In a phase 2 multi-center open label randomized trial sponsored by the National Institutes of Health, simultaneous pancreas-kidney (SPK) recipients were randomized to a calcineurin inhibitor (CNI) based immunosuppressive regimen (tacrolimus) (n=21) or an investigational arm using low-dose CNI plus co-stimulation blockade (belatacept) with intended CNI withdrawal (n=22). Both arms included induction therapy with rabbit ATG, mycophenolate sodium or mycophenolate mofetil, and rapid withdrawal of steroids. Enrollment and CNI withdrawal were stopped after 43/60 planned subjects had been enrolled. At that time the rate of biopsy proven acute rejection (BPAR) of the pancreas was low in both groups until CNI was withdrawn, with four of the five pancreas rejections occurring during or after CNI withdrawal. The rate of BPAR of kidney allografts was low in both control (9.5%) and investigational (9.1%) arms. Pancreas graft survival at 52 weeks, defined by insulin independence, was 21 (100%) in the control group and 19 (86%) in the investigational arm. One subject in the investigational arm died with functioning pancreas and kidney grafts. Renal function at week 52 was similar in both arms. Costimulation blockade with belatacept did not provide sufficient immunosuppression to reliably prevent pancreas rejection in SPK transplants undergoing CNI withdrawal.

中文翻译：

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胰腺和肾联合移植后钙调神经磷酸酶抑制剂撤药的挑战：一项前瞻性随机临床试验的结果。

在美国国立卫生研究院主办的一项 2 期多中心开放标签随机试验中，同时胰肾 (SPK) 接受者被随机分配至基于钙调神经磷酸酶抑制剂 (CNI) 的免疫抑制方案（他克莫司）（n=21）或研究性方案手臂使用低剂量 CNI 加共刺激阻断 (belatacept) 并有意撤除 CNI (n=22)。两组均包括用兔 ATG、霉酚酸钠或吗替麦考酚酯进行诱导治疗，并快速停用类固醇。43/60 计划受试者入组后，停止入组和 CNI 退出。当时，活检证实胰腺急性排斥反应 (BPAR) 的发生率在 CNI 撤回之前均较低，其中 5 例胰腺排斥中有 4 例发生在 CNI 撤回期间或之后。对照组 (9.5%) 和研究组 (9.1%) 的同种异体肾移植物的 BPAR 率均较低。52 周时，根据胰岛素独立性定义，对照组的胰腺移植存活率为 21 周（100%），研究组为 19 周（86%）。研究组中的一名受试者死亡，但胰腺和肾移植功能正常。第 52 周时，两组的肾功能相似。使用belatacept进行共刺激阻断并不能提供足够的免疫抑制来可靠地预防正在进行CNI撤药的SPK移植物中的胰腺排斥。