Randomized trial of dual antibody induction therapy with steroid avoidance in renal transplantation

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Given our previous experience using dual-induction therapy with antithymocyte globulin (ATG)/daclizumab (Dac) (each with fewer doses than if used alone), we chose to compare two distinct dual-induction strategies. Methods: Single-center, open-label randomized trial of 200 primary kidney transplant recipients was performed: (group I, n=100) ATG/Dac (3 ATG, 2 Dac doses) versus (group II, n=100) ATG/alemtuzumab (1 dose each), with maintenance consisting of reduced tacrolimus dosing (rTd), enteric-coated mycophenolate sodium (EC-MPS), and early corticosteroid withdrawal. One half of standard EC-MPS dosing was targeted in group II to avoid severe leukopenia previously seen with alemtuzumab. The goal in both arms was to achieve rapid and effective lymphocyte depletion while simultaneously allowing reduced maintenance immunosuppression. Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR). Results: With median follow-up of 38 months, there were no differences in BPAR rates: 14 of 100 vs. 13 of 100 (including borderline) and 10 of 100 vs. 9 of 100 (excluding borderline) in groups I and II, respectively (nonsignificant). Actuarial patient/graft survival at 48 months was 96%/91% in group I vs. 92%/83% in group II (N.S.). Mean estimated glomerular filtration rate (±standard error) at 36 months was 72.1±3.3 vs. 67.5±3.3 in groups I and II (N.S.). Greater incidence of leukopenia occurred in group II at month 1 only (P=0.002). Percentages having EC-MPS withheld/discontinued due to leukopenia, gastrointestinal symptoms, and infection were 12 of 100, 7 of 100, and 0 of 100 in group I vs. 19 of 100, 0 of 100, and 2 of 100 in group II, respectively (P±0.01). Rates of new onset diabetes mellitus after transplantation and infections were equally low in both groups (no lymphoproliferative disorders were observed). Conclusions. These two distinct dual-induction therapies with rTd, EC-MPS, and planned early corticosteroid withdrawal resulted in favorable rates of BPAR and all secondary outcomes.

Original languageEnglish
Pages (from-to)1348-1357
Number of pages10
JournalTransplantation
Volume92
Issue number12
DOIs
StatePublished - Dec 27 2011

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Mycophenolic Acid
Kidney Transplantation
Antilymphocyte Serum
Leukopenia
Steroids
Antibodies
Tacrolimus
Biopsy
Adrenal Cortex Hormones
Maintenance
Lymphocyte Depletion
Lymphoproliferative Disorders
Incidence
Graft Survival
Therapeutics
Infection
Glomerular Filtration Rate
Immunosuppression
Diabetes Mellitus
Transplantation

Keywords

  • Alemtuzumab
  • Antithymocyte globulin
  • Biopsy-proven acute rejection
  • Daclizumab
  • Enteric-coated mycophenolate sodium
  • Graft survival
  • Renal transplantation
  • Steroid avoidance
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation

Cite this

Randomized trial of dual antibody induction therapy with steroid avoidance in renal transplantation. / Ciancio, Gaetano; Gaynor, Jeffrey; Sageshima, Junichiro; Guerra, Giselle; Zarak, Alberto; Roth, David; Brown, Randolph; Kupin, Warren; Chen, Linda J; Hanson, Lois; Tueros, Lissett; Ruiz, Phillip; Livingstone, Alan; Burke, George W.

In: Transplantation, Vol. 92, No. 12, 27.12.2011, p. 1348-1357.

Research output: Contribution to journalArticle

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T1 - Randomized trial of dual antibody induction therapy with steroid avoidance in renal transplantation

