).…”

Autoantigen Discovery in the Hair Loss Disorder, Alopecia Areata: Implication of Post-Translational Modifications

“…Treatment of AA is difficult; there is no FDA-approved drug, and there is currently no cure. Despite this, a broad range of treatment modalities can be used, including topical, systemic, and intralesional corticosteroids; topical immunotherapy; topical minoxidil; anthralin; and Psoralen plus Ultraviolet A (PUVA), and more recently JAK inhibitors (20,21).…”