Avoidance of CNI and steroids using belatacept-Results of the Clinical Trials in Organ Transplantation 16 trial.Mannon, R. B., et al.
American Journal of Transplantation 2020 [record in progress]
The aim of this study was to report the results of the Clinical Trials in Organ Transplantation 16 (CTOT-16) trial that investigated steroid-free belatacept-based strategies using induction with either basiliximab or rabbit antithymocyte globulin (rATG) and tacrolimus.
Participants were randomized to one of three groups: group 1, where patients received rATG induction followed by a rapid methylprednisolone taper and maintenance therapy consisting of tacrolimus and MMF; group 2, in which the patients were given rATG induction, a rapid methylprednisolone taper and maintenance belatacept and MMF; and group 3, with patients receiving basiliximab, a rapid methylprednisolone taper, tacrolimus, and maintenance immunosuppression consisting of belatacept and mycophenolate.
69 kidney transplant recipients.
The primary endpoint was the mean glomerular filtration rate (GFR) measured at 52 weeks posttransplant. The secondary endpoints were acute rejection episodes, new onset diabetes or impaired fasting glucose at 52 weeks, fasting lipid profiles, haemoglobin A1C measurements, and the incidence of treated diabetes.
This manuscript reports the findings of the CTOT-16 study, investigating CNI and steroid avoidance with de-novo belatacept in renal transplantation. Patients were randomized to one of 3 groups – (1) rATG, tacrolimus and MMF, (2) rATG, belatacept and MMF and (3) basiliximab, belatacept and MMF with a rapid tacrolimus taper. The study was halted early due to concerns regarding excess rejection episodes in the 2 belatacept arms (>30% in both arms). Despite these findings, eGFR, graft losses and formation of de-novo DSAs did not differ at 12 months. The study appears well designed and reported with more methodological detail provided in the supplementary content. Clearly the excess rejection limits the use of these regimens in standard practice. Other studies have shown promise with a combination of belatacept and mTOR inhibitors, and this approach may be more effective at preventing rejection than combination with MMF.
Allocation was concealed through central randomisation. One participant from group 1 and one participant from group 2 requested withdrawal from the study. As part of the study protocol, they were followed by labs and medical records only (“limited follow-up). No others were lost or did not complete the study.
ClinicalTrials.gov - NCT01856257