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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/Book"><div class="meta-content fm-sec"><div class="iconblock whole_rhythm clearfix no_top_margin"><a href="http://www.journalslibrary.nihr.ac.uk/eme" title="NIHR Journals Library" class="img_link icnblk_img" ref="pagearea=logo&targetsite=external&targetcat=link&targettype=publisher"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-ukeme0804-lrg.png" alt="Cover of Using cardiovascular magnetic resonance to define mechanisms of comorbidity and to measure the effect of biological therapy: the CADERA observational study" /></a><div class="icnblk_cntnt"><h1 id="_NBK568919_"><span itemprop="name">Using cardiovascular magnetic resonance to define mechanisms of comorbidity and to measure the effect of biological therapy: the CADERA observational study</span></h1><p><i>Efficacy and Mechanism Evaluation, No. 8.4</i></p><p class="contrib-group"><span itemprop="author">Sven Plein</span>, <span itemprop="author">Bara Erhayiem</span>, <span itemprop="author">Graham Fent</span>, <span itemprop="author">Jacqueline Andrews</span>, <span itemprop="author">John Greenwood</span>, <span itemprop="author">Paul Baxter</span>, <span itemprop="author">Elizabeth M Hensor</span>, <span itemprop="author">Sue Pavitt</span>, and <span itemprop="author">Maya H Buch</span>.</p><a data-jig="ncbitoggler" href="#__NBK568919_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK568919_ai__"><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Sven Plein</span>,<sup>1</sup> <span itemprop="author">Bara Erhayiem</span>,<sup>1</sup> <span itemprop="author">Graham Fent</span>,<sup>1</sup> <span itemprop="author">Jacqueline Andrews</span>,<sup>2</sup> <span itemprop="author">John Greenwood</span>,<sup>1</sup> <span itemprop="author">Paul Baxter</span>,<sup>3</sup> <span itemprop="author">Elizabeth M Hensor</span>,<sup>2,4</sup> <span itemprop="author">Sue Pavitt</span>,<sup>5</sup> and <span itemprop="author">Maya H Buch</span><sup>2,6,7</sup><sup>,*</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup> Department of Biomedical Imaging Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK</div><div class="affiliation"><sup>2</sup> Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK</div><div class="affiliation"><sup>3</sup> Department of Specialist Science Education, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK</div><div class="affiliation"><sup>4</sup> National Institute for Health Research Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK</div><div class="affiliation"><sup>5</sup> Dental Translational Clinical Research Unit, School of Dentistry, University of Leeds, Leeds, UK</div><div class="affiliation"><sup>6</sup> Centre for Musculoskeletal Research, Division of Musculoskeletal & Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK</div><div class="affiliation"><sup>7</sup> NIHR Manchester Biomedical Research Centre, Manchester, UK</div><div class="affiliation"><sup>*</sup> Corresponding author<span class="before-email-separator">; </span><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.ca.retsehcnam@hcub.ayam" class="oemail">ku.ca.retsehcnam@hcub.ayam</a></div></div><div class="half_rhythm">Southampton (UK): <a href="http://www.journalslibrary.nihr.ac.uk/eme" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">NIHR Journals Library</span></a>; <span itemprop="datePublished">2021 Mar</span>.</div><div class="half_rhythm"><ul class="inline_list"><li><span class="label"><a data-jig="ncbidialog" href="#_ncbi_dlg_cpyrght_NBK568919" data-jigconfig="modal:true">Copyright and
