DataSheet_1_Effectiveness of immunosuppressant use for the treatment of immune checkpoint inhibitor-induced liver injury: A systematic review and meta-analysis.docx

BackgroundImmune-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.
AimAnalysis of the effectiveness of immunosuppression for immune-related liver injury.
MethodsWe 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.
ResultsA 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.
ConclusionFindings 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 registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022313454.

背景 免疫检查点抑制剂诱发的免疫性肝损伤（Immune-mediated liver injury caused by checkpoint inhibitors，ILICI）是临床管理中极具挑战性的难题。尽管免疫抑制剂被广泛用于ILICI的临床管理，但目前尚无大规模研究为其最优患者管理方案提供确凿依据。
目的 分析免疫抑制治疗针对免疫检查点抑制剂诱发的免疫性肝损伤的临床有效性。
方法 本研究针对ILICI患者接受免疫抑制治疗后的临床结局开展系统评价与荟萃分析。检索了2000年至2022年1月1日期间PubMed、Ovid及Cochrane图书馆收录的相关文献。本研究的主要结局指标为免疫抑制治疗针对ILICI的应答率，并基于癌症类型、免疫检查点抑制剂治疗方案及肝损伤严重程度进行亚组分析；次要结局指标为接受免疫抑制治疗的ILICI患者的中位恢复时间。
结果 共纳入30项研究，涉及1120例患者。糖皮质激素治疗组的ILICI合并应答率为79%（95%置信区间0.73~0.84），吗替麦考酚酯治疗组的合并应答率为93%（95%置信区间0.79~1.0）。在接受糖皮质激素治疗的患者中，中位恢复时间为47.59天（95%置信区间39.79~55.40），而所有免疫抑制治疗方案的中位恢复时间为37.74天（95%置信区间31.12~44.35）。
结论 本研究结果证实，糖皮质激素与吗替麦考酚酯均可有效治疗ILICI。本次研究得出的中位恢复时间可为患者及临床医师提供有益参考，帮助建立合理的治疗预期并制定恰当的治疗管理方案。未来需开展前瞻性随机对照试验，以明确ILICI免疫抑制治疗的标准化管理路径。
系统评价注册信息：https://www.crd.york.ac.uk/PROSPERO/，注册编号CRD42022313454。