title: The effects of tocilizumab on osteitis, synovitis and erosion progression in rheumatoid arthritis: results from the ACT-RAY MRI substudy.
abstract: OBJECTIVE
  To examine the imaging-detected mechanism of reduction of structural joint damage progression by tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) using MRI.
  
  
  METHODS
  In a substudy of a randomised, double-blind, phase 3b study (ACT-RAY) of biologic-naïve patients with RA who were methotrexate (MTX)-inadequate responders, 63 patients were randomised to continue MTX or receive placebo (PBO), both in combination with TCZ 8 mg/kg every 4 weeks, with optional additional disease-modifying antirheumatic drugs at week 24 if Disease Activity Score of 28 joints < 3.2. The most symptomatic hand was imaged with 0.2 Tesla extremity MRI at weeks 0, 2, 12 and 52. MR images were scored using Outcome Measures in Rheumatology-Rheumatoid Arthritis Magnetic Resonance Imaging Score. Predictors of week 52 erosion progression were determined by logistic regression analysis.
  
  
  RESULTS
  TCZ + PBO (n=32) demonstrated mean improvements in synovitis from baseline to weeks 2 (-0.92; p=0.0011), 12 (-1.86; p<0.0001) and 52 (-3.35; p<0.0001), while TCZ + MTX (n=31) had mean improvements in synovitis at week 12 (-0.88; p=0.0074), but not week 52 (-1.00; p=0.0711). TCZ+PBO demonstrated mean reductions in osteitis at weeks 12 (-5.10; p=0.0022) and 52 (-8.56; p=0.0006), while TCZ+MTX had mean reductions at weeks 2 (-0.21; p<0.05) and 12 (-3.63; p=0.0008), but not week 52 (-2.31; p=0.9749). Mean erosion scores did not worsen in either group. MRI erosion scores at weeks 12 and 52 correlated strongly with radiography erosion scores at week 52 (r>0.80). Baseline synovitis and worsening of osteitis predicted erosion progression.
  
  
  CONCLUSIONS
  Rapid suppression of synovitis and osteitis with reduction in structural joint damage progression occurred with TCZ, as monotherapy or in combination with MTX, through week 52.
authors: University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, , Leeds, UK.
authors: Philip G
authors: PG
authors: Conaghan
authors: Charles
authors: C
authors: Peterfy
authors: Ewa
authors: E
authors: Olech
authors: Jeffrey
authors: J
authors: Kaine
authors: David
authors: D
authors: Ridley
authors: Julie
authors: J
authors: Dicarlo
authors: Josh
authors: J
authors: Friedman
authors: Jenny
authors: J
authors: Devenport
authors: Orrin
authors: O
authors: Troum
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010000:Osteitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013585:Synovitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate
keywords: DMARDs (biologic); Disease Activity; Magnetic Resonance Imaging; Rheumatoid Arthritis; Synovitis