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Mechanism of Action

Will this be considered a turning point for the treatment of rheumatoid arthritis?

Olumiant® (baricitinib) is a selective, reversible inhibitor of JAK1 and JAK2, modulating inflammation in RA.1,2


The following videos overview the role of JAK inhibitors in modulating inflammation in rheumatoid arthritis. The videos are also available to download.

Cytokines and their implication in rheumatoid arthritis

The JAK/STAT pathway and rheumatoid arthritis

Mechanism of Action of JAK inhibitors

Olumiant (baricitinib) Mechanism of Action

Olumiant (baricitinib) vs other JAK inhibitors

Role of JAKs


Janus kinases (JAKs) play an important role in the process of inflammation and joint damage associated with RA.1-3


A large number of cytokines signal via the intracellular JAK-STAT pathway, which mediates cytokine signals involved in the pathogenesis of inflammatory diseases.9


Janus kinase (JAK) inhibitors have emerged as a new small molecule therapy for autoimmune disease. These drugs simultaneously target multiple cytokine signalling pathways known to be involved in the pathogenesis of these diseases.9


Olumiant directly modulates signalling of a number of cytokines implicated in RA, including IL-6 and interferons, thereby returning the inflammatory response toward a more normal state.1-3,5,6

Hear from Professor John Isaacs discussing the JAK/STAT pathway

Immunogenicity and small molecule therapy


Olumiant, which is administered as an oral, once-daily tablet1 has emerged as an alternative option to biologic therapy, which usually require subcutaneous or intravenous injection.11


In addition, small molecule inhibitors offer an alternative therapy given the lack of immunogenicity and reduced inter-patient pharmacokinetic variability, as compared with monoclonal antibodies such as the bDMARDs9


Short Half-Life compared with Biologic DMARDs


Olumiant has a short half-life (12.5 hours), enabling a short washout period.1 Renal elimination of unchanged, active drug is the principal mechanism of clearance.1

References

  1. Olumiant (baricitinib) Summary of product characteristics. January 2018.
  2. Shi JG, et al. J Clin Pharmacol 2014;54(12):1345-61.
  3. Shuai K, et al. Nat Rev Immunol 2003;3(11):900-11.
  4. Mócsai A, et al. BMC Medicine 2014;12:43.
  5. O'She JJ et al. Annu Rev Med 2015;66:311-283
  6. McInnes I et al. Poster presented at 37th EWRR. 2017
  7. Schwartz DM, et al. Nat Rev Rheumatol 2016;12:25–36.
  8. Swierkot J, et al. Adv Clin Exp Med 2016;25:709–17.
  9. Boland, et al. Gastroenterol Clin North Am. 2014;43(3): 603-617.
  10. Seidel HM, et al. Oncogene 2000;19:2645–56.
  11. Zhao, L, et al. Acta Pharmacol Sin. 2012; 33(11): 1339-1347.

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