Conversion from Calcineurin Inhibitor to Belatacept-based Maintenance Immunosuppression in Renal Transplant Recipients: a Randomized Phase 3b Trial.Budde, K., et al.
Journal of the American Society of Nephrology 2021 [record in progress].
This study aimed to assess the safety and efficacy of switching from calcineurin inhibitors (CNI)-based to belatacept-based maintenance immunosuppressive treatment in renal transplant patients.
Participants were randomised to either the belatacept conversion group or the CNI continuation group.
446 stable adult kidney transplant recipients.
The primary outcome was the percentage of patients surviving with a functioning graft. Secondary outcome included patient survival, graft survival, incidence and severity of biopsy-proven acute rejection (BPAR), renal function, mean changes in systolic and diastolic blood pressure, proportion of patients with preexisting donor-specific antibodies, and adverse events.
This large multicentre phase 3b study randomised renal transplant recipients 6-60 months post-transplant to continue CNI, or to switch to Belatacept-based immunosuppression. The primary endpoint (survival with a functioning graft at 24 months) did not differ between groups. There was, however, a clinically significant superior GFR in the Belatacept arm with lower rate of de novo DSA, tempered by numerically higher acute rejection rates. It should be noted that the population recruited is relatively low risk, with no recent acute rejection, stable function and EBV seropositive due to risk of PTLD. In reality, the study is underpowered to demonstrate non-inferiority for the primary endpoint, although outcomes in both arms in this respect were excellent. Longer-term follow-up will be interesting to see, as it is quite possible that the improvements in graft function and reduction in dnDSA seen will translate to better long-term graft survival.
ClinicalTrials.gov - NCT01820572