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

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

Author information

1
Formerly Alexion Pharmaceuticals, Boston, Massachusetts.
2
Independent Consultant, Bellevue, Washington.
3
Department of Transplant Surgery, Guy's and St Thomas', Evelina London Children's and Great Ormond Street Hospitals NHS Trust, London, UK.
4
NYU Langone Transplant Institute, New York University Langone Medical Center, New York, New York.
5
The William J. von Liebig Center for Transplantation and Clinical Regeneration and Division of Transplantation Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
6
Department of Surgery, Columbia University, New York, New York.
7
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
8
Department of Internal Medicine, Section of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
9
Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts.
10
Independent statistics consultant, Guilford, Connecticut.
11
Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S970, Paris, France.
12
Department of Nephrology and Organ Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Institut National de la Santé et de la Recherche Médicale, Unité U1160, Paris, France.

Abstract

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

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