Transplant Trial Watch

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

Marks, W. H., Mamode, N. et al. (2019).

American Journal of Transplantation 19: 19.


Aims
To evaluate the safety and efficacy of eculizumab in preventing acute antibody-mediated rejection (AMR) in kidney transplant recipients who require desensitization.

Interventions
Patients were randomised into standard post transplantation care or eculizumab for 9 weeks from the day of transplantation.

Participants
102 patients who required a kidney transplant and required pretransplantation desensitization.

Outcomes
Primary outcome was assessed as treatment failure, which included the occurrence of: biopsy-proven AMR (Banff 2007 grades II or III); graft loss; patient death; or loss to follow-up.

Follow-up
36 months.

CET Conclusions
This phase II industry-led multicenter study investigated the role of eculizumab as part of a desensitization protocol in living donor renal transplantation. 102 patients were randomized, and the study found no difference in the composite primary efficacy outcome of antibody mediated rejection, graft loss and death. All biopsies were reassessed centrally, and a beneficial effect of eculizumab was only found in post-hoc analysis when grade I AMR was included in efficacy failure. The study was open-label, although the central pathologists were blinded to study allocation. Treatment failure rates were significantly lower in the standard-care arm than expected, which ultimately resulted in an underpowered study. It is therefore unlikely that eculizumab will become part of standard care on the basis of these results, especially given the costs involved and the increasing success of paired-exchange programs.

Jadad score
3

Data analysis
Per protocol analysis

Allocation concealment
Yes

Trial registration
Clnicaltrials.gov- NCT01399593 and EudraCT number - 2010-019630-28

Funding source
Industry funded