Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept

Am J Transplant. 2017 Oct;17(10):2712-2719. doi: 10.1111/ajt.14377. Epub 2017 Jul 3.

Abstract

The intent of this National Institutes of Health-sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate. Nineteen primary, Epstein-Barr virus-immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance mycophenolate mofetil. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively. Patients in group 3 were induced with basiliximab, received 3 mo of tacrolimus, and maintained on belatacept. There was one death with a functioning allograft due to endocarditis (group 1). There were three graft losses due to vascular thrombosis (all group 2) and one graft loss due to glomerular disease (group 1). Biopsy-proven acute cellular rejection was more frequent in the belatacept-treated groups, with 10 treated episodes in seven participants compared with one episode in group 1; however, estimated GFR was similar between groups at week 52. There were no episodes of posttransplant lymphoproliferative disorder or opportunistic infections in any group. Protocol enrollment was halted prematurely because of a high rate of serious adverse events. Such negative outcomes pose challenges to clinical investigators, who ultimately must weigh the risks and benefits in randomized trials.

Keywords: fusion proteins and monoclonal antibodies: belatacept; immunosuppressant; immunosuppression/immune modulation; kidney transplantation/nephrology; rejection; translational research/science.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Abatacept / therapeutic use*
  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Aged
  • Calcineurin Inhibitors / therapeutic use*
  • Female
  • Glomerular Filtration Rate
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Treatment Outcome
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Abatacept