Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis.
Age of Onset
Severity of Illness Index
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.
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.
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).
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.