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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\u003EResults from the Treatment of Emphysema with a Selective Retinoid Agonist [TESRA; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00413205\u0026amp;atom=%2Fspmdc%2F11%2F4%2F10.1.atom\u0022\u003ENCT00413205\u003C\/a\u003E] study showed that emphysema patients had a mixed response to treatment with the retinoid agonist palovarotene. Treatment with palovarotene failed to meet the primary endpoint of improving lung function (FEV1) in the overall analysis.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ELower Respiratory Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EChronic Obstructive Pulmonary Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EResults from the Treatment of Emphysema with a Selective Retinoid Agonist (TESRA; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00413205\u0026amp;atom=%2Fspmdc%2F11%2F4%2F10.1.atom\u0022\u003ENCT00413205\u003C\/a\u003E) study showed that emphysema patients had a mixed response to treatment with the retinoid agonist palovarotene. Treatment with palovarotene failed to meet the primary endpoint of improving lung function (FEV\u003Csub\u003E1\u003C\/sub\u003E) in the overall analysis. However, the subset of patients with lower lobe emphysema had a significant reduction in the rate of decline in lung function.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EA post hoc analysis in the lower lung suggested that palovarotene was associated with less worsening over time in most outcomes in patients with lower lung emphysema predominance. \u201cThese findings are very much post hoc and preliminary and require confirmation using a more detailed analysis of emphysema progression in different parts of the lung. However, the observations from this hypothesis-generating study do suggest that they need to be tested again but in a group of patients identified beforehand as having predominant lower lung emphysema,\u201d said Paul W. Jones, MD, PhD, St. George\u0027s University of London, London, United Kingdom.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003ETESRA was a Phase 2, double-blind, randomized, placebo-controlled, multicenter trial that involved investigators at 69 centers in 12 countries. Palovarotene is an oral retinoid agonist that is selective for the gamma receptor, which is thought to play a key role in alveolar formation. In preclinical models of emphysema, the drug reduced inflammation, promoted structural repair, and improved lung function.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003ETESRA involved ex-smokers who had computed tomography-documented emphysema, baseline postbronchodilator FEV\u003Csub\u003E1\u003C\/sub\u003E \u0026lt;70% of predicted, and baseline TL\u003Csub\u003ECO\u003C\/sub\u003E \u0026lt;70% of predicted. They were randomized 2:1 to palovarotene 5 mg\/day or placebo, both in addition to optimized therapy for chronic obstructive pulmonary disease (COPD). Treatment and follow-up continued for 2 years. The primary outcome was the change in FEV\u003Csub\u003E1\u003C\/sub\u003E after 2 years.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EWhen the trial ended, patients in the palovarotene arm had a 4.5-ml improvement in FEV\u003Csub\u003E1\u003C\/sub\u003E compared with the placebo group, a difference that failed to achieve statistical significance (p=0.86).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EFour regions of interest had been identified in the lungs: upper quartile, upper half, lower half, and lowest quartile. Patients in the placebo arm had greater loss of lung function in the lower half and lowest quartile, compared with the upper half and upper quartile. A post hoc analysis of these regions of interest showed that in patients who were treated with placebo, the change in FEV\u003Csub\u003E1\u003C\/sub\u003E in the lower half of the lung averaged \u221256.7 ml at 12 months and \u2212124.4 ml at 24 months and \u221256.2 ml at 12 months and \u2212174.7 ml at 24 months in the lower quartile. In contrast, the rate of loss of FEV\u003Csub\u003E1\u003C\/sub\u003E in patients who were treated with paloverotene was less: lower half \u221233.0 ml and \u221240.9 ml at 12 and 24 months; lowest quartile: \u221256.2 ml and \u221246.0 ml at 12 and 24 months. A similar response pattern emerged with respect to DL\u003Csub\u003ECO\u003C\/sub\u003E, 6-minute walk distance, and quality of life.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EIn addition to optimal COPD therapy, in patients with lower lung emphysema, palovarotene significantly reduced the decline in DL\u003Csub\u003ECO\u003C\/sub\u003E and FEV\u003Csub\u003E1\u003C\/sub\u003E, which may be suggestive of a disease-modifying effect.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\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\/11\/4\/10.1.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?nzn2pe\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}