Randomized trial of mycophenolate mofetil versus enteric-coated mycophenolate sodium in primary renal transplantation with tacrolimus and steroid avoidance: Four-year analysis

Gaetano Ciancio, Jeffrey Gaynor, Alberto Zarak, Junichiro Sageshima, Giselle Guerra, David Roth, Randolph Brown, Warren Kupin, Linda J Chen, Lissett Tueros, Lois Hanson, Phillip Ruiz, George W Burke

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Abstract

Background: Our single-center, open-labeled randomized trial of 150 adult, primary kidney transplant recipients receiving 2 g mycophenolate mofetil (group A, n=75) versus 1.440 g enteric-coated mycophenolate sodium (group B, n=75), with reduced maintenance tacrolimus dosing, steroid elimination at 1 week, and combined rabbit antithymocyte globulin/daclizumab induction, previously showed at 1 year posttransplant low biopsy-proven acute rejection (BPAR), acceptably high renal function, and no differences in incidence of symptomatic gastrointestinal (GI) side effects between the two groups. This report includes 3 additional years of follow-up with similar endpoints as in the original study. Methods: Rates of developing first BPAR, graft failure (death censored and uncensored), death, and adverse events (GI toxicity, infections requiring hospitalization, and new onset diabetes mellitus after transplantation) during the first 48 months posttransplant were compared between the two groups using an intent-to-treat approach. Results: At 48 months posttransplant, patient/graft survival in groups A and B was 97%/90% vs. 96%/86%, respectively (not significant [NS]). Twenty-seven patients experienced BPAR (including borderline), with actuarial 19% (14/75) vs. 18% (13/75) in groups A and B, respectively (NS). Geometric mean*/standard error serum creatinine level and arithmetic mean calculated glomerular filtration rate (±standard error) at 48 months in groups A and B, respectively, were 1.25*/1.06 and 69.2±3.9 vs. 1.20*/1.05 and 71.2±3.2 (NS). Incidence of new onset diabetes mellitus after transplantation (22% vs. 15%), infections requiring hospitalization (31% vs. 39%), and GI side effects (45% vs. 52%) seemed equivalent. Conclusions: This is the first long-term, randomized trial comparing enteric-coated mycophenolate sodium versus mycophenolate mofetil along with reduced maintenance tacrolimus dosing and steroid avoidance, which resulted in similarly low-BPAR rates, acceptably high renal function at 48 months, and an equivalent side effect profile.

Original languageEnglish
Pages (from-to)1198-1205
Number of pages8
JournalTransplantation
Volume91
Issue number11
DOIs
StatePublished - Jun 15 2011

Fingerprint

Mycophenolic Acid
Tacrolimus
Kidney Transplantation
Steroids
Biopsy
Kidney
Diabetes Mellitus
Hospitalization
Transplantation
Maintenance
Antilymphocyte Serum
Incidence
Graft Rejection
Graft Survival
Infection
Glomerular Filtration Rate
Creatinine
Rabbits
Serum

Keywords

  • Biopsy-proven acute rejection
  • Enteric-coated mycophenolate sodium
  • Graft survival
  • Mycophenolate mofetil
  • Renal transplant recipients
  • Steroid avoidance
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation

Cite this

@article{31de40f311294d0683217f22431590e7,
title = "Randomized trial of mycophenolate mofetil versus enteric-coated mycophenolate sodium in primary renal transplantation with tacrolimus and steroid avoidance: Four-year analysis",
abstract = "Background: Our single-center, open-labeled randomized trial of 150 adult, primary kidney transplant recipients receiving 2 g mycophenolate mofetil (group A, n=75) versus 1.440 g enteric-coated mycophenolate sodium (group B, n=75), with reduced maintenance tacrolimus dosing, steroid elimination at 1 week, and combined rabbit antithymocyte globulin/daclizumab induction, previously showed at 1 year posttransplant low biopsy-proven acute rejection (BPAR), acceptably high renal function, and no differences in incidence of symptomatic gastrointestinal (GI) side effects between the two groups. This report includes 3 additional years of follow-up with similar endpoints as in the original study. Methods: Rates of developing first BPAR, graft failure (death censored and uncensored), death, and adverse events (GI toxicity, infections requiring hospitalization, and new onset diabetes mellitus after transplantation) during the first 48 months posttransplant were compared between the two groups using an intent-to-treat approach. Results: At 48 months posttransplant, patient/graft survival in groups A and B was 97{\%}/90{\%} vs. 96{\%}/86{\%}, respectively (not significant [NS]). Twenty-seven patients experienced BPAR (including borderline), with actuarial 19{\%} (14/75) vs. 18{\%} (13/75) in groups A and B, respectively (NS). Geometric mean*/standard error serum creatinine level and arithmetic mean calculated glomerular filtration rate (±standard error) at 48 months in groups A and B, respectively, were 1.25*/1.06 and 69.2±3.9 vs. 1.20*/1.05 and 71.2±3.2 (NS). Incidence of new onset diabetes mellitus after transplantation (22{\%} vs. 15{\%}), infections requiring hospitalization (31{\%} vs. 39{\%}), and GI side effects (45{\%} vs. 52{\%}) seemed equivalent. Conclusions: This is the first long-term, randomized trial comparing enteric-coated mycophenolate sodium versus mycophenolate mofetil along with reduced maintenance tacrolimus dosing and steroid avoidance, which resulted in similarly low-BPAR rates, acceptably high renal function at 48 months, and an equivalent side effect profile.",
keywords = "Biopsy-proven acute rejection, Enteric-coated mycophenolate sodium, Graft survival, Mycophenolate mofetil, Renal transplant recipients, Steroid avoidance, Tacrolimus",
author = "Gaetano Ciancio and Jeffrey Gaynor and Alberto Zarak and Junichiro Sageshima and Giselle Guerra and David Roth and Randolph Brown and Warren Kupin and Chen, {Linda J} and Lissett Tueros and Lois Hanson and Phillip Ruiz and Burke, {George W}",
year = "2011",
month = "6",
day = "15",
doi = "10.1097/TP.0b013e3182003d76",
language = "English",
volume = "91",
pages = "1198--1205",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Randomized trial of mycophenolate mofetil versus enteric-coated mycophenolate sodium in primary renal transplantation with tacrolimus and steroid avoidance

