Long-term exposure to belatacept in recipients of extended criteria donor kidneys.
Charpentier B, Medina Pestana JO, et al.American Journal of Transplantation 2013; 13(11): 2884-2891.
Aims
This long term extension trial (LTE) aimed to evaluate the long term safety and tolerability of belatacept in patients that had completed 36 months of treatment in the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-Extended criteria donors (BENEFIT-EXT).
Interventions
The randomised groups of patients were administered with either an intensive or less intensive belatacept regime, or cyclosporine. All patients received basiliximab induction, mycophenolate mofetil, and corticosteroids.
Participants
304 de novo adult recipients of extended criteria donor renal allografts. The LTE population was a subset of the original intention to treat population.
Outcomes
The primary outcome of this LTE was to assess the safety and tolerability of belatacept with prolonged exposure, the frequency of adverse events, serious adverse events and deaths. Secondary outcomes included the mean change in serum lipids from baseline to 5 years, and calculated glomerular filtration rate.
Follow-up
Up to 5 years.
CET Conclusions
This long term follow up of the BENEFIT-EXT donor study which included patients who at 3 years following entrance to the trial remained on their assigned treatment. This was around two thirds of the patients who were on belatacept and somewhat less of the patients who were on cyclosporine. Follow-up to 5 years meant further patients were lost to the study but these were evenly distributed between the three arms. The significant findings were that renal function was superior in both belatacept arms and that there were less cardiovascular risk factors seen in the belatacept arms. However PTLD was more frequent with belatacept but only in EBV negative recipients. Thus continued treatment with belatacept to 5 years continued to show no additional safety concerns and furthermore the need for regular intravenous infusions did not appear to be a negative influence on patients continuing in the long term follow-up. There was some potential for bias in that only patients who were doing well, and thus remained on the assigned treatment, were eligible for the long term extension. This is discussed at some length by the authors as a weakness of the study but one that obviously was not in their control. In summary, in recipients of extended criteria kidneys, long term use of belatacept has an acceptable safety profile with a number of benefits especially improved renal function.
Quality notes
Previously assessed in Durrbach A, Pestana JM, Pearson T, et al. A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am J Transplant 2010; 10: 547–557.
Trial registration
ClinicalTrials.gov – NCT00114777