期刊
DIGESTIVE DISEASES
卷 32, 期 -, 页码 74-81出版社
KARGER
DOI: 10.1159/000367832
关键词
Crohn's disease; Ulcerative colitis; IL-12; Biologic therapies; Leukocyte trafficking
TNF antagonists have revolutionized the treatment of IBD. Nevertheless, between 30 and 45% of patients discontinue infliximab and other TNF antagonists over a 2- to 6-year period due to nonresponse, loss of response, or adverse events. Accordingly, the need for novel therapies grows each year. Recent studies have demonstrated the promise of new drugs with distinct modes of action for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). These include agents targeting leukocyte trafficking, therapies directed against IL-12/23 and Janus kinases (JAK), and antibodies against the classic inflammatory cytokine, IL-6. The anti-alpha(4)-integrin antibody, natalizumab, was the first effective antitrafficking agent for CD; however, its use has been greatly limited by the risk of progressive multifocal leukoencephalopathy. Therefore, second-generation antitrafficking agents have focused on restricting leukocyte blockade to the intestine through mechanisms interfering with alpha(4)beta(7)-integrin and its interaction with mucosal addressin cellular adhesion molecule 1. IL-23 is a cytokine central to the adaptive immune responses that characterize IBD. Ustekinumab, targeting the p40 subunit of IL-12 and IL-23, and the oral JAK inhibitor tofacitinib have proven to be effective in phase 2 trials in CD and UC, respectively. In addition, antibodies targeting the proinflammatory cytokine IL-6 are being studied in CD. Each of the approaches described have promise as well as limitations, so it is likely that the search for novel agents in IBD will continue. (C) 2014 S. Karger AG, Basel
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据