Belatacept

Immunosuppressive therapy designed to prevent kidney graft rejection usually consists of a triple-drug combination including a corticosteroid, a calcineurin inhibitor (ciclosporin or tacrolimus) and a drug that inhibits cell proliferation (azathioprine or mycophenolate mofetil). Belatacept is closely related to abatacept, an immunosuppressant marketed for rheumatic diseases. It is now authorised in the European Union for the prevention of kidney graft rejection, as a replacement for the calcineurin inhibitor. Two randomised controlled trials compared belatacept (2 doses) versus ciclosporin as part of the immunosuppressive regimen in respectively 666 and 534 patients. After 3 years of follow-up, survival with a functioning graft did not differ between the groups (about 80% in the trial closest to European protocols). Only the use of a high dose of belatacept instead of ciclosporin resulted in better preservation of renal function, but this is not the authorised dose. Lymphomas, particularly those affecting the central nervous system, were more frequent with belatacept in both trials (1.4% versus 0.9%). The risk was particularly high in patients receiving the high dose of belatacept, and in patients who were seronegative for Epstein-Barr virus. Overall, the risk of infections seems to be similar with belatacept and ciclosporin, but certain severe infections were more frequent with belatacept, including progressive multifocal leukoencephalopathy and tuberculosis. Unlike ciclosporin, belatacept plasma concentrations do not need to be monitored. However, intravenous belatacept administration is less convenient than oral ciclosporin administration, especially during long-term treatment. Overall, it is better to continue to use ciclosporin, a better-documented drug, as part of immunosuppressive therapy after kidney transplantation.