T2 - Four-year analysis

AU - Ciancio, Gaetano

AU - Gaynor, Jeffrey

AU - Zarak, Alberto

AU - Sageshima, Junichiro

AU - Guerra, Giselle

AU - Roth, David

AU - Brown, Randolph

AU - Kupin, Warren

AU - Chen, Linda J

AU - Tueros, Lissett

AU - Hanson, Lois

AU - Ruiz, Phillip

AU - Burke, George W

PY - 2011/6/15

Y1 - 2011/6/15

N2 - Background: Our single-center, open-labeled randomized trial of 150 adult, primary kidney transplant recipients receiving 2 g mycophenolate mofetil (group A, n=75) versus 1.440 g enteric-coated mycophenolate sodium (group B, n=75), with reduced maintenance tacrolimus dosing, steroid elimination at 1 week, and combined rabbit antithymocyte globulin/daclizumab induction, previously showed at 1 year posttransplant low biopsy-proven acute rejection (BPAR), acceptably high renal function, and no differences in incidence of symptomatic gastrointestinal (GI) side effects between the two groups. This report includes 3 additional years of follow-up with similar endpoints as in the original study. Methods: Rates of developing first BPAR, graft failure (death censored and uncensored), death, and adverse events (GI toxicity, infections requiring hospitalization, and new onset diabetes mellitus after transplantation) during the first 48 months posttransplant were compared between the two groups using an intent-to-treat approach. Results: At 48 months posttransplant, patient/graft survival in groups A and B was 97%/90% vs. 96%/86%, respectively (not significant [NS]). Twenty-seven patients experienced BPAR (including borderline), with actuarial 19% (14/75) vs. 18% (13/75) in groups A and B, respectively (NS). Geometric mean*/standard error serum creatinine level and arithmetic mean calculated glomerular filtration rate (±standard error) at 48 months in groups A and B, respectively, were 1.25*/1.06 and 69.2±3.9 vs. 1.20*/1.05 and 71.2±3.2 (NS). Incidence of new onset diabetes mellitus after transplantation (22% vs. 15%), infections requiring hospitalization (31% vs. 39%), and GI side effects (45% vs. 52%) seemed equivalent. Conclusions: This is the first long-term, randomized trial comparing enteric-coated mycophenolate sodium versus mycophenolate mofetil along with reduced maintenance tacrolimus dosing and steroid avoidance, which resulted in similarly low-BPAR rates, acceptably high renal function at 48 months, and an equivalent side effect profile.

AB - Background: Our single-center, open-labeled randomized trial of 150 adult, primary kidney transplant recipients receiving 2 g mycophenolate mofetil (group A, n=75) versus 1.440 g enteric-coated mycophenolate sodium (group B, n=75), with reduced maintenance tacrolimus dosing, steroid elimination at 1 week, and combined rabbit antithymocyte globulin/daclizumab induction, previously showed at 1 year posttransplant low biopsy-proven acute rejection (BPAR), acceptably high renal function, and no differences in incidence of symptomatic gastrointestinal (GI) side effects between the two groups. This report includes 3 additional years of follow-up with similar endpoints as in the original study. Methods: Rates of developing first BPAR, graft failure (death censored and uncensored), death, and adverse events (GI toxicity, infections requiring hospitalization, and new onset diabetes mellitus after transplantation) during the first 48 months posttransplant were compared between the two groups using an intent-to-treat approach. Results: At 48 months posttransplant, patient/graft survival in groups A and B was 97%/90% vs. 96%/86%, respectively (not significant [NS]). Twenty-seven patients experienced BPAR (including borderline), with actuarial 19% (14/75) vs. 18% (13/75) in groups A and B, respectively (NS). Geometric mean*/standard error serum creatinine level and arithmetic mean calculated glomerular filtration rate (±standard error) at 48 months in groups A and B, respectively, were 1.25*/1.06 and 69.2±3.9 vs. 1.20*/1.05 and 71.2±3.2 (NS). Incidence of new onset diabetes mellitus after transplantation (22% vs. 15%), infections requiring hospitalization (31% vs. 39%), and GI side effects (45% vs. 52%) seemed equivalent. Conclusions: This is the first long-term, randomized trial comparing enteric-coated mycophenolate sodium versus mycophenolate mofetil along with reduced maintenance tacrolimus dosing and steroid avoidance, which resulted in similarly low-BPAR rates, acceptably high renal function at 48 months, and an equivalent side effect profile.

KW - Biopsy-proven acute rejection

KW - Enteric-coated mycophenolate sodium

KW - Graft survival

KW - Mycophenolate mofetil

KW - Renal transplant recipients

KW - Steroid avoidance

KW - Tacrolimus

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U2 - 10.1097/TP.0b013e3182003d76

DO - 10.1097/TP.0b013e3182003d76

M3 - Article

C2 - 21107305

AN - SCOPUS:79958295104

VL - 91

SP - 1198

EP - 1205

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 11

ER -