Alefacept combined with tacrolimus, mycophenolate mofetil and steroids in de novo kidney transplantation: a randomized controlled trial

Am J Transplant. 2013 Jul;13(7):1724-33. doi: 10.1111/ajt.12303. Epub 2013 Jun 3.

Abstract

Memory T cells play a central role in mediating allograft rejection and are a rational target for immunosuppressive therapy. Alefacept is a recombinant LFA3/IgG1 fusion protein that reduces the number of memory T cells in both psoriatic lesions and the peripheral circulation of psoriasis patients. This study evaluated the efficacy and safety of alefacept compared with placebo when combined with tacrolimus, mycophenolate mofetil and corticosteroids in de novo renal transplant recipients. Between December 2007 and March 2009 patients were randomized in a double-blind fashion to receive alefacept (n = 105) or placebo (n = 107) for 3 months and were then followed for a further 3 months. The primary efficacy endpoint was the incidence of biopsy-confirmed acute T cell mediated rejection (Banff grade ≥ 1) through Month 6. Memory T cell counts were significantly reduced in the alefacept group from Week 3 to study end compared with placebo. However, there was no significant difference between the alefacept and placebo groups for the primary efficacy endpoint (alefacept, 11.0% vs. placebo, 7.0%, p = 0.3). Patient and graft survival as well as renal function was similar between treatment groups. Safety and tolerability were generally similar between the treatment arms. Malignancy was higher in the alefacept treatment arm.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alefacept
  • Biopsy
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Routes
  • Drug Therapy, Combination
  • Follow-Up Studies
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use
  • Graft Rejection / drug therapy*
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Humans
  • Immunosuppression Therapy / methods*
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Methylprednisolone / administration & dosage
  • Methylprednisolone / therapeutic use*
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / therapeutic use*
  • Retrospective Studies
  • Tacrolimus / administration & dosage
  • Tacrolimus / therapeutic use*
  • Tissue Donors
  • Treatment Outcome
  • Young Adult

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Recombinant Fusion Proteins
  • Alefacept
  • Mycophenolic Acid
  • Tacrolimus
  • Methylprednisolone