Alopecia areata (AA) is a non-scarring alopecia, which affects about 1-2% of the population. As Prof. Brett King (Yale University School of Medicine, USA) emphasised, there is a high medical need for treatment options, especially for advanced disease [1]. Research using human clinical samples and a mouse model demonstrated that cytotoxic T lymphocytes mediate AA in part through JAK signalling [2]. IL-15 and IFNγ are key cytokines in the development of AA and can be blocked by JAK inhibitors.
The first report of the efficacy of a JAK inhibitor was published after a psoriasis patient with concomitant AA was treated with tofacitinib and experienced a complete regrowth of hair [3]. After this experience, a first open-label trial with the JAK inhibitor tofacitinib was performed. In this trial, 32% of patients experienced a 50% or greater improvement in the Severity of Alopecia Tool (SALT) [4]. Another 32% of patients showed a hair growth of 5-50%, and 36% did not respond to treatment.
Since then, several publications have demonstrated efficacy of oral tofacitinib and ruxolitinib [5-9]. In a retrospective study with 90 patients, oral tofacitinib led to a clinic response in 77% of patients, with 58% achieving a greater than 50% change in SALT score over 4-18 months of treatment [6]. JAK inhibitors have also been effective in the treatment of adolescents or preadolescents [7,8]. According to the results of a pilot trial including 10 patients, tofacitinib is also active as a 2% ointment [10].
Prof. King recommended to start tofacitinib in a dose of 5 mg twice daily, or ruxolitinib 10 mg twice daily. All patients have to be screened for HIV, HBV, HCV, and tuberculosis prior to treatment. In addition, a complete blood count and comprehensive metabolic panel should be performed prior to treatment and 1 month after starting treatment, and then 3-4 months thereafter.
“I re-evaluate my patients in week 12, and consider increasing the dose if hair regrowth is inadequate”, said Prof. King. A near-complete scalp hair regrowth is usually seen after 6-12 months of treatment. Unfortunately, treatment is likely necessary for maintenance of hair regrowth. The scalp usually responds better than eyebrows and eyelashes.
Vitiligo: a disfiguring autoimmune disease
In the last decade, research has determined the autoimmune pathways responsible for progression of vitiligo. Gene expression profiling in lesional skin of patients and a mouse model of vitiligo indicated an increase in expression of IFNγ and IFNγ-induced genes [11-13]. In this context, vitiligo is more similar to AA than it is to psoriasis [14]. Accordingly, the JAK/STAT pathways also play a key role in the pathogenesis of vitiligo. Both tofacitinib and ruxolitinib have shown efficacy in vitiligo patients [15,16].
In a 20-week, open-label, proof-of concept trial, 9 vitiligo patients were treated with 1.5% ruxolitinib cream twice daily [17]. At week 20, 4 patients with significant facial involvement had a 76% improvement of facial vitiligo. Three out of 8 patients responded on body surfaces, and 1 patient responded on acral surfaces [17]. “Ruxolitinib cream may therefore offer a valuable new treatment option,” concluded Prof. King.
Another trial hinted to the fact that repigmentation in vitiligo using tofacitinib may require concomitant light exposure [18]. In this retrospective case series, 5 patients achieved some repigmentation at sites of either sunlight exposure or low-dose narrowband ultraviolet B phototherapy.
Three clinical trials are currently ongoing with JAK inhibitors in vitiligo: 2 studies of topical JAK inhibitors (i.e. a phosphate cream and a topical solution), and a phase 2b study with a novel oral JAK inhibitor.
- King B. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
- Xing L, et al. Nat Med 2014;20:1043-9.
- Craiglow BG, King BA. J Invest Dermatol 2014;134:2988-90.
- Kennedy Crispin M, et al. JCI Insight 2016;1:e89776.
- Mackay-Wiggan J, et al. JCI Insight 2016;1:e89790.
- Liu LY, et al. J Am Acad Dermatol 2017;76:22-28.
- Liu LY, King BA. J Investig Dermatol Symp Proc 2018:19:S18-20.
- Craiglow BG, King BA. J Am Acad Dermatol 2019:80:568-570.
- Liu LY, King BA. J Am Acad Dermatol 2019:80:566-68.
- Liu LY, et al. J Am Acad Dermatol 2018;78:403-404.
- Rashigi M, Harris JE. Ann Transl Med 2015;3:343.
- Harris JE, et al. J Invest Dermatol 2012; 132:1869-76.
- Rashigi M, et al. Sci Transl Med 2014; 6:223ra23.
- Harris JE. Exp Dermatol 2013;22:785-9.
- Craiglow BG, King BA. JAMA Dermatol 2015; 151:1110-2.
- Harris JE, et al. J Am Acad Dermatol 2016; 74:370-1.
- Rothstein B, et al. J Am Acad Dermatol 2017;76:1054-1060.
- Liu LY, et al. J Am Acad Dermatol 2017;77(4):675-82.e1.
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Table of Contents: WCD 2019
Featured articles
Letter from the Editor
Insights into pathogenesis of AD define novel therapeutic targets
Treating Psoriasis in 2019
Choosing the right biologic in psoriasis
Registries – an important research tool in biologics
Atopic Dermatitis – What is New
Insights into pathogenesis of AD define novel therapeutic targets
Combinations are hot in AD treatment
Dermal Reactions to Systemic Drugs
Cutaneous adverse events due to EGFR inhibitors
Management strategies for drug-induced mucositis
Skin toxicity of immune checkpoint inhibitors
Lupus Erythematosus Today
New targets and biologics for cutaneous lupus erythematosus
Novel lupus classification will aid future research
Hidradenitis Suppurativa
Various guidelines with much overlap
Antibiotics in hidradenitis suppurativa
Biologicals beyond TNF blockade
Small Molecules – What to Expect
Novel treatment options for many dermatologic indications
Long awaited oral therapy for moderate-to-severe AD
Novel treatment options in alopecia areata and vitiligo
Optimising the Management of Keloids
Keloids: a faulty switch in wound healing?
What the future of keloid treatment could hold
Malignant Melanoma – Advances in Management
Will malignant melanoma become a curable disease?
Best of the Posters
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