Recent trials in immunosuppression and their consequences for current therapy

Curr Opin Organ Transplant. 2014 Aug;19(4):387-94. doi: 10.1097/MOT.0000000000000093.

Abstract

Purpose of review: Although the scarcity of clinical trials with de-novo immunosuppression has been typical over the last 2 years, several attempts have been made in drug conversion, dosing optimization, and bioequivalence. On the basis of recent clinical and animal studies, future directions of management and treatment are outlined.

Recent findings: Studies with new tacrolimus formulations showed better bioavailability and lower doses, which might translate into less toxicity. The long-term results of studies with costimulation blockade confirmed their safety and efficacy. Calcineurin inhibitor (CNI)-free regimens based on mTOR inhibitors were shown to be associated with increased risk of the humoral response. Therefore, ongoing trials are predominantly designed to minimize calcineurin inhibitor dose only. Biologics, such as B-cell-specific agents (bortezomib and rituximab) and complement inhibitors (eculizumab) used to treat antibody-mediated rejection, recurrence of glomerulonephritis, are shifted to more preventive applications. The pretransplant quantification of alloreactive memory/effector T cell response may help to better stratify a patient's immunologic risk and allow for drug minimization.

Summary: 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. In the future, research aims to focus on biomarker-driven immunosuppression and cell therapy approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcineurin / metabolism
  • Calcineurin Inhibitors / therapeutic use
  • Graft Rejection / drug therapy
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • TOR Serine-Threonine Kinases
  • Calcineurin
  • Tacrolimus