title: Subclinical synovitis detected by macrophage PET, but not MRI, is related to short-term flare of clinical disease activity in early RA patients: an exploratory study.
abstract: BACKGROUND
  Residual subclinical synovitis can still be present in joints of rheumatoid arthritis (RA) patients despite clinical remission and has been linked to ongoing radiological damage. The aim of the present study was to assess subclinical synovitis by positron emission tomography (PET; macrophage tracer (11)C-(R)-PK11195) in early RA patients with minimal disease activity without clinically apparent synovitis (MDA); and its relationship with clinical outcome and magnetic resonance imaging (MRI), respectively.
  
  
  METHODS
  Baseline PET and MRI of hands/wrists were performed in 25 early MDA RA patients (DAS 44 < 1.6; no tender/swollen joints) on combined DMARD therapy. PET tracer uptake (semi-quantitative score: 0-3) and MRI synovitis and bone marrow edema (OMERACT RAMRIS) were assessed in MCP, PIP and wrist joints (22 joints/patient; cumulative score).
  
  
  RESULTS
  Eleven of 25 patients (44 %) showed enhanced tracer uptake in ≥ 1 joint. Fourteen of these 25 (56 %) patients developed a flare within 1 year: 8/11 (73 %) with a positive, and 6/14 (43 %) with a negative PET. In the latter, in 5/6 patients flare was located outside the scan region. Median cumulative PET scores of patients with a subsequent flare in the hands or wrists were significantly higher than those of patients without a flare (1.5 [IQR 0.8-5.3] vs 0.0 [IQR 0.0-1.0], p = 0.04); significance was lost when all flares were considered (1.0 [IQR 0.0-4.0] vs 0.0 [IQR 0.0-1.0], p = 0.10). No difference in cumulative MRI scores was observed between both groups.
  
  
  CONCLUSIONS
  Positive PET scans were found in almost half of early RA patients with MDA. Patients with a subsequent flare in hand or wrist had higher cumulative PET scores but not MRI scores, suggesting that subclinical arthritis on PET may predict clinical flare in follow-up.
authors.affiliation: Department of Rheumatology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, 1081, HV, The Netherlands. y.gent@vumc.nl.
authors.forename: Yoony Y J
authors.initials: YY
authors.lastname: Gent
authors.affiliation: Department of Rheumatology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, 1081, HV, The Netherlands. m.terwee@vumc.nl.
authors.forename: Marieke M
authors.initials: MM
authors.lastname: Ter Wee
authors.affiliation: Department of Rheumatology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, 1081, HV, The Netherlands. ae.voskuyl@vumc.nl.
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
authors.affiliation: Department of Rheumatology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, 1081, HV, The Netherlands. d.denuyl@vumc.nl.
authors.forename: Debby
authors.initials: D
authors.lastname: den Uyl
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, 1081, HV, The Netherlands. n.ahmadi@vumc.nl.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Ahmadi
authors.affiliation: Department of Rheumatology, Jan van Breemen Research Institute | Reade, Amsterdam, dr. Jan van Breemenstraat 2, Amsterdam, 1056, AB, The Netherlands. cristina_dowling@hotmail.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Dowling
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, 1081, HV, The Netherlands. c.vankuijk@vumc.nl.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Kuijk
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, 1081, HV, The Netherlands. os.hoekstra@vumc.nl.
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.affiliation: Department of Rheumatology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, 1081, HV, The Netherlands. m.boers@vumc.nl.|Department of Clinical Epidemiology & Biostatistics, VU University Medical Center, De Boelelaan 1117, Amsterdam, 1081, HV, The Netherlands. m.boers@vumc.nl.
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.affiliation: Department of Rheumatology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, 1081, HV, The Netherlands. wf.lems@vumc.nl.
authors.forename: Willem F
authors.initials: WF
authors.lastname: Lems
authors.affiliation: Department of Rheumatology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, 1081, HV, The Netherlands. j.vanderlaken@vumc.nl.
authors.forename: Conny J
authors.initials: CJ
authors.lastname: van der Laken
mesh_terms: D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007546:Isoquinolines; D008264:Macrophages / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013585:Synovitis / Q000000981:diagnostic imaging* / Q000473:pathology
chemical_list: D007546:Isoquinolines; D019275:Radiopharmaceuticals; C037850:PK 11195