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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\u003ETralokinumab, a human immunoglobulin-G4 monoclonal antibody, potently and specifically neutralizes interleukin (IL)-13, a pleiotropic cytokine thought to be a central mediator of asthma [Mitchell J et al. \u003Cem\u003ECurr Opin Investig Drugs\u003C\/em\u003E 2010]. This article presents the overall results from A Phase 2b, Randomized, Double-Blind Study to Evaluate the Efficacy of Tralokinumab in Adults With Asthma [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01402986\u0026amp;atom=%2Fspmdc%2F14%2F11%2F11.1.atom\u0022\u003ENCT01402986\u003C\/a\u003E; Brightling CE et al. \u003Cem\u003EAm J Crit Care Med\u003C\/em\u003E 2014].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EAsthma\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary \u0026amp; Critical Care\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EAsthma\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ETralokinumab, a human immunoglobulin-G4 monoclonal antibody, potently and specifically neutralizes interleukin (IL)-13, a pleiotropic cytokine thought to be a central mediator of asthma [Mitchell J et al. \u003Cem\u003ECurr Opin Investig Drugs\u003C\/em\u003E 2010]. Christopher E. Brightling, MBBS, University of Leicester, Leicester, United Kingdom, presented the overall results from A Phase 2b, Randomized, Double-Blind Study to Evaluate the Efficacy of Tralokinumab in Adults With Asthma [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01402986\u0026amp;atom=%2Fspmdc%2F14%2F11%2F11.1.atom\u0022\u003ENCT01402986\u003C\/a\u003E; Brightling CE et al. \u003Cem\u003EAm J Crit Care Med\u003C\/em\u003E 2014]. In brief, the study showed that acute exacerbation rates (AERs) were reduced with the every-2-week (Q2W), but not the every-4-week (Q4W), tralokinumab dosing regimen compared with placebo and that tralokinumab was well tolerated and safe, with similar rates of adverse events in all groups.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EEligible patients at screening had severe asthma with forced expiratory volume in 1 second (FEV\u003Csub\u003E1\u003C\/sub\u003E) reversibility of \u226512% and \u2265200 mL within 3 years of screening and \u22652 exacerbations in the prior year. Following a 5-week run-in period, subjects with FEV\u003Csub\u003E1\u003C\/sub\u003E of 40% to 80% predicted or Asthma Control Questionnaire 6 (ACQ-6) scores \u22651.5 were randomly assigned to receive subcutaneous tralokinumab 300 mg every 2 weeks for 52 weeks (Q2W group; n=150) or every 4 weeks for 12 weeks and then every 4 weeks to Week 48 (Q4W group; n=151) or placebo (n=151). Subjects received fluticasone 500 mg and salmeterol 50 mg or equivalent and were continued on prestudy control medications. The primary end point was the AER over 52 weeks, with secondary end points of FEV\u003Csub\u003E1\u003C\/sub\u003E, ACQ-6 scores, and safety.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe mean age of the study patients was 50 years, 65% were women, 56% were Caucasian, and 34% were Asian. The average baseline FEV\u003Csub\u003E1\u003C\/sub\u003E was 68.6%.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe primary efficacy endpoint of AER, defined as the use or increase in dose of systemic corticosteroids for \u22653 consecutive days for asthma symptoms, at 52 weeks was not significantly reduced in either tralokinumab dosing regimen (Q2W, 7%; 95% CI, \u221230% to 33% [p=0.67]; Q4W, \u22122%; 95% CI, \u221246% to 29% [p=0.91]) in the intention-to-treat analysis.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe secondary end point of percentage change in FEV\u003Csub\u003E1\u003C\/sub\u003E increased significantly in the Q2W group (7.10%; 95% CI, 2.35% to 11.84%; p=0.003) but not the Q4W group (1.57%; 95% CI, \u22123.22% to 6.35%; p=0.52). There were trends for improvements in measures of health status, measured by the ACQ-6 and Asthma Quality of Life Questionnaire (AQLQ) in the overall study.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EInvestigation of biomarkers in predefined subgroups revealed a trend toward a reduction in AER in patients with FEV\u003Csub\u003E1\u003C\/sub\u003E reversibility and elevated levels of periostin or dipeptidyl peptidase-4 (DPP-4) treated with Q2W tralokinumab compared with placebo. In the Q2W group, there were greater improvements in ACQ-6 and AQLQ scores in the patients with FEV\u003Csub\u003E1\u003C\/sub\u003E reversibility and high levels of periostin and DPP-4.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe frequency of treatment-emergent serious adverse events or adverse events was similar within the safety population (tralokinumab Q2W, 89.3%; tralokinumab Q4W, 84.8%; placebo, 84.8%).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EAlthough there was not an overall reduction in AER in either tralokinumab dosing regimen compared with placebo, the trends toward improvements in AER in the predefined subgroup analysis in subjects with airway reversibility and high levels of periostin or DPP-4 are hypothesis generating and suggest populations that may benefit from IL-13 blockade in future 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\/11\/11.1.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?nzp1rp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}