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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\u003EThe protein fragments that are generated from metalloproteinase (MMP)-mediated protein destruction are known as neoepitopes, which serve as biomarkers of inflammation in patients with rheumatoid arthritis (RA). The aim of Randomized, Double-Blind Study of Safety and Prevention of Structural Joint Damage During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Rheumatoid Arthritis study [LITHE; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00106535\u0026amp;atom=%2Fspmdc%2F12%2F9%2F15.atom\u0022\u003ENCT00106535\u003C\/a\u003E] was to identify biomarker profiles that are associated with early response to tocilizumab in patients with RA, using neoepitope markers.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInflammatory Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatoid Arthritis Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EProteolytic enzymes, such as matrix metalloproteinase (MMP), are unregulated in inflamed tissue. The protein fragments that are generated from MMP-mediated protein destruction are known as neoepitopes, which serve as biomarkers of inflammation in patients with rheumatoid arthritis (RA). The aim of this study, presented by Anne C. Bay-Jensen, MS, PhD, Nordic Bioscience, Harlev, Denmark, was to identify biomarker profiles that are associated with early response to tocilizumab in patients with RA, using neoepitope markers.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe Randomized, Double-Blind Study of Safety and Prevention of Structural Joint Damage During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Rheumatoid Arthritis study [LITHE; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00106535\u0026amp;atom=%2Fspmdc%2F12%2F9%2F15.atom\u0022\u003ENCT00106535\u003C\/a\u003E] examined the efficacy of tocilizumab in a Phase 3, 3-arm, randomized, parallel-group study of 1196 patients with moderate or severe active RA who had inadequate response to methotrexate. This analysis included a subset of patients from the tocilizumab 8 mg\/kg plus methotrexate arm (TCZ8; n=206) and from the placebo plus methotrexate arm (n=211). Nonresponders were escape patients from the TCZ8 arm, defined as \u0026lt;20% improvement in both swollen joint count (SJC) and tender joint count (TJC) at Week 16.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe effect of TCZ8 (n=168) versus placebo (n=112) on serum biomarkers was monitored from baseline to Week 52. Patients who were receiving rescue treatment were excluded. An early-response profile was determined by subdividing TCZ8-treated patients into responders (n=91) and nonresponders (n=29). Serum biomarkers were measured, including the inflammation markers\u0027 total C-reactive protein (CRP), the neoepitope MMP-degraded CRP (CRPM), and citrullinated and MMP-generated vimentin fragments (VICM); the cartilage degradation and synovium turnover markers MMP3 and the MMP-degraded type II and III collagen (C2M and C3M, respectively); and the bone turnover markers osteocalcin, cathepsin K-mediated type 1 collagen degradation (CTX-I), and MMP-degraded type I collagen (ICTP).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EIn response to TCZ8, CRP was significantly blocked whereas CRPM continued to decrease over time (p\u0026lt;0.0001 for both at Weeks 4 and 52). TCZ8 significantly inhibited C2M (p\u0026lt;0.001 at Week 4; p\u0026lt;0.01 at Week 52) and C3M (p\u0026lt;0.0001 at Weeks 4 and 52) levels compared with baseline. From baseline, the mean % change in CRPM (responders, about \u221224% vs nonresponders, about \u221260%; OR, 4.0; 95% CI, 1.7 to 9.4; p=0.0014), but not in CRP (responders, about \u221264% vs nonresponders, about \u221214%; OR, 1.6; p=0.18), at 4 weeks was predictive of TCZ8 response. The mean % change from baseline in C2M (responders, about \u221210% vs nonresponders, about +10%; OR, 5.8; 95% CI, 2.2 to 15; p=0.0003) and in C3M (responders, about \u221223% vs nonresponders, about \u221210%; OR, 9.6; 95% CI, 2.8 to 33; p=0.0004) was highly predictive of TCZ8 response.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ETCZ8 strongly inhibited markers of cartilage degradation (C2M) and inflammation-mediated tissue turnover (C3M, CRPM), which may explain, in part, the beneficial effect of TCZ on the joints. In contrast to traditional CRP and the other markers that were measured, the novel neoepitope biomarkers of cartilage and synovial turnover discriminated between early TCZ8 responders and nonresponders. These neoepitope markers may reflect the same predictive effect with other doses of TCZ or other biologic interventions.\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\/9\/15.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?nzng4p\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}