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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\n            \u003Cp id=\u0022p-1\u0022\u003EIn scleroderma, drug treatment of skin disease is difficult to assess due to the lack of easily measured endpoints. The modified Rodnan skin score (mRSS) is one method used to differentiate systemic sclerosis (SSc) disease subtypes, but it does not change much over short periods. This article discusses results from the Fresolimumab in Systemic Sclerosis [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01284322\u0026amp;atom=%2Fspmdc%2F12%2F19%2F21.2.atom\u0022\u003ENCT01284322\u003C\/a\u003E] study showing that transforming growth factor-\u03b2 a-response genes correlate with the mRSS and may provide a means to more quickly assess drug efficacy for skin fibrosis in early phase trials.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatological Autoimmune Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EIn scleroderma, drug treatment of skin disease is difficult to assess due to the lack of easily measured endpoints. The modified Rodnan skin score (mRSS) is one method used to differentiate systemic sclerosis (SSc) disease subtypes, but it does not change much over short periods. Robert Lafyatis, MD, Boston University School of Medicine, Boston, Massachusetts, USA, reported results from the Fresolimumab in Systemic Sclerosis [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01284322\u0026amp;atom=%2Fspmdc%2F12%2F19%2F21.2.atom\u0022\u003ENCT01284322\u003C\/a\u003E] study showing that transforming growth factor-\u03b2 a (TGF\u03b2)-response genes correlate with the mRSS and may provide a means to more quickly assess drug efficacy for skin fibrosis in early phase trials. For example, TGF\u03b2 signature genes, cartilage oligomeric protein (COMP), and thrombospondin (THS1) showed decreased expression in most SSc patients after treatment with fresolimumab (GC1008), a first-in-class pan-neutralizing anti-TGF\u03b2 human antibody.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIn the first part of a Phase 2, open-label study, 7 early SSc patients were administered 2 doses of fresolimumab (1 mg\/kg) at Week 0 and Week 4. Skin biopsies taken on the first day prior to treatment and at 3, 7, and 24 weeks after treatment were analyzed for gene expression by reverse transcription polymerase chain reaction, microarray, and nanostring. Seven weeks after treatment, there was a significant (p\u0026lt;0.05) decline in the primary study outcome of expression of THS1 and COMP. The relative mRNA expression of COMP and THS1 correlated with mRSS (R\u003Csup\u003E2\u003C\/sup\u003E=0.44 and 0.58, respectively, for baseline skin biopsies) and with each other (R\u003Csup\u003E2\u003C\/sup\u003E=0.73), suggesting these mRNAs are coregulated. Microarray data also indicate decreased expression of TGF\u03b2 signature genes, which was confirmed by nanostring data.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn general, fresolimumab was tolerated with 1 severe adverse event of severe bleeding from a patient with known gastric antral vascular ectasia. There were no malignant or premalignant lesions, or apparent aggravation of interstitial lung disease.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ESkin biomarkers are sensitive measures of skin disease, offering operator-blinded assessment of mRSS. Unlike mRSS, which changes slowly, the mRNA biomarker can be assessed after a short period; thus, drug efficacy for skin fibrosis in early phase clinical trials maybe assessed more quickly.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe results of this trial showed that using skin mRNA expression biomarkers for measuring therapeutic-induced changes in SSc implicates TGF\u03b2 in SSc pathogenesis.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\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\/12\/19\/21.2.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?nzn5hd\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}