Randomized trial of three induction antibodies in kidney transplantation

Long-Term results

Gaetano Ciancio, Jeffrey J. Gaynor, Giselle Guerra, Junichiro Sageshima, Linda Chen, Adela Mattiazzi, David Roth, Warren Kupin, Lissett Tueros, Sandra Flores, Lois Hanson, Rodrigo Vianna, George W. Burke

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

BACKGROUND: In searching for an optimal induction regimen, we conducted two separate randomized trials of 38 living donor and 90 deceased donor adult, primary kidney transplant recipients comparing antithymocyte globulin (Thymoglobulin) (group A, N=43) versus alemtuzumab (group B, N=43) versus daclizumab (group C, N=42), using exactly the same three treatment arms in each trial. METHODS: For the purpose of maximizing statistical power, results from the two randomized trials were combined. Groups A and C received standard maintenance dosing with tacrolimus (TAC), mycophenolate mofetil (MMF), and corticosteroids. Because of intense lymphodepletion expected with alemtuzumab use (and hoped-for achievement of a truer immunoregulatory state), group B received lower TAC and MMF dosing and corticosteroid avoidance. Long-Term target TAC trough level and MMF dosing were 5 to 7 ng/mL and 1,000 mg b.i.d. in groups A and C; 4 to 6 ng/mL and 500 mg b.i.d. in group B. RESULTS: With median follow-up of 95 months, biopsy-proven cute rejection incidence was similar in the three groups (8/43, 14/43, and 12/42, P=0.34), but biopsy-proven chronic allograft injury incidence was significantly higher in group B (19/43) in comparison with groups A (9/43) and C (7/42) combined (P=0.0008). Mean calculated creatinine clearance was significantly lower in group B versus the average of groups A and C means throughout 60 months posttransplant (62.9±4.2 vs. 83.6±6.9 and 79.8±5.9 at 60 months, P=0.01), and death-censored graft failure was significantly higher in group B (13/43) versus groups A (5/43) and C (5/42) combined (P=0.009). Total infection and new-onset diabetes after transplant rates were not significantly different. Ad hoc analysis suggested that the inferior results in group B were specifically a result of reduced dosing and greater withholding of TAC and MMF occurring in that group. CONCLUSIONS: Long-Term results clearly indicate inferior clinical outcomes in group B.

Original languageEnglish (US)
Pages (from-to)1128-1138
Number of pages11
JournalTransplantation
Volume97
Issue number11
DOIs
StatePublished - Jun 19 2014
Externally publishedYes

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Mycophenolic Acid
Tacrolimus
Kidney Transplantation
Antibodies
Adrenal Cortex Hormones
Transplants
Biopsy
Antilymphocyte Serum
Living Donors
Incidence
Allografts
Creatinine
Arm
Maintenance
Tissue Donors
Kidney
Wounds and Injuries
Infection
alemtuzumab

Keywords

  • Alemtuzumab
  • Antithymocyte globulin
  • Biopsy-proven acute rejection
  • Biopsy-proven chronic allograft injury
  • Campath-1H
  • Daclizumab
  • Death-censored graft survival
  • Long-Term follow-up.

ASJC Scopus subject areas

  • Transplantation

Cite this

Randomized trial of three induction antibodies in kidney transplantation : Long-Term results. / Ciancio, Gaetano; Gaynor, Jeffrey J.; Guerra, Giselle; Sageshima, Junichiro; Chen, Linda; Mattiazzi, Adela; Roth, David; Kupin, Warren; Tueros, Lissett; Flores, Sandra; Hanson, Lois; Vianna, Rodrigo; Burke, George W.

In: Transplantation, Vol. 97, No. 11, 19.06.2014, p. 1128-1138.

Research output: Contribution to journalArticle

Ciancio, G, Gaynor, JJ, Guerra, G, Sageshima, J, Chen, L, Mattiazzi, A, Roth, D, Kupin, W, Tueros, L, Flores, S, Hanson, L, Vianna, R & Burke, GW 2014, 'Randomized trial of three induction antibodies in kidney transplantation: Long-Term results', Transplantation, vol. 97, no. 11, pp. 1128-1138. https://doi.org/10.1097/01.TP.0000441089.39840.66
Ciancio, Gaetano ; Gaynor, Jeffrey J. ; Guerra, Giselle ; Sageshima, Junichiro ; Chen, Linda ; Mattiazzi, Adela ; Roth, David ; Kupin, Warren ; Tueros, Lissett ; Flores, Sandra ; Hanson, Lois ; Vianna, Rodrigo ; Burke, George W. / Randomized trial of three induction antibodies in kidney transplantation : Long-Term results. In: Transplantation. 2014 ; Vol. 97, No. 11. pp. 1128-1138.
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T1 - Randomized trial of three induction antibodies in kidney transplantation

T2 - Long-Term results

AU - Ciancio, Gaetano

AU - Gaynor, Jeffrey J.

