CMV infections after two doses of daclizumab versus thymoglobulin in renal transplant patients receiving mycophenolate mofetil, steroids and delayed cyclosporine A.
BACKGROUND
Cytomegalovirus (CMV) infection is a major complication after renal transplantation and is involved in graft rejection. The anti-interleukin-2-receptor antibody daclizumab reduces the incidence of acute rejection without increasing the incidence of CMV infection.


METHODS
This multicentre, randomized trial compared safety and efficacy, at 1 year, of two doses of daclizumab (54 patients, group D) with thymoglobulin (55 patients, group T) plus delayed cyclosporine (CsA), MMF (mycophenolate mofetil) and steroids in first cadaver kidney transplant patients. Primary criterion was CMV infection/syndrome/disease. D+/R- patients received oral ganciclovir prophylaxis for 90 days.


RESULTS
Status for CMV was identical in the both groups. The incidence of CMV infection/syndrome/disease was 39% in group D versus 51% in group T (NS). Time to onset of CMV replication was delayed in group D (P = 0.015) and mean number of pp65-positive cells was lower at 4 and 6 months (P < 0.001). Incidence of symptomatic CMV episodes was not reduced in whole group D (5.6% versus 16.4%, NS), but lower in D+/R+ and D-/R+ patients without chemoprophylaxis, compared to group T (2.8% versus 21.6%, P = 0.028). Patient and graft survivals and incidence of biopsy-proven acute rejection were identical.


CONCLUSIONS
Limited dosing regimen of daclizumab with MMF, steroids and delayed CsA introduction was safe and effective. The incidence of CMV infection was not significantly different, but without chemoprophylaxis, clinical manifestations and viral replication were reduced with this regimen.
Abou-Ayache
Ramzi
R
CHU Poitiers, Service de Néphrologie, France. r.abou-ayache@chu-poitiers.fr
Büchler
Mathias
M
Lepogamp
Patrick
P
Westeel
Pierre-François
PF
Le Meur
Yannick
Y
Etienne
Isabelle
I
Lobbedez
Thierry
T
Toupance
Olivier
O
Caillard
Sophie
S
Goujon
Jean-Michel
JM
Bergougnoux
Loïc
L
Touchard
Guy
G
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D016572:Cyclosporine / Q000008:administration & dosage; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000188:drug therapy*; D000077561:Daclizumab; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000008:administration & dosage*; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000401:mortality / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011183:Postoperative Complications / Q000188:drug therapy / Q000821:virology; D012016:Reference Values; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D003692:Delayed-Action Preparations; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000077561:Daclizumab; C512542:thymoglobulin; D009173:Mycophenolic Acid; D015774:Ganciclovir