Halleck Fabian, Böhmig Georg A, Couzi Lionel, Rostaing Lionel, Einecke Gunilla, Lefaucheur Carmen, Legendre Christophe, Montgomery Robert, Hughes Peter, Chandraker Anil, Wyburn Kate, Halloran Phil, Maldonado Angela Q, Sjöholm Kristoffer, Runström Anna, Lefèvre Paola, Tollemar Jan, Jordan Stanley
Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Clin Transplant. 2024 Jul;38(7):e15383. doi: 10.1111/ctr.15383.
Antibody-mediated rejection (ABMR) poses a barrier to long-term graft survival and is one of the most challenging events after kidney transplantation. Removing donor specific antibodies (DSA) through therapeutic plasma exchange (PLEX) is a cornerstone of antibody depletion but has inconsistent effects. Imlifidase is a treatment currently utilized for desensitization with near-complete inactivation of DSA both in the intra- and extravascular space.
This was a 6-month, randomized, open-label, multicenter, multinational trial conducted at 14 transplant centers. Thirty patients were randomized to either imlifidase or PLEX treatment. The primary endpoint was reduction in DSA level during the 5 days following the start of treatment.
Despite considerable heterogeneity in the trial population, DSA reduction as defined by the primary endpoint was 97% for imlifidase compared to 42% for PLEX. Additionally, imlifidase reduced DSA to noncomplement fixing levels, whereas PLEX failed to do so. After antibody rebound in the imlifidase arm (circa days 6-12), both arms had similar reductions in DSA. Five allograft losses occurred during the 6 months following the start of ABMR treatment-four within the imlifidase arm (18 patients treated) and one in the PLEX arm (10 patients treated). In terms of clinical efficacy, the Kaplan-Meier estimated graft survival was 78% for imlifidase and 89% for PLEX, with a slightly higher eGFR in the PLEX arm at the end of the trial. The observed adverse events in the trial were as expected, and there were no apparent differences between the arms.
Imlifidase was safe and well-tolerated in the ABMR population. Despite meeting the primary endpoint of maximum DSA reduction compared to PLEX, the trial was unsuccessful in demonstrating a clinical benefit of imlifidase in this heterogenous ABMR population.
EudraCT number: 2018-000022-66, 2020-004777-49; ClinicalTrials.gov identifier: NCT03897205, NCT04711850.
抗体介导的排斥反应（ABMR）是长期移植物存活的障碍，也是肾移植后最具挑战性的事件之一。通过治疗性血浆置换（PLEX）去除供体特异性抗体（DSA）是抗体清除的基石，但效果并不一致。伊姆利菲酶是一种目前用于脱敏的治疗方法，可使血管内和血管外空间的DSA几乎完全失活。
这是一项在14个移植中心进行的为期6个月的随机、开放标签、多中心、跨国试验。30名患者被随机分为伊姆利菲酶治疗组或PLEX治疗组。主要终点是治疗开始后5天内DSA水平的降低。
尽管试验人群存在相当大的异质性，但伊姆利菲酶治疗组的主要终点定义的DSA降低率为97%，而PLEX治疗组为42%。此外，伊姆利菲酶将DSA降低到非补体固定水平，而PLEX未能做到。在伊姆利菲酶治疗组抗体反弹后（大约第6 - 12天），两组的DSA降低情况相似。在ABMR治疗开始后的6个月内发生了5例移植肾丢失——伊姆利菲酶治疗组（治疗18例患者）中有4例，PLEX治疗组（治疗10例患者）中有1例。在临床疗效方面，伊姆利菲酶治疗组的Kaplan - Meier估计移植肾存活率为78%，PLEX治疗组为89%，试验结束时PLEX治疗组的估算肾小球滤过率（eGFR）略高。试验中观察到的不良事件与预期一致，两组之间没有明显差异。
伊姆利菲酶在ABMR人群中安全且耐受性良好。尽管与PLEX相比达到了最大程度降低DSA的主要终点，但该试验未能证明伊姆利菲酶在这种异质性ABMR人群中的临床益处。
欧洲临床试验数据库（EudraCT）编号：2018 - 000022 - 66，2020 - 004777 - 49；美国国立医学图书馆临床试验注册库（ClinicalTrials.gov）标识符：NCT03897205，NCT04711850。
