Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial

Am J Transplant. 2019 Oct;19(10):2876-2888. doi: 10.1111/ajt.15364. Epub 2019 Apr 19.


We report results of a phase 2, randomized, multicenter, open-label, two-arm study evaluating the safety and efficacy of eculizumab in preventing acute antibody-mediated rejection (AMR) in sensitized recipients of living-donor kidney transplants requiring pretransplant desensitization (NCT01399593). In total, 102 patients underwent desensitization. Posttransplant, 51 patients received standard of care (SOC) and 51 received eculizumab. The primary end point was week 9 posttransplant treatment failure rate, a composite of: biopsy-proven acute AMR (Banff 2007 grade II or III; assessed by blinded central pathology); graft loss; death; or loss to follow-up. Eculizumab was well tolerated with no new safety concerns. No significant difference in treatment failure rate was observed between eculizumab (9.8%) and SOC (13.7%; P = .760). To determine whether data assessment assumptions affected study outcome, biopsies were reanalyzed by central pathologists using clinical information. The resulting treatment failure rates were 11.8% and 21.6% for the eculizumab and SOC groups, respectively (nominal P = .288). When reassessment included grade I AMR, the treatment failure rates were 11.8% (eculizumab) and 29.4% (SOC; nominal P = .048). This finding suggests a potential benefit for eculizumab compared with SOC in preventing acute AMR in recipients sensitized to their living-donor kidney transplants (EudraCT 2010-019630-28).

Keywords: clinical research/practice; complement biology; donors and donation: living; immunosuppressant - fusion proteins and monoclonal antibodies; kidney transplantation/nephrology; rejection: antibody-mediated (ABMR); sensitization.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Complement Inactivating Agents / therapeutic use
  • Desensitization, Immunologic / methods*
  • Female
  • Follow-Up Studies
  • Graft Rejection / etiology
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Graft Survival / immunology
  • Histocompatibility Testing
  • Humans
  • Isoantibodies / adverse effects*
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / mortality*
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation / adverse effects*
  • Living Donors
  • Male
  • Middle Aged
  • Patient Safety
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Complement Inactivating Agents
  • Isoantibodies
  • eculizumab

Associated data

  • EudraCT/2010‐019630‐28