Interleukin 2 receptor antagonists for kidney transplant recipients

Abstract

Background: Interleukin 2 receptor antagonists (IL2Ra) are used as induction therapy for prophylaxis against acute rejection in kidney transplant recipients. Use of IL2Ra has increased steadily, with 38% of new kidney transplant recipients in the United States, and 23% in Australasia receiving IL2Ra in 2002.

Objectives: This study aims to systematically identify and summarise the effects of using an IL2Ra, as an addition to standard therapy, or as an alternative to other antibody therapy.

Search strategy: The Cochrane Renal Group's specialised register (June 2003), the Cochrane Controlled Trials Register (in The Cochrane Library issue 3, 2002), MEDLINE (1966-November 2002) and EMBASE (1980-November 2002). Reference lists and abstracts of conference proceedings and scientific meetings were hand-searched from 1998-2003. Trial groups, authors of included reports and drug manufacturers were contacted.

Selection criteria: Randomised controlled trials (RCTs) in all languages comparing IL2Ra to placebo, no treatment, other IL2Ra or other antibody therapy.

Data collection and analysis: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) with 95% confidence intervals (CI).

Main results: One hundred and seventeen reports from 38 trials involving 4893 participants were included. Where IL2Ra were compared with placebo (17 trials; 2786 patients), graft loss was not significantly different at one (RR 0.83, 95% CI 0.66 to 1.04) or three years (RR 0.88, 95% CI 0.64 to 1.22). Acute rejection (AR) was significantly reduced at six months (RR 0.66, 95% CI 0.59 to 0.74) and at one year (RR 0.67, 95% CI 0.60 to 0.75). At one year, cytomegalovirus (CMV) infection (RR 0.82, 95% CI 0.65 to 1.03) and malignancy (RR 0.67, 95% CI 0.33 to 1.36) were not significantly different. Where IL2Ra were compared with other antibody therapy no significant differences in treatment effects were demonstrated, but adverse effects strongly favoured IL2Ra.

Reviewer's conclusions: Given a 40% risk of rejection, seven patients would need treatment with IL2Ra to prevent one patient having rejection, with no definite improvement in graft or patient survival. There is no apparent difference between basiliximab and daclizumab. IL2Ra are as effective as other antibody therapies and with significantly fewer side effects