Coronary Artery Disease Evaluation in Rheumatoid Arthritis (CADERA): study protocol for a randomized controlled trial.

backgroundThe incidence of cardiovascular disease (CVD) in rheumatoid arthritis (RA) is increased compared to the general population. Immune dysregulation and systemic inflammation are thought to be associated with this increased risk. Early diagnosis with immediate treatment and tight control of RA forms a central treatment paradigm. It remains unclear, however, whether using tumor necrosis factor inhibitors (TNFi) to achieve remission confer additional beneficial effects over standard therapy, especially on the development of CVD. METHODS/

designCoronary Artery Disease Evaluation in Rheumatoid Arthritis (CADERA) is a prospective cardiovascular imaging study that bolts onto an existing single-centre, randomized controlled trial, VEDERA (Very Early versus Delayed Etanercept in Rheumatoid Arthritis). VEDERA will recruit 120 patients with early, treatment-naïve RA, randomized to TNFi therapy etanercept (ETN) combined with methotrexate (MTX), or therapy with MTX with or without additional synthetic disease modifying anti-rheumatic drugs with escalation to ETN following a 'treat-to-target' regimen. VEDERA patients will be recruited into CADERA and undergo cardiac magnetic resonance (CMR) assessment with; cine imaging, rest/stress adenosine perfusion, tissue-tagging, aortic distensibility, T1 mapping and late gadolinium imaging. Primary objectives are to detect the prevalence and change of cardiovascular abnormalities by CMR between TNFi and standard therapy over a 12-month period. All patients will enter an inflammatory arthritis registry for long-term follow-up. DISCUSSION: CADERA is a multi-parametric study describing cardiovascular abnormalities in early, treatment-naïve RA patients, with assessment of changes at one year between early biological therapy and conventional therapy. TRIALS REGISTRATION: This trial was registered with Current Controlled Trials (registration number: ISRCTN50167738) on 8 November 2013.