ORIGINAL ARTICLE
Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies

https://doi.org/10.1111/ajt.15397Get rights and content
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The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P < .001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35).

KEYWORDS

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

Abbreviations

AMR
antibody-mediated rejection
BFXM
B cell flow crossmatch
CDC
complement-dependent cytotoxicity
CI
confidence interval
DGF
delayed graft function
DSA
donor-specific antibody
HLA
human leukocyte antigen
IdeS
IgG-degrading endopeptidase derived from Streptococcus pyogenes
IgG
immunoglobulin G
IVIg
intravenous immunoglobulin
mcs
mean channel shift
MFI
mean fluorescence intensity
MMF
mycophenolate mofetil
PP
plasmapheresis
SAE
serious adverse event
SCr
serum creatinine
SD
standard deviation
TAC
tacrolimus
TEAE
treatment-emergent adverse event
TFXM
T cell flow crossmatch

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All C10-002 Study Investigators are listed in the Supporting Information.