title: A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA.
  
  
  METHODS
  A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of 186 (62 per group) patients will be required to determine a 36% difference in pharmacological treatment escalation between the three groups with intermediate dispersion of data with 90% power at a 5% level of significance.
  
  
  CONCLUSIONS
  This study will determine if monitoring RA and undifferentiated inflammatory arthritis patients using MRI and X-ray every 6 months over 2 years provides incremental evidence over standard of care to influence pharmacotherapeutic decision-making and ultimately hinder disease progression.
  
  
  BACKGROUND
  This trial has been registered at ClinicalTrials.gov: NCT00808496 (registered on 12 December 2008).
authors.affiliation: UNCOVER Clinical Research Company, Milton, ON, Canada. tavarerv@gmail.com.
authors.forename: Ruben
authors.initials: R
authors.lastname: Tavares
authors.forename: Karen Anne
authors.initials: KA
authors.lastname: Beattie
authors.forename: William George
authors.initials: WG
authors.lastname: Bensen
authors.forename: Raja S
authors.initials: RS
authors.lastname: Bobba
authors.forename: Alfred A
authors.initials: AA
authors.lastname: Cividino
authors.forename: Karen
authors.initials: K
authors.lastname: Finlay
authors.forename: Ron
authors.initials: R
authors.lastname: Goeree
authors.forename: Lawrence Errol
authors.initials: LE
authors.lastname: Hart
authors.forename: Erik
authors.initials: E
authors.lastname: Jurriaans
authors.forename: Maggie J
authors.initials: MJ
authors.lastname: Larche
authors.forename: Naveen
authors.initials: N
authors.lastname: Parasu
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Tarride
authors.forename: Colin E
authors.initials: CE
authors.lastname: Webber
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Adachi
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D001175:Arthrography / Q000592:standards*; D002985:Clinical Protocols; D003661:Decision Support Techniques; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000592:standards*; D009864:Ontario; D011237:Predictive Value of Tests; D012107:Research Design; D059039:Standard of Care; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents