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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\u003EData from a Phase 2b study suggest that baricitinib, an oral JAK1\/JAK2 inhibitor, is an efficacious treatment for rheumatoid arthritis when used in combination with traditional disease-modifying antirheumatic drugs.\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\u003EData from a Phase 2b study, presented by Edward Keystone, MD, University of Toronto, Toronto, Ontario, Canada, suggest that baricitinib, an oral JAK1\/JAK2 inhibitor, is an efficacious treatment for rheumatoid arthritis (RA) when used in combination with traditional disease-modifying antirheumatic drugs (DMARDs).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EJAK tyrosine kinases differentially mediate signal transduction for a variety of cytokines that are involved in inflammatory conditions. JAK1 and JAK2 particularly affect IL-6, IL-12, IL-23, INF-\u03b3, and INF-\u03b1\/\u03b2, suggesting that inhibition of JAK1 or JAK2 would lead to immunomodulation or perhaps immunosuppression. This was a double-blind, placebo-controlled, randomized study to assess the effect of 4 doses of baricitinib, a potent, reversible inhibitor of JAK1 and JAK2, in patients with RA. Eligible subjects had \u22658 swollen and \u22658 tender joints, based on the 66\/68 joint count; were on a stable dose of methotrexate for at least 12 weeks or corticosteroids for 6 weeks; and had a maximum C-reactive protein (CRP) level \u0026gt;1.2x the upper limit of normal or an erythrocyte sedimentation rate \u0026gt;28 mm\/hr. Subjects were randomized to placebo (n=98) or baricitinib 1, 2, 4, or 8 mg daily (\u223c50 subjects each) in combination with methotrexate and treated for 12 weeks. The primary study endpoint was the ACR20 response at Week 12 for the combined 4- and 8-mg dose groups versus placebo. Major secondary endpoints included ACR20\/50\/70 and DAS28-CRP response at 12 weeks, safety and tolerability, pharmacokinetics, and patient-reported outcomes.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EA total of 301 subjects (mostly women, mean disease duration of \u223c5.5 years) were enrolled. Subjects in this study had active disease (tender joint count 22\/68; swollen joint count 16\/66; mean DAS28-CRP score of 5.5; mean Health Assessment Questionnaire [HAQ] score 1.2). At 12 weeks, 76% of subjects who received either 4 or 8 mg of baricitinib achieved the primary endpoint of ACR20 response compared with 41% of placebo-treated patients (p\u0026lt;0.001). Treatment with baricitinib also led to significant (p\u0026lt;0.05) improvements in ACR20\/50\/70 at all doses except 2 mg (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). DAS28-CRP \u0026lt;2.6 response was achieved by 37% of subjects in the 4-mg group and 22% of those in the 8-mg group (p\u0026lt;0.05 vs placebo). The onset of efficacy was rapid for ACR20\/50\/70 and DAS28-CRP, with statistically significant differences seen after 2 weeks of therapy. Simplified Disease Activity Index and Clinical Disease Activity Index remission was achieved more frequently by patients in the 4-mg group (18% and 22%, respectively; both p\u0026lt;0.05 vs placebo). Sixty percent of subjects in the 4-mg group and 67% of those in the 8-mg group achieved the minimum clinically important difference for the HAQ-Disability Index compared with placebo (41%) at Week 12.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/9\/13\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022ACR Responses by Dose at 12 Weeks.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-20036531\u0022 data-figure-caption=\u0022ACR Responses by Dose at 12 Weeks.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/9\/13\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/9\/13\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/9\/13\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14209\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\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EACR Responses by Dose at 12 Weeks.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from E. Keystone, MD. Keystone et al. \u003Cem\u003EAnn Rheum Dis\u003C\/em\u003E 2012;71[Suppl3].\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-6\u0022\u003EAdverse events (AEs) were mild, and no new safety signals were reported. Dose-dependent decreases in hemoglobin, small increases in serum creatinine, and increases in low- and high-density lipoprotein cholesterol were observed. Seven serious AEs were reported in 6 patients (2 in the placebo group, 3 in the 2-mg group, 1 in the 8-mg group). No deaths or opportunistic infections occurred in the active treatment groups. One patient in the placebo group was diagnosed with an opportunistic infection of toxocariasis. A similar rate of infection was observed in the placebo group (12%) and the combined treatment groups (14%), representing the most common treatment-emergent AE.\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\/13.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_figures.js?nznfwd\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_openurl.js?nznfwd\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}