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慢性活动性抗体介导的排斥反应:确定白细胞介素-6阻断作用的契机。

Chronic Active Antibody-mediated Rejection: Opportunity to Determine the Role of Interleukin-6 Blockade.

作者信息

Berger Mel, Baliker Mary, Van Gelder Teun, Böhmig Georg A, Mannon Roslyn B, Kumar Deepali, Chadban Steve, Nickerson Peter, Lee Laurie A, Djamali Arjang

机构信息

Departments of Pediatrics and Pathology, Case Western Reserve University, Cleveland, OH.

Patient Advocate, Middle Town, WI.

出版信息

Transplantation. 2024 May 1;108(5):1109-1114. doi: 10.1097/TP.0000000000004822. Epub 2023 Nov 9.

Abstract

Chronic active antibody-mediated rejection (caAMR) is arguably the most important cause of late kidney allograft failure. However, there are no US Food and Drug Administration (FDA)-approved treatments for acute or chronic AMR and there is no consensus on effective treatment. Many trials in transplantation have failed because of slow and/or inadequate enrollment, and no new agent has been approved by the FDA for transplantation in over a decade. Several lines of evidence suggest that interleukin-6 is an important driver of AMR, and clazakizumab, a humanized monoclonal antibody that neutralizes interleukin-6, has shown promising results in phase 2 studies. The IMAGINE trial (Interleukin-6 Blockade Modifying Antibody-mediated Graft Injury and Estimated Glomerular Filtration Rate Decline) (NCT03744910) is the first to be considered by the FDA using a reasonably likely surrogate endpoint (slope of estimated glomerular filtration rate decline >1 y) for accelerated approval and is the only ongoing clinical trial for the treatment of chronic rejection. This trial offers us the opportunity to advance the care for our patients in need, and this article is a call to action for all transplant providers caring for patients with caAMR.

摘要

慢性活动性抗体介导的排斥反应(caAMR)可以说是晚期肾移植失败的最重要原因。然而,美国食品药品监督管理局(FDA)尚未批准用于急性或慢性AMR的治疗方法,并且在有效治疗方面也没有达成共识。许多移植试验因入组缓慢和/或入组不足而失败,并且十多年来没有新的药物获得FDA批准用于移植。多项证据表明,白细胞介素-6是AMR的重要驱动因素,而人源化单克隆抗体克拉扎珠单抗可中和白细胞介素-6,在2期研究中已显示出有前景的结果。IMAGINE试验(白细胞介素-6阻断改善抗体介导的移植物损伤和估计肾小球滤过率下降)(NCT03744910)是FDA首次考虑使用合理可能的替代终点(估计肾小球滤过率下降斜率>1年)进行加速批准的试验,也是唯一一项正在进行的治疗慢性排斥反应的临床试验。该试验为我们提供了改善有需要患者治疗的机会,本文呼吁所有照顾caAMR患者的移植医疗服务提供者采取行动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6013/11042519/a35a1482644b/tpa-108-1109-g001.jpg

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