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免疫抑制剂用于治疗免疫检查点抑制剂所致肝损伤的有效性:一项系统评价和荟萃分析。

Effectiveness of immunosuppressant use for the treatment of immune checkpoint inhibitor-induced liver injury: A systematic review and meta-analysis.

作者信息

Chen Kefan, He Junhao, Xu Jing, Chen Jie

机构信息

Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

出版信息

Front Oncol. 2023 Mar 24;13:1088741. doi: 10.3389/fonc.2023.1088741. eCollection 2023.

Abstract

BACKGROUND

Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a challenging clinical management issue. Although immunosuppressants are widely used to manage ILICI, no large-scale studies have proved definitive evidence for the most effective form of patient management.

AIM

Analysis of the effectiveness of immunosuppression for immune-related liver injury.

METHODS

We performed a systematic review and meta-analysis of the clinical outcomes of immunosuppressive treatment of ILICI patients. A literature search of PubMed, Ovid, and Cochrane Library was completed for dates from 2000 to January 1, 2022. The primary outcome was the response rate to immunosuppressive therapy for ILICI, with subgroup analysis based on the type of cancer, immune checkpoint inhibitor regimen, and severity of liver injury. The secondary outcome was the median time to recovery from ILICI with immunosuppressive therapy.

RESULTS

A total of 30 studies that included 1120 patients were collected. The pooled ILICI response rate was 79% (95% CI 0.73-0.84) for treatment with corticosteroids and 93% (95% CI 0.79-1.0) for treatment with mycophenolate mofetil. For ILICI treated with corticosteroids, the median recovery time was 47.59 (95% CI 39.79-55.40) days compared to 37.74 (95% CI 31.12-44.35) days for all forms of immunosuppression.

CONCLUSION

Findings support the effectiveness of corticosteroids and mycophenolate mofetil for the treatment of ILICI. The identified median time to recovery is a beneficial guide for patients and physicians, allowing for realistic expectations and appropriate treatment management. Future prospective randomized controlled trials are required to define a standardized management approach to immunosuppressive therapy of ILICI.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022313454.

摘要

背景

检查点抑制剂引起的免疫介导性肝损伤(ILICI)是一个具有挑战性的临床管理问题。尽管免疫抑制剂被广泛用于管理ILICI,但尚无大规模研究能证明哪种患者管理形式最为有效的确切证据。

目的

分析免疫抑制对免疫相关肝损伤的有效性。

方法

我们对ILICI患者免疫抑制治疗的临床结果进行了系统评价和荟萃分析。完成了对PubMed、Ovid和Cochrane图书馆从2000年至2022年1月1日的文献检索。主要结局是ILICI免疫抑制治疗的缓解率,并根据癌症类型、免疫检查点抑制剂方案和肝损伤严重程度进行亚组分析。次要结局是接受免疫抑制治疗后从ILICI恢复的中位时间。

结果

共收集了30项研究,纳入1120例患者。使用皮质类固醇治疗的ILICI汇总缓解率为79%(95%CI 0.73 - 0.84),使用霉酚酸酯治疗的为93%(95%CI 0.79 - 1.0)。对于接受皮质类固醇治疗的ILICI,中位恢复时间为47.59天(95%CI 39.79 - 55.40),而所有形式免疫抑制治疗的中位恢复时间为37.74天(95%CI 31.12 - 44.35)。

结论

研究结果支持皮质类固醇和霉酚酸酯治疗ILICI的有效性。确定的中位恢复时间对患者和医生是有益的指导,有助于形成现实的预期并进行适当的治疗管理。未来需要进行前瞻性随机对照试验来确定ILICI免疫抑制治疗的标准化管理方法。

系统评价注册

https://www.crd.york.ac.uk/PROSPERO/,标识符CRD42022313454。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c28/10080119/bb2e402a5022/fonc-13-1088741-g001.jpg

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