JAK Inhibitors for Atopic Dermatitis Clinical and Experimental Dermatology

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• The authors review the use of JAK inhibitors (Jakinibs) for the treatment of atopic dermatitis (AD). The pathogenesis of AD is complex and thought to involve the JAK-signal transducer and activator of transcription along with spleen tyrosine kinase pathways. Jakinibs target various receptors in these pathways, including the receptor tyrosine kinases JAK1, JAK2, JAK3, and tyrosine kinase 2. Abrocitinib, upadacitinib, baricitinib, and gusacitinib are the oral Jakinibs that have been studied mostly in patients with moderate to severe AD. Topical Jakinibs, such as ruxolitinib, tofacitinib, and deglocitinib, have also been studied as a potential treatment option for AD for either localized involvement or as an adjunct to systemic therapy. Phase II and III trials have been conducted and demonstrate the effectiveness of Jakinibs in AD, especially for the rapid improvement of pruritus. While this appears to be a safe treatment option, complete blood count, liver enzymes, and lipids will likely need to be monitored in certain patients.

• Jakinibs represent a novel therapeutic option for patients with AD, which could soon be added to the treatment armamentarium for this chronic dermatologic disease. Further studies comparing efficacy among Jakinibs along with that of dupilumab and newer biologics are needed.

– Alex  Noble, MD

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Joy L. Mosser-GoldfarbMD

There have been significant advances in the treatment of atopic dermatitis in the last few years. Janus kinase inhibitors are among the most awaited therapies for dermatologists. This article provides a concise discussion of the mechanism of action of Jakinibs and a brief introduction to both the oral and topical therapies currently being studied in clinical trials.

Take-away point: There are four JAKs (JAK1, JAK2, JAK3 and TYK2) that phosphorylate STAT signaling activation of cytokines, such as IL-4, IL-13, IL-31, IL-22, thymic stromal lymphopoietin (TSLP), and IFN-γ. Inhibition of the JAK/STAT pathway blocks multiple mediators that cause inflammation, epidermal hyperplasia, and skin barrier dysfunction in atopic dermatitis.

These new therapies may prove to be superior to more selective biologics.

Abstract 

Atopic dermatitis (AD) is chronic, pruritic, inflammatory skin disease that affects a significant portion of the population in industrialized nations. For nonresponders to conventional therapies, AD can significantly reduce sleep quality and quality of life. AD pathogenesis is multifactorial and involves multiple immune pathways, with recent evidence of T helper (Th)2, Th17 and Th22 axis attenuation in various AD endotypes and racial subtypes. Inhibition of the conserved Janus kinase (JAK) signalling pathway represents a promising therapeutic avenue to reduce the activation of multiple proinflammatory mediators involved in AD pathogenesis. JAK inhibitors exist in both oral and topical forms with variable specificity for the receptor tyrosine kinases JAK1, JAK2, JAK3 and tyrosine kinase 2. Oral formulations include abrocitinib, upadacitinib, baricitinib and gusacitinib, and are most appropriate for patients with moderate to severe AD. Emerging topical formulation in development include ruxolitinib and deglocitinib, which may be used in patients with localized AD and also adjunctively with systemic therapy in patients with more severe disease. With observed rapidity in itch relief and accompanying dramatic reduction in inflammatory lesion count, JAK inhibitors represent a promising new treatment to revolutionize the management of AD.

Clinical and Experimental Dermatology

JAK Inhibitors for Atopic Dermatitis: A Promising Treatment Modality

Clin Exp Dermatol 2021 Jan 23;[EPub Ahead of Print], AM Cartron, TH Nguyen, YS Roh, MM Kwatra, SG Kwatra 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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