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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EA monoclonal antibody that blocks white blood cell adhesion to gut mucosal cells reduced the symptoms of moderate to severe ulcerative colitis in patients treated for 12 weeks in the randomized double-blind placebo-controlled TURANDOT trial. The antibody dose of 22.5 mg was most effective. No safety issues were evident.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eulcerative colitis\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Einflammatory bowel disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ehumanized monoclonal antibody\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eintegrin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ETURANDOT\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENCT01620255\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPF-00547659\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Egastroenterology clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EThe randomized placebo-controlled double-blind TURANDOT trial [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01620255\u0026amp;atom=%2Fspmdc%2F15%2F14%2F10.atom\u0022\u003ENCT01620255\u003C\/a\u003E] substantiated the efficacy and safety of a monoclonal antibody that blocks white blood cell adhesion to gut mucosa in the treatment of moderate to severe ulcerative colitis (UC).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAs explained by Walter Reinisch, MD, McMaster University Health Centre, Hamilton, Ontario, Canada, inflammatory bowel disease features translocation of white blood cells into the gut mucosa. An important part of this translocation involves the binding of the \u03b14\u03b27 integrin on some white blood cells to the mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) receptor on endothelial cells [Feagan BG et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2013; Sandborn WJ et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E. 2013]. Blocking this binding may be beneficial in inflammatory bowel disease. The fully humanized monoclonal antibody PF-00547659 (PF) targets immunoglobulin G2 MAdCAM-1. The antibody does not hamper the immune function of the central nervous system and does not cross-react with vascular cell adhesion protein 1.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the TURANDOT trial, 357 patients with moderate to severe UC were randomized to subcutaneously delivered placebo or 7.5-, 22.5-, 75-, or 225-mg doses of PF. Doses were given at 0, 4, and 8 weeks in the 12-week trial, with subsequent 24-month follow-up or enrollment in an open-label extension phase. The researchers reported here on the 12-week treatment.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EPatients were aged 18 to 65 years, with biopsy-confirmed UC, Mayo endoscopy subscore \u2265\u20052, active disease beyond the rectum, Mayo score \u2265\u20056, and failure on or intolerance to \u2265\u20051 conventional therapy. Exclusion criteria included enteric infection, use of parenteral steroids with a dose of prednisone equivalent \u0026gt;\u200520 mg, recent biologic therapy, and any history of anti-integrin therapy. The primary efficacy end point was the proportion of patients in clinical remission at week 12, defined as a total Mayo score \u2264\u20052 points with no individual subscore \u0026gt;\u20051 point. There were also several secondary efficacy end points, including the proportion of patients with a clinical response at week 12, defined as a decrease in total Mayo score by \u2265\u20053 points and \u2265\u200530% decrease in subscore for rectal bleeding of \u2265\u20051 point or absolute subscore of \u2264\u20051.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EBaseline demographic and clinical characteristics in the 5 arms were comparable. The primary efficacy end point was met, with improved remission in all PF arms compared with placebo at week 12 and with the differences for 7.5, 22.5, and 75 mg of PF being significant when compared with placebo (all \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.05; \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16778\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16778\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16778\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EPrimary Efficacy End Point Results: Clinical Remission at Week 12\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EIn secondary responses, improvements in clinical response at week 12 for all PF doses (7.5 mg, 38.0%; 22.5 mg, 54.2%; 75 mg, 45.1%; 225 mg, 50.0%) were significantly improved (all \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.05) compared with placebo (28.8%). All doses of PF resulted in rates of mucosal healing (endoscopy subscore \u2264\u20051 point; 7.5 mg, 15.5%; 22.5 mg, 27.8%; 75 mg, 25.4%; 225 mg, 14.3%) that exceeded the rate in the placebo arm (8.2%), with the improvements for 22.5 and 75 mg of PF being significant (both \u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.05). These trends in improvement were evident both in treatment-na\u00efve and treatment-experienced patients.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EFecal calprotectin declined in all treatment groups relative to placebo, with the decline being less rapid in the 7.5-mg PF arm. PF doses \u0026gt;\u20057.5 mg suppressed soluble MAdCAM-1 by \u0026gt;90%. Adverse events were comparable in type and prevalence in the 5 study arms.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EThe TURANDOT trial met its primary and secondary end points, with no safety issues. Increased remission of symptoms was evident in patients with moderate to severe UC who had failed \u2265\u20051 treatment before trial enrollment, with the 22.5-mg dose giving the best response.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/14\/10.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlhap\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzlhap\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}