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Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis: results from the Norfolk Arthritis Register
  1. Jennifer H Humphreys1,
  2. Marije K Verheul2,
  3. Anne Barton3,4,
  4. Alexander J MacGregor5,
  5. Mark Lunt1,
  6. Rene EM Toes2,
  7. Deborah PM Symmons1,4,
  8. Leendert A Trouw2,
  9. Suzanne MM Verstappen1
  1. 1Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, UK
  2. 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
  4. 4NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academic Health Science Centre, Manchester, UK
  5. 5Arthritis Research UK Centre for Genetics and Genomics, University of Manchester, Manchester, UK
  1. Correspondence to Dr Suzanne MM Verstappen, Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK; suzanne.verstappen{at}manchester.ac.uk

Abstract

Objectives Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years’ follow-up in a cohort of patients with inflammatory polyarthritis (IP).

Methods Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model.

Results 1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model.

Conclusions Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA.

  • Early Rheumatoid Arthritis
  • Disease Activity
  • Autoantibodies
  • Epidemiology
  • Rheumatoid Arthritis

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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