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Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms: a prospective observational cohort study
  1. C Rakieh1,
  2. J L Nam1,2,
  3. L Hunt1,2,
  4. E M A Hensor1,2,
  5. S Das1,
  6. L-A Bissell1,2,
  7. E Villeneuve1,3,
  8. D McGonagle1,2,
  9. R Hodgson1,2,
  10. A Grainger1,2,
  11. R J Wakefield1,2,
  12. P G Conaghan1,2,
  13. P Emery1,2
  1. 1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK
  2. 2NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  3. 3Rheumatology Department, Centre Hospitalier de l'Université de Montréal Hôpital, Montréal, Quebec, Canada
  1. Correspondence to Professor Paul Emery, Leeds Institute of Rheumatic & Musculoskeletal Disease, NIHR Leeds, Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital Leeds, Teaching Hospitals NHS Trust, Leeds LS7 4SA, UK; P.emery{at}


Objectives To monitor progression to inflammatory arthritis (IA) in individuals with non-specific musculoskeletal (MSK) symptoms and positive anticyclic citrullinated peptide (anti-CCP) antibodies. To develop a pragmatic model to predict development of IA in this patient group.

Methods In this prospective observational cohort, patients with new non-specific MSK symptoms and positive anti-CCP were recruited from regional primary care and secondary care referrals. Clinical, imaging and serological parameters were assessed at baseline. Cox regression analysis was performed to identify predictors of progression to IA and develop a risk score to stratify patients at presentation.

Findings 100 consecutive patients (73 women, mean age 51 years) were followed up for median 19.8 months (range 0.1–69.0); 50 developed IA after a median 7.9 months (range 0.1–52.4), 34 within 12 months. The majority (43/50) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis. A model for progression to IA was devised using four variables: tenderness of hand or foot joints, early morning stiffness ≥30 min, high-positive autoantibodies, and positive ultrasonographic power Doppler signal. None of the five individuals at low risk (score 0) progressed to IA, compared with 31% of 29 at moderate risk (1–2) and 62% of 66 at high risk (≥3). Adding shared epitope increased the number at low risk (score 0–1; 0/11 progressed).

Conclusions In patients presenting with non-specific MSK symptoms and anti-CCP, the risk of progression to IA could be quantified using data available in clinical practice. The proposed risk score may be used to stratify patients for early therapeutic intervention.

Trial registration number NCT02012764 at

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

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