Targeting JAK3 in kidney transplantation: Current status and future options

David Wojciechowski, Flavio Vincenti

Research output: Contribution to journalReview article

20 Scopus citations

Abstract

Purpose of review: This review will discuss the mechanism of action and important clinical trial data in renal transplantation for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib, formerly known as CP-690,550 and tasocitinib. Recent findings: JAKs are cytoplasmic tyrosine kinases that participate in the signaling of a broad range of cell surface receptors, particularly members of the cytokine receptor common gamma (cγ) chain family. JAK3 inhibition has immunosuppressive effects and treatment with tofacitinib in clinical trials has demonstrated efficacy in autoimmune disorders such as psoriasis and rheumatoid arthritis. Nonhuman primate models of renal transplantation demonstrated prolonged graft survival with tofacitinib compared with vehicle control. Renal transplant clinical trials in humans have demonstrated tofacitinib to be noninferior to cyclosporine in terms of rejection rates and graft survival. There was also a lower rate of new-onset diabetes after transplant. However, there was a trend toward more infections, including cytomegalovirus and BK virus nephritis. Summary: Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined.

Original languageEnglish (US)
Pages (from-to)614-619
Number of pages6
JournalCurrent Opinion in Organ Transplantation
Volume16
Issue number6
DOIs
StatePublished - Dec 1 2011

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Keywords

  • JAK3
  • kidney transplant
  • tofacitinib

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation

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