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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\u003ESecretion of interleukin (IL)-23 by myeloid dendritic cells plays a role in the initiation of psoriasis. In addition, chronic psoriasis is maintained, at least in part, by the continued secretion of IL-23, which promotes the secretion of chemokines and antimicrobial peptides by keratinocytes, resulting in amplification that causes further IL-23 secretion. This article discusses the combination of IL-23 blockade with a single dose of the monoclonal antibody BI 655066 in the Single Rising Dose Study of BI 655066 in Patients With Moderate and Severe Psoriasis [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01577550\u0026amp;atom=%2Fspmdc%2F14%2F37%2F12.atom\u0022\u003ENCT01577550\u003C\/a\u003E].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ESkin Diseases\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDermatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDermatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ESkin Diseases\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDermatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EInterleukin (IL)-23 blockade with a single dose of the monoclonal antibody BI 655066 was safe and well tolerated in the Single Rising Dose Study of BI 655066 in Patients With Moderate and Severe Psoriasis [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01577550\u0026amp;atom=%2Fspmdc%2F14%2F37%2F12.atom\u0022\u003ENCT01577550\u003C\/a\u003E] presented by James Krueger, MD, PhD, Rockefeller University, New York, New York, USA.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ESecretion of IL-23 by myeloid dendritic cells plays a role in the initiation of psoriasis [Lowes MA et al. \u003Cem\u003EAnn Rev Immunol\u003C\/em\u003E. 2014]. In addition, chronic psoriasis is maintained, at least in part, by the continued secretion of IL-23, which promotes the secretion of chemokines and antimicrobial peptides by keratinocytes, resulting in amplification that causes further IL-23 secretion. BI 655066 is a monoclonal antibody that selectively targets the p19 subunit of IL-23 to prevent IL-23 activity. The purpose of this first-in-human study was to evaluate the safety and tolerability of BI 655066 in patients with moderate to severe plaque psoriasis.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn this study of 39 patients with moderate to severe plaque psoriasis with a Psoriasis Area and Severity Index (PASI) score \u2265 12, patients were randomly assigned to receive a single intravenous (IV) dose (0.01, 0.05, 0.25, 1.00, 3.00, or 5.00 mg\/kg) of BI 655066 (n = 18) or placebo (n = 6), and 15 patients were randomly assigned to receive a single 0.25 mg\/kg or 1.00 mg\/kg dose of subcutaneous (SC) BI 655066 (n = 13) or placebo (n = 2). End points included safety; PASI at 0, 2, 4, 12, or 24 weeks; and skin biopsies for histology and next-generation RNA sequencing analysis at 0 and 8 weeks.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe mean change in PASI score was significantly higher among patients who received IV or SC BI 655066 compared with patients who received placebo, in a pooled analysis (\u003Cem\u003EP\u003C\/em\u003E \u0026lt; .01; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\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\/14\/37\/12\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effect of BI 655066 on PASI Score\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1290143\u0022 data-figure-caption=\u0022Effect of BI 655066 on PASI Score\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\/37\/12\/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\/37\/12\/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\/37\/12\/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\/12111\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\u003EEffect of BI 655066 on PASI Score\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EIV, intravenous; PASI, Psoriasis Area and Severity Index; SC, subcutaneous.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003E\n            \u003Csup\u003Ea\u003C\/sup\u003EIV and SC BI 655066 groups combined.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced with permission from J Krueger, MD, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EIn patients who received SC BI 655066, the mean improvement in PASI score was about 90% at week 12 and 100% at week 16; PASI-100 was maintained by 66% of patients who entered an optional long-term follow-up period for up to 66 weeks. In addition, immunohisto-chemical analysis of a skin biopsy sample harvested from a patient who received 0.25 mg\/kg of SC BI 655066 demonstrated a decrease in markers associated with psoriasis at 8 weeks, including K16, K167, S100A7, Lipocalin, \u03b2-defensin, CD3, CD11c, and DC-lamp. Furthermore, next-generation sequencing analysis found that treatment with BI 655066 resulted in normalization of psoriatic lesions similar to that of nonlesional skin.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EAny adverse event (AE) occurred in 20 of 31 (65%) patients who received BI 655066 and in 7 of 8 (88%) of patients who received placebo. Serious AEs, including recurrent alcoholic pancreatitis, recurrent stroke, transient ischemic attack, and myositis, occurred in 13% of patients who received BI 655066 compared with none of the patients who received placebo. Common AEs included nasopharyngitis, headache, and upper respiratory tract infection.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe results of this study show that the novel drug BI 655066 appears to be safe and well tolerated in patients with moderate to severe plaque psoriasis. In a subset of the study patients, the improvement in the secondary end point of mean change in PASI score was maintained at 1 year. This trial was not powered to evaluate efficacy end points, however. The effect of BI 655066 is being evaluated in an ongoing phase 2b study.\u003C\/p\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\/37\/12.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?nzop1d\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?nzop1d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}