Calcineurin inhibitors (CNIs) are standard of care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial evaluated the efficacy and safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients.

Stable adult kidney transplant recipients 6–60 months post-transplantation under CNI-based immunosuppression were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary end point was the percentage of patients surviving with a functioning graft at 24 months.

Overall, 446 renal transplant recipients were randomized to belatacept conversion (n=223) or CNI continuation (n=223). The 24-month rates of survival with graft function were 98% and 97% in the belatacept and CNI groups, respectively (adjusted difference, 0.8; 95.1% CI, –2.1 to 3.7). In the belatacept conversion versus CNI continuation groups, 8% versus 4% of patients experienced biopsy-proven acute rejection (BPAR), respectively, and 1% versus 7% developed de novo donor-specific antibodies (dnDSAs), respectively. The 24-month eGFR was higher with belatacept (55.5 versus 48.5 ml/min per 1.73 m² with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had post-transplant lymphoproliferative disorder.

Switching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate but a lower incidence of dnDSA.

Clinical Trial registry name and registration number: A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix® (Belatacept)-Based, NCT01820572

钙调神经磷酸酶抑制剂 (CNI) 是肾移植后的标准治疗，但它们与肾毒性和长期移植物存活率降低有关。Belatacept 是一种选择性 T 细胞共刺激阻滞剂，被批准用于预防肾移植排斥反应。该 3 期试验评估了在肾移植受者中从基于 CNI 的转换为基于 belatacept 的维持免疫抑制的有效性和安全性。

在基于 CNI 的免疫抑制下移植后 6-60 个月稳定的成人肾移植受者被随机（1：1）转换为 belatacept 或继续使用他们已建立的 CNI 进行治疗。主要终点是 24 个月时移植物存活的患者百分比。

总体而言，446 名肾移植受者被随机分配至贝拉西普转换组（n = 223）或 CNI 继续（n = 223）。belatacept 和 CNI 组的 24 个月移植物功能存活率分别为 98% 和 97%（校正差异，0.8；95.1% CI，–2.1 至 3.7）。在 belatacept 转换组与 CNI 继续组中，分别有 8% 和 4% 的患者经历了活检证实的急性排斥反应 (BPAR)，分别有 1% 和 7% 的患者产生了新的供体特异性抗体 (dnDSAs )。贝拉西普的 24 个月 eGFR 更高（55.5 对比 48.5 ml/min/1.73 m ²与 CNI）。两组的严重不良事件、感染和停药发生率相似，没有意外不良事件。belatacept 组中的一名患者患有移植后淋巴增生性疾病。

将稳定的肾移植受者从基于 CNI 的免疫抑制转换为基于 belatacept 的免疫抑制与类似的死亡率或移植物丢失率、肾功能改善以及 BPAR 率在数值上更高但 dnDSA 发生率较低相关。

临床试验注册名称和注册编号：转换为基于 Nulojix®（Belatacept）后维持性肾移植接受者的研究，NCT01820572