The short-term efficacy and safety of everolimus in combination with tacrolimus have been described in several clinical trials. Yet, detailed long-term data comparing the use of everolimus or mycophenolate in kidney transplant recipients receiving tacrolimus are lacking.
ABSTRACT
BACKGROUND
The short-term efficacy and safety of everolimus in combination with tacrolimus have been described in several clinical trials. Yet, detailed long-term data comparing the use of everolimus or mycophenolate in kidney transplant recipients receiving tacrolimus are lacking.
METHODS
This is a 5-y follow-up post hoc analysis of a prospective trial including 288 patients who were randomized to receive a single 3-mg/kg dose of rabbit antithymocyte globulin, tacrolimus, everolimus (EVR), and prednisone (rabbit antithymocyte globulin/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (basiliximab/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (basiliximab/mycophenolate, n = 101).
RESULTS
There were no differences in the incidence of treatment failure (31.8% versus 40.2% versus 34.7%, P = 0.468), de novo donor-specific HLA antibodies (6.5% versus 11.7% versus 4.0%, P = 0.185), patient (92.9% versus 94.1% versus 92.1%, P = 0.854), and death-censored graft (87.1% versus 90.2% versus 85.1%, P = 0.498) survivals. Using a sensitive analysis, the trajectories of estimated glomerular filtration rate were comparable in the intention-to-treat (P = 0.145) and per protocol (P = 0.354) populations. There were no differences in study drug discontinuation rate (22.4% versus 30.4% versus 17.8%, P = 0.103).
CONCLUSIONS
In summary, this analysis in a cohort of de novo low/moderate immunologic risk kidney transplant recipients suggests that the use of a single 3 mg/kg rabbit antithymocyte globulin dose followed by EVR combined with reduced tacrolimus concentrations was associated with similar efficacy and renal function compared with the standard of care immunosuppressive regimen.
CET CONCLUSION
REVIEWER:
Mr John O’Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of OxfordThis paper reports the 5-year outcomes from a previously published trial comparing 3 different immune suppression regimens. The number lost to follow up was small and similar between the study arms. The primary outcome was a composite “treatment failure” defined as biopsy proven rejection >1A, graft loss, death or loss to follow up. There was no significant difference in the rate of this primary outcome. There was no significant difference GFR. There was however a higher risk of post-transplant diabetes with the groups receiving everolimus (30-33% versus 15%). In this group of low/moderate risk renal transplant recipients, all three immune suppression regimens were associated with acceptable outcomes. Similar proportions of each group were still receiving their randomised therapy at 5 years.
STUDY DETAILS
AIMS :
This post hoc analysis aimed to report the 5-year follow-up outcomes of a randomised controlled trial investigating the efficacy and safety of everolimus compared to mycophenolate in kidney transplant recipients receiving tacrolimus-based immunosuppressive regimen.
INTERVENTIONS :
Participants in the original trial were randomised to one of three groups: rabbit antithymocyte globulin ( r-ATG) plus everolimus, basiliximab plus everolimus, or basiliximab plus mycophenolate.
PARTICIPANTS :
300 de novo kidney transplant recipients.
OUTCOMES :
The main outcomes included assessment of treatment failure, treated clinical acute rejection episodes, serum HLA antibodies, estimated glomerular filtration rate (eGFR), proteinuria, blood pressure, body mass index (BMI), high-density lipoprotein cholesterol (HDL)/ low-density lipoprotein cholesterol (LDL), posttransplant diabetes mellitus (PTDM), use of lipidlowering agents, major adverse cardiovascular events (MACEs), and malignancies.
FOLLOW UP :
5 years
Fuente. www.transplantlibrary.com