Switching from calcineurin inhibitor-based regimens to a belatacept-based regimen in renal transplant recipients: a randomized phase II study.
OBJECTIVE
Prolonged use of calcineurin inhibitors (CNIs) in kidney transplant recipients is associated with renal and nonrenal toxicity and an increase in cardiovascular risk factors. Belatacept-based regimens may provide a treatment option for patients who switch from CNI-based maintenance immunosuppression.


METHODS
This is a randomized, open-label Phase II trial in renal transplant patients with stable graft function and receiving a CNI-based regimen. Patients who were ≥6 months but ≤36 months after transplantation were randomized to either switch to belatacept or continue CNI treatment. All patients received background maintenance immunosuppression. The primary end point was the change in calculated GFR (cGFR) from baseline to month 12.


RESULTS
Patients were randomized either to switch to belatacept (n=84) or to remain on a CNI-based regimen (n=89). At month 12, the mean (SD) change from baseline in cGFR was higher in the belatacept group versus the CNI group. Six patients in the belatacept group had acute rejection episodes, all within the first 6 months; all resolved with no allograft loss. By month 12, one patient in the CNI group died with a functioning graft, whereas no patients in the belatacept group had graft loss. The overall safety profile was similar between groups.


CONCLUSIONS
The study identifies a potentially safe and feasible method for switching stable renal transplant patients from a cyclosporine- or tacrolimus-based regimen to a belatacept-based regimen, which may allow improved renal function in patients currently treated with CNIs.
Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France. rostaing.l@chu-toulouse.fr
Lionel
L
Rostaing
Pablo
P
Massari
Valter Duro
VD
Garcia
Eduardo
E
Mancilla-Urrea
Georgy
G
Nainan
Maria
M
del Carmen Rial
Steven
S
Steinberg
Flavio
F
Vincenti
Rebecca
R
Shi
Greg
G
Di Russo
Dolca
D
Thomas
Josep
J
Grinyó
D000069594:Abatacept; D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D065095:Calcineurin Inhibitors; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
D065095:Calcineurin Inhibitors; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept