Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France.
Clin J Am Soc Nephrol. 2011 Feb;6(2):430-9. doi: 10.2215/CJN.05840710. Epub 2010 Nov 4.
Prolonged use of calcineurin inhibitors (CNIs) in kidney transplant recipients is associated with renal and nonrenal toxicity and an increase in cardiovascular risk factors. Belatacept-based regimens may provide a treatment option for patients who switch from CNI-based maintenance immunosuppression.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a randomized, open-label Phase II trial in renal transplant patients with stable graft function and receiving a CNI-based regimen. Patients who were ≥6 months but ≤36 months after transplantation were randomized to either switch to belatacept or continue CNI treatment. All patients received background maintenance immunosuppression. The primary end point was the change in calculated GFR (cGFR) from baseline to month 12.
Patients were randomized either to switch to belatacept (n=84) or to remain on a CNI-based regimen (n=89). At month 12, the mean (SD) change from baseline in cGFR was higher in the belatacept group versus the CNI group. Six patients in the belatacept group had acute rejection episodes, all within the first 6 months; all resolved with no allograft loss. By month 12, one patient in the CNI group died with a functioning graft, whereas no patients in the belatacept group had graft loss. The overall safety profile was similar between groups.
The study identifies a potentially safe and feasible method for switching stable renal transplant patients from a cyclosporine- or tacrolimus-based regimen to a belatacept-based regimen, which may allow improved renal function in patients currently treated with CNIs.
在肾移植受者中，长期使用钙调磷酸酶抑制剂（CNI）与肾毒性和非肾毒性以及心血管危险因素增加有关。基于贝利尤单抗的治疗方案可能为那些从 CNI 维持性免疫抑制治疗转换的患者提供一种治疗选择。
设计、设置、参与者和测量方法：这是一项在具有稳定移植物功能且接受 CNI 基础维持免疫抑制治疗的肾移植患者中进行的随机、开放标签的 II 期试验。患者在移植后≥6 个月但≤36 个月时被随机分为贝利尤单抗组或继续 CNI 治疗组。所有患者均接受背景维持性免疫抑制治疗。主要终点是从基线到 12 个月时估算肾小球滤过率（eGFR）的变化。
患者被随机分为贝利尤单抗组（n=84）或继续 CNI 组（n=89）。在 12 个月时，贝利尤单抗组的 eGFR 较基线的平均（SD）变化高于 CNI 组。贝利尤单抗组中有 6 例患者发生急性排斥反应，均发生在最初的 6 个月内；所有患者均未发生移植物丢失而痊愈。在 12 个月时，CNI 组中有 1 例患者因有功能的移植物而死亡，而贝利尤单抗组中没有患者发生移植物丢失。两组的总体安全性特征相似。
该研究确定了一种潜在安全且可行的方法，可使稳定的肾移植患者从环孢素或他克莫司为基础的方案转换为贝利尤单抗为基础的方案，这可能使目前接受 CNI 治疗的患者肾功能得到改善。
