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Extended report
The effects of tocilizumab on osteitis, synovitis and erosion progression in rheumatoid arthritis: results from the ACT-RAY MRI substudy
  1. Philip G Conaghan1,
  2. Charles Peterfy2,
  3. Ewa Olech3,
  4. Jeffrey Kaine4,
  5. David Ridley5,
  6. Julie DiCarlo2,
  7. Josh Friedman6,
  8. Jenny Devenport6,
  9. Orrin Troum7
  1. 1University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK
  2. 2Spire Sciences, Inc, Boca Raton, Florida, USA
  3. 3University of Nevada School of Medicine, Las Vegas, Nevada, USA
  4. 4Sarasota Arthritis Center, Sarasota, Florida, USA
  5. 5Saint Paul Rheumatology, Eagan, Minnesota, USA
  6. 6Genentech, Inc, South San Francisco, California, USA
  7. 7University of Southern California, Santa Monica, California, USA
  1. Correspondence to Professor Philip G Conaghan, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK; p.conaghan{at}leeds.ac.uk

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.

  • Rheumatoid Arthritis
  • DMARDs (biologic)
  • Magnetic Resonance Imaging
  • Disease Activity
  • Synovitis

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