title: Validity of early MRI structural damage end points and potential impact on clinical trial design in rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials.
  
  
  METHODS
  In a randomised trial of early methotrexate-naïve RA (GO-BEFORE), RAMRIS scores were determined from MRIs and van der Heijde-Sharp (vdHS) scores from radiographs, at baseline, week 12, week 24 and week 52. Progression in damage scores was defined as change >0.5. Associations of X-ray and MRI outcomes with clinical features were evaluated for convergent validity. Iterative Wilcoxon rank sum tests and tests of proportion estimated the sample size required to detect differences between combination therapy (methotrexate+golimumab) and methotrexate-monotherapy arms in (A) change in damage score and (B) proportion of patients progressing.
  
  
  RESULTS
  Patients with early MRI progression had higher DAS28, C reactive protein (CRP) and vdHS at baseline, and higher 2-year HAQ. Associations were similar to those with 1-year vdHS progression. Differences in change in structural damage between treatment arms achieved significance with fewer subjects when 12-week or 24-week MRI erosion score was the outcome (150 patients; 100 among an enriched sample with baseline-synovitis >5) compared with the 52-week vdHS (275 patients). Differences in the proportion progressing could be detected in 234 total subjects with 12-week MRI in an enriched sample whereas 1-year X-ray required between 468 and 1160 subjects.
  
  
  CONCLUSIONS
  Early MRI erosion progression is a valid measure of structural damage that could substantially decrease sample size and study duration if used as structural damage end point in RA clinical trials.
authors.affiliation: Philadelphia Veterans' Affairs Medical Center, Philadelphia, Pennsylvania, USA University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Joshua F
authors.initials: JF
authors.lastname: Baker
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.affiliation: Janssen Research & Development, LLC., Horsham, Pennsylvania, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Baker
authors.affiliation: Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy; D018450:Disease Progression; D023381:Endpoint Determination / Q000379:methods*; D005260:Female; D033023:Foot Joints / Q000000981:diagnostic imaging; D050823:Hand Joints / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011859:Radiography; D015203:Reproducibility of Results; D012107:Research Design; D018401:Sample Size; D012720:Severity of Illness Index; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C529000:golimumab; D008727:Methotrexate
keywords: Anti-TNF; Magnetic Resonance Imaging; Rheumatoid Arthritis