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免疫检查点抑制剂相关结肠炎治疗与并发症的回顾性分析:组织学溃疡作为类固醇难治性病程的潜在预测指标

Retrospective Analysis of Treatment and Complications of Immune Checkpoint Inhibitor-Associated Colitis: Histological Ulcerations as Potential Predictor for a Steroid-Refractory Disease Course.

作者信息

Burla Julian, Bluemel Sena, Biedermann Luc, Barysch Marjam J, Dummer Reinhard, Levesque Mitchell P, Gubler Christoph, Morell Bernhard, Rogler Gerhard, Scharl Michael

机构信息

Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

出版信息

Inflamm Intest Dis. 2020 Aug;5(3):109-116. doi: 10.1159/000507579. Epub 2020 May 26.

Abstract

BACKGROUND/AIMS: Among the severe immune-related adverse events (irAEs) that occur with immune checkpoint inhibitor (ICI) therapy, colitis is the most frequent one. This study aimed at describing the experience from the largest gastroenterology unit in Switzerland with immune checkpoint inhibitor-associated colitis (ICIAC), its clinical presentation, management, and outcomes.

METHODS

We performed a retrospective review of patients who were referred for the evaluation of ICIAC between January 2011 and October 2018 to the Division of Gastroenterology and Hepatology, University Hospital Zurich.

RESULTS

Thirty-three patients with immune-related colitis grade 3 or 4 met the inclusion criteria and were analyzed in detail: All patients had diarrhea, 64% had abdominal pain, 42% had bloody stool, 27% had emesis, and 18% developed fever. In total, 33% were successfully treated with corticosteroids alone; 66% were steroid-refractory and treated with infliximab or vedolizumab. Two of these patients developed severe complications requiring surgery. All patients reached complete remission of ICIAC and its symptoms. At colonoscopy, ulcerations were seen in 37% of steroid-refractory versus 63% of steroid-responsive cases. Deep histological ulcerations invading the submucosa were only present in steroid-refractory cases.

CONCLUSION

ICIAC is a severe irAE which frequently requires high-dose steroids and a close follow-up due to deleterious complications. The detection of histologically diagnosed deep ulcerations may predict a steroid-refractory course and may warrant early application of infliximab. However, larger studies are required to confirm our findings.

摘要

背景/目的:在免疫检查点抑制剂(ICI)治疗引发的严重免疫相关不良事件(irAE)中,结肠炎最为常见。本研究旨在描述瑞士最大的胃肠病学科室在免疫检查点抑制剂相关性结肠炎(ICIAC)方面的经验、临床表现、管理及结局。

方法

我们对2011年1月至2018年10月转诊至苏黎世大学医院胃肠病学和肝病科评估ICIAC的患者进行了回顾性研究。

结果

33例3级或4级免疫相关性结肠炎患者符合纳入标准并进行了详细分析:所有患者均有腹泻,64%有腹痛,42%有便血,27%有呕吐,18%发热。总体而言,33%的患者仅用皮质类固醇成功治疗;66%对类固醇难治,接受英夫利昔单抗或维多珠单抗治疗。其中2例患者出现严重并发症需要手术。所有患者的ICIAC及其症状均完全缓解。结肠镜检查时,37%的类固醇难治性病例与63%的类固醇反应性病例可见溃疡。仅在类固醇难治性病例中存在侵犯黏膜下层的深部组织学溃疡。

结论

ICIAC是一种严重的irAE,由于有害并发症,常需要大剂量类固醇和密切随访。组织学诊断的深部溃疡的检测可能预示类固醇难治性病程,可能需要早期应用英夫利昔单抗。然而,需要更大规模的研究来证实我们的发现。

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Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis.维多珠单抗治疗免疫检查点抑制剂诱导的小肠结肠炎。
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