title: MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16.
abstract: OBJECTIVE
  To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0-4; CZP 200 mg every 2 weeks at weeks 6-16) or placebo→CZP (placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200 mg every 2 weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures.
  
  
  RESULTS
  Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group.
  
  
  CONCLUSIONS
  CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT01235598.
authors.affiliation: Copenhagen Center for Arthritis Research, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: Department of Rheumatology & Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: L T H
authors.initials: LT
authors.lastname: Jacobsson
authors.affiliation: Department of Rheumatology & Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Schaufelberger
authors.affiliation: Department of Rheumatology, Gentofte Hospital, Gentofte, Denmark.
authors.forename: M Sejer
authors.initials: MS
authors.lastname: Hansen
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J W J
authors.initials: JW
authors.lastname: Bijlsma
authors.affiliation: Medica Pro Familia, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Dudek
authors.affiliation: Rheuma Medicus, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Rell-Bakalarska
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Staelens
authors.affiliation: UCB Pharma, Raleigh, North Carolina, USA.
authors.forename: R
authors.initials: R
authors.lastname: Haake
authors.affiliation: UCB Pharma, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Sundman-Engberg
authors.affiliation: Department of Rheumatology, The Parker Institute, Frederiksberg, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Bliddal
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000068582:Certolizumab Pegol; D004311:Double-Blind Method; D005260:Female; D050823:Hand Joints / Q000473:pathology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010000:Osteitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D013585:Synovitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol
keywords: Anti-TNF; Inflammation; Magnetic Resonance Imaging; Rheumatoid Arthritis; Synovitis