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Review

 

The effect of JAK1/JAK2 inhibition in rheumatoid arthritis: efficacy and safety of baricitinib

1, 2, 3, 4, 5, 6, 7, 8

 

  1. Cardiff University School of Medicine, Cardiff, Wales, UK. ChoyEH@cardiff.ac.uk
  2. Hôpitaux Universitaires Paris-Centre, Paris, France.
  3. Hospital Universitario Marqués de Valdecilla, IDIVAL School of Medicine, University of Cantabria, Santander, Spain.
  4. Division of Rheumatology, Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO, Milan, Italy.
  5. Eli Lilly and Company, Indianapolis, USA.
  6. Eli Lilly Regional Operations GmbH, Vienna, Austria.
  7. Lilly S.A., Alcobendas, Madrid, Spain.
  8. Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, Klinikum der Universität München, Munich, Germany.

CER11619
2019 Vol.37, N°4
PI 0694, PF 0704
Review

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PMID: 30767864 [PubMed]

Received: 14/08/2018
Accepted : 19/11/2018
In Press: 11/02/2019
Published: 27/06/2019

Abstract

Numerous cytokines have been implicated in the pathogenesis of inflammatory diseases, and their dysregulation is a main feature of rheumatoid arthritis (RA). Cytokines stimulate signal transduction through several intracellular pathways, including Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathways, leading to changes in cell activation, proliferation and survival. Consequently, agents that selectively target elements of the JAK/STAT pathways have received significant attention in recent years as potential new treatments for the disease. Baricitinib, an oral selective inhibitor of JAK1 and JAK2, offers an effective treatment for RA in a wide range of patients. The in vitro selectivity of different JAK inhibitors is an important consideration given that key cytokines, growth factors and hormone receptors involved in the pathogenesis of RA signal through specific JAKs. However, it is complex and far from understood how the in vitro effects of JAK inhibitors extrapolate into in vivo and clinical effects in individual patients. This narrative review focuses on the clinical efficacy and safety of baricitinib, but also provides an overview of its mechanism of action in relation to JAK1/JAK2 signalling and discusses the possible clinical implications in patients with RA.

Rheumatology Article