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


CONCLUSIONS
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.


BACKGROUND
This trial was registered with Current Controlled Trials (registration number: ISRCTN50167738) on 8 November 2013.
Bara
B
Erhayiem
Sue
S
Pavitt
Paul
P
Baxter
Jacqueline
J
Andrews
John P
JP
Greenwood
Maya H
MH
Buch
Multidisciplinary Cardiovascular Research Centre & Leeds Institute for Cardiovascular and Metabolic Medicine, Worsley Building, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK. s.plein@leeds.ac.uk.
Sven
S
Plein
D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D002985:Clinical Protocols; D003287:Contrast Media; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D004739:England / Q000453:epidemiology; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D019028:Magnetic Resonance Imaging, Cine; D008727:Methotrexate / Q000627:therapeutic use; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D018501:Antirheumatic Agents; D003287:Contrast Media; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept; D008727:Methotrexate