CD25 blockade in kidney transplant patients randomized to standard-dose or high-dose basiliximab with cyclosporine, or high-dose basiliximab in a calcineurin inhibitor-free regimen.
Thibault G, Paintaud G, et al.Transplant International 2015 [record in progress]
Aims
To compare the saturation of T-cell CD25 receptors with an increased cumulative dose of basiliximab in de novo kidney transplant recipients not receiving calcineurin inhibitor (CNI) therapy.
Interventions
Patients were randomized to one of three groups and received a cumulative dose of either 40mg basiliximab with cyclosproine (CsA) maintenance therapy (control group), 80mg basiliximab with CsA maintenance therapy (high basiiliximab), or 80mg basiliximab with everolimus (CNI-free).
Participants
16 adult kidney transplant recipients aged 18-65 years requiring basiliximab induction
Outcomes
The primary outcome was the area under the effect (AUE) curve for saturation of the CD25 antigen of IL-2 receptors. Secondary outcomes included basiliximab binding to CD25 receptors, lymphocyte population phenotype, basiliximab pharmacokinetics, BPAR, graft loss, death, renal function, adverse events, serious adverse events, infections and discontinuation of the study or study treatment.
Follow-up
24 weeks
CET Conclusions
This pharmacokinetic study aimed to assess the degree of CD25 saturation with high dose (80mg ) basiliximab induction in de novo kidney transplant recipients with standard or CNI-free immunosuppression with everolimus. Recruitment was stopped after 16 patients due to an excess of acute rejection in the CNI-free arm. Given that the main aim of this study was to assess the CD25 saturation kinetics with a higher than normal dose of basiliximab (this was the primary outcome), far too much emphasis is placed on the clinical outcomes. There is not enough statistical power here to draw any firm conclusions regarding efficacy. The finding of excess acute rejection would, however, be in keeping with a previous systematic review of CNI elimination with everolimus (http://www.transplantlibrary.com/article/25027805). It is possible that lymphocyte depleting induction (ATG or Alemtuzumab) may be necessary for a safe mTOR and CNI-free regimen in de novo patients.
Data analysis
Modified intention-to-treat analysis
Trial registration
Clinicaltrials.gov - NCT01596062