Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: Results from a double-blind randomized placebo-controlled trial
Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: Results from a double-blind randomized placebo-controlled trial
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DOI：
10.1053/jlts.2002.30302
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发表时间：
2002-02-01
影响因子：
4.6
通讯作者：
Nashan, B
中科院分区：
文献类型：
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作者：
Neuhaus, P;Clavien, PA;Nashan, B
巴利昔单抗是一种高亲和力的嵌合单克隆抗体，可有效减少肾移植受者的急性排斥反应。我们评估了这种抗体在肝移植受者中同样改善结果的能力。成人受体的主要尸体肝移植随机治疗，分层丙型肝炎病毒（HCV）血清阳性。患者分别在第0天和第4天接受40 mg巴利昔单抗（n = 188）或安慰剂（n = 193），两次20 mg推注，加上环孢霉素和类固醇。主要疗效变量为活检证实的急性排斥反应及其复合终点，包括死亡或移植物丢失，并在6个月和12个月时按HCV队列进行评估。由于HCV阳性和HCV阴性队列之间的疗效反应差异，引入了一项额外的分析，将HCV复发作为治疗失败的一个组成部分，称为无问题移植。在12个月的研究期间监测安全性和耐受性。所有381例患者均可评估，治疗组之间的背景特征无明显有意义的差异。巴利昔单抗组移植后6个月活检证实的急性排斥反应率为35.1%，安慰剂组为43.5%。死亡、移植物丢失或首次活检证实的急性排斥反应的发生率分别为44.1%和52.8%。排异反应的减少主要集中在HCV阴性组（相对于安慰剂组为14.5%; P = 0.034），HCV阳性组的差异要小得多（2.9%）。对于HCV阳性患者，巴利昔单抗组12个月时的无问题移植率为26.6%，安慰剂组为11.6%（P = 0.020），巴利昔单抗组12个月时的无问题移植率为39.7%，安慰剂组为30.1%（P = 0.035）。两个治疗组的感染和其他不良事件发生率相似。在12个月的研究中，有56例死亡（巴利昔单抗组25例死亡;安慰剂组31例死亡）。静脉推注耐受性良好。40 mg巴利昔单抗联合环孢霉素和类固醇进行免疫预防，可降低急性排斥反应的发生率，且无临床相关的安全性或耐受性问题。HCV复发对疗效结果的影响可以在未来的试验中通过使用无问题移植的概念来解释，将复发作为治疗失败的一个组成部分。
Basiliximab, a high-affinity chimeric monoclonal antibody, is effective in reducing acute rejection episodes in renal allograft recipients. We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients. Adult recipients of a primary cadaveric liver transplant were randomized to treatment, stratified by hepatitis C virus (HCV) seropositivity. Patients were administered 40 mg of basiliximab (n = 188) or placebo (n = 193) as two 20-mg bolus injections days 0 and 4, plus cyclosporine and steroids. Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point, including death or graft loss, and were assessed at 6 and 12 months and by HCV cohort. Because of differential efficacy responses between HCV-positive and HCV-negative cohorts, an additional analysis incorporating HCV recurrence as a component of treatment failure, termed problem-free transplant, was introduced. Safety and tolerability were monitored over the 12 months of the study. All 381 patients were assessable, and no meaningful differences in background characteristics were apparent between treatment groups. Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1% in the basiliximab group versus 43.5% in the placebo group. For death, graft loss, or first biopsy-confirmed acute rejection, rates were 44.1% versus 52.8%, respectively. The reduction in rejection episodes was concentrated in the HCV-negative cohort (14.5% relative to placebo; P = .034), with a much smaller difference (2.9%) in the HCV-positive cohort. For HCV-positive patients, problem-free transplant was shown at 12 months in 26.6% of the basiliximab group versus 11.6% in the placebo group (P = .020) and for all patients at 12 months in 39.7% of the basiliximab group versus 30.1% in the placebo group (P = .035). The incidence of infection and other adverse events was similar across the two treatment groups. There were 56 deaths (25 deaths, basiliximab group; 31 deaths, placebo group) over the 12-month study. The intravenous bolus injection was well tolerated. Immunoprophylaxis with 40 mg of basiliximab, in combination with cyclosporine and steroids, reduces the incidence of acute rejection episodes with no clinically relevant safety or tolerability concerns. The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant, incorporating recurrence as a component of treatment failure.