Interleukin-2 receptor monoclonal antibodies in renal transplantation: meta-analysis of randomised trials.
OBJECTIVE
To study the effect of interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft loss, deaths, and rate of infection and malignancy in patients with renal transplants.


METHODS
Meta-analysis of published data.


METHODS
Medline, Embase, and Cochrane library for years 1996-2003 plus search of medical editors' trial amnesty and contact with manufacturers of the antibodies.


METHODS
Randomised controlled trials comparing interleukin-2 receptor antibodies with placebo or no additional treatment in patients with renal transplants receiving ciclosporin based immunosuppression.


RESULTS
Eight randomised controlled trials involving 1871 patients met the selection criteria (although only 1858 patients were analysed). Interleukin-2 receptor antibodies significantly reduced the risk of acute rejection (odds ratio 0.51, 95% confidence interval 0.42 to 0.63). There were no significant differences in the rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23), overall incidence of infections (0.97, 0.77 to 1.24), incidence of cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to 0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar for all ciclosporin based immunosuppression regimens (test for heterogeneity P=1.0).


CONCLUSIONS
Adding interleukin-2 receptor antibodies to ciclosporin based immunosuppression reduces episodes of acute rejection at six months by 49%. There is no evidence of an increased risk of infective complications. Longer follow up studies are needed to confirm whether interleukin-2 receptor antibodies improve long term graft and patient survival.
Adu
Dwomoa
D
Department of Nephrology, Queen Elizabeth Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk
Cockwell
Paul
P
Ives
Natalie J
NJ
Shaw
Jonathan
J
Wheatley
Keith
K
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016572:Cyclosporine