title: Effect of a treat-to-target strategy based on methotrexate and intra-articular betamethasone with or without additional cyclosporin on MRI-assessed synovitis, osteitis, tenosynovitis, bone erosion, and joint space narrowing in early rheumatoid arthritis: results from a 2-year randomized double-blind placebo-controlled trial (CIMESTRA).
abstract: OBJECTIVE
  To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect.
  
  
  METHODS
  In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods.
  
  
  RESULTS
  Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups.
  
  
  CONCLUSIONS
  In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.
authors: a Copenhagen Centre for Arthritis Research, Centre for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.|b Department of Rheumatology , Slagelse Hospital , Slagelse , Denmark.
authors: S
authors: S
authors: Møller-Bisgaard
authors: b Department of Rheumatology , Slagelse Hospital , Slagelse , Denmark.
authors: B J
authors: BJ
authors: Ejbjerg
authors: c Department of Radiology , Sheba Medical Centre , Tel Hashomer , Israel.
authors: I
authors: I
authors: Eshed
authors: d King Christian X's Hospital for Rheumatic Diseases , Graasten , Denmark.
authors: K
authors: http://orcid.org/0000-0002-5475-7610
authors: K
authors: Hørslev-Petersen
authors: a Copenhagen Centre for Arthritis Research, Centre for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.|e The DANBIO Registry, Centre for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.
authors: M L
authors: ML
authors: Hetland
authors: f Department of Radiology , Aarhus University Hospital , Aarhus , Denmark.
authors: A G
authors: AG
authors: Jurik
authors: g Department of Radiology , Herlev-Gentofte University Hospital , Herlev , Denmark.
authors: H
authors: H
authors: Thomsen
authors: h Department of Radiology , Odense University Hospital , Odense , Denmark.
authors: T
authors: T
authors: Torfing
authors: i Department of Rheumatology , Aarhus University Hospital , Aarhus , Denmark.
authors: K
authors: K
authors: Stengaard-Pedersen
authors: j Department of Rheumatology , Odense University Hospital , Odense , Denmark.
authors: P
authors: P
authors: Junker
authors: k Zitelab ApS , Copenhagen , Denmark.
authors: N S
authors: NS
authors: Krogh
authors: l Department of Rheumatology , Vejle Hospital , Vejle , Denmark.
authors: T
authors: T
authors: Lottenburger
authors: j Department of Rheumatology , Odense University Hospital , Odense , Denmark.
authors: T
authors: T
authors: Ellingsen
authors: m Department of Rheumatology , Herlev-Gentofte University Hospital , Gentofte , Denmark.
authors: L S
authors: LS
authors: Andersen
authors: a Copenhagen Centre for Arthritis Research, Centre for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.
authors: H
authors: H
authors: Skjødt
authors: n Department of Epidemiology , Institute of Public Health, University of Southern Denmark , Odense , Denmark.
authors: A J
authors: AJ
authors: Svendsen
authors: i Department of Rheumatology , Aarhus University Hospital , Aarhus , Denmark.
authors: U
authors: U
authors: Tarp
authors: i Department of Rheumatology , Aarhus University Hospital , Aarhus , Denmark.
authors: I T
authors: IT
authors: Hansen
authors: m Department of Rheumatology , Herlev-Gentofte University Hospital , Gentofte , Denmark.
authors: J
authors: J
authors: Pødenphant
authors: j Department of Rheumatology , Odense University Hospital , Odense , Denmark.
authors: J K
authors: JK
authors: Pedersen
authors: j Department of Rheumatology , Odense University Hospital , Odense , Denmark.
authors: H
authors: H
authors: Lindegaard
authors: o Centre for Functional and Diagnostic Imaging and Research , Danish Research Centre for Magnetic Resonance (DRCMR), Copenhagen University Hospital Hvidovre , Hvidovre , Denmark.|p Biomedical Engineering, Elektro , Technical University of Denmark (DTU) , Lyngby , Denmark.
authors: L G
authors: LG
authors: Hanson
authors: q Department of Radiology , Copenhagen University Hospita Hvidovrel , Hvidovre , Denmark.
authors: A
authors: A
authors: Vestergaard
authors: a Copenhagen Centre for Arthritis Research, Centre for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.
authors: D
authors: D
authors: Glinatsi
authors: a Copenhagen Centre for Arthritis Research, Centre for Rheumatology and Spine Diseases , Rigshospitalet , Glostrup , Denmark.
authors: M
authors: M
authors: Østergaard
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000503:physiopathology; D001623:Betamethasone / Q000008:administration & dosage*; D001847:Bone Diseases / Q000188:drug therapy / Q000209:etiology; D016572:Cyclosporine / Q000008:administration & dosage*; D004311:Double-Blind Method; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D062072:Patient Acuity; D013585:Synovitis / Q000188:drug therapy / Q000209:etiology; D052256:Tendinopathy / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D016572:Cyclosporine; D001623:Betamethasone; D008727:Methotrexate