title: Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis.
abstract: OBJECTIVE
  To determine whether ultrasound can identify anti-cyclic citrullinated peptide (anti-CCP) antibody-positive patients without clinical synovitis (CS) who progress to inflammatory arthritis (IA).
  
  
  METHODS
  In a prospective study, anti-CCP-positive patients without CS underwent ultrasound imaging of 32 joints (wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints (MTPs)) and were monitored for the development of IA. Associations between baseline ultrasound findings (grey scale (GS), power Doppler (PD) and erosions) and (1) progression to IA and (2) development of CS within an individual joint were measured.
  
  
  RESULTS
  Consecutive anti-CCP-positive patients (n=136; mean age 51 years, 100 women) were followed up for median of 18.3 months (range 0.1-79.6). At baseline 96% had GS, 30% had PD and 21% had one or more erosions. IA developed in 57 patients (42%) after median of 8.6 months (range 0.1-52.4). Ultrasound abnormalities (GS ≥2, PD ≥1 or erosion ≥1) were found in 86% at baseline compared with 67% of non-progressors (χ2=6.3, p=0.012). Progression to IA was significantly higher in those with ultrasound findings in any joint (excluding MTPs for GS) (GS ≥2: 55% vs 24%, HR (95% CI) 2.3 (1.0 to 4.9), p=0.038; PD ≥2: 75% vs 32%, 3.7 (2.0 to 6.9), p<0.001 and erosion ≥1: 71% vs 34%, 2.9 (1.7 to 5.1), p<0.001). Furthermore, progression occurred earlier with PD ≥2 (median 7.1 vs 52.4 months) and erosion ≥1 (15.4 vs 46.5). At the individual joint level, the trend for progression to CS was more significant for GS and PD (GS ≥2: 26% vs 3%, 9.4 (5.1 to 17.5), p<0.001; PD ≥2: 55% vs 4%, 31.3 (15.6 to 62.9), p<0.001).
  
  
  CONCLUSIONS
  Ultrasound features of joint inflammation may be detected in anti-CCP-positive patients without CS. Ultrasound findings predict progression (and rate of progression) to IA, with the risk of progression highest in those with PD signal.
  
  
  BACKGROUND
  NCT02012764; Results.
authors.affiliation: University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.|Leeds Teaching Hospitals NHS Trust, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors.forename: Jackie L
authors.initials: JL
authors.lastname: Nam
authors.affiliation: University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.|Leeds Teaching Hospitals NHS Trust, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors.forename: Elizabeth M A
authors.initials: EM
authors.lastname: Hensor
authors.affiliation: University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.|Leeds Teaching Hospitals NHS Trust, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Hunt
authors.affiliation: University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.|Leeds Teaching Hospitals NHS Trust, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.affiliation: University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.|Leeds Teaching Hospitals NHS Trust, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wakefield
authors.affiliation: University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.|Leeds Teaching Hospitals NHS Trust, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007596:Joints / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D014463:Ultrasonography / Q000379:methods
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: Ant-CCP; Early Rheumatoid Arthritis; Synovitis; Ultrasonography