Papers

Interleukin-2 receptor monoclonal antibodies in renal transplantation: meta-analysis of randomised trials

Dwomoa Adu, consultant nephrologist, ^a Paul Cockwell, consultant nephrologist, ^a Natalie J Ives, statistician, ^b Jonathan Shaw, house physician, ^a Keith Wheatley, professor. ^b

^a Department of Nephrology, Queen Elizabeth Hospital, Birmingham, B15 2TH, ^b Birmingham Clinical Trials Unit, Park Grange, Birmingham B15 2RR

Correspondence to: D Adu dwomoa.adu{at}uhb.nhs.uk

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.
Design: Meta-analysis of published data.
Data sources: Medline, Embase, and Cochrane library for years 1996-2003 plus search of medical editors' trial amnesty and contact with manufacturers of the antibodies.
Selection of studies: 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.

What is already known on this topic Episodes of acute rejection reduce graft survival in patients with renal transplants Increasing immunosuppression to reduce rejection can increase infection and malignancy What this study adds Addition of interleukin-2 receptor antibodies to ciclosporin based immunosuppression regimens halves the risk of acute rejection Patients receiving antibodies did not have an increased risk of infection The effects on graft loss and mortality at one year were not significant