Tofacitinib in kidney transplantation

David Wojciechowski, Flavio Vincenti

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Introduction: This review will discuss the mechanism of action and important kidney transplant clinical trial data for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib, formerly known as CP-690,550 and tasocitinib. Areas covered: Successful kidney transplantation requires adequate immunosuppression. Current maintenance immunosuppressive protocols which rely on calcineurin inhibitors have long-term nephrotoxicity and negative impact on cardiometabolic risk factors. 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 to 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. Expert opinion: Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined.

Original languageEnglish (US)
Pages (from-to)1193-1199
Number of pages7
JournalExpert Opinion on Investigational Drugs
Volume22
Issue number9
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

Kidney Transplantation
Clinical Trials
Graft Survival
Immunosuppressive Agents
Transplants
Janus Kinase 3
Interleukin Receptor Common gamma Subunit
BK Virus
Kidney
Nephritis
Cytomegalovirus Infections
Expert Testimony
Cell Surface Receptors
tofacitinib
Psoriasis
Protein-Tyrosine Kinases
Immunosuppression
Primates
Cyclosporine
Rheumatoid Arthritis

Keywords

  • Janus kinase 3
  • Kidney transplant
  • Tofacitinib

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Tofacitinib in kidney transplantation. / Wojciechowski, David; Vincenti, Flavio.

In: Expert Opinion on Investigational Drugs, Vol. 22, No. 9, 01.09.2013, p. 1193-1199.

Research output: Contribution to journalReview article

Wojciechowski, David ; Vincenti, Flavio. / Tofacitinib in kidney transplantation. In: Expert Opinion on Investigational Drugs. 2013 ; Vol. 22, No. 9. pp. 1193-1199.
@article{13e1ea58c27a4804911a76e315cafd9f,
title = "Tofacitinib in kidney transplantation",
abstract = "Introduction: This review will discuss the mechanism of action and important kidney transplant clinical trial data for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib, formerly known as CP-690,550 and tasocitinib. Areas covered: Successful kidney transplantation requires adequate immunosuppression. Current maintenance immunosuppressive protocols which rely on calcineurin inhibitors have long-term nephrotoxicity and negative impact on cardiometabolic risk factors. 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 to 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. Expert opinion: Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined.",
keywords = "Janus kinase 3, Kidney transplant, Tofacitinib",
author = "David Wojciechowski and Flavio Vincenti",
year = "2013",
month = "9",
day = "1",
doi = "10.1517/13543784.2013.811231",
language = "English (US)",
volume = "22",
pages = "1193--1199",
journal = "Expert Opinion on Investigational Drugs",
issn = "1354-3784",
publisher = "Taylor and Francis Ltd.",
number = "9",

}

TY - JOUR

T1 - Tofacitinib in kidney transplantation

AU - Wojciechowski, David

AU - Vincenti, Flavio

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Introduction: This review will discuss the mechanism of action and important kidney transplant clinical trial data for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib, formerly known as CP-690,550 and tasocitinib. Areas covered: Successful kidney transplantation requires adequate immunosuppression. Current maintenance immunosuppressive protocols which rely on calcineurin inhibitors have long-term nephrotoxicity and negative impact on cardiometabolic risk factors. 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 to 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. Expert opinion: Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined.

AB - Introduction: This review will discuss the mechanism of action and important kidney transplant clinical trial data for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib, formerly known as CP-690,550 and tasocitinib. Areas covered: Successful kidney transplantation requires adequate immunosuppression. Current maintenance immunosuppressive protocols which rely on calcineurin inhibitors have long-term nephrotoxicity and negative impact on cardiometabolic risk factors. 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 to 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. Expert opinion: Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined.

KW - Janus kinase 3

KW - Kidney transplant

KW - Tofacitinib

UR - http://www.scopus.com/inward/record.url?scp=84882283486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882283486&partnerID=8YFLogxK

U2 - 10.1517/13543784.2013.811231

DO - 10.1517/13543784.2013.811231

M3 - Review article

C2 - 23841583

AN - SCOPUS:84882283486

VL - 22

SP - 1193

EP - 1199

JO - Expert Opinion on Investigational Drugs

JF - Expert Opinion on Investigational Drugs

SN - 1354-3784

IS - 9

ER -