Clinical, Endoscopic, and Histologic Characteristics of Ipilimumab-Associated Colitis
Clinical, Endoscopic, and Histologic Characteristics of Ipilimumab-Associated Colitis
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DOI：
10.1016/j.cgh.2015.12.028
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发表时间：
2016-06-01
影响因子：
12.6
通讯作者：
de Boer, Nanne Klaas
中科院分区：
文献类型：
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作者：
Verschuren, Eduard Cornelis;van den Eertwegh, Alfonsus Johannes;de Boer, Nanne Klaas
背景与目的：ipilimumab是一种抗细胞毒性T淋巴细胞相关抗原-4的单抗，用于治疗转移性黑色素瘤，可引起免疫相关的不良反应，如小肠结肠炎。方法：我们对2007年4月至2012年9月间连续27例因抗去势前列腺癌或转移性黑色素瘤而接受爱普利单抗注射治疗后发展为结肠炎的患者进行了回顾性分析。临床、内窥镜和组织学信息收集自荷兰阿姆斯特丹的弗吉尼亚大学医学中心数据库。结果：所有患者均有腹泻(每天3~20次)，26%并发直肠失血，30%有腹痛。这些症状通常在2次注射ipilimumab(范围1-4)后开始出现，除1名患者(没有接受结肠炎治疗)外，所有患者都服用了皮质类固醇。12名患者患有激素难治性结肠炎，他们接受英夫利昔单抗(5 mg/kg)治疗。所有患者的腹泻症状均缓解。84%的患者在内窥镜下发现了结肠红斑，所有患者都没有血管图案。在组织学分析中，结肠活检标本的范围从正常结构到严重的活动性炎症。72%的样本检出上皮中性粒细胞，92%的标本检出隐匿炎，60%的标本检出隐窝脓肿。在40%的结肠活检标本中发现隐窝异常，这表明是慢性疾病。结论：在一项回顾分析中，我们将ipilimumab相关性结肠炎腹泻与各种内窥镜和组织学特征联系起来。对于激素耐药的患者，先用皮质类固醇激素治疗，然后再用英夫利昔单抗治疗，所有病例均获得成功。
BACKGROUND & AIMS: Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte-associated antigen-4, is a treatment for metastatic melanoma that can induce immune-related adverse effects, such as enterocolitis. We aimed to characterize the clinical, endoscopic, and histologic features of ipilimumab-induced colitis and evaluate the efficacy of therapy for this reaction.METHODS: We performed a retrospective analysis of 27 consecutive patients who developed colitis after treatment with ipilimumab infusion therapy for castration-resistant prostate cancer or metastatic melanoma, from April 2007 through September 2012. Clinical, endoscopic, and histologic information was collected from the database of the VU University Medical Center, Amsterdam, The Netherlands. Selected cases were ascertained by cross-checking with endoscopy reports.RESULTS: All patients had diarrhea (range, 3-20 stools per day); 26% had concurrent rectal blood loss and 30% had abdominal pain. These symptoms usually started after 2 infusions of ipilimumab (range, 1-4) and all patients except for 1 (who received no treatment for colitis) were given corticosteroids. Twelve patients had steroid-refractory colitis, for which they received infliximab (5 mg/kg). Diarrhea resolved in all the patients. Colon erythema was detected by endoscopy in 84% of patients, with an absent vascular pattern in all patients. In histologic analyses, colon biopsy specimens ranged from having normal architecture to severe active inflammation. Intraepithelial neutrophilic leucocytes were detected in 72% of samples, cryptitis in 92%, and crypt abscesses in 60%. Crypt irregularities were found in 40% of colon biopsy specimens, indicating chronic disease.CONCLUSIONS: In a retrospective analysis, we associated ipilimumab-associated colitis diarrhea with a variety of endoscopic and histologic features. Treatment with corticosteroids, followed by infliximab in steroid-refractory patients, was successful for all cases.