Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination

Results of a randomized trial

Burkhard Tönshoff, Robert Ettenger, Luca Dello Strologo, Stephen D Marks, Lars Pape, Helio Tedesco-Silva, Anna Bjerre, Martin Christian, Matthias Meier, El-Djouher Martzloff, Barbara Rauer, Jennifer Ng, Patricia Lopez

Research output: Contribution to journalArticle

Abstract

In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3% with EVR/rTAC and 5.8% with sTAC/MMF (difference 4.4%; P = .417). BPAR occurred in 9.6% and 5.6% of patients, respectively. Patient and renal allograft survival were 100%. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6% and 13% of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0% and 11.1% of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.

Original languageEnglish
JournalAmerican Journal of Transplantation
DOIs
Publication statusE-pub ahead of print - Aug 20 2018

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Tacrolimus
Mycophenolic Acid
Steroids
Pediatrics
Transplants
Kidney
Biopsy
Sexual Maturation
Graft Rejection
Immunosuppressive Agents
Random Allocation
Glomerular Filtration Rate
Kidney Transplantation
Allografts
Everolimus
Incidence
Growth
Infection
Pharmaceutical Preparations

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Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination : Results of a randomized trial. / Tönshoff, Burkhard; Ettenger, Robert; Dello Strologo, Luca; Marks, Stephen D; Pape, Lars; Tedesco-Silva, Helio; Bjerre, Anna; Christian, Martin; Meier, Matthias; Martzloff, El-Djouher; Rauer, Barbara; Ng, Jennifer; Lopez, Patricia.

In: American Journal of Transplantation, 20.08.2018.

Research output: Contribution to journalArticle

Tönshoff, Burkhard ; Ettenger, Robert ; Dello Strologo, Luca ; Marks, Stephen D ; Pape, Lars ; Tedesco-Silva, Helio ; Bjerre, Anna ; Christian, Martin ; Meier, Matthias ; Martzloff, El-Djouher ; Rauer, Barbara ; Ng, Jennifer ; Lopez, Patricia. / Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination : Results of a randomized trial. In: American Journal of Transplantation. 2018.
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title = "Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination: Results of a randomized trial",
abstract = "In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3{\%} with EVR/rTAC and 5.8{\%} with sTAC/MMF (difference 4.4{\%}; P = .417). BPAR occurred in 9.6{\%} and 5.6{\%} of patients, respectively. Patient and renal allograft survival were 100{\%}. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6{\%} and 13{\%} of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0{\%} and 11.1{\%} of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.",
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TY - JOUR

T1 - Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination

T2 - Results of a randomized trial

AU - Tönshoff, Burkhard

AU - Ettenger, Robert

AU - Dello Strologo, Luca

AU - Marks, Stephen D

AU - Pape, Lars

AU - Tedesco-Silva, Helio

AU - Bjerre, Anna

AU - Christian, Martin

AU - Meier, Matthias

AU - Martzloff, El-Djouher

AU - Rauer, Barbara

AU - Ng, Jennifer

AU - Lopez, Patricia

N1 - © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

PY - 2018/8/20

Y1 - 2018/8/20

N2 - In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3% with EVR/rTAC and 5.8% with sTAC/MMF (difference 4.4%; P = .417). BPAR occurred in 9.6% and 5.6% of patients, respectively. Patient and renal allograft survival were 100%. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6% and 13% of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0% and 11.1% of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.

AB - In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3% with EVR/rTAC and 5.8% with sTAC/MMF (difference 4.4%; P = .417). BPAR occurred in 9.6% and 5.6% of patients, respectively. Patient and renal allograft survival were 100%. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6% and 13% of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0% and 11.1% of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.

U2 - 10.1111/ajt.15081

DO - 10.1111/ajt.15081

M3 - Article

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

ER -