JAK inhibitors in the treatment of atopic dermatitis

Chovatiya, Raj; Paller, Amy S.

doi:10.1016/j.jaci.2021.08.009

Cited by 175 publications

(151 citation statements)

References 87 publications

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“…Molecular mechanisms of JAK-STAT signaling have been described elsewhere. [144][145][146][147][148][149] Most cytokines signal via heterodimer cytokine receptors, activating their intracellular domain JAKs, thereby initiating STAT (signal transducers of NFAT [nuclear factor of activated T-cells]) activation. Four JAKs have been described (JAK1, JAK2, JAK3, Tyk2).…”

Section: Cytokine-jak Signaling and Role For Pruritus In Admentioning

confidence: 99%

Neuroimmune communication regulating pruritus in atopic dermatitis

Steinhoff

Faried

Pandey

et al. 2022

Journal of Allergy and Clinical Immunology

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Section: Cytokine-jak Signaling and Role For Pruritus In Admentioning

confidence: 99%

Neuroimmune communication regulating pruritus in atopic dermatitis

Steinhoff

Faried

Pandey

et al. 2022

Journal of Allergy and Clinical Immunology

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“…Small-molecule JAKis target structures involved in downstream signaling of multiple pro-inflammatory cytokines. 214…”

Section: Broad-acting: Small-molecule Jakismentioning

confidence: 99%

“…Small‐molecule JAKis target structures involved in downstream signaling of multiple pro‐inflammatory cytokines 214 . JAKis can offer broad protection and have an intermediate level of risk between biologic drugs, which block specific extracellular molecules, and conventional immunosuppressants.…”

Section: Treatmentmentioning

confidence: 99%

Atopic dermatitis: pathomechanisms and lessons learned from novel systemic therapeutic options

Bieber

Paller

Kabashima

et al. 2022

Acad Dermatol Venereol

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Atopic dermatitis (AD) is a chronic, heterogenous, inflammatory skin disorder associated with a high skin-related health burden, typically starting in childhood and often persisting into adulthood. AD is characterized by a wide range of clinical phenotypes, reflecting multiple underlying pathophysiological mechanisms and interactions between genetics, immune system dysregulation and environmental factors. In this review, we describe the diverse cellular and molecular mechanisms involved in AD, including the critical role of T-cell-driven inflammation, primarily via T helper (Th) 2-and Th17derived cytokines, many of which are mediated by the Janus kinase (JAK) signaling pathway. These local inflammatory processes interact with sensory neuronal pathways, contributing to the clinical manifestations of AD, including itch, pain and sleep disturbance. The recent elucidation of the molecular pathways involved in AD has allowed treatment strategies to evolve from broad-acting systemic immunosuppressive therapies to more targeted agents, including JAK inhibitors and cytokine-specific biologic agents. Evidence from the clinical development of these targeted therapies has reinforced and expanded our understanding of the pathophysiological mechanisms underlying AD and holds promise for individualized treatment strategies tailored to specific AD subtypes.

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“…Both topical and oral Janus kinase (JAK) inhibitors that target the JAK/STAT signaling cascade common to many inflammatory mediator and growth factor receptors, have shown efficacy in clinical trials for patients with moderate-to-severe AD. 170 The JAK inhibitors (depending on their JAK specificity) target multiple cytokines pathways including Th2 (IL-4, IL-13, IL-31 and TSLP), Th22 (IL-22), and Th1 (IFN-γ, IL-12, and IL-23) and therefore are much less selective than biologics.…”

Section: How Barrier Defects Lead To Admentioning

confidence: 99%