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Permissions</a></span></li></ul></div><div id="_ncbi_dlg_cpyrght_NBK568919" style="display:none" title="Copyright and Permissions"><div><div>Copyright © Queen’s Printer and Controller of HMSO 2021. This work was produced by Plein et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.</div><div class="half_rhythm"></div></div></div><div class="bk_noprnt"><form method="get" action="/books/n/ukeme0804/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div></div></div><div class="body-content whole_rhythm" itemprop="text"><div itemprop="description"><h2>Headline</h2><p>This study provides evidence of the changes in aortic distensibility in early rheumatoid arthritis and shows improvement of these at 1 year with DMARD therapy</p></div><div itemprop="description"><h2>Abstract</h2><div id="abs1-1"><h4 class="inline">Background:</h4><p>The VEDERA (Very Early vs. Delayed Etanercept in Rheumatoid Arthritis) randomised controlled trial compared the effect of conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy with biologic DMARD (bDMARD) therapy using the tumour necrosis factor inhibitor etanercept in treatment-naive, early rheumatoid arthritis patients. The CADERA (Coronary Artery Disease Evaluation in Rheumatoid Arthritis) trial was a bolt-on study in which VEDERA patients underwent cardiovascular magnetic resonance imaging to detect preclinical cardiovascular disease at baseline and following treatment.</p></div><div id="abs1-2"><h4 class="inline">Objectives:</h4><p>To evaluate whether or not patients with treatment-naive early rheumatoid arthritis have evidence of cardiovascular disease compared with matched control subjects; whether or not this is modifiable with DMARD therapy; and whether or not bDMARDs confer advantages over csDMARDs.</p></div><div id="abs1-3"><h4 class="inline">Design:</h4><p>The VEDERA patients underwent cardiovascular magnetic resonance imaging at baseline and at 1 and 2 years after treatment.</p></div><div id="abs1-4"><h4 class="inline">Setting:</h4><p>The setting was a tertiary centre rheumatology outpatient clinic and specialist cardiovascular magnetic resonance imaging unit.</p></div><div id="abs1-5"><h4 class="inline">Participants:</h4><p>Eighty-one patients completed all assessments at baseline, 71 completed all assessments at 1 year and 56 completed all assessments at 2 years. Patients had no history of cardiovascular disease, had had rheumatoid arthritis symptoms for ≤ 1 year, were DMARD treatment-naive and had a minimum Disease Activity Score-28 of 3.2. Thirty control subjects without cardiovascular disease were approximately individually matched by age and sex to the first 30 CADERA patients. Patients with a Disease Activity Score-28 of ≥ 2.6 at 48 weeks were considered non-responders.</p></div><div id="abs1-6"><h4 class="inline">Interventions:</h4><p>In the VEDERA trial patients were randomised to group 1, immediate etanercept and methotrexate, or group 2, methotrexate ± additional csDMARD therapy in a treat-to-target approach, with a switch to delayed etanercept and methotrexate in the event of failure to achieve clinical remission at 6 months.</p></div><div id="abs1-7"><h4 class="inline">Main outcome measures:</h4><p>The primary outcome measure was difference in baseline aortic distensibility between control subjects and the early rheumatoid arthritis group and the baseline to year 1 change in aortic distensibility in the early rheumatoid arthritis group. Secondary outcome measures were myocardial perfusion reserve, left ventricular strain and twist, left ventricular ejection fraction and left ventricular mass.</p></div><div id="abs1-8"><h4 class="inline">Results:</h4><p>Baseline aortic distensibility [geometric mean (95% confidence interval)] was significantly reduced in patients (<i>n</i> = 81) compared with control subjects (<i>n</i> = 30) [3.0 × 10<sup>–3</sup>/mmHg (2.7 × 10<sup>–3</sup>/mmHg to 3.3 × 10<sup>–3</sup>/mmHg) vs. 4.4 × 10<sup>–3</sup>/mmHg (3.7 × 10<sup>–3</sup>/mmHg to 5.2 × 10<sup>–3</sup>/mmHg), respectively; <i>p</i> < 0.001]. Aortic distensibility [geometric mean (95% confidence interval)] improved significantly from baseline to year 1 across the whole patient cohort (<i>n</i> = 81, with imputation for missing values) [3.0 × 10<sup>–3</sup>/mmHg (2.7 × 10<sup>–3</sup>/mmHg to 3.4 × 10<sup>–3</sup>/mmHg) vs. 3.6 × 10<sup>–3</sup>/mmHg (3.1 × 10<sup>–3</sup>/mmHg to 4.1 × 10<sup>–3</sup>/mmHg), respectively; <i>p</i> < 0.001]. No significant difference in aortic distensibility improvement between baseline and year 1 was seen in the following comparisons (geometric