title: Enriching case selection for imminent RA: the use of anti-CCP antibodies in individuals with new non-specific musculoskeletal symptoms - a cohort study.
abstract: OBJECTIVE
  Around 1% of the population test positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies. This biomarker predicts the progression to rheumatoid arthritis (RA) but over a variable time frame. To increase its clinical relevance, this study sought to determine (1) if the proportion of anti-CCP-positive individuals could be enriched by case selection of people attending primary care with new non-specific musculoskeletal (MSK) symptoms but without clinical synovitis (CS) and (2) whether these individuals progress rapidly to inflammatory arthritis (IA), in particular RA.
  
  
  METHODS
  In this prospective cohort study, individuals aged ≥18 years with new non-specific MSK symptoms, without CS, were recruited from primary care in the UK. Anti-CCP-positive individuals were invited for follow-up in the rheumatology department, Leeds. Those who tested negative were sent questionnaires 12 months later.
  
  
  RESULTS
  2028 individuals were recruited. Of these, 2.8% (57/2028) were anti-CCP positive, of whom 47% (27/57) developed IA - 24 RA, 1 undifferentiated IA (UIA), 2 polymyositis; 92.6% (25/27) within 12 months, median 1.8 months (IQR 1.0-4.3, range 0.3-16.1). Of the anti-CCP-negative individuals, 1.3% (20/1559) developed IA (1 UIA, 13 RA, 6 psoriatic arthritis); 75% (15/20) within 12 months. The relative risk for developing RA within 12 months in the anti-CCP-positive group was 66.8 (95% CI 32.2 to 138.4, p<0.001); for IA, it was 45.5 (95% CI 25.4 to 81.6, p<0.001).
  
  
  CONCLUSIONS
  Selecting individuals with new non-specific MSK symptoms without CS enriched the prevalence of anti-CCP positivity to 2.8%. Those who tested positive had a high risk of rapidly developing RA. The cost-effectiveness of this approach will need to be determined.
  
  
  BACKGROUND
  NCT02012764.
authors.affiliation: University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Nam
authors.affiliation: University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, 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 NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, 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 NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: Ant-CCP; Autoantibodies; Early Rheumatoid Arthritis; Rheumatoid Arthritis