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 language | English (US) |
|---|---|
| Pages (from-to) | 1128-1138 |
| Number of pages | 11 |
| Journal | Transplantation |
| Volume | 97 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jun 19 2014 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=84902157549&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902157549&partnerID=8YFLogxK
U2 - 10.1097/01.TP.0000441089.39840.66
DO - 10.1097/01.TP.0000441089.39840.66
M3 - Article
VL - 97
SP - 1128
EP - 1138
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 11
ER -