title: A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or without adalimumab effectively reduces MRI synovitis, osteitis and tenosynovitis and halts structural damage progression in early rheumatoid arthritis: results from the OPERA randomised controlled trial.
abstract: OBJECTIVE
  To investigate whether a treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid injections suppresses MRI inflammation and halts structural damage progression in patients with early rheumatoid arthritis (ERA), and whether adalimumab provides an additional effect.
  
  
  METHODS
  In a double-blind, placebo-controlled trial, 85 disease-modifying antirheumatic drug-naïve patients with ERA were randomised to receive methotrexate, intra-articular glucocorticosteroid injections and placebo/adalimumab (43/42). Contrast-enhanced MRI of the right hand was performed at months 0, 6 and 12. Synovitis, osteitis, tenosynovitis, MRI bone erosion and joint space narrowing (JSN) were scored with validated methods. Dynamic contrast-enhanced MRI (DCE-MRI) was carried out in 14 patients.
  
  
  RESULTS
  Synovitis, osteitis and tenosynovitis scores decreased highly significantly (p<0.0001) during the 12-months' follow-up, with mean change scores of -3.7 (median -3.0), -2.2 (-1) and -5.3 (-4.0), respectively. No overall change in MRI bone erosion and JSN scores was seen, with change scores of 0.1 (0) and 0.2 (0). The tenosynovitis score at month 6 was significantly lower in the adalimumab group, 1.3 (0), than in the placebo group, 3.9 (2), Mann-Whitney: p<0.035. Furthermore, the osteitis score decreased significantly during the 12-months' follow-up in the adalimumab group, but not in the placebo group, Wilcoxon: p=0.001-0.002 and p=0.062-0.146. DCE-MRI parameters correlated closely with conventional MRI inflammatory parameters. Clinical measures decreased highly significantly during follow-up.
  
  
  CONCLUSIONS
  A treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid in patients with ERA effectively decreased synovitis, osteitis and tenosynovitis and halted structural damage progression as judged by MRI. The findings suggest that addition of adalimumab is associated with further suppression of osteitis and tenosynovitis.
authors.affiliation: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark.
authors.forename: Mette Bjørndal
authors.initials: MB
authors.lastname: Axelsen
authors.affiliation: Department of Radiology, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Eshed
authors.affiliation: King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark South Jutland Hospital, Institute of Regional Health Services Research, University of Southern Denmark, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.affiliation: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark The DANBIO Registry, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.affiliation: Department of Radiology, Copenhagen University Hospital at Herlev, Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Møller
authors.affiliation: Department of Rheumatology C, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
authors.affiliation: Department of Rheumatology, Copenhagen University Hospital at Gentofte, Gentofte, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Pødenphant
authors.affiliation: Department of Rheumatology, Aarhus University Hospital in Aalborg, Aalborg, Denmark.
authors.forename: Annette
authors.initials: A
authors.lastname: Schlemmer
authors.affiliation: Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark.
authors.forename: Torkell
authors.initials: T
authors.lastname: Ellingsen
authors.affiliation: Department of Medicine, Vejle Regional Hospital, Vejle, Denmark.
authors.forename: Palle
authors.initials: P
authors.lastname: Ahlquist
authors.affiliation: Department of Rheumatology C, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Lindegaard
authors.affiliation: Department of Rheumatology, Vendsyssel Hospital, Hjørring, Denmark.
authors.forename: Asta
authors.initials: A
authors.lastname: Linauskas
authors.affiliation: Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark.
authors.forename: Mette Yde
authors.initials: MY
authors.lastname: Dam
authors.affiliation: Department of Rheumatology, Viborg Regional Hospital, Viborg, Denmark.
authors.forename: Ib
authors.initials: I
authors.lastname: Hansen
authors.affiliation: Department of Medicine, Vejle Regional Hospital, Vejle, Denmark.
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Horn
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Christian Gytz
authors.initials: CG
authors.lastname: Ammitzbøll
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anette
authors.initials: A
authors.lastname: Jørgensen
authors.affiliation: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.
authors.forename: Sophine B
authors.initials: SB
authors.lastname: Krintel
authors.affiliation: King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark South Jutland Hospital, Institute of Regional Health Services Research, University of Southern Denmark, Denmark.
authors.forename: Johnny
authors.initials: J
authors.lastname: Raun
authors.affiliation: Zitelabs Aps, Copenhagen, Denmark.
authors.forename: Niels S
authors.initials: NS
authors.lastname: Krogh
authors.affiliation: Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark Department of Medicine and Oncology, Copenhagen University Hospital at Herlev, Herlev, Denmark.
authors.forename: Julia Sidenius
authors.initials: JS
authors.lastname: Johansen
authors.affiliation: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark The DANBIO Registry, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital at Glostrup, Glostrup, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002985:Clinical Protocols; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D008279:Magnetic Resonance Imaging; D008297:Male; D008662:Metacarpophalangeal Joint / Q000473:pathology; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010000:Osteitis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D010347:Patient Care Planning; D012720:Severity of Illness Index; D013585:Synovitis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D013717:Tenosynovitis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome; D014221:Triamcinolone / Q000627:therapeutic use*; D014955:Wrist Joint / Q000473:pathology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014221:Triamcinolone; D000068879:Adalimumab; D008727:Methotrexate
keywords: Magnetic Resonance Imaging; Rheumatoid Arthritis; Treatment