Møller Christian H, Gustafsson Finn, Gluud Christian, Steinbrüchel Daniel A
Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
J Heart Lung Transplant. 2008 Aug;27(8):835-42. doi: 10.1016/j.healun.2008.05.013. Epub 2008 Jun 30.
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.
约半数心脏移植中心在心脏移植后使用诱导治疗。白细胞介素-2受体拮抗剂（IL-2Ras）越来越多地用于诱导治疗。我们对评估IL-2Ras的随机试验进行了系统评价。
检索截至2007年11月的CENTRAL、PubMed、EMBASE和科学网，查找比较IL-2Ra与安慰剂/未治疗或另一种抗体诱导治疗的随机试验。由两名研究人员独立提取数据并评估质量。结局指标为死亡率、活检证实的急性排斥反应（≥3A 级）、感染和恶性肿瘤。数据以相对风险（RR）及95%置信区间（CI）表示。
我们发现9项评估IL-2Ra作为心脏移植后诱导治疗的随机试验。所有试验均为高偏倚风险试验。4项试验比较了IL-2Ra与安慰剂/未治疗，3项试验比较了IL-2Ra与多克隆抗体，2项试验比较了IL-2Ra与单克隆抗体。随访时间为6至12个月，2项试验的随访时间长达10年。当采用固定效应模型对IL-2Ra与安慰剂/未治疗进行荟萃分析时，IL-2Ra显著降低了急性排斥反应的风险（RR 0.73，95%CI 0.59至0.90），但采用随机效应模型时则不然（RR 0.73，95%CI 0.46至1.17）。与多克隆抗体相比，IL-2Ra显著增加了急性排斥反应（RR 2.99，95%CI 1.42至6.28），但与单克隆抗体相比则未增加（RR 0.94，95%CI 0.74至1.20）。在死亡率、感染或恶性肿瘤方面未发现显著差异。
心脏移植后使用诱导治疗的证据稀少。本系统评价未发现有令人信服的证据表明其对生存有益或能减少心脏同种异体移植排斥反应。因此，心脏移植中常规使用IL-2Ra仍缺乏依据。
