Belatacept-Based Immunosuppression With Simultaneous Calcineurin Inhibitor Avoidance and Early Corticosteroid Withdrawal: A Prospective, Randomized Multicenter Trial.Woodle, E. S., Kaufman, D. et al. (2019).
American Journal of Transplantation [record in progress].
This trial compares two belatacept-based calcineurin inhibitor avoidance (CNIA)/ early corticosteroid withdrawal (ESW) regimens with a tacrolimus-based ESW regimen to determine the safety and efficacy of these regimens.
Kidney transplant recipients were randomized to receive alemtuzumab/belatacept (n=107), or rabbit antithymocyte globulin (rATG)/belatacept (n=104), or rATG/ tacrolimus (n=105).
316 patients, ≥ 18 years of age, and recipients of a living or deceased donor kidney transplant were enrolled between September 2012 and December 2016.
The primary outcomes measured included: the rate of the composite endpoint at 12 months of patient death, or allograft loss, or eGFR < 45ml/min/1.73m2. Secondary endpoints included: composite endpoint at 6 months, rates of each of the three individual components of the composite endpoint, biopsy confirmed acute rejection (BCAR) stratified by type (acute cellular rejection (ACR), antibody mediated rejection (AMR), or mixed acute rejection (MAR), death censored graft survival, proportion of patients with eGFR (MDRD) <30ml/min/1.73m2, and proportion of patients developing anti-HLA antibodies aga
This 3-arm study investigated the use of CNI avoidance using belatacept and lymphocyte depleting induction therapy with either rATG or Alemtuzumab. No difference was seen in the primary composite endpoint (death, graft loss or GFR <45 ml/min) or in renal function at 12 months, but acute cellular rejection rates were higher in the belatacept arms. These results are perhaps surprising in that the renal function benefit from belatacept seen in the BENEFIT studies was not replicated. However, a trend towards improved eGFR distribution appears to be emerging at 12 months (figures 2i and 2j), suggesting that longer-term follow-up data will be essential to determine any potential benefit from sustained CNI avoidance. One limitation of the study is that the original sample-size calculation was based on incidence of the primary endpoint of 50% in the control tacrolimus group; in fact it only occurred in 13.3% leaving the study underpowered to detect a difference in the primary endpoint. Inclusion criteria were quite limited, with exclusion of DCD and ECD donors and sensitised recipients.
ClinicalTrials.gov - NCT01729494