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炎症性肠病治疗的未来:我们从何处去?

The future of inflammatory bowel disease therapy: where do we go from here?

机构信息

Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, CA 92093-0956, USA. wsandborn @ ucsd.edu

出版信息

Dig Dis. 2012;30 Suppl 3:140-4. doi: 10.1159/000342742. Epub 2013 Jan 3.

DOI:10.1159/000342742
PMID:23295705
Abstract

There are six important trends that will impact the future of inflammatory bowel disease therapy. (1) Increased use of the biomarkers C-reactive protein (CRP) and fecal calprotectin, and increased imaging with colonoscopy and MRI enterography. (2) Increased use of pharmacokinetics to customize drug dosing for individual patients. Multiple factors impact the pharmacokinetics of monoclonal antibodies including the presence of antidrug antibodies, concomitant immunosuppression and low serum albumin and high CRP concentrations. (3) Evolution of treatment end points from symptoms to deep remission (a combination of both clinical remission and mucosal healing) to the prevention of bowel damage (in Crohn's disease) and surgery in the short-to-intermediate term and prevention of disability in the longer term. (4) Evolving data demonstrate that azathioprine monotherapy is minimally effective as a disease modification agent in Crohn's disease. Use of azathioprine as a monotherapy will decline. (5) Combination therapy with azathioprine and infliximab is superior to monotherapy with either agent. Use of combination therapy will increase. (6) There is a rich pipeline of novel therapeutic agents. Treatment strategies that appear particularly appealing include selective anti-integrin therapy with vedolizumab (anti-α4β7), etrolizumab (anti-β7 antibody) and PF-00547,659 (anti-MAdCAM-1 antibody), anti-interleukin 12/23p40 therapy with ustekinumab and Janus kinase 1, 2 and 3 inhibition with toafacitinib.

摘要

有六个重要的趋势将影响炎症性肠病治疗的未来。(1)更多地使用生物标志物 C 反应蛋白(CRP)和粪便钙卫蛋白,并更多地进行结肠镜和 MRI 肠造影检查。(2)更多地使用药代动力学来为个体患者定制药物剂量。多种因素影响单克隆抗体的药代动力学,包括存在抗药物抗体、同时使用免疫抑制剂以及低血清白蛋白和高 CRP 浓度。(3)从症状到深度缓解(临床缓解和黏膜愈合的结合)再到预防肠道损伤(在克罗恩病中)和短期到中期的手术以及长期预防残疾的治疗终点演变。(4)不断发展的数据表明,硫唑嘌呤单药治疗作为克罗恩病的疾病修饰剂效果最小。硫唑嘌呤单药治疗的使用将减少。(5)硫唑嘌呤和英夫利昔单抗联合治疗优于单一药物治疗。联合治疗的使用将增加。(6)有丰富的新型治疗药物管线。特别有吸引力的治疗策略包括使用 vedolizumab(抗-α4β7)、etrolizumab(抗-β7 抗体)和 PF-00547,659(抗-MAdCAM-1 抗体)选择性抗整合素治疗,以及使用 ustekinumab 进行抗白细胞介素 12/23p40 治疗和使用 tofacitinib 抑制 Janus 激酶 1、2 和 3。

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