Belatacept-based immunosuppression in de novo liver transplant recipients: 1-year experience from a phase II randomized study.
Klintmalm GB, Feng S, et al.American Journal of Transplantation 2014; 14(8): 1817-1827
Aims
To evaluate the safety and efficacy of belatacept in first liver transplant recipients from a deceased donor, in order to identify an optimal immunosuppressive regimen.
Interventions
Patients were administered with one of the following regimens: 1) basiliximab plus belatacept high dose (HD) and mycophenolate mofetil (MMF), 2) belatacept HD plus MMF, 3) belatacept low dose (LD) plus MMF, 4) tacrolimus plus MMF or 5) tacrolimus alone. All patients received corticosteroids.
Participants
260 de novo adult liver transplant recipients.
Outcomes
The primary outcomes included the composite incidence of acute rejection, graft loss and death at 6 months after transplantation. Secondary outcomes included the incidence, severity, treatment and outcome of acute rejection by 12 months, graft loss and death by 12 months, measured and calculated glomerular filtration rate (GFR), incidence of hepatitis c virus recurrence by 12 months, incidence rates of cardiovascular and metabolic co-morbidities and the overall safety of belatacept.
Follow-up
12 months.
CET Conclusions
This phase 2 randomised study in recipients of first liver transplants has explored several immunosuppressive protocols based on belatacept in comparison with tacrolimus alone and tacrolimus plus MMF as described above. The endpoint was a composite endpoint comprising acute rejection, graft loss and death by month 6. The composite end point was higher in all the belatacept groups compared with the two tacrolimus groups. On the positive side the calculated GFR was significantly higher in the belatacept treated patients at one year. There were two cases of Post-transplant lymphoproliferative disorder and one case of progressive multifocal leukoencephalopathy in the belatacept treated patients. Thus these findings are in contrast to outcomes in the renal transplant trials of belatacept, and although there was a follow-up beyond 12 months there was an increase in death and graft loss in the high dose belatacept group and on the advice of the DMC the study was terminated. Thus in this well conducted study there was no support for the use of a belatacept based immunosuppressive protocol compared to the standard tacrolimus plus MMF in liver transplantation.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov-NCT00555321