means): group 1 (<i>n</i> = 40 at baseline) versus group 2 (<i>n</i> = 41 at baseline): 3.8 × 10<sup>–3</sup>/mmHg versus 3.4 × 10<sup>–3</sup>/mmHg, <i>p</i> = 0.49; combined groups 1 and 2 non-responders (<i>n</i> = 38) versus combined groups 1 and 2 responders (<i>n</i> = 43): 3.5 × 10<sup>–3</sup>/mmHg versus 3.6 × 10<sup>–3</sup>/mmHg, <i>p</i> = 0.87; group 1 non-responders (<i>n</i> = 17) versus group 1 responders (<i>n</i> = 23): 3.6 × 10<sup>–3</sup>/mmHg versus 3.9 × 10<sup>–3</sup>/mmHg, <i>p</i> = 0.73. There was a trend towards a 10–30% difference in aortic distensibility between (group 1) responders who received first-line etanercept (<i>n</i> = 23) and (group 2) responders who never received etanercept (<i>n</i> = 13): 3.9 × 10<sup>–3</sup>/mmHg versus 2.8 × 10<sup>–3</sup>/mmHg, <i>p</i> = 0.19; ratio 0.7 (95% confidence interval 0.4 to 1.2), <i>p</i> = 0.19; ratio adjusted for baseline aortic distensibility 0.8 (95% confidence interval 0.5 to 1.2), <i>p</i> = 0.29; ratio fully adjusted for baseline characteristics 0.9 (95% confidence interval 0.6 to 1.4), <i>p</i> = 0.56.</p></div><div id="abs1-9"><h4 class="inline">Conclusions:</h4><p>The CADERA establishes evidence of the vascular changes in early rheumatoid arthritis compared with controls and shows improvement of vascular changes with rheumatoid arthritis DMARD therapy. Response to rheumatoid arthritis therapy does not add further to modification of cardiovascular disease but, within the response to either strategy, etanercept/methotrexate may confer greater benefits over standard methotrexate/csDMARD therapy.</p></div><div id="abs1-10"><h4 class="inline">Trial registration:</h4><p>Current Controlled Trials ISRCTN89222125 and ClinicalTrials.gov <a href="https://clinicaltrials.gov/show/NCT01295151" title="Study NCT01295151" ref="pagearea=abstract&targetsite=external&targetcat=link&targettype=clinical-trial">NCT01295151</a>.</p></div><div id="abs1-11"><h4 class="inline">Funding:</h4><p>This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in <i>Efficacy and Mechanism Evaluation</i>; Vol. 8, No. 4. See the NIHR Journals Library website for further project information. Pfizer Inc. (New York, NY, USA) supported the parent study, VEDERA, through an investigator-sponsored research grant reference WS1092499.</p></div></div><div><h2>Contents</h2><div class="bktoc_all_cntnr top align_right" style="display:none"><ul class="inline_list_right"><li><a class="bktoc_all_exp" href="#">Expand All</a></li><li style="margin-left:.8em"><a class="bktoc_all_clps" href="#">Collapse All</a></li></ul></div><ul id="toc_tllNBK568919_toc_abs2" class="simple-list toc toc-toggle"><li class="half_rhythm" id="toc_itm_NBK568919_toc_abs2"><a class="toc-item" href="/books/n/ukeme0804/abs2/">Plain English summary</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_abs3"><a class="toc-item" href="/books/n/ukeme0804/abs3/">Scientific summary</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s1"><a class="toc-item" href="/books/n/ukeme0804/s1/">Chapter 1. Introduction</a><ul id="toc_lst_NBK568919_toc_s1" class="simple-list toc bktoc_lst_exp"><li class="half_rhythm" id="toc_itm_NBK568919_toc_s1-1"><a class="toc-item" href="/books/n/ukeme0804/s1/#s1-1">Background</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s1-2"><a class="toc-item" href="/books/n/ukeme0804/s1/#s1-2">Rheumatoid arthritis time course and excess cardiovascular disease</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s1-3"><a class="toc-item" href="/books/n/ukeme0804/s1/#s1-3">Therapeutic strategies in new-onset early rheumatoid arthritis</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s1-4"><a class="toc-item" href="/books/n/ukeme0804/s1/#s1-4">Effect of rheumatoid arthritis disease-modifying anti-rheumatic drug therapy on cardiovascular disease outcomes</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s1-5"><a class="toc-item" href="/books/n/ukeme0804/s1/#s1-5">Cardiovascular magnetic resonance studies in rheumatoid arthritis</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s1-6"><a class="toc-item" href="/books/n/ukeme0804/s1/#s1-6">The VEDERA