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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\u003EInterstitial lung disease (ILD) in patients with systemic sclerosis (SSc) frequently results in ventilatory restriction, a major cause of death in these individuals. Clinical trials in patients with SSc-related ILD have traditionally used forced vital capacity percentage (FVC%) predicted as a primary outcome measure [Hoyles RK et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2006; Tashkin DP et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2006]. This article discusses the development of a composite outcome measure to assess treatment response in patients with SSc\u2014ILD in clinical studies, and to create a more comprehensive measure than FVC% alone.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatological Autoimmune Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELower Respiratory Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatological Autoimmune Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELower Respiratory Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EInterstitial lung disease (ILD) in patients with systemic sclerosis (SSc) frequently results in ventilatory restriction, a major cause of death in these individuals. Clinical trials in patients with SSc-related ILD have traditionally used forced vital capacity percentage (FVC%) predicted as a primary outcome measure [Hoyles RK et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E 2006; Tashkin DP et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2006]. Cyclophosphamide treatment of patients with SSc has been associated with improvements in clinically meaningful outcome measures other than FVC%. Elizabeth Volkmann, MD, University of California at Los Angeles, Los Angeles, California, USA, discussed the development of a composite outcome measure that included the FVC%, the computer-based quantitative lung fibrosis in the zone of maximum fibrosis (QLF-ZM) score from thoracic high-resolution computed tomography (CT) lung scans, the scleroderma modified Health Assessment Questionnaire Disability Index (HAQ-DI), and the Transition Dyspnea Index (TDI) for SSc-related ILD.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe objective of the analysis reported by Dr. Volkmann was to develop a composite outcome measure to assess treatment response in patients with SSc\u2013ILD in clinical studies, and to create a more comprehensive measure than FVC% alone. The Scleroderma Lung Study I [SLSI; Tashkin DP et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2006] compared oral cyclophosphamide with placebo in patients with active SSc and ILD. Of the 158 patients enrolled in the SLSI trial, 83 (41 treated with cyclophosphamide and 42 treated with placebo) had baseline and 12-month follow-up CT available and were analyzed for this presentation. There was no significant difference in baseline characteristics between the two treatment groups.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EA univariate analysis that tested for treatment effects for individual outcomes, including FVC% predicted, total lung capacity predicted (TLC), QLF-ZM and whole-lung (WL) scores, quantitative interstitial lung disease (QILD)\u2013ZM and \u2013WL scores, HAQ-DI, TDI, and the visual analogue scale for breathing (VAS-B), was conducted to determine which variables had a significant treatment effect at 12 months. The results are shown in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/14600\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/14600\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14600\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EUnivariate Analysis for Treatment Effects\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EPrincipal component analyses were then conducted that combined those variables with significant treatment effect to assess the difference between treatment groups. The composite outcome composed of FVC% predicted, QLF, HAQ-DI, and TDI demonstrated a strong treatment effect favoring cyclophosphamide (p=0.0005). Another analysis was performed that eliminated FVC% from the composite outcome, combining TDI, HAQ-DI, and QLF-ZM; this did not change the overall treatment effect (p=0.0004). Both composite outcome measures demonstrated a more robust treatment effect than FVC% predicted alone.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003ELimitations to this analysis include a possible bias arising from selecting only patients with complete outcome data, although Dr. Volkmann commented that there were no differences in baseline characteristics between patients included in this analysis and all patients in SLSI. The quantitative imaging analysis used in this study is a novel approach and is currently not widely available for clinical use.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EA composite outcome with structural (QLF), physiologic (FVC% and TDI), and patient-oriented (HAQ-DI) outcomes may serve as a more comprehensive measure of treatment response in SSc\u2013ILD than the current standard of FVC%. The most robust treatment effect was observed in the composite outcome that included QLF, TDI, and HAQ-DI but did not include FVC%. Analysis of additional data sets is needed to validate this model.\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\/17\/21.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?nzp3o1\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_tables.js?nzp3o1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}