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抗体制剂介导排斥反应的传统治疗方法的补充?在肺移植中使用依库珠单抗:综述及早期中心经验。

A Complement to Traditional Treatments for Antibody-Mediated Rejection? Use of Eculizumab in Lung Transplantation: A Review and Early Center Experience.

机构信息

Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA.

Division of Pulmonary and Critical Care, Department of Medicine, Northwestern Memorial Hospital, Chicago, IL, USA.

出版信息

Ann Pharmacother. 2024 Sep;58(9):947-955. doi: 10.1177/10600280231213112. Epub 2023 Nov 23.

Abstract

OBJECTIVE

To review the efficacy and safety of eculizumab for prevention and treatment of antibody-mediated rejection (AMR) in lung transplant recipients (LTRs).

DATA SOURCES

A literature search of PubMed and the Cochrane Controlled Trials Register (2007 to mid-October 2023) was performed using the following search terms: , and .

STUDY SELECTION AND DATA EXTRACTION

All relevant English-language studies were reviewed and considered.

DATA SYNTHESIS

Eculizumab, a monoclonal antibody that binds complement protein C5 to inhibit its cleavage and subsequent generation of the membrane attack complex, is currently approved to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia and neuromyelitis optica spectrum disorder. Given the role of antibodies directed against donor antigens that are produced by allospecific B-cells and plasma cells in AMR, eculizumab is being investigated for use within this indication. Three case reports have described the successful use of eculizumab for the prevention and treatment of AMR in LTRs. Given this lack of robust data, evidence for the use of eculizumab in other solid organ transplant recipients is of increased value. Early experiences from a single center's use of eculizumab in LTRs are also described.

RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE

Lung transplant is a recognized treatment for end-stage lung disease, though complications posttransplant can be associated with significant morbidity and mortality. While prevention and management of AMR remains a substantial challenge without comprehensive guidance from societal guidelines, recently published literature may be helpful to guide clinical practice using alternative treatment options. However, this remains an area of great clinical importance, given the impact of AMR on long-term allograft function.

CONCLUSIONS

Optimizing use of current therapies, as well as identifying and advancing novel therapeutic modalities such as eculizumab, are vital for the improvement of AMR prevention and treatment in LTRs to extend long-term allograft function and survival.

摘要

目的

综述依库珠单抗在预防和治疗肺移植受者(LTR)抗体介导排斥反应(AMR)中的疗效和安全性。

资料来源

通过以下检索词在 PubMed 和 Cochrane 对照试验注册库(2007 年至 2023 年 10 月中旬)进行文献检索:、和。

研究选择和数据提取

回顾并考虑了所有相关的英文研究。

数据综合

依库珠单抗是一种单克隆抗体,可与补体蛋白 C5 结合以抑制其裂解和随后膜攻击复合物的生成,目前已被批准用于治疗阵发性夜间血红蛋白尿、非典型溶血尿毒综合征、全身性重症肌无力和视神经脊髓炎谱系障碍。鉴于针对供体抗原的抗体在 AMR 中的作用,这些抗体是由同种异体 B 细胞和浆细胞产生的,因此正在研究依库珠单抗在该适应症中的应用。已有三项病例报告描述了依库珠单抗在 LTR 中预防和治疗 AMR 的成功应用。鉴于缺乏强有力的数据,在其他实体器官移植受者中使用依库珠单抗的证据更具价值。还描述了单一中心在 LTR 中使用依库珠单抗的早期经验。

与患者护理和临床实践的相关性

肺移植是治疗终末期肺病的一种公认方法,但移植后出现的并发症可能与严重的发病率和死亡率相关。虽然没有来自社会指南的全面指导,预防和管理 AMR 仍然是一个重大挑战,但最近发表的文献可能有助于指导使用替代治疗方案的临床实践。然而,鉴于 AMR 对长期移植物功能的影响,这仍然是一个非常重要的临床领域。

结论

优化现有治疗方法的使用,以及确定和推进依库珠单抗等新型治疗方式,对于改善 LTR 中 AMR 的预防和治疗,以延长长期移植物功能和生存至关重要。

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