University of Alabama at Birmingham, Birmingham, USA.
N Engl J Med. 2011 May 19;364(20):1909-19. doi: 10.1056/NEJMoa1009546.
There are few comparisons of antibody induction therapy allowing early glucocorticoid withdrawal in renal-transplant recipients. The purpose of the present study was to compare induction therapy involving alemtuzumab with the most commonly used induction regimens in patient populations at either high immunologic risk or low immunologic risk.
In this prospective study, we randomly assigned patients to receive alemtuzumab or conventional induction therapy (basiliximab or rabbit antithymocyte globulin). Patients were stratified according to acute rejection risk, with a high risk defined by a repeat transplant, a peak or current value of panel-reactive antibodies of 20% or more, or black race. The 139 high-risk patients received alemtuzumab (one dose of 30 mg, in 70 patients) or rabbit antithymocyte globulin (a total of 6 mg per kilogram of body weight given over 4 days, in 69 patients). The 335 low-risk patients received alemtuzumab (one dose of 30 mg, in 164 patients) or basiliximab (a total of 40 mg over 4 days, in 171 patients). All patients received tacrolimus and mycophenolate mofetil and underwent a 5-day glucocorticoid taper in a regimen of early steroid withdrawal. The primary end point was biopsy-confirmed acute rejection at 6 months and 12 months. Patients were followed for 3 years for safety and efficacy end points.
The rate of biopsy-confirmed acute rejection was significantly lower in the alemtuzumab group than in the conventional-therapy group at both 6 months (3% vs. 15%, P<0.001) and 12 months (5% vs. 17%, P<0.001). At 3 years, the rate of biopsy-confirmed acute rejection in low-risk patients was lower with alemtuzumab than with basiliximab (10% vs. 22%, P=0.003), but among high-risk patients, no significant difference was seen between alemtuzumab and rabbit antithymocyte globulin (18% vs. 15%, P=0.63). Adverse-event rates were similar among all four treatment groups.
By the first year after transplantation, biopsy-confirmed acute rejection was less frequent with alemtuzumab than with conventional therapy. The apparent superiority of alemtuzumab with respect to early biopsy-confirmed acute rejection was restricted to patients at low risk for transplant rejection; among high-risk patients, alemtuzumab and rabbit antithymocyte globulin had similar efficacy. (Funded by Astellas Pharma Global Development; INTAC ClinicalTrials.gov number, NCT00113269.).
在肾移植受者中，能够早期停用糖皮质激素的抗体诱导治疗方案比较少见。本研究的目的是比较在高免疫风险或低免疫风险患者人群中应用阿仑单抗诱导治疗与最常用的诱导方案。
在这项前瞻性研究中，我们将患者随机分配接受阿仑单抗或常规诱导治疗（巴利昔单抗或兔抗胸腺细胞球蛋白）。根据急性排斥反应风险进行分层，高风险定义为：重复移植、群体反应性抗体的峰或当前值＞20%，或黑种人。139 例高风险患者接受阿仑单抗（30mg 剂量，70 例）或兔抗胸腺细胞球蛋白（4 天内共 6mg/kg，69 例）。335 例低风险患者接受阿仑单抗（30mg 剂量，164 例）或巴利昔单抗（4 天内共 40mg，171 例）。所有患者均接受他克莫司和霉酚酸酯治疗，并采用早期激素撤药方案进行 5 天的糖皮质激素减量。主要终点是 6 个月和 12 个月时经活检证实的急性排斥反应。对患者进行 3 年随访，以评估安全性和疗效终点。
与常规治疗组相比，阿仑单抗组在 6 个月（3% vs. 15%，P<0.001）和 12 个月（5% vs. 17%，P<0.001）时经活检证实的急性排斥反应发生率显著降低。在 3 年时，低风险患者中阿仑单抗的经活检证实的急性排斥反应率低于巴利昔单抗（10% vs. 22%，P=0.003），但在高风险患者中，阿仑单抗与兔抗胸腺细胞球蛋白之间无显著差异（18% vs. 15%，P=0.63）。所有 4 个治疗组的不良事件发生率相似。
与常规治疗相比，移植后第一年阿仑单抗诱导治疗后经活检证实的急性排斥反应发生率较低。阿仑单抗在早期经活检证实的急性排斥反应方面的优势仅限于排斥反应风险低的患者；在高风险患者中，阿仑单抗和兔抗胸腺细胞球蛋白的疗效相似。（由安斯泰来制药全球开发公司资助；INTAC 临床试验.gov 编号，NCT00113269。）
