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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\u003EEvidence from both animal and human models regarding the proinflammatory cytokine interleukin-17 (IL-17) and the T-helper cell (Th17) that secretes it provides a compelling rationale for therapeutic targeting of IL-17 in rheumatoid arthritis (RA). Ixekizumab (LY2439821) is a humanized monoclonal antibody that is used in the treatment of autoimmune diseases [Peck A and Mellins ED. \u003Cem\u003EInfect Immun\u003C\/em\u003E 2010; Sarkar S and Fox DA. \u003Cem\u003ERheum Dis Clin North Am\u003C\/em\u003E 2010]. This article presents results from an international Phase 2, 2 Dose-Ranging Study of Multiple Subcutaneous Doses of LY2439821 in Patients With Active Rheumatoid Arthritis on Concomitant DMARD Therapy [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00966875\u0026amp;atom=%2Fspmdc%2F12%2F9%2F14.atom\u0022\u003ENCT00966875\u003C\/a\u003E].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatoid Arthritis Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EEvidence from both animal and human models regarding the proinflammatory cytokine interleukin-17 (IL-17) and the T-helper cell (Th17) that secretes it provides a compelling rationale for therapeutic targeting of IL-17 in rheumatoid arthritis (RA). Ixekizumab (LY2439821) is a humanized monoclonal antibody that is used in the treatment of autoimmune diseases [Peck A and Mellins ED. \u003Cem\u003EInfect Immun\u003C\/em\u003E 2010; Sarkar S and Fox DA. \u003Cem\u003ERheum Dis Clin North Am\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EMark C. Genovese, MD, Stanford University, Palo Alto, California, USA, presented results from an international (75 locations in the United States, Europe, South America, and Asia) Phase 2, 2 Dose-Ranging Study of Multiple Subcutaneous Doses of LY2439821 (an Anti-IL-17 Antibody) in Patients With Active Rheumatoid Arthritis on Concomitant DMARD Therapy [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00966875\u0026amp;atom=%2Fspmdc%2F12%2F9%2F14.atom\u0022\u003ENCT00966875\u003C\/a\u003E]. Two patient populations were evaluated: biologic disease modifying anti-rheumatic drug [bDMARD]-na\u00efve patients and tumor necrosis factor alpha-inadequate responder [TNF\u03b1-IR] patients. To satisfy the TNF\u03b1-IR requirement, patients must have been treated with at least one biologic TNF\u03b1-inhibitor and had either an insufficient response to at least 3 months of treatment or have been intolerant to treatment, regardless of the treatment duration. All subjects were required to have at least 6 swollen and 6 tender joints and an elevated C-reactive protein (CRP) level. Baseline demographics and clinical characteristics are shown in \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\/14212\/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\/14212\/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\/14212\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 \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EBaseline Demographics and Clinical Characteristics.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EIn this randomized, double-blind study, bDMARD-na\u00efve patients (n=260) received subcutaneous placebo or ixekizumab (3, 10, 30, 80, or 180 mg), and TNF\u03b1-IR patients (n=188) received placebo or ixekizumab (80 or 180 mg) at Weeks 0, 1, 2, 4, 6, 8, and 10 with concomitant DMARD therapy. The objectives of the study were to determine the dose-response relationship of ixekizumab in bDMARD-na\u00efve patients, based on the ACR20 response rate (primary) by logistic regression at Week 12. Secondary endpoints included ACR50, ACR70, and ACR20 responders at Week 12 in the TNF\u03b1-IR group, Disease Activity Score (DAS) 28 and EULAR28 responses, safety, and tolerability compared with placebo.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003E\u201cAll patients had active disease, significant disability, elevated acute-phase proteins, and fairly high (\u223c6.0) DAS28-CRP scores,\u201d Dr. Genovese noted.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EThere was a significant dose-response relationship in bDMARD-na\u00efve patients at Week 12 (p=0.031 using ACR20; p\u0026lt;0.001 using DAS28-CRP). At Week 12, significant ixekizumab-versus-placebo differences were seen for DAS28 and EULAR28 responses in bDMARD-na\u00efve patients and in TNF\u03b1-IR patients for all doses, with a rapid onset of efficacy within 1 week after the first dose and with increasing magnitude of reductions with increasing doses. A rapid onset of clinical efficacy (ACR20, DAS28, and CRP values dropped) occurred within 3 days. Clinical disease activity index (CDAI) responses indicated the effects of ixekizumab extend beyond the acute-phase proteins.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EThere were no deaths. The frequency of treatment-emergent adverse events (AEs) was similar across treatment arms (range: 45% to 62%). More patients experienced infections in the treatment arms (37% combined) compared with placebo (18%), with no observed dose relationship. Treatment-emergent serious AEs occurred in 2 patients in the placebo group (1.7%) and 16 ixekizumab-treatment patients (4.8%). Upper respiratory tract infection, urinary tract infection, systemic allergic\/hypersensitivity reaction, injection-site pain, and headache were the most frequent treatment-emergent AEs in both groups. No mycobacterial or systemic fungal infections were observed. Most patients had grade 1 neutrophil counts through Week 12. The safety profile was comparable with that of other biologic therapies.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003E\u201cIt appears that ixekizumab results in significant improvements in symptoms and signs, in both the biologic DMARD-na\u00efve patients as well as the anti-TNF inadequate-responder groups,\u201d Dr. Genovese said.\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\/14.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\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzng4p\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}