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Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques
  1. Philip G Conaghan1,
  2. Mikkel Østergaard2,
  3. Michael A Bowes3,
  4. Chunying Wu4,
  5. Thomas Fuerst4,
  6. Désirée van der Heijde5,
  7. Fedra Irazoque-Palazuelos6,
  8. Oscar Soto-Raices7,
  9. Pawel Hrycaj8,
  10. Zhiyong Xie9,
  11. Richard Zhang9,
  12. Bradley T Wyman9,
  13. John D Bradley9,
  14. Koshika Soma9,
  15. Bethanie Wilkinson9
  1. 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK
  2. 2Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  3. 3Imorphics Ltd, Manchester, UK
  4. 4BioClinica Inc., Newark, California, USA
  5. 5Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  6. 6Centro de Investigación y Tratamiento Reumatológico SC.CINTRE, México City, México
  7. 7Mindful Rheumatix, San Juan, Puerto Rico
  8. 8Department of Rheumatology and Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland
  9. 9Pfizer Inc, Groton, Connecticut, USA
  1. Correspondence to Dr 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

Objectives To explore the effects of tofacitinib—an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)—with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand.

Methods In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant.

Results In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were −1.55 (90% CI −2.52 to −0.58) for tofacitinib + MTX and −1.74 (−2.72 to −0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were −0.63 (−1.58 to 0.31) for tofacitinib + MTX and −0.52 (−1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy.

Conclusions These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage.

Trial registration number NCT01164579.

  • DMARDs (synthetic)
  • Inflammation
  • Magnetic Resonance Imaging
  • Methotrexate
  • Rheumatoid Arthritis

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