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

Ann Rheum Dis. 2016 Jun;75(6):1139-44. doi: 10.1136/annrheumdis-2015-207326. Epub 2015 Oct 6.

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.

Keywords: Autoantibodies; Disease Activity; Early Rheumatoid Arthritis; Epidemiology; Rheumatoid Arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Carbamates / immunology*
  • Disability Evaluation
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology
  • Prognosis
  • Registries
  • Rheumatoid Factor / blood
  • Severity of Illness Index

Substances

  • Autoantibodies
  • Biomarkers
  • Carbamates
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor