Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine.
Shihab F.S, Cibrik D, et al.Clinical Transplantation. 2013; 27(2): 217-226
Aims
To investigate the correlation of clinical events with everolimus trough concentrations in newly transplanted kidney transplant recipients receiving everolimus with reduced exposure cyclosporine (CsA) and steroids.
Interventions
Participants were randomized into one of three groups; everolimus 0.75 mg b.i.d targeting a trough concentration of 3-8 ng/mL with reduced CsA, everolimus 1.5 mg b.i.d targeting a trough concentration of 6-12 ng/mL or MPA as enteric coated mycophenolate sodium 720 mg b.i.d with standard CsA.
Participants
556 adult primary, de novo kidney transplant recipients.
Outcomes
The primary endpoint was the efficacy failure, defined as treated biopsy-proven acute rejection (BPAR), graft loss, death, or loss to follow-up.
Follow-up
24 months.
CET Conclusions
This pre planned analysis of data from a large randomised controlled trial comparing two doses of everolimus with reduced dose cyclosporine and a control group receiving standard dose cyclosporine with MPA suggested that there was an association between exposure to everolimus as measured by trough levels and clinical complications in patients receiving reduced exposure CSA. The original trial from which this data was extracted was methodologically sound but it is difficult to be sure what the conclusions are from this study other than that low trough levels of everolimus were less effective than high levels and there was an increased rate of complications, such as wound healing and hypercholesterolemia at higher exposure levels. Thus the exposure of patients to everolimus when cyclosporine dose is reduced should be a protocol to be used with considerable caution.
Data analysis
Strict intention-to-treat analysis
Quality notes
Score based on Tedesco S, Cibrik D, et al. Everolimus plus reduced-exposure CsA versus mycophenolic acid plus standard-exposure CsA in renal-transplant recipients. American Journal of Transplantation 2010; 10: 1401.
Trial registration
ClinicalTrials.gov - NCT00251004