Introduction
The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a crucial component of immune function, and JAK inhibitors allow dermatologists to regulate this pathway in certain disease states. Once bound to ligands, JAKs phosphorylate cytokine receptors and STAT proteins, which translocate to the nucleus and activate transcription of immunologic proteins.1 Four JAK isoforms have been identified: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). The different isoforms bind varyingly to cytokines including interleukin (IL)- 2, IL-4, IL-7, IL-9, IL-15, and IL-21. While the first-generation JAK inhibitors — tofacitinib, ruxolitinib, and baricitinib — block multiple JAK isoforms, second generation JAK inhibitors, such as decernotinib, abrocitinib, and upadacitinib, target a particular JAK, reducing adverse effects.
The first Food and Drug Administration (FDA)-approved JAK inhibitor, ruxolitinib, was originally for the treatment of myelofibrosis, and now topical ruxolitinib is approved for both atopic dermatitis (AD) and vitiligo. Abrocitinib and upadacitinib are approved for the treatment of AD. Tofacitinib is approved for the treatment of psoriatic arthritis (PsA) and currently studied in psoriasis, alopecia areata (AA), and AD.2 Baricitnib is the most recent addition to the JAK inhibitors approved for dermatologic use, specifically for AA. The ability of JAK inhibitors to modulate immune function make them ideal therapies for numerous dermatoses, many of which have yet to be FDA approved; therefore, JAK inhibitors are becoming more important than ever for dermatologists to have in their treatment armamentarium. This review examines the offlabel uses and possible future indications of JAK inhibitors in dermatology summarized in Table 1.
Alopecia Areata
With baricitinib, JAK inhibitors have introduced the first FDAapproved therapy for AA. Other JAK inhibitors have been investigated and some are aiming to seek approval for AA. Studies indicate tofacitinib 5 mg twice daily and ruxolitinib 15 to 25 mg twice daily induce significant hair regrowth in patients with AA after 3 to 6 months.3 Other studies with topical tofacitinib 1%-2% and ruxolitinib 0.6%-2% both applied twice daily also indicate success in 3 to 6 months, however to a lesser extent than oral therapies.4
Dermatomyositis
The majority of reports of the use of JAK inhibitors in dermatomyositis (DM) involve oral ruxolitinib or tofacitinib and indicate significant improvement.5 Specifically, tofacitinib 11 mg extended release given daily to patients with DM resulted in
The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a crucial component of immune function, and JAK inhibitors allow dermatologists to regulate this pathway in certain disease states. Once bound to ligands, JAKs phosphorylate cytokine receptors and STAT proteins, which translocate to the nucleus and activate transcription of immunologic proteins.1 Four JAK isoforms have been identified: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). The different isoforms bind varyingly to cytokines including interleukin (IL)- 2, IL-4, IL-7, IL-9, IL-15, and IL-21. While the first-generation JAK inhibitors — tofacitinib, ruxolitinib, and baricitinib — block multiple JAK isoforms, second generation JAK inhibitors, such as decernotinib, abrocitinib, and upadacitinib, target a particular JAK, reducing adverse effects.
The first Food and Drug Administration (FDA)-approved JAK inhibitor, ruxolitinib, was originally for the treatment of myelofibrosis, and now topical ruxolitinib is approved for both atopic dermatitis (AD) and vitiligo. Abrocitinib and upadacitinib are approved for the treatment of AD. Tofacitinib is approved for the treatment of psoriatic arthritis (PsA) and currently studied in psoriasis, alopecia areata (AA), and AD.2 Baricitnib is the most recent addition to the JAK inhibitors approved for dermatologic use, specifically for AA. The ability of JAK inhibitors to modulate immune function make them ideal therapies for numerous dermatoses, many of which have yet to be FDA approved; therefore, JAK inhibitors are becoming more important than ever for dermatologists to have in their treatment armamentarium. This review examines the offlabel uses and possible future indications of JAK inhibitors in dermatology summarized in Table 1.
Alopecia Areata
With baricitinib, JAK inhibitors have introduced the first FDAapproved therapy for AA. Other JAK inhibitors have been investigated and some are aiming to seek approval for AA. Studies indicate tofacitinib 5 mg twice daily and ruxolitinib 15 to 25 mg twice daily induce significant hair regrowth in patients with AA after 3 to 6 months.3 Other studies with topical tofacitinib 1%-2% and ruxolitinib 0.6%-2% both applied twice daily also indicate success in 3 to 6 months, however to a lesser extent than oral therapies.4
Dermatomyositis
The majority of reports of the use of JAK inhibitors in dermatomyositis (DM) involve oral ruxolitinib or tofacitinib and indicate significant improvement.5 Specifically, tofacitinib 11 mg extended release given daily to patients with DM resulted in
