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Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis
  1. Jackie L Nam1,2,
  2. Elizabeth M A Hensor1,2,
  3. Laura Hunt1,2,
  4. Philip G Conaghan1,2,
  5. Richard J Wakefield1,2,
  6. Paul Emery1,2
  1. 1University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK
  2. 2Leeds Teaching Hospitals NHS Trust, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK
  1. Correspondence to Professor Paul Emery, University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital, Second Floor, Chapeltown Road, Leeds LS7 4SA, UK; p.emery{at}


Objectives 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).

Conclusion 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.

Trial registration number NCT02012764; Results.

  • Ant-CCP
  • Ultrasonography
  • Synovitis
  • Early Rheumatoid Arthritis

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