Tofacitinib in kidney transplantation

  title={Tofacitinib in kidney transplantation},
  author={David Wojciechowski and Flavio G Vincenti},
  journal={Expert Opinion on Investigational Drugs},
  pages={1193 - 1199}
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… 

Targeting JAK/STAT Signaling to Prevent Rejection After Kidney Transplantation: A Reappraisal.

It is believed that Jak inhibitors are a good and useful addition to the immunosuppressive armentarium for kidney transplant patients, and that new studies with personalized drug dosing, improved immune monitoring, and better patient selection should be performed.

Emerging drugs for prevention of T-cell mediated rejection in liver and kidney transplantation

In this review, the current standard of care in immunosuppressive therapy, including the use of steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of rapamycin inhibitors, will be discussed and new immunosppressive agents showing promising early data after liver and kidney transplantation will be explored.

Recent trials in immunosuppression and their consequences for current therapy

Despite clinical trials with innovative protocols with already established agents, tacrolimus-based and induction-based protocols have been shown to be the mainstay of immunosuppressive regimens and research aims to focus on biomarker-driven Immunosuppression and cell therapy approaches.

Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs

The mechanism of immunosuppressants, new agents' discovery, and current therapeutic protocols in the transplantation are discussed, and the importance of individualized drug use is shown.


A case of a 48-year-old patient who had suffered from polyarthritis from his age 40, which led to complete remission of the disease, without the need of basic or corticosteroid therapy, raised a question of timely introduction of immunomodulators in thepolyarthritis treatment steps.

Immunosuppressive Drugs in Solid Organ Transplantation

The current state of immunosuppressive agents is reviewed with an emphasis on drug classes, mechanisms, monitoring, major side effects, and current immunosppressive practices.

The Selective JAK1/3-Inhibitor R507 Mitigates Obliterative Airway Disease Both With Systemic Administration and Aerosol Inhalation

Oral and inhaled R507 was significantly more effective in reducing airway obliteration and preserved the morphology of the airway epithelium, and is a very well-tolerated immunosuppressant that similarly diminished obliterative airway disease with systemic or inhaled administration.

What's new in clinical solid organ transplantation by 2013.

The trends in numbers and survival have been reviewed as well as the most relevant problems such as organ preservation, ischemia reperfusion injuries, and rejections with particular regards to the antibody mediated rejection that involves all solid organs.



Immunosuppression by the JAK3 Inhibitor CP-690,550 Delays Rejection and Significantly Prolongs Kidney Allograft Survival in Nonhuman Primates

CP-690,550 is the first reported JAK3 inhibitor combining efficacy and good tolerability in a preclinical model of allotransplantation in nonhuman primates and thus has interesting potential for immunosuppression in humans.

Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes.

Calcineurin‐Inhibitor‐Free Immunosuppression Based on the JAK Inhibitor CP‐690,550: A Pilot Study in De Novo Kidney Allograft Recipients

  • S. BusqueJ. Leventhal G. Chan
  • Medicine, Biology
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2009
The data suggest that coadministration of CP‐690,550 30 mg BID with MMF is associated with overimmunosuppression, and the efficacy/safety profile was comparable to the tacrolimus control group, excepting a higher rate of viral infection.

Randomized Phase 2b Trial of Tofacitinib (CP‐690,550) in De Novo Kidney Transplant Patients: Efficacy, Renal Function and Safety at 1 Year

  • F. VincentiH. Tedesco Silva G. Chan
  • Medicine
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2012
Tofacitinib was equivalent to CsA in preventing acute rejection, was associated with improved renal function and less chronic allograft histological injury, but had side‐effects at the doses evaluated.

Prevention of Organ Allograft Rejection by a Specific Janus Kinase 3 Inhibitor

It is believed JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.

Drug-related dyslipidemia after renal transplantation.

  • A. MathisN. DaveG. KnippG. Friedman
  • Medicine, Biology
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 2004
PURPOSE The frequency, onset, mechanisms, and causes of dyslipidemia after renal transplantation are reviewed in the context of the adverse impact of lipid alterations, recent guidelines, and the

Janus kinase 3: a novel target for selective transplant immunosupression

One Jak3 inhibitor shows at least 40-fold greater selective inhibition for Jak3 than for Jak2, is robustly synergistic with calcineurin antagonists, and, either alone or in combination with cyclosporin, produces no adverse effects in rodents preconditioned to be at heightened risk for nephrotoxicity, bone marrow suppression, or altered lipid metabolism.

The Effect of the JAK Inhibitor CP-690,550 on Peripheral Immune Parameters in Stable Kidney Allograft Patients

The role of JAK3 in the homeostasis and function of select lymphocyte subpopulations is demonstrated and may provide a novel mechanism for the modulation of allogeneic responses in patients after transplantation.

Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis.

Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo.

What's Next in the Pipeline

  • F. VincentiA. Kirk
  • Biology, Medicine
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2008
The preclinical pipeline is not only full but promises to address previously neglected targets and fulfill unmet medical needs in transplant therapeutics.