trial</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s1-7"><a class="toc-item" href="/books/n/ukeme0804/s1/#s1-7">The CADERA study rationale</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s1-8"><a class="toc-item" href="/books/n/ukeme0804/s1/#s1-8">The clinical unmet need</a></li></ul></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2"><a class="toc-item" href="/books/n/ukeme0804/s2/">Chapter 2. Clinical trial methods</a><ul id="toc_lst_NBK568919_toc_s2" class="simple-list toc bktoc_lst_exp"><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-1"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-1">Objectives</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-2"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-2">Design</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-3"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-3">Patient and public involvement</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-4"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-4">Participants</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-5"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-5">Interventions</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-6"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-6">Study procedures</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-7"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-7">Outcome measures</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-8"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-8">Patient withdrawal</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-9"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-9">Sample size and power calculation</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-10"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-10">Blinding</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s2-11"><a class="toc-item" href="/books/n/ukeme0804/s2/#s2-11">Analysis</a></li></ul></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s3"><a class="toc-item" href="/books/n/ukeme0804/s3/">Chapter 3. Clinical trial results</a><ul id="toc_lst_NBK568919_toc_s3" class="simple-list toc bktoc_lst_exp"><li class="half_rhythm" id="toc_itm_NBK568919_toc_s3-1"><a class="toc-item" href="/books/n/ukeme0804/s3/#s3-1">Patient recruitment</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s3-2"><a class="toc-item" href="/books/n/ukeme0804/s3/#s3-2">Primary objectives</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s3-3"><a class="toc-item" href="/books/n/ukeme0804/s3/#s3-3">Secondary objectives</a></li></ul></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s4"><a class="toc-item" href="/books/n/ukeme0804/s4/">Chapter 4. Discussion</a><ul id="toc_lst_NBK568919_toc_s4" class="simple-list toc bktoc_lst_exp"><li class="half_rhythm" id="toc_itm_NBK568919_toc_s4-1"><a class="toc-item" href="/books/n/ukeme0804/s4/#s4-1">Baseline assessment</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s4-2"><a class="toc-item" href="/books/n/ukeme0804/s4/#s4-2">Treatment effects</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s4-3"><a class="toc-item" href="/books/n/ukeme0804/s4/#s4-3">Study limitations</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s4-4"><a class="toc-item" href="/books/n/ukeme0804/s4/#s4-4">Conclusion</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_s4-5"><a class="toc-item" href="/books/n/ukeme0804/s4/#s4-5">Recommendations</a></li></ul></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_ack1"><a class="toc-item" href="/books/n/ukeme0804/ack1/">Acknowledgements</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_ref1"><a class="toc-item" href="/books/n/ukeme0804/ref1/">References</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_app1"><a class="toc-item" href="/books/n/ukeme0804/app1/">Appendix 1. The VEDERA trial design</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_app2"><a class="toc-item" href="/books/n/ukeme0804/app2/">Appendix 2. The CADERA study design</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_app3"><a class="toc-item" href="/books/n/ukeme0804/app3/">Appendix 