Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis

J Rheumatol. 2014 Dec;41(12):2361-9. doi: 10.3899/jrheum.140082. Epub 2014 Oct 1.

Abstract

Objective: Rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are believed to be associated with more severe rheumatoid arthritis; however, studies in early inflammatory arthritis (EIA) have yielded conflicting results. Our study determined the prognosis of baseline ACPA-negative and RF-negative patients.

Methods: Patients enrolled in the Canadian Early Arthritis Cohort had IgM RF and IgG anticyclic citrullinated peptide antibodies 2 (anti-CCP2) measured at baseline. Remission was defined as a Disease Activity Score of 28 joints (DAS28) < 2.6 using logistic regression accounting for confounders at 12-month and 24-month followup.

Results: Of the 841 patients, 216 (26%) were negative for both RF and anti-CCP2. Compared to seropositive subjects, seronegative subjects were older (57 ± 15 vs 51 ± 14 yrs), more males proportionately (31% vs 23%), and had shorter length of symptoms (166 ± 87 vs 192 ± 98 days), and at baseline had higher mean swollen joint count (SJC; 8.8 ± 6.8 vs 6.5 ± 5.6), DAS28 (5.0 ± 1.6 vs 4.8 ± 1.5), and erosive disease (32% vs 24%, p < 0.05). Treatment was similar between the 2 groups. At 24-month followup, seronegative compared to seropositive subjects had greater mean change (Δ ± SD) in disease activity measures: ΔSJC counts (-6.9 ± 7.0 vs -5.1 ± 5.9), ΔDAS28 (-2.4 ± 2.0 vs -1.8 ± 1.8), and ΔC-reactive protein (-11.0 ± 17.9 vs -6.4 ± 17.5, p < 0.05). Accounting for confounders, antibody status was not significantly associated with remission. However, at 12-month followup, ACPA-positive subjects were independently more likely to have new erosive disease (OR 2.94, 95% CI 1.45-5.94).

Conclusion: Although seronegative subjects with EIA have higher baseline DAS28 compared to seropositive subjects, they have a good response to treatment and are less likely to develop erosive disease during followup.

Keywords: ANTICITRULLINATED PROTEIN ANTIBODIES; PROGNOSIS; RHEUMATOID ARTHRITIS; RHEUMATOID FACTOR.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Age of Onset
  • Aged
  • Antibodies, Anti-Idiotypic / blood*
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / immunology*
  • Biomarkers / blood
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Prognosis
  • Prospective Studies
  • Rheumatoid Factor / blood*
  • Severity of Illness Index
  • Sex Factors

Substances

  • Antibodies, Anti-Idiotypic
  • Biomarkers
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor