A Randomized Controlled Clinical Trial Comparing Belatacept With Tacrolimus After De Novo Kidney Transplantation.
de Graav G, Baan CC, et al.Transplantation 2017; 11: 11.
Aims
To compare the acute rejection (AR) rate between belatacept and tacrolimus treated patients, and to investigate predictive immunological biomarkers for AR.
Interventions
Participants were randomly assigned to receive either tacrolimus or belatacept.
Participants
40 adult patients aged ≥18 years scheduled to receive a single-organ, blood group AB0-compatible kidney from a living donor at the Erasmus MC in the Netherlands.
Outcomes
The primary outcome measured was the incidence of biopsy-proven AR within the first year after transplantation. Pretransplant circulating frequencies of CD8+CD28-, CD4+CD57+PD1- and end-stage terminally differentiated memory CD8+CD28++ T cells, as well as their intracellular expression of a Granzyme B were also measured.
Follow-up
1 year
CET Conclusions
This interesting single-centre RCT randomised 40 renal transplant recipients to belatacept or tacrolimus for one year after transplantation. Despite relatively robust baseline immunosuppression (basiliximab, 1g MMF bd and prednisolone) and low risk recipients (live donors, PRA <30%), a worryingly high risk of biopsy proven acute rejection was seen in the belatacept arm (55%) compared to the tacrolimus arm (10%). 3 grafts were lost in the belatacept arm due to acute rejection. Of interest, the authors also investigated a number of potential biomarkers that may predict the risk of rejection with belatacept. None of the investigated biomarkers demonstrated a relationship with post-transplant rejection. The study can only really be regarded as exploratory in nature, as the numbers are small and no power calculation was performed. Drug levels for tacrolimus and MPA are not reported. Nonetheless, the results are concerning and suggest that belatacept should probably only be used with depleting antibody induction. Also of concern is that of the 88 screened patients eligible for the study, 48 refused to take part due to concerns about rejection and the inconvenience of monthly infusions. This may further limit the utility of belatacept as a routine immunosuppressant.
Data analysis
Available case analysis
Trial registration
Dutch Trial Register - NTR4242