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Rheumatology (Oxford, England)
05 05, 2022;61 (5): 1783-1794.

A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition.

Iain B McInnes, Zoltán Szekanecz, Dennis McGonagle, Walter P Maksymowych, Alexander Pfeil, Ralph Lippe, In-Ho Song, Apinya Lertratanakul, Thierry Sornasse, Ana Biljan, Atul Deodhar
Author Information
  1. Iain B McInnes: College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
  2. Zoltán Szekanecz: Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. ORCID
  3. Dennis McGonagle: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
  4. Walter P Maksymowych: Division of Rheumatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. ORCID
  5. Alexander Pfeil: Department of Internal Medicine III, Jena University Hospital-Friedrich Schiller University Jena, Jena. ORCID
  6. Ralph Lippe: AbbVie Deutschland GmbH & Co. KG, Wiesbaden, Germany.
  7. In-Ho Song: AbbVie Inc., North Chicago, IL, USA.
  8. Apinya Lertratanakul: AbbVie Inc., North Chicago, IL, USA.
  9. Thierry Sornasse: AbbVie Inc., North Chicago, IL, USA.
  10. Ana Biljan: AbbVie Inc., North Chicago, IL, USA.
  11. Atul Deodhar: Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR, USA.
PMID: 34668515 DOI: 10.1093/rheumatology/keab740

Abstract

Spondyloarthritis (SpA) comprises a group of chronic inflammatory diseases with overlapping clinical, genetic and pathophysiological features including back pain, peripheral arthritis, psoriasis, enthesitis and dactylitis. Several cytokines are involved in the pathogenesis of SpA, variously contributing to each clinical manifestation. Many SpA-associated cytokines, including IL-23, IL-17, IL-6, type I/II interferon and tumour necrosis factor signal directly or indirectly via the Janus kinase (JAK)-signal transducer and activator of transcription pathway. JAK signalling also regulates development and maturation of cells of the innate and adaptive immune systems. Accordingly, disruption of this signalling pathway by small molecule oral JAK inhibitors can inhibit signalling implicated in SpA pathogenesis. Herein we discuss the role of JAK signalling in the pathogenesis of SpA and summarize the safety and efficacy of JAK inhibition by reference to relevant SpA clinical trials.

Keywords

AS Janus kinase inhibitor PsA spondyloarthritis

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MeSH Term

Cytokines
Humans
Janus Kinase Inhibitors
Janus Kinases
STAT Transcription Factors
Signal Transduction
Spondylarthritis

Chemicals

Cytokines
Janus Kinase Inhibitors
STAT Transcription Factors
Janus Kinases
Journal Article Review Research Support, Non-U.S. Gov't

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