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本文引用的文献

1
EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors.EULAR 针对癌症免疫治疗中使用检查点抑制剂引起的风湿免疫相关不良事件的诊断和管理的考虑要点。
Ann Rheum Dis. 2021 Jan;80(1):36-48. doi: 10.1136/annrheumdis-2020-217139. Epub 2020 Apr 23.
2
Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation.免疫检查点抑制剂诱导的炎症性关节炎在免疫治疗停止后仍然存在。
Ann Rheum Dis. 2020 Mar;79(3):332-338. doi: 10.1136/annrheumdis-2019-216109. Epub 2019 Sep 20.
3
Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis.滑膜组织多功能 T 细胞与银屑病关节炎中 DAPSA 的关联。
Ann Rheum Dis. 2019 Mar;78(3):350-354. doi: 10.1136/annrheumdis-2018-214138. Epub 2019 Jan 9.
4
Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.免疫检查点抑制剂相关致命性毒性作用:系统评价和荟萃分析。
JAMA Oncol. 2018 Dec 1;4(12):1721-1728. doi: 10.1001/jamaoncol.2018.3923.
5
JAK/STAT Blockade Alters Synovial Bioenergetics, Mitochondrial Function, and Proinflammatory Mediators in Rheumatoid Arthritis.JAK/STAT 阻断剂改变类风湿关节炎滑膜生物能量学、线粒体功能和促炎介质。
Arthritis Rheumatol. 2018 Dec;70(12):1959-1970. doi: 10.1002/art.40569. Epub 2018 Oct 27.
6
Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.免疫检查点抑制剂PD-1通路在类风湿性关节炎疾病进展的各个阶段滑膜中下调。
PLoS One. 2018 Feb 28;13(2):e0192704. doi: 10.1371/journal.pone.0192704. eCollection 2018.
7
Augmented Th17 Differentiation Leads to Cutaneous and Synovio-Entheseal Inflammation in a Novel Model of Psoriatic Arthritis.增强的 Th17 分化导致银屑病关节炎新型模型中的皮肤和滑膜-腱膜炎症。
Arthritis Rheumatol. 2018 Jun;70(6):855-867. doi: 10.1002/art.40447. Epub 2018 Apr 18.
8
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade.与免疫检查点阻断相关的免疫相关不良事件。
N Engl J Med. 2018 Jan 11;378(2):158-168. doi: 10.1056/NEJMra1703481.
9
Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series.托珠单抗成功治疗免疫检查点抑制剂相关关节炎:病例系列。
Ann Rheum Dis. 2017 Dec;76(12):2061-2064. doi: 10.1136/annrheumdis-2017-211560. Epub 2017 Aug 22.
10
Ex-Th17 (Nonclassical Th1) Cells Are Functionally Distinct from Classical Th1 and Th17 Cells and Are Not Constrained by Regulatory T Cells.前Th17(非经典Th1)细胞在功能上与经典Th1和Th17细胞不同,且不受调节性T细胞的限制。
J Immunol. 2017 Mar 15;198(6):2249-2259. doi: 10.4049/jimmunol.1600737. Epub 2017 Feb 6.

首例托法替布治疗免疫检查点抑制剂相关性关节炎。

First use of tofacitinib to treat an immune checkpoint inhibitor-induced arthritis.

机构信息

EULAR Centre for Arthritis and Rheumatic Disease, St. Vincent's University Hospital, Dublin, Ireland.

Molecular Rheumatology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

出版信息

BMJ Case Rep. 2021 Feb 4;14(2):e238851. doi: 10.1136/bcr-2020-238851.

DOI:10.1136/bcr-2020-238851
PMID:33541985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7868229/
Abstract

Immune checkpoint inhibitors have revolutionised cancer treatment; however, immune-related adverse events do occur, with up to 7% developing inflammatory arthritis. Common rheumatoid arthritis therapies such as methotrexate, prednisolone and biologics have been used to treat this arthritis in small, uncontrolled case series with varying success. In this case of personalised medicine, we report the first use of tofacitinib, a small molecular inhibitor of the Janus kinase-signal transducer and activator of transcription pathway, to treat checkpoint inhibitor-related inflammatory arthritis. This resulted in a rapid clinical response and complete, sustained remission of the arthritis with associated marked reduction in synovial molecular and cellular immune response.

摘要

免疫检查点抑制剂彻底改变了癌症治疗;然而,免疫相关不良反应确实会发生,多达 7%的患者会发生炎症性关节炎。在一些小型、非对照的病例系列研究中,曾使用甲氨蝶呤、泼尼松龙和生物制剂等常见的类风湿关节炎治疗药物来治疗此类关节炎,但疗效不一。在这种个体化医学的情况下,我们报告了使用托法替布(一种 Janus 激酶信号转导和转录激活因子通路的小分子抑制剂)治疗检查点抑制剂相关炎症性关节炎的首例病例。这导致了快速的临床反应和关节炎的完全、持续缓解,同时也显著降低了滑膜分子和细胞免疫反应。