Interleukin-2 Receptor Antagonists as Induction Therapy After Heart Transplantation: Systematic Review With Meta-Analysis of Randomized Trials

Abstract

About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras. We searched CENTRAL, PubMed, EMBASE and Web of Science up to November 2007 for randomized trials comparing IL-2Ra vs placebo/no treatment or another antibody induction therapy. Data were extracted and quality was assessed independently by two investigators. Outcome measures were mortality, biopsy-proven acute rejection (Grade > or =3A), infections and malignancy. Data were presented as the relative risk (RR) with 95% confidence interval (CI). We found 9 randomized trials evaluating IL-2Ra as induction therapy after heart transplantation. All were high-bias risk trials. Four trials compared IL-2Ra with placebo/no treatment, 3 trials compared IL-2Ra with polyclonal antibody and 2 trials compared IL-2Ra with monoclonal antibody. Follow-up ranged from 6 to 12 months, except for 2 trials with up to 10 years of follow-up. When IL-2Ra vs placebo/no treatment was meta-analyzed with a fixed-effect model, IL-2Ra significantly reduced the risk of acute rejection (RR 0.73, 95% CI 0.59 to 0.90), but not according to a random-effects model (RR 0.73, 95% CI 0.46 to 1.17). IL-2Ra significantly increased acute rejection when compared with polyclonal antibody (RR 2.99, 95% CI 1.42 to 6.28), but not when compared with monoclonal antibody (RR 0.94, 95% CI 0.74 to 1.20). No significant differences were found regarding mortality, infections or malignancy. Evidence for the use of induction therapy after heart transplantation is sparse. This systematic review found no convincing evidence of a survival benefit or reduction in cardiac allograft rejection. Thus, the routine use of IL-2Ra in cardiac transplantation remains unsupported.