Five-Year Outcomes in Kidney Transplant Patients Converted From Cyclosporine to Everolimus: The Randomized ZEUS Study
Budde K, Lehner F, et alAmerican Journal of Transplantation 2015; 15: 119–128
Aims
Everolimus based immunosuppression was assessed for elimination of calcineurin inhibitor exposure and optimisation of renal-graft function while maintaining efficacy
Interventions
Switch to everolimus therapy or remain on cyclosporine based therapy.
Participants
232 de novo kidney transplant recipients, 123 converted to everolimus and 109 on cyclosporine.
Outcomes
Primary efficacy outcome was eGFR. Secondary outcomes were biopsy proven acute rejection, graft survival and adverse events.
Follow-up
5 years
CET Conclusions
This manuscript reports the 5-year outcomes of the ZEUS study, in which de novo kidney transplant recipients on cyclosporine (CsA) based immunosuppression were randomised to continue CsA, or to switch to everolimus at 4.5 months post-transplant. The results show an improvement in eGFR of 5.3 ml/min in the ITT population, increasing to 8.2 ml/min in the per-protocol group. There was an excess of mild episodes of acute rejection (Banff grade I) in the everolimus arm, but this did not translate to worse function or an increase in graft loss overall. Follow-up was good for a study of this duration, with 5-year data available for 91% of those who completed the 1 year study, and just over 75% of those who were randomised. 62% of everolimus and 77% of the CsA patients were still taking the assigned study drug at 5 years. The incidence of adverse events was similar between arms, although there was a higher incidence of serious events in the everolimus arm (17.4% vs 11.7%). Whilst these results are very encouraging, it is worth noting that in a contemporary group of patients receiving tacrolimus in place of cyclosporine, it is possible that the difference in BPAR would be larger still, so these results need to be replicated in a comparison of tacrolimus and everolimus.
Data analysis
Strict intention-to-treat analysis
Quality notes
Pre4viously assessed as Budde, K., T. Becker, et al. (2011). "Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial." Lancet 377(9768): 837-847.
Trial registration
ClinicalTrials.gov - NCT00154310