Keown Paul, Balshaw Robert, Khorasheh Shideh, Chong Mei, Marra Carlo, Kalo Zoltan, Korn Alex
Department of Medicine, University of British Columbia, Vancouver, British Columbia and Syreon Corporation, Vancouver, British Columbia, Canada.
BioDrugs. 2003;17(4):271-9. doi: 10.2165/00063030-200317040-00006.
Basiliximab is a high-affinity chimeric monoclonal antibody directed against the alpha-chain of the interleukin (IL)-2 receptor. Individual studies have shown that it is highly effective in preventing acute rejection and causes no measurable incremental toxicity. However, incorporation of basiliximab immunoprophylaxis into routine practice depends upon the demonstration of benefit across treatment regimens and quantitation of the treatment effect.
This study employed a meta-analysis to examine the clinical benefit of basiliximab. Parameter estimates were derived from four randomised prospective double-blind studies conducted in 93 renal transplant centres in 18 countries. A total of 1185 adult primary allograft recipients were randomised within the centres to receive either basiliximab 20mg intravenously on days 0 and 4 or placebo, in addition to double or triple immunosuppression consisting of cyclosporin-microemulsion (Neoral((R))The use of tradenames is for product identification purposes only and does not imply endorsement.), corticosteroids, and azathioprine or mycophenolate mofetil. Key clinical events included patient and graft survival, graft rejection and complications. Analysis was performed using a variable model; odds ratios and the numbers needed to treat (NNT) to benefit or to harm one patient were calculated for each principal outcome at 6 or 12 months post-transplant.
Basiliximab reduced the relative risk (RR) and absolute risk (AR) of clinical and biopsy-proven acute graft rejection across all treatment regimens. The overall RR of clinical acute graft rejection was decreased by 35% in patients receiving basiliximab. AR was reduced by 15.6% (pooled incidence: 28.8% vs 44.4%, p < 0.0001), and the NNT for efficacy was six. The reduction in RR of biopsy-proven rejection was similar (32%) with an absolute risk reduction (ARR) of 11.7% (pooled incidence: 25.1% vs 36.8%, p < 0.0001) and NNT of nine over 6 months. There was a concomitant reduction in the risk of graft loss which did not reach statistical significance (p = 0.14). The RR of graft loss was reduced by 26% with an AR reduction of 2.3% (pooled incidence: 6.4% vs 8.7%) and an NNT of 42 over 6 months. The risk of death was unchanged.
Immunoprophylaxis with basiliximab produces a significant reduction in the RR and AR of clinical and biopsy-proven acute graft rejection with a trend towards a concomitant reduction in the risk of graft loss. The magnitude of protection provided by basiliximab, the fact that it is observed across treatment regimens and the safety of this therapy are arguments for its routine use in renal transplantation.
巴利昔单抗是一种高亲和力的嵌合单克隆抗体，可针对白细胞介素（IL）-2受体的α链。个别研究表明，它在预防急性排斥反应方面非常有效，且不会产生可测量的额外毒性。然而，将巴利昔单抗免疫预防纳入常规治疗取决于其在不同治疗方案中的益处证明及治疗效果的量化。
本研究采用荟萃分析来检验巴利昔单抗的临床益处。参数估计值来自于在18个国家的93个肾移植中心进行的四项随机前瞻性双盲研究。共有1185名成年原发性同种异体移植受者在各中心内被随机分组，除了接受由环孢素微乳剂（新山地明（R）使用商品名仅用于产品识别目的，并不意味着认可）、皮质类固醇和硫唑嘌呤或霉酚酸酯组成的双重或三重免疫抑制外，在第0天和第4天分别静脉注射20mg巴利昔单抗或安慰剂。关键临床事件包括患者和移植物存活、移植物排斥反应及并发症。分析采用可变模型；计算移植后6个月或12个月时每个主要结局的比值比及使一名患者受益或受害所需治疗人数（NNT）。
巴利昔单抗降低了所有治疗方案中临床及活检证实的急性移植物排斥反应的相对风险（RR）和绝对风险（AR）。接受巴利昔单抗治疗的患者临床急性移植物排斥反应的总体RR降低了35%。AR降低了15.6%（合并发生率：28.8%对44.4%，p<0.0001），疗效的NNT为6。活检证实的排斥反应RR的降低相似（32%），绝对风险降低（ARR）为11.7%（合并发生率：25.1%对36.8%，p<0.0001），6个月内的NNT为9。移植物丢失风险也随之降低，但未达到统计学显著性（p = 0.14）。移植物丢失的RR降低了26%，AR降低了2.3%（合并发生率：6.4%对8.7%），6个月内的NNT为42。死亡风险未改变。
巴利昔单抗免疫预防可显著降低临床及活检证实的急性移植物排斥反应的RR和AR，且有使移植物丢失风险随之降低的趋势。巴利昔单抗提供的保护程度、在不同治疗方案中均观察到这一事实以及该疗法的安全性，均支持其在肾移植中常规使用。
