Goring Sarah M, Levy Adrian R, Ghement Isabella, Kalsekar Anupama, Eyawo Oghenowede, L'Italien Gilbert J, Kasiske Bertram
Oxford Outcomes Ltd , Vancouver, BC , Canada.
Curr Med Res Opin. 2014 Aug;30(8):1473-87. doi: 10.1185/03007995.2014.898140. Epub 2014 Apr 3.
Belatacept is a first in-class co-stimulation blocker developed for primary maintenance immunosuppression following renal transplantation. The objective of this study was to estimate the efficacy of belatacept relative to tacrolimus and cyclosporine among adults receiving a single kidney transplant. A systematic review was conducted of randomized clinical trials (RCTs) published between January 1990 and December 2013 using EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, and unpublished study reports from two belatacept RCTs. Bayesian network meta-analysis (NMA) methods were used to compare the efficacy measures, mortality, graft loss, acute rejection and glomerular filtration rate (GFR). Heterogeneity was quantified using statistical metrics and potential sources were evaluated using meta-regression and subgroup analysis. A total of 28 RCTs comparing tacrolimus with cyclosporine, and three comparing belatacept with cyclosporine, were identified. All three agents provided comparable graft and patient survival, despite a higher risk of acute rejection associated with belatacept and cyclosporine. Belatacept was associated with significant improvement in GFR versus cyclosporine. Compared with tacrolimus, this difference was clinically meaningful yet statistically non-significant. The probability of being the best treatment was highest for belatacept for graft survival (68%), patient survival (97%) and renal function (89%), and highest for tacrolimus for acute rejection (99%).Variability in donor, recipient, and trial characteristics was present in the included RCTs; however, minimal statistical heterogeneity was detected in the analysis of acute rejection, graft or patient survival, and none of the characteristics were found to be significantly associated with relative effect. Although the direction of effect of immunosuppressants on GFR was consistent across RCTs, precise estimation of its magnitude was limited by a small number of RCTs and heterogeneity in relative effect sizes. Clinicians often seek an alternative to CNIs due to their nephrotoxic effects. The results of this indirect comparison indicate that belatacept is an effective immunosuppressive agent in renal transplantation among adults.
贝拉西普是首个用于肾移植术后主要维持免疫抑制的共刺激阻断剂。本研究的目的是评估贝拉西普相对于他克莫司和环孢素在接受单肾移植的成人中的疗效。我们使用EMBASE、MEDLINE、Cochrane对照试验中央注册库以及两项贝拉西普随机对照试验的未发表研究报告，对1990年1月至2013年12月期间发表的随机临床试验（RCT）进行了系统评价。采用贝叶斯网络荟萃分析（NMA）方法比较疗效指标、死亡率、移植物丢失、急性排斥反应和肾小球滤过率（GFR）。使用统计指标对异质性进行量化，并使用荟萃回归和亚组分析评估潜在来源。共识别出28项比较他克莫司与环孢素的RCT，以及3项比较贝拉西普与环孢素的RCT。尽管贝拉西普和环孢素与急性排斥反应的风险较高相关，但所有三种药物的移植物和患者生存率相当。与环孢素相比，贝拉西普与GFR的显著改善相关。与他克莫司相比，这种差异具有临床意义，但在统计学上不显著。在移植物存活（68%）、患者存活（97%）和肾功能（89%）方面，贝拉西普成为最佳治疗方法的概率最高，而在急性排斥反应方面，他克莫司成为最佳治疗方法的概率最高（99%）。纳入的RCT中存在供体、受体和试验特征的差异；然而，在急性排斥反应、移植物或患者存活分析中检测到的统计异质性最小，并且未发现任何特征与相对效应显著相关。尽管免疫抑制剂对GFR的作用方向在各RCT中一致，但其大小的精确估计受到少数RCT和相对效应大小异质性的限制。由于钙调神经磷酸酶抑制剂（CNIs）的肾毒性作用，临床医生经常寻求其替代药物。这项间接比较的结果表明，贝拉西普在成人肾移植中是一种有效的免疫抑制剂。
