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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\u003EThis article discusses a post hoc analysis of 5 studies of the humanized monoclonal antibody ranibizumab directed against vascular endothelial growth factor-A in the treatment of diabetic macular edema. The analysis focuses on the arterial thromboembolic events associated with ranibizumab that have been reported in controlled clinical trials.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERetinal Diseases Ophthalmology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERetinal Diseases\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOphthalmology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOphthalmology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EMarco Zarbin, MD, PhD, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA, described a post hoc analysis of 5 studies of the humanized monoclonal antibody ranibizumab directed against vascular endothelial growth factor (VEGF)-A in the treatment of diabetic macular edema (DME) [Gaudreault J et al. \u003Cem\u003ERetina\u003C\/em\u003E. 2007]. The analysis focused on the arterial thromboembolic events (ATEs) associated with ranibizumab that have been reported in controlled clinical trials.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EVEGF suppression in patients with cancer increases the risk of hypertension and ATEs [Semeraro F et al. \u003Cem\u003EExpert Opin Drug Saf\u003C\/em\u003E. 2014], but the situation is less clear in patients being treated for DME. The analysis looked at the long-term incidence (up to 3 years) of ATEs in patients with DME who were receiving ranibizumab.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EData from 5 studies collectively involving 881 patients were pooled and analyzed. The 1-year RESOLVE study used 0.3, 0.5, 0.6, and 1.0 mg ranibizumab PRN [Massin P et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E. 2010]. The remaining studies\u2014the 1-year RESTORE and REVEAL studies [Mitchell P et al. \u003Cem\u003EOphthalmology\u003C\/em\u003E. 2011], the 2-year RESTORE extension study [Lang GE et al. \u003Cem\u003EOphthalmology\u003C\/em\u003E. 2013], the 2-year RETAIN study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01183468\u0026amp;atom=%2Fspmdc%2F14%2F43%2F8.atom\u0022\u003ENCT01183468\u003C\/a\u003E], and the 3-year RESTORE extension study [Schmidt-Erfurth U et al. \u003Cem\u003EOphthalmology\u003C\/em\u003E. 2014]\u2014used ranibizumab 0.5 mg PRN.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe baseline characteristics\u2014age, sex, ethnicity, hemoglobin A\u003Csub\u003E1c\u003C\/sub\u003E, and duration of diabetes\u2014across the 5 trials were similar after exclusion of patients with prior ATEs.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EIn the RESOLVE, RESTORE, and REVEAL trials, the 1-year incidence of ATEs was similar in the ranibizumab arm (2.9%; n = 350 in the treatment arm) and in the control arm (3.8%; n = 287 in the sham\/laser arm). The annualized proportion of nonmyocardial ATEs in ranibizumab-treated patients was 1.7% annually at 1 year, 2.8% annually at 2 years (RESTORE extension and RETAIN trials), and 1.6% annually at 3 years (RESTORE extension trial). The annualized rate of myocardial infarction was 1.7%, 0.6%, and 0.0% annually at 1, 2, and 3 years, respectively. The incidence of vascular death in patients receiving ranibizumab 0.5 mg was similar to controls, and was comparable in patients treated for 2 or 3 years.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThe analysis has several limitations. The 5 studies were not powered to detect differences in safety events. Data are also insufficient on the use of anti-VEGF drugs in patients at high risk of DME, which reflects a tendency to exclude patients that are predisposed to treatment complications. For example, data on file with Novartis indicate that 3.4% of the patients in DME trials treated with ranibizumab 0.5 mg had experienced a prior stroke or transient ischemic attack. More knowledge on the patients who are at greater risk of complications is warranted.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003ESuch real-world evidence will be forthcoming in the LUMINOUS study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01318941\u0026amp;atom=%2Fspmdc%2F14%2F43%2F8.atom\u0022\u003ENCT01318941\u003C\/a\u003E] being coordinated by Novartis, which has enrolled 30 000 patients at approximately 500 sites from \u0026gt; 40 countries globally. The prospective 5-year observational study will evaluate the long-term safety and efficacy of ranibizumab in real-world clinical practice.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EFor now, there is no evidence to suggest any difference in safety between ranibizumab 0.5 mg and the control (sham\/laser) in the 5 studies.\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\/43\/8.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?nzoisd\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}