摘要
目的分析免疫检查点抑制剂(ICI)相关结肠炎患者的临床及预后特征。方法采用回顾性观察性研究方法。收集2016年1月至2024年5月北京友谊医院诊治的ICI相关结肠炎患者的临床资料。临床严重程度可采用美国国家癌症研究所常见不良反应术语评定标准(CTCAE)分级、Mayo评分、Truelove&Witts评分进行评估,内镜严重程度采用Mayo内镜评分(MES)、溃疡性结肠炎内镜严重程度指数(UCEIS)、MD安德森癌症中心内镜炎症分级(MD分级)进行评估。采用Spearman秩相关分析不同评分的相关性。结果共纳入15例患者,男性10例,女性5例;中位年龄64.0(55.5,71.0)岁。13例患者采用程序性细胞死亡蛋白1(PD⁃1)单克隆抗体治疗,2例患者采用程序性死亡配体1(PD⁃L1)单克隆抗体治疗。中位起病时间为接受ICI治疗后66.5(41.0,168.0)d。所有患者均出现腹泻,仅25%患者表现为腹痛,20%~33%患者出现发热、腹胀、恶心、呕吐,炎性指标多无特异性。14例接受CT检查的患者中,左半结肠受累10例,主要表现为结肠管壁增厚,其中全层受累6例;无异常2例。12例接受结肠镜检查患者中,除1例未见异常,11例存在直肠、乙状结肠受累,降结肠、升结肠、回肠末端受累比例依次降低,受累黏膜主要表现为血管纹理消失、黏膜充血水肿、糜烂至浅溃疡、管腔狭窄,5例病变呈类似于溃疡性结肠炎的连续性分布,6例病变呈节段性分布,其中1例内镜下表现为直肠孤立性深溃疡。相关性分析发现,MES、UCEIS、MD分级之间具有显著相关性(均P<0.001);Truelove&Witts评分与Mayo评分具有显著相关性(ρ=0.88,P<0.001);在内镜和临床评分比较中,Mayo评分与内镜评分(MES、UCEIS、MD分级)呈显著正相关(均P<0.05),其次True⁃love&Witts评分与内镜评分呈正相关(均P<0.05),CTCAE⁃腹泻评分仅与MD分级呈正相关(P=0.034),而CTCAE⁃结肠炎评分与内镜评分无显著相关性(均P>0.05)。15例患者平均随访13.5个月,其中10例行糖皮质激素(简称激素)治疗,5例行其他治疗。激素治疗患者的临床应答良好,部分轻中度患者激素快速减量随访无复发,但2例小肠受累者均出现肠穿孔。结论ICI相关结肠炎患者临床主要表现为腹泻,影像学提示结肠管壁增厚,内镜下左半结肠受累最多,Truelove&Witts评分与Mayo评分相关,激素治疗起效迅速,小肠受累者预后差。
Objective To analyze the clinical and prognostic characteristics of patients with immune checkpoint inhibitor(ICI)⁃related colitis.Methods A retrospective observational research method was conducted.Clinical data from patients diagnosed with ICI⁃related colitis at Beijing Friendship Hospital between January 2016 and May 2024 were collected.Clinical severity was assessed using the common terminology criteria for adverse event(CTCAE)grading,Mayo Score,Truelove&Witts Score,and endoscopic severity was assessed using Mayo endoscopic score(MES),ulcerative colitis endoscopic index of severity(UCEIS),and MD Anderson Cancer Center endoscopic inflammation grading(MD grading).Spearman rank correlation analysis was performed to evaluate the correlation between different scoring systems.Results A total of 15 patients were included,with 10 males and 5 females,and the median age was 64.0(55.5,71.0)years.Thirteen patients were treated with programmed cell death protein 1(PD⁃1)monoclonal antibodies,and 2 patients were treated with programmed cell death⁃ligand 1(PD⁃L1)monoclonal antibodies.The median onset time of the 15 patients was 66.5(41.0,168.0)days after ICI treatment.All patients had diarrhea,only 25%patients presented with abdominal pain,and 20%⁃33%patients had fever,abdominal distension,nausea,and vomiting.Most of the inflammatory indicators were non⁃specific.Among the 14 patients who underwent CT examinations,2 patients had no abnormal manifestations,10 patients had left colon involvement,mainly manifested as thickening of the colon wall,and 6 of these patients had full⁃thickness involvement.Among the 12 patients who underwent colonoscopy examination,except for one patient with no abnormalities,11 patients had rectal and sigmoid colon involvement,the proportions of the descending colon,ascending colon,and terminal ileum involvement decreased successively,and the involved mucosa was mainly manifested as disappearance of vascular texture,mucosal congestion and edema,erosion to shallow ulcers,and lumen stenosis.The lesions in 5 patients were distributed continuously similar to ulcerative colitis,and the lesions in 6 patients were distributed segmentally,1 of them had an isolated deep ulcer in the rectum under endoscopy.Correlation analysis revealed significant correlations between endoscopic scores(MES,UCEIS,and MD grading;allP<0.001).Truelove&Witts score strongly correlated with the Mayo score(ρ=0.88,P<0.001).Among clinical⁃endoscopic comparisons,the Mayo score exhibited the strong positive correlation with endoscopic scores(allP<0.05),followed by the Truelove&Witts score(allP<0.05),and CTCAE diarrhea grading only had positive correlation with MD grading(P=0.034).However,CTCAE colitis grading showed no significant correlation with endoscopic scores(allP>0.05).During a mean follow⁃up of 13.5 months,10 patients received corticosteroid therapy,and 5 received alternative treatments.Corticosteroid⁃treated patients showed favorable clinical responses,and rapid tapering feasible occurred in parts of mild⁃to⁃moderate patients without relapse.However,perforation occurred in 2 patients with small bowel involvement.Conclusions The main clinical manifestations of patients with ICI⁃related colitis are diarrhea.Imaging studies suggest thickening of the colonic wall.Endoscopic findings show the highest involvement in the left colon.Truelove&Witts score and Mayo score is strongly correlated.Corticosteroid therapy exhibits a rapid response,and the prognosis of patients with small intestine involvement is poor.
作者
陈炜
朱思莹
张希
吴咏冬
宗晔
Chen Wei;Zhu Siying;Zhang Xi;Wu Yongdong;Zong Ye(Department of Gastroenterology,Beijing Friendship Hospital,Capital Medical University,State Key Laboratory for Digestive Health,National Clinical Research Center for Digestive Diseases,Beijing 100050,China)
出处
《中华炎性肠病杂志(中英文)》
2025年第4期326-333,共8页
Chinese Journal of Inflammatory Bowel Diseases
基金
国家重点研发计划(2023YFC2507300)
北京友谊医院种子计划(YYZZ202215)。
关键词
免疫检查点抑制剂相关结肠炎
免疫检查点抑制剂
免疫相关不良反应
临床特征
预后特征
程序性细胞死亡蛋白1
程序性死亡配体1
Immune checkpoint inhibitor⁃related colitis
Immune checkpoint inhibitors
Immune⁃related adverse events
Clinical characteristics
Prognostic characteristics
Programmed cell death protein 1
Programmed cell death⁃ligand 1
