Five-year outcomes in kidney transplant patients randomized to everolimus with cyclosporine withdrawal or low-exposure cyclosporine versus standard therapy
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Five-year outcomes in kidney transplant patients randomized to everolimus with cyclosporine withdrawal or low-exposure cyclosporine versus standard therapy. / Sommerer, Claudia; Duerr, Michael; Witzke, Oliver; Lehner, Frank; Arns, Wolfgang; Kliem, Volker; Ackermann, Daniel; Guba, Markus; Jacobi, Johannes; Hauser, Ingeborg A; Stahl, Rolf; Reinke, Petra; Rath, Thomas; Veit, Justyna; Mehrabi, Arianeb; Porstner, Martina; Budde, Klemens; HERAKLES Study Group.
in: AM J TRANSPLANT, Jahrgang 18, Nr. 12, 12.2018, S. 2965-2976.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Five-year outcomes in kidney transplant patients randomized to everolimus with cyclosporine withdrawal or low-exposure cyclosporine versus standard therapy
AU - Sommerer, Claudia
AU - Duerr, Michael
AU - Witzke, Oliver
AU - Lehner, Frank
AU - Arns, Wolfgang
AU - Kliem, Volker
AU - Ackermann, Daniel
AU - Guba, Markus
AU - Jacobi, Johannes
AU - Hauser, Ingeborg A
AU - Stahl, Rolf
AU - Reinke, Petra
AU - Rath, Thomas
AU - Veit, Justyna
AU - Mehrabi, Arianeb
AU - Porstner, Martina
AU - Budde, Klemens
AU - HERAKLES Study Group
N1 - © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.
PY - 2018/12
Y1 - 2018/12
N2 - HERAKLES was a 1-year randomized, multicenter trial. Patients were randomized at 3 months after kidney transplantation to remain on cyclosporine-based therapy, switch to everolimus without a calcineurin inhibitor (CNI), or switch to everolimus with low-exposure cyclosporine. Overall, 417 of 497 (83.9%) patients from the core study entered a 4-year extension study. The randomized regimen was continued to year 5 in 75.9%, 41.9% and 24.6% of patients in the standard-CNI, CNI-free and low-CNI groups, respectively. Adjusted estimated GFR at year 5 was significantly higher in the CNI-free group versus standard CNI (difference 7.2 mL/min/1.73 m2 , P < .001) or low CNI (difference 7.6 mL/min/1.73 m2 , P < .001). For patients who continued randomized therapy for 5 years, differences were 14.4 mL/min/1.73 m2 and 10.1 mL/min/1.73 m2 , respectively. Biopsy-proven acute rejection occurred during the 4-year extension study in 7.6%, 8.6%, and 9.0% of patients in the standard-CNI, CNI-free and low-CNI groups, respectively (P = .927). In conclusion, conversion to a CNI-free everolimus regimen 3 months after kidney transplantation improved long-term graft function, particularly in patients who continued the CNI-free regimen. Low CNI with everolimus did not improve renal function. Efficacy was comparable between groups but frequent immunosuppression changes should be taken into account.
AB - HERAKLES was a 1-year randomized, multicenter trial. Patients were randomized at 3 months after kidney transplantation to remain on cyclosporine-based therapy, switch to everolimus without a calcineurin inhibitor (CNI), or switch to everolimus with low-exposure cyclosporine. Overall, 417 of 497 (83.9%) patients from the core study entered a 4-year extension study. The randomized regimen was continued to year 5 in 75.9%, 41.9% and 24.6% of patients in the standard-CNI, CNI-free and low-CNI groups, respectively. Adjusted estimated GFR at year 5 was significantly higher in the CNI-free group versus standard CNI (difference 7.2 mL/min/1.73 m2 , P < .001) or low CNI (difference 7.6 mL/min/1.73 m2 , P < .001). For patients who continued randomized therapy for 5 years, differences were 14.4 mL/min/1.73 m2 and 10.1 mL/min/1.73 m2 , respectively. Biopsy-proven acute rejection occurred during the 4-year extension study in 7.6%, 8.6%, and 9.0% of patients in the standard-CNI, CNI-free and low-CNI groups, respectively (P = .927). In conclusion, conversion to a CNI-free everolimus regimen 3 months after kidney transplantation improved long-term graft function, particularly in patients who continued the CNI-free regimen. Low CNI with everolimus did not improve renal function. Efficacy was comparable between groups but frequent immunosuppression changes should be taken into account.
KW - Journal Article
U2 - 10.1111/ajt.14897
DO - 10.1111/ajt.14897
M3 - SCORING: Journal article
C2 - 29722128
VL - 18
SP - 2965
EP - 2976
JO - AM J TRANSPLANT
JF - AM J TRANSPLANT
SN - 1600-6135
IS - 12
ER -