Randomized trial of three induction antibodies in kidney transplantation: long-term results.
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.
1 Miami Transplant Institute, Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, and Jackson Memorial Hospital, Miami, FL. 2 Miami Transplant Institute, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, and Jackson Memorial Hospital, Miami, FL. 3 Address correspondence to: Gaetano Ciancio, M.D., Miami Transplant Institute, Jackson Memorial Hospital and The Department of Surgery, University of Miami Miller School of Medicine, P.O. Box 012440 (R-440), Miami, FL 33101.
Gaetano
G
Ciancio
Jeffrey J
JJ
Gaynor
Giselle
G
Guerra
Junichiro
J
Sageshima
Linda
L
Chen
Adela
A
Mattiazzi
David
D
Roth
Warren
W
Kupin
Lissett
L
Tueros
Sandra
S
Flores
Lois
L
Hanson
Rodrigo
R
Vianna
George W
GW
Burke
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D002102:Cadaver; D003404:Creatinine / Q000097:blood; D000077561:Daclizumab; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016559:Tacrolimus / Q000008:administration & dosage; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D003404:Creatinine; D000077561:Daclizumab; C512542:thymoglobulin; D009173:Mycophenolic Acid; D016559:Tacrolimus