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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.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\n            \u003Cp id=\u0022p-1\u0022\u003EDenosumab is a fully human monoclonal antibody that binds to and inhibits RANK Ligand (RANKL), a key mediator of osteoclast formation, function, and survival. This article discusses an ongoing, double-blind, placebo-controlled, phase 2 study was conducted to determine if denosumab treatment could reduce the progression of bone erosions in patients with RA who were on background methotrexate.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EDenosumab is a fully human monoclonal antibody that binds to and inhibits RANK Ligand (RANKL), a key mediator of osteoclast formation, function, and survival. There is no detectable binding to TNF\u03b1, TNF\u03b2, TRAIL, or CD40L. RANKL-driven osteoclast activity has been implicated in the bone erosions that are characteristic of rheumatoid arthritis (RA).\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EThis ongoing, double-blind, placebo-controlled, phase 2 study was conducted to determine if denosumab treatment could reduce the progression of bone erosions in patients with RA who were on background methotrexate (MTX). Based on previous pharmacokinetic studies of denosumab in postmenopausal women, a 6 month dosing schedule was selected for this initial trial [Bekker PJ et al. \u003Cem\u003EJ Bone Miner Res\u003C\/em\u003E 2004; Peterson M et al. \u003Cem\u003EJ Bone Miner Res\u003C\/em\u003E 2003].\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EA total of 227 patients (9 patients never received test article) were randomly assigned to receive subcutaneous injections of denosumab 60 mg (n=71) or 180 mg (n=72) or placebo (n=75) every 6 months. Of this group, 2 patients discontinued from the 60 mg group, 6 discontinued from the 180 mg group, and 6 discontinued from the placebo group. Radiographs of the hands and feet were taken at baseline, 6, and 12 months. Randomization was stratified for prior use of biologics and current steroid use. Change from baseline in MRI erosion scores at 6 months was the primary endpoint. Key secondary endpoints included changes in the modified Sharp erosion score (ES), modified Sharp joint space narrowing score (JSN), and modified total Sharp score (TSS) from baseline and at months 6 and 12. Radiographs of the hands\/wrist and feet were analyzed using the van der Heijde-modified Sharp method. Increasing scores reflected increased damage. Safety was monitored throughout the study.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe mean change in ES at 6 months was significantly (p=0.02) less for patients treated with 180 mg of denosumab vs placebo. Data for 209 patients are included in the 12 month analysis. At 12 months, the change was significantly (p\u22640.01) less for both doses of denosumab.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003ENo significant differences were noted for any treatment group for ACR response. Modeling of data for collagen C-telopeptide Type II (CTX-II, a biomarker of cartilage turnover) suggests that the dose\/frequency used in this study may not have been sufficient to preserve cartilage. The radiographic erosion scores were consistent with MRI erosion scores analyzed at the primary endpoint of the study.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAdverse events were similar across the 3 treatment groups. The most frequent, occurring at \u226510%, were flare, upper respiratory infection, sinusitis, nasopharyngitis, and influenza.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EDenosumab treatment (60 mg and 180 mg) every 6 months reduced progression of TSS and ES, but not JSN vs placebo. No change in ACR response was noted. The incidence of adverse events was similar among the placebo and denosumbab 60 mg and 180 mg treatment groups.\u003C\/p\u003E\n         \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\/11156\/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\/11156\/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\/11156\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\u003C\/div\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EProfessor D\u00e9sir\u00e9e van der Heijde, MD, Leiden University Medical Center and lead author of the study commented, \u201cThese data show the significant potential of denosumab, revealing that patients receiving denosumab experienced a reduced progression of erosions compared to control\u2026\u201d\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2007 MD Conference Express\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\/7\/4\/14.2.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?nzm9je\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?nzm9je\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}