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与生物制剂相关的结肠炎。

Colitis associated with biological agents.

机构信息

Division of Gastroenterology, Department of Medicine, University of British Columbia Hospital, Vancouver, BC V6T 1W5, Canada.

出版信息

World J Gastroenterol. 2012 Apr 28;18(16):1871-4. doi: 10.3748/wjg.v18.i16.1871.

Abstract

In the past, there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity. Now, a variety of new biological monoclonal antibody agents, usually administered by infusion, have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents, adverse effects have been documented, including apparently new forms of immune-mediated inflammatory bowel disease. In some, only limited symptoms have been recorded, but in others, severe colitis with serious complications, such as bowel perforation has been recorded. In others, adverse effects may have a direct vascular or ischemic basis, while other intestinal effects may be related to a superimposed infection. Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases, or be responsible for disease exacerbation. Dramatic and well documented side effects have been observed with ipilimumab, a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4, a key negative feedback regulator of the T-cell anti-tumor response. This agent has frequently been used in the treatment of different malignancies, notably, malignant melanoma. Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated. One of these is a form of enterocolitis that may be severe, and occasionally, fatal. Other agents include rituximab (an anti-CD20 monoclonal antibody), bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents, including infliximab, adalimumab and etanercept.

摘要

过去,人们非常关注许多可能产生结肠毒性的药物和化学物质。现在,在过去十年左右的时间里,临床上出现了各种新的生物单克隆抗体药物,通常通过输注给药,用于治疗不同的慢性炎症或恶性疾病。对于其中一些药物,已经记录到了不良反应,包括显然是新形式的免疫介导的炎症性肠病。在某些情况下,仅记录到有限的症状,但在其他情况下,已经记录到严重的结肠炎伴有严重并发症,如肠穿孔。在其他情况下,不良反应可能具有直接的血管或缺血基础,而其他肠道效应可能与叠加感染有关。一些新发生的溃疡性结肠炎或克罗恩病病例也可能归因于用于治疗这些疾病的相同药物,或者是疾病恶化的原因。在使用 ipilimumab(一种用于减少和克服细胞毒性 T 淋巴细胞抗原 4 的人源化单克隆抗体,细胞毒性 T 淋巴细胞抗原 4 是 T 细胞抗肿瘤反应的关键负反馈调节剂)时,已经观察到了明显的、有充分记录的副作用。该药物已广泛用于治疗多种恶性肿瘤,尤其是恶性黑色素瘤。该药物的副作用发生率高达 40%,这些副作用被认为主要是免疫介导的。其中一种是严重的,偶尔甚至是致命的肠炎。其他药物包括利妥昔单抗(一种抗 CD20 单克隆抗体)、贝伐单抗(一种针对血管内皮生长因子的单克隆抗体)和抗肿瘤坏死因子药物,包括英夫利昔单抗、阿达木单抗和依那西普。

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