AU - Ciancio, Gaetano

AU - Gaynor, Jeffrey

AU - Sageshima, Junichiro

AU - Guerra, Giselle

AU - Zarak, Alberto

AU - Roth, David

AU - Brown, Randolph

AU - Kupin, Warren

AU - Chen, Linda J

AU - Hanson, Lois

AU - Tueros, Lissett

AU - Ruiz, Phillip

AU - Livingstone, Alan

AU - Burke, George W

PY - 2011/12/27

Y1 - 2011/12/27

N2 - Background: Given our previous experience using dual-induction therapy with antithymocyte globulin (ATG)/daclizumab (Dac) (each with fewer doses than if used alone), we chose to compare two distinct dual-induction strategies. Methods: Single-center, open-label randomized trial of 200 primary kidney transplant recipients was performed: (group I, n=100) ATG/Dac (3 ATG, 2 Dac doses) versus (group II, n=100) ATG/alemtuzumab (1 dose each), with maintenance consisting of reduced tacrolimus dosing (rTd), enteric-coated mycophenolate sodium (EC-MPS), and early corticosteroid withdrawal. One half of standard EC-MPS dosing was targeted in group II to avoid severe leukopenia previously seen with alemtuzumab. The goal in both arms was to achieve rapid and effective lymphocyte depletion while simultaneously allowing reduced maintenance immunosuppression. Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR). Results: With median follow-up of 38 months, there were no differences in BPAR rates: 14 of 100 vs. 13 of 100 (including borderline) and 10 of 100 vs. 9 of 100 (excluding borderline) in groups I and II, respectively (nonsignificant). Actuarial patient/graft survival at 48 months was 96%/91% in group I vs. 92%/83% in group II (N.S.). Mean estimated glomerular filtration rate (±standard error) at 36 months was 72.1±3.3 vs. 67.5±3.3 in groups I and II (N.S.). Greater incidence of leukopenia occurred in group II at month 1 only (P=0.002). Percentages having EC-MPS withheld/discontinued due to leukopenia, gastrointestinal symptoms, and infection were 12 of 100, 7 of 100, and 0 of 100 in group I vs. 19 of 100, 0 of 100, and 2 of 100 in group II, respectively (P±0.01). Rates of new onset diabetes mellitus after transplantation and infections were equally low in both groups (no lymphoproliferative disorders were observed). Conclusions. These two distinct dual-induction therapies with rTd, EC-MPS, and planned early corticosteroid withdrawal resulted in favorable rates of BPAR and all secondary outcomes.

AB - Background: Given our previous experience using dual-induction therapy with antithymocyte globulin (ATG)/daclizumab (Dac) (each with fewer doses than if used alone), we chose to compare two distinct dual-induction strategies. Methods: Single-center, open-label randomized trial of 200 primary kidney transplant recipients was performed: (group I, n=100) ATG/Dac (3 ATG, 2 Dac doses) versus (group II, n=100) ATG/alemtuzumab (1 dose each), with maintenance consisting of reduced tacrolimus dosing (rTd), enteric-coated mycophenolate sodium (EC-MPS), and early corticosteroid withdrawal. One half of standard EC-MPS dosing was targeted in group II to avoid severe leukopenia previously seen with alemtuzumab. The goal in both arms was to achieve rapid and effective lymphocyte depletion while simultaneously allowing reduced maintenance immunosuppression. Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR). Results: With median follow-up of 38 months, there were no differences in BPAR rates: 14 of 100 vs. 13 of 100 (including borderline) and 10 of 100 vs. 9 of 100 (excluding borderline) in groups I and II, respectively (nonsignificant). Actuarial patient/graft survival at 48 months was 96%/91% in group I vs. 92%/83% in group II (N.S.). Mean estimated glomerular filtration rate (±standard error) at 36 months was 72.1±3.3 vs. 67.5±3.3 in groups I and II (N.S.). Greater incidence of leukopenia occurred in group II at month 1 only (P=0.002). Percentages having EC-MPS withheld/discontinued due to leukopenia, gastrointestinal symptoms, and infection were 12 of 100, 7 of 100, and 0 of 100 in group I vs. 19 of 100, 0 of 100, and 2 of 100 in group II, respectively (P±0.01). Rates of new onset diabetes mellitus after transplantation and infections were equally low in both groups (no lymphoproliferative disorders were observed). Conclusions. These two distinct dual-induction therapies with rTd, EC-MPS, and planned early corticosteroid withdrawal resulted in favorable rates of BPAR and all secondary outcomes.

KW - Alemtuzumab

KW - Antithymocyte globulin

KW - Biopsy-proven acute rejection

KW - Daclizumab

KW - Enteric-coated mycophenolate sodium

KW - Graft survival

KW - Renal transplantation

KW - Steroid avoidance

KW - Tacrolimus

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