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      Patient considerations in the management of ulcerative colitis - role of vedolizumab.

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          Abstract

          Ulcerative colitis (UC) is a subtype of inflammatory bowel disease which causes inflammation of the large intestine and affects approximately 7.6-24.6 per 100,000 persons. The therapeutic goal for UC patients is inducing remission, maintaining remission, and ideally, obtaining mucosal healing. Vedolizumab, approved by the US Food and Drug Administration in May 2014 for the treatment of moderate-to-severe UC and Crohn's disease, is a newly developed anti-integrin therapy. This review focuses on the preclinical development of vedolizumab and data from early trials, and details the results of the landmark trails that led to its approval in the USA with a specific focus on the management of UC. Additionally, data on safety and the current UC management protocols are also discussed.

          Most cited references20

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          Ulcerative colitis.

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            The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases.

            Vedolizumab is a humanized monoclonal antibody that targets the alpha(4)beta(7) integrin exclusively, and modulates inflammation in the gastrointestinal tract without inducing the systemic immunosuppression that characterizes anti-alpha(4) chain monoclonal antibodies, such as natalizumab. This unique pharmacologic profile is largely attributable to four determinants. The first determinant is the restriction of the expression of the alpha(4)beta(7) integrin to subsets of leukocytes. Vedolizumab does not bind to the majority of memory CD4(+) T lymphocytes (60%), neutrophils, and most monocytes. The highest level of vedolizumab binding is to a subset (approximately 25%) of human peripheral blood memory CD4(+) T lymphocytes that include gut-homing interleukin 17 T-helper lymphocytes. Vedolizumab also binds to eosinophils at high levels, and to naive T-helper lymphocytes, naive and memory cytotoxic T lymphocytes, B lymphocytes, natural killer cells, and basophils at lower levels; vedolizumab binds to memory CD4(+) T and B lymphocytes with subnanomolar potency (EC(50) = 0.3-0.4 nM). The second determinant is binding specificity; vedolizumab binds exclusively to the alpha(4)beta(7) integrin, and not to the alpha(4)beta(1) and alpha(E)beta(7) integrins. The third determinant is selective antagonism; vedolizumab selectively inhibits adhesion of alpha(4)beta(7)-expressing cells to mucosal addressin cell adhesion molecule 1 (median inhibition concentration [IC(50)] = 0.02-0.06 microg/ml) and fibronectin (IC(50) = 0.02 microg/ml), but not vascular cell adhesion molecule 1. The fourth determinant is the gastrointestinal-specific tropism of the alpha(4)beta(7) integrin function. These pharmacologic properties of vedolizumab, in conjunction with the gastrointestinal tropism of alpha(4)beta(7) integrin function, may ultimately confer an improved risk-to-benefit profile for patients with inflammatory bowel diseases.
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              Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus.

              The medical management of ulcerative colitis (UC) has improved through the development of new therapies and novel approaches that optimize existing drugs. Previous Canadian consensus guidelines addressed the management of severe UC in the hospitalized patient. We now present consensus guidelines for the treatment of ambulatory patients with mild to severe active UC.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and clinical risk management
                Informa UK Limited
                1176-6336
                1176-6336
                2015
                : 11
                Affiliations
                [1 ] Division of Gastroenterology and Hepatology, Lenox Hill Hospital-NSLIJ, New York, NY, USA.
                Article
                tcrm-11-1235
                10.2147/TCRM.S65650
                4548764
                26316768
                98a4c5e5-5244-4893-adc5-51d1326dedfd
                History

                immunomodulator drugs,inflammation,infliximab,mucosal healing,remission,ulcerative colitis

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