贝伐珠单抗联合钙调磷酸酶抑制剂和慢性皮质类固醇免疫抑制避免：一项前瞻性、随机、多中心试验的两年结果。

Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial.

机构信息

University of Wisconsin, Madison, Wisconsin.

University of Cincinnati College of Medicine, Cincinnati, Ohio.

出版信息

Clin J Am Soc Nephrol. 2021 Sep;16(9):1387-1397. doi: 10.2215/CJN.13100820. Epub 2021 Jul 7.

DOI:10.2215/CJN.13100820

PMID:34233921

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8729588/

Abstract

BACKGROUND AND OBJECTIVES

Immunosuppressive therapy in kidney transplantation is associated with numerous toxicities. CD28-mediated T-cell costimulation blockade using belatacept may reduce long-term nephrotoxicity, compared with calcineurin inhibitor-based immunosuppression. The efficacy and safety of simultaneous calcineurin inhibitor avoidance and rapid steroid withdrawal were tested in a randomized, prospective, multicenter study.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study reports the 2-year results of a randomized clinical trial of 316 recipients of a new kidney transplant. All kidney transplants were performed using rapid steroid withdrawal immunosuppression. Recipients were randomized in a 1:1:1 ratio to receive belatacept with alemtuzumab induction, belatacept with rabbit anti-thymocyte globulin (rATG) induction, or tacrolimus with rATG induction. The composite end point consisted of death, kidney allograft loss, or an eGFR of <45 ml/min per 1.73 m at 2 years.

RESULTS

The composite end point was observed for 11 of 107 (10%) participants assigned to belatacept/alemtuzumab, 13 of 104 (13%) participants assigned to belatacept/rATG, and 21 of 105 (21%) participants assigned to tacrolimus/rATG (for belatacept/alemtuzumab versus tacrolimus/rATG, =0.99; for belatacept/rATG versus tacrolimus/rATG, =0.66). Patient and graft survival rates were similar between all groups. An eGFR of <45 ml/min per 1.73 m was observed for nine of 107 (8%) participants assigned to belatacept/alemtuzuab, eight of 104 (8%) participants assigned to belatacept/rATG, and 20 of 105 (19%) participants assigned to tacrolimus/rATG (<0.05 for each belatacept group versus tacrolimus/rATG). Biopsy sample-proven acute rejection was observed for 20 of 107 (19%) participants assigned to belatacept/alemtuzuab, 26 of 104 (25%) participants assigned to belatacept/rATG, and seven of 105 (7%) participants assigned to tacrolimus/rATG (for belatacept/alemtuzumab versus tacrolimus/rATG, =0.006; for belatacept/rATG versus tacrolimus/rATG, <0.001). Gastrointestinal and neurologic adverse events were less frequent with belatacept versus calcineurin-based immunosuppression.

CONCLUSIONS

Overall 2-year outcomes were similar when comparing maintenance immunosuppression using belatacept versus tacrolimus, and each protocol involved rapid steroid withdrawal. The incidence of an eGFR of <45 ml/min per 1.73 m was significantly lower with belatacept compared with tacrolimus, but the incidence of biopsy sample-proven acute rejection significantly higher.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER

Belatacept Early Steroid Withdrawal Trial, NCT01729494.

摘要

背景与目的

在肾移植中，免疫抑制治疗与多种毒性有关。与基于钙调磷酸酶抑制剂的免疫抑制相比，使用 belatacept 阻断 CD28 介导的 T 细胞共刺激可能会降低长期肾毒性。本随机、前瞻性、多中心研究旨在测试同时避免使用钙调磷酸酶抑制剂和快速撤停类固醇的疗效和安全性。

设计、地点、参与者和测量：本研究报告了一项新肾移植受者的随机临床试验的 2 年结果。所有的肾移植均采用快速撤停类固醇的免疫抑制方案。受者以 1:1:1 的比例随机分为 belatacept 联合 alemtuzumab 诱导、belatacept 联合兔抗胸腺细胞球蛋白（rATG）诱导或他克莫司联合 rATG 诱导。复合终点包括死亡、肾移植失败或 2 年内 eGFR<45ml/min/1.73m。

结果

belatacept/alemtuzumab 组有 11 例（10%）、belatacept/rATG 组有 13 例（13%）和 tacrolimus/rATG 组有 21 例（21%）发生复合终点（belatacept/alemtuzumab 与 tacrolimus/rATG 相比，=0.99；belatacept/rATG 与 tacrolimus/rATG 相比，=0.66）。各组患者和移植物存活率相似。belatacept/alemtuzumab 组有 9 例（8%）、belatacept/rATG 组有 8 例（8%）和 tacrolimus/rATG 组有 20 例（19%）发生 eGFR<45ml/min/1.73m（belatacept 各组与 tacrolimus/rATG 相比，<0.05）。belatacept/alemtuzumab 组有 20 例（19%）、belatacept/rATG 组有 26 例（25%）和 tacrolimus/rATG 组有 7 例（7%）发生经活检证实的急性排斥反应（belatacept/alemtuzumab 与 tacrolimus/rATG 相比，=0.006；belatacept/rATG 与 tacrolimus/rATG 相比，<0.001）。与基于钙调磷酸酶抑制剂的免疫抑制相比，belatacept 组胃肠道和神经系统不良事件的发生率较低。