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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\u003EAn investigational anti-interferon-a monoclonal antibody, sifalimumab, reduced global disease activity in patients with systemic lupus erythematosus (SLE). This article presents results from a phase 2b study of sifalimumab in patients with moderate to severe SLE.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELupus\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELupus\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EAn investigational anti-interferon (IFN)-\u03b1 monoclonal antibody, sifalimumab, reduced global disease activity in patients with systemic lupus erythematosus (SLE). Munther Khamashta, MD, St Thomas\u0027 Hospital, London, United Kingdom, presented results from a phase 2b study of sifalimumab in patients with moderate to severe SLE.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EType I IFNs play a key role in the pathogenesis of SLE [Crow MK. \u003Cem\u003EJ Immunol\u003C\/em\u003E. 2014; Elkon KB, Wiedman A. \u003Cem\u003ECurr Opin Rheumatol\u003C\/em\u003E. 2012; Elkon KB, Stone V V. \u003Cem\u003EJ Interferon Cytokine Res.\u003C\/em\u003E 2011; R\u00f6nnblom L et al. \u003Cem\u003ESemin Immunol\u003C\/em\u003E. 2011; Dall\u0027era MC et al. \u003Cem\u003EAnn Rhuem Dis.\u003C\/em\u003E 2005]. Type I IFNs activate multiple pathways central to SLE pathogenesis [Kirou KA et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E. 2005], including activation of monocytes, dendritic cells, neutrophils, T cells, and B cells. IFN-\u03b1 is the predominant subtype of type I IFNs [Hillyer P et al. \u003Cem\u003EImmunol Cell Biol\u003C\/em\u003E. 2012]. Sifalimumab is a fully human monoclonal antibody binding and neutralizing the majority of IFN-\u03b1 subtypes [Merrill JT et al. \u003Cem\u003EAnn Rheum Dis.\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EThe study included 431 adults with moderate to severe SLE and with a SLE Disease Activity Index 2000 \u2265 6 and a Physician\u0027s Global Assessment \u2265 1.0 at screening. Patients were receiving standard-of-care treatment at the time that they were randomized to placebo or 1 of 3 monthly doses of sifalimumab administered intravenously: 200, 600, or 1200 mg. The primary end point was the percentage of patients that responded as measured by the Systemic Lupus Erythematosus Responder Index (SRI) at week 52. Approximately 85% of the patients in each randomized group completed the study.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe percentage of patients that achieved an SRI-4 response at week 52 was higher for sifalimumab at all doses vs placebo (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). The effect size for response vs placebo was 13.0% with 200 mg (\u003Cem\u003EP\u003C\/em\u003E = .057), 11.1% with 600 mg (\u003Cem\u003EP\u003C\/em\u003E = .094), and 14.4% with 1200 mg (\u003Cem\u003EP\u003C\/em\u003E = .031).\u003C\/p\u003E\n         \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\/14\/51\/7\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Primary End Point: SRI Response\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-855268862\u0022 data-figure-caption=\u0022Primary End Point: SRI Response\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\/14\/51\/7\/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\/14\/51\/7\/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\/14\/51\/7\/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\/15623\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-6\u0022 class=\u0022first-child\u0022\u003EPrimary End Point: SRI Response\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EOR, odds ratio; Q4W, every 4 weeks; SRI, Systemic Lupus Erythematosus Responder Index.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from M Khamashta, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EThe percentage of responders using the more stringent SRI-6 was also higher at all doses of sifalimumab (placebo, 37.4%; 200 mg, 50.0%; 600 mg, 43.5%; 1200 mg, 53.3%). The effect size for response vs placebo was 12.6% with 200 mg (\u003Cem\u003EP\u003C\/em\u003E = .051), 6.1% with 600 mg (\u003Cem\u003EP\u003C\/em\u003E = .301), and 15.9% with 1200 mg (\u003Cem\u003EP\u003C\/em\u003E = .016).\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EThe British Isles Lupus Assessment Group-based Combined Lupus Assessment response at week 52 was also higher in patients randomized to sifalimumab compared with placebo (placebo, 36.1%; 200 mg, 45.4%; 600 mg, 46.7%; 1200 mg, 48.1%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EA Cutaneous Lupus Erythematosus Disease Area and Severity Index response (\u2265 4-point reduction from baseline) in patients with moderate to severe skin involvement was achieved by more patients randomized to sifalimumab compared with placebo (placebo, 48.6%; 200 mg, 72.7%; 600 mg, 57.6%; 1200 mg, 73.1%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EThe number of patients with \u2265 8 swollen and \u2265 8 tender joints at baseline who achieved a \u2265 50% decrease in swollen and tender joint count was an exploratory end point. On this measure, the response rate is higher at all doses of sifalimumab (placebo, 36.8%; 200 mg, 53.7%; 600 mg, 57.9%; 1200 mg, 60.5%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EResponse rates on the SRI-4 were higher than placebo with sifalimumab regardless of high or low IFN gene signatures.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EMost commonly reported adverse events (AEs) were similar across groups, including worsening SLE (sifalimumab 30.0% vs placebo 34.3%), urinary tract infection (17.6% vs 13.9%), and headache (13.3% vs 13.9%). Serious AEs occurred in 18.3% of the sifalimumab group vs 17.6% of the placebo group. Herpes zoster infection was more common in sifalimumab recipients vs placebo (5.9% vs 0.9%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EThe overall efficacy results suggest that 1200 mg monthly is the most efficacious dose of sifalimumab for use in moderate to severe SLE.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 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\/14\/51\/7.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?nzodu1\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?nzodu1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}