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 language | English (US) |
|---|---|
| Pages (from-to) | 1348-1357 |
| Number of pages | 10 |
| Journal | Transplantation |
| Volume | 92 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 27 2011 |
| Externally published | Yes |
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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 J.; Sageshima, Junichiro; Guerra, Giselle; Zarak, Alberto; Roth, David; Brown, Randolph; Kupin, Warren; Chen, Linda; Hanson, Lois; Tueros, Lissett; Ruiz, Phillip; Livingstone, Alan S.; Burke, George W.
In: Transplantation, Vol. 92, No. 12, 27.12.2011, p. 1348-1357.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Randomized trial of dual antibody induction therapy with steroid avoidance in renal transplantation
AU - Ciancio, Gaetano
AU - Gaynor, Jeffrey J.
AU - Sageshima, Junichiro
AU - Guerra, Giselle
AU - Zarak, Alberto
AU - Roth, David
AU - Brown, Randolph
AU - Kupin, Warren
AU - Chen, Linda
AU - Hanson, Lois
AU - Tueros, Lissett
AU - Ruiz, Phillip
AU - Livingstone, Alan S.
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
UR - http://www.scopus.com/inward/record.url?scp=84858415496&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858415496&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e3182384b21
DO - 10.1097/TP.0b013e3182384b21
M3 - Article
C2 - 22027927
AN - SCOPUS:84858415496
VL - 92
SP - 1348
EP - 1357
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 12
ER -