3. Additional tables</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_app4"><a class="toc-item" href="/books/n/ukeme0804/app4/">Appendix 4. Protocol amendments July 2018</a></li><li class="half_rhythm" id="toc_itm_NBK568919_toc_g1"><a class="toc-item" href="/books/n/ukeme0804/g1/">List of abbreviations</a></li></ul><div class="bktoc_all_cntnr align_right" style="display:none"><ul class="inline_list_right"><li><a class="bktoc_all_exp" href="#">Expand All</a></li><li style="margin-left:.8em"><a class="bktoc_all_clps" href="#">Collapse All</a></li></ul></div></div><div class="pmc_boxed-text-box fm-sec whole_rhythm"><h3>About the Series</h3><div class="half_rhythm"><div>Efficacy and Mechanism Evaluation</div></div><div class="half_rhythm"><div>ISSN (Print): 2050-4365</div><div>ISSN (Electronic): 2050-4373</div></div></div><div><p>Declared competing interests of authors: Maya H Buch reports grants and personal fees from Pfizer Inc. (New York, NY, USA), grants from Roche-Chugai (Tokyo, Japan) and UCB (Brussels, Belgium) and personal fees from AstraZeneca plc (Cambridge, UK), Bristol-Myers Squibb Co. (New York, NY, USA), Mitsubishi Tanabe Pharma Corp. (Osaka, Japan), Sandoz (Holzkirchen, Germany), R-Pharm (Moscow, Russia), Sanofi (Paris, France), Merck Serono (Darmstadt, Germany) and Roche-Chugai outside the submitted work. Elizabeth M Hensor reports grants from the National Institute for Health Research (NIHR) and grants from Versus Arthritis [formerly Arthritis Research UK (London, UK)] outside the submitted work. Sue Pavitt is NIHR Clinical Research Network (CRN) National Specialty Lead for Oral and Dental Health. She also reports non-financial support from NIHR CTU Standing Advisory Committee and from NIHR EME outside the submitted work. In addition, the NIHR CRN Specialty Leadership role attracts one programmed activity of funding outside the submitted work. Graham Fent reports support from Novartis International AG (Basel, Switzerland) outside the submitted work.</p></div><div><div id="n1-1"><h2>Article history</h2><p>The research reported in this issue of the journal was funded by the EME programme as project number 11/117/27. The contractual start date was in April 2013. The final report began editorial review in November 2018 and was accepted for publication in August 2019. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The EME editors and production house have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the final report document. However, they do not accept liability for damages or losses arising from material published in this report.</p></div></div><p class="small">Last reviewed: November 2018; Accepted: August 2019.</p></div></div>
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<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © Queen’s Printer and Controller of HMSO 2021. This work was produced by Plein <i>et al.</i> under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.</div><div class="small"><span class="label">Bookshelf ID: NBK568919</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/33780206" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">33780206</a></span>DOI: <a href="http://dx.crossref.org/10.3310/eme08040" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">10.3310/eme08040</a></div><div style="margin-top:2em" class="bk_noprnt"><div class="pagination bk_noprnt"><span class="inactive page_link prev">< Prev</span><a class="active page_link next" href="/books/n/ukeme0804/abs2/" title="Next page in this title">Next ></a></div></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK568919/?report=reader">PubReader</a></li><li><a href="/books/NBK568919/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK568919" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK568919" style="display:none" title="Cite this Page"><div class="bk_tt">Plein S, Erhayiem B, Fent G, et al. Using cardiovascular magnetic resonance to define mechanisms of comorbidity and to measure the effect of biological therapy: the CADERA observational study. Southampton (UK): NIHR Journals Library; 2021 Mar. 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