Treatment of alopecia universalis with topical Janus kinase inhibitors – a double blind, placebo, and active controlled pilot study

Bokhari, Laita; Sinclair, Rodney

doi:10.1111/ijd.14192

Cited by 57 publications

(44 citation statements)

References 18 publications

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“…In both interface-dermatitis featuring LP (NCT03697460) and graft-versus-host-disease (NCT03395340), topical formulations of JAK inhibitor ruxolitinib are currently evaluated in phase II clinical trials. In AD, PSO, vitiligo and alopecia areata, topically administered JAK inhibitors have been tested in clinical studies with some promising results concerning safety, tolerability and efficacy, awaiting further investigations (53)(54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

Selective Janus Kinase 1 Inhibition Is a Promising Therapeutic Approach for Lupus Erythematosus Skin Lesions

et al. 2020

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Background: Cutaneous lupus erythematosus (CLE) is an interferon (IFN)-driven autoimmune skin disease characterized by an extensive cytotoxic lesional inflammation with activation of different innate immune pathways. Aim of our study was to investigate the specific role of Janus kinase 1 (JAK1) activation in this disease and the potential benefit of selective JAK1 inhibitors as targeted therapy in a preclinical CLE model. Methods: Lesional skin of patients with different CLE subtypes and healthy controls (N = 31) were investigated on JAK1 activation and expression of IFN-associated mediators via immunohistochemistry and gene expression analyses. The functional role of JAK1 and efficacy of inhibition was evaluated in vitro using cultured keratinocytes stimulated with endogenous nucleic acids. Results were confirmed in vivo using an established lupus-prone mouse model. Results: Proinflammatory immune pathways, including JAK/STAT signaling, are significantly upregulated within inflamed CLE skin. Here, lesional keratinocytes and dermal immune cells strongly express activated phospho-JAK1. Selective pharmacological JAK1 inhibition significantly reduces the expression of typical proinflammatory mediators such as CXCL chemokines, BLyS, TRAIL, and AIM2 in CLE in vitro models and also improves skin lesions in lupus-prone TREX1 −/−-mice markedly. Conclusion: IFN-associated JAK/STAT activation plays a crucial role in the pathophysiology of CLE. Selective inhibition of JAK1 leads to a decrease of cytokine expression, reduced immune activation, and decline of keratinocyte cell death. Topical treatment with a JAK1-specific inhibitor significantly improves CLE-like skin lesions in a lupus-prone TREX1 −/−-mouse model and appears to be a promising therapeutic approach for CLE patients.

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Section: Discussionmentioning

confidence: 99%

Selective Janus Kinase 1 Inhibition Is a Promising Therapeutic Approach for Lupus Erythematosus Skin Lesions

et al. 2020

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“…Tofacitinib is a JAK1 and JAK3 inhibitor approved for the treatment of rheumatoid arthritis, and it has recently shown to be successful for treating alopecia areata [135][136][137]. Tofacitinib treatment has resulted in hair growth and its mechanisms have shown to involve decreasing clonally expanded CD8 + T cell populations in alopecia areata scalp [48], reducing chemokine CXCL10 levels [136], and promoting angiogenesis by upregulation of vascular endothelial growth factor (VEGF) [60].…”

Section: Inhibitors Of Ifn-γ Induced Signallingmentioning

confidence: 99%

“…However, the drug has failed to completely remove CD8 + cells from affected skin or blood, which could explain the relapse after the treatment stops [48]. Topical tofacitinib and ruxolitinib have also shown to be effective and cause hair growth in alopecia areata patients [137]. Despite the effectiveness of tofacitinib, more investigation is needed as results have shown to vary based on disease severity and treatment progression [24].…”

Section: Inhibitors Of Ifn-γ Induced Signallingmentioning

confidence: 99%

Alopecia areata: A multifactorial autoimmune condition

Simakou

Butcher

Reid

et al. 2019

Journal of Autoimmunity

194

151

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Highlights  Alopecia areata is a polygenic and multifactorial autoimmune disease characterised by non-scarring hair loss.  Autoreactive CD8 + , CD4 + , natural killer cells and plasmacytoid dendritic cells infiltrate around the hair follicles during the growth (anagen) phase.  Increased cytokine activity, particularly IFN-γ, results in disruption of the hair follicle immune privilege and premature termination of the anagen phase, followed by hair follicle atrophy and dystrophy in persistent disease.

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“…[91][92][93][94][95] The topical formulations of these new drugs (tofacitinib 2% ointment, ruxolitinib 1% ointment) are very interesting in order to minimize the adverse effects without losing effectiveness; nowadays few data are available but they seem to be a promising treatment option in both adults and pediatric aa patients. [96][97][98][99][100][101] these drugs can be administered in both active and chronic phase of aa.…”

Section: Minoxidilmentioning

confidence: 99%

Italian Guidelines in diagnosis and treatment of alopecia areata

Rossi¹,

Mellai²,

Piraccini³

et al. 2019

G Ital Dermatol Venereol

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Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration. The italian Study Group for Cutaneous annexial disease of the italian Society of dermatology proposes these italian guidelines for diagnosis and

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Treatment of alopecia universalis with topical Janus kinase inhibitors – a double blind, placebo, and active controlled pilot study

Abstract: Our findings suggest that topical JAK inhibitors could be developed as a potential new treatment for AA and alternative to clobetasol dipropionate 0.05% ointment.

Cited by 57 publications

References 18 publications

Selective Janus Kinase 1 Inhibition Is a Promising Therapeutic Approach for Lupus Erythematosus Skin Lesions

Selective Janus Kinase 1 Inhibition Is a Promising Therapeutic Approach for Lupus Erythematosus Skin Lesions

Alopecia areata: A multifactorial autoimmune condition

Italian Guidelines in diagnosis and treatment of alopecia areata

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