AU - Guerra, Giselle

AU - Sageshima, Junichiro

AU - Chen, Linda

AU - Mattiazzi, Adela

AU - Roth, David

AU - Kupin, Warren

AU - Tueros, Lissett

AU - Flores, Sandra

AU - Hanson, Lois

AU - Vianna, Rodrigo

AU - Burke, George W.

PY - 2014/6/19

Y1 - 2014/6/19

N2 - BACKGROUND: In searching for an optimal induction regimen, we conducted two separate randomized trials of 38 living donor and 90 deceased donor adult, primary kidney transplant recipients comparing antithymocyte globulin (Thymoglobulin) (group A, N=43) versus alemtuzumab (group B, N=43) versus daclizumab (group C, N=42), using exactly the same three treatment arms in each trial. METHODS: For the purpose of maximizing statistical power, results from the two randomized trials were combined. Groups A and C received standard maintenance dosing with tacrolimus (TAC), mycophenolate mofetil (MMF), and corticosteroids. Because of intense lymphodepletion expected with alemtuzumab use (and hoped-for achievement of a truer immunoregulatory state), group B received lower TAC and MMF dosing and corticosteroid avoidance. Long-Term target TAC trough level and MMF dosing were 5 to 7 ng/mL and 1,000 mg b.i.d. in groups A and C; 4 to 6 ng/mL and 500 mg b.i.d. in group B. RESULTS: With median follow-up of 95 months, biopsy-proven cute rejection incidence was similar in the three groups (8/43, 14/43, and 12/42, P=0.34), but biopsy-proven chronic allograft injury incidence was significantly higher in group B (19/43) in comparison with groups A (9/43) and C (7/42) combined (P=0.0008). Mean calculated creatinine clearance was significantly lower in group B versus the average of groups A and C means throughout 60 months posttransplant (62.9±4.2 vs. 83.6±6.9 and 79.8±5.9 at 60 months, P=0.01), and death-censored graft failure was significantly higher in group B (13/43) versus groups A (5/43) and C (5/42) combined (P=0.009). Total infection and new-onset diabetes after transplant rates were not significantly different. Ad hoc analysis suggested that the inferior results in group B were specifically a result of reduced dosing and greater withholding of TAC and MMF occurring in that group. CONCLUSIONS: Long-Term results clearly indicate inferior clinical outcomes in group B.

AB - BACKGROUND: In searching for an optimal induction regimen, we conducted two separate randomized trials of 38 living donor and 90 deceased donor adult, primary kidney transplant recipients comparing antithymocyte globulin (Thymoglobulin) (group A, N=43) versus alemtuzumab (group B, N=43) versus daclizumab (group C, N=42), using exactly the same three treatment arms in each trial. METHODS: For the purpose of maximizing statistical power, results from the two randomized trials were combined. Groups A and C received standard maintenance dosing with tacrolimus (TAC), mycophenolate mofetil (MMF), and corticosteroids. Because of intense lymphodepletion expected with alemtuzumab use (and hoped-for achievement of a truer immunoregulatory state), group B received lower TAC and MMF dosing and corticosteroid avoidance. Long-Term target TAC trough level and MMF dosing were 5 to 7 ng/mL and 1,000 mg b.i.d. in groups A and C; 4 to 6 ng/mL and 500 mg b.i.d. in group B. RESULTS: With median follow-up of 95 months, biopsy-proven cute rejection incidence was similar in the three groups (8/43, 14/43, and 12/42, P=0.34), but biopsy-proven chronic allograft injury incidence was significantly higher in group B (19/43) in comparison with groups A (9/43) and C (7/42) combined (P=0.0008). Mean calculated creatinine clearance was significantly lower in group B versus the average of groups A and C means throughout 60 months posttransplant (62.9±4.2 vs. 83.6±6.9 and 79.8±5.9 at 60 months, P=0.01), and death-censored graft failure was significantly higher in group B (13/43) versus groups A (5/43) and C (5/42) combined (P=0.009). Total infection and new-onset diabetes after transplant rates were not significantly different. Ad hoc analysis suggested that the inferior results in group B were specifically a result of reduced dosing and greater withholding of TAC and MMF occurring in that group. CONCLUSIONS: Long-Term results clearly indicate inferior clinical outcomes in group B.

KW - Alemtuzumab

KW - Antithymocyte globulin

KW - Biopsy-proven acute rejection

KW - Biopsy-proven chronic allograft injury

KW - Campath-1H

KW - Daclizumab

KW - Death-censored graft survival

KW - Long-Term follow-up.

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DO - 10.1097/01.TP.0000441089.39840.66

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