title: 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.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  NCT01164579.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.affiliation: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: Imorphics Ltd, Manchester, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bowes
authors.affiliation: BioClinica Inc., Newark, California, USA.
authors.forename: Chunying
authors.initials: C
authors.lastname: Wu
authors.affiliation: BioClinica Inc., Newark, California, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fuerst
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Désirée
authors.identifier: http://orcid.org/0000-0002-5781-158X
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Centro de Investigación y Tratamiento Reumatológico SC.CINTRE, México City, México.
authors.forename: Fedra
authors.initials: F
authors.lastname: Irazoque-Palazuelos
authors.affiliation: Mindful Rheumatix, San Juan, Puerto Rico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Soto-Raices
authors.affiliation: Department of Rheumatology and Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Hrycaj
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Wyman
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Bradley
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Koshika
authors.initials: K
authors.lastname: Soma
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Bethanie
authors.initials: B
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015519:Bone Density / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001855:Bone Marrow Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004487:Edema / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006225:Hand / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D013585:Synovitis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome; D014955:Wrist Joint / Q000000981:diagnostic imaging
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D008727:Methotrexate
keywords: DMARDs (synthetic); Inflammation; Magnetic Resonance Imaging; Methotrexate; Rheumatoid Arthritis