Prognosis of Seronegative Patients in a Large Prospective Cohort of Patients with Early Inflammatory Arthritis

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 (Delta +/- SD) in disease activity measures: Delta SJC counts (-6.9 +/- 7.0 vs -5.1 +/- 5.9), Delta DAS28 (-2.4 +/- 2.0 vs -1.8 +/- 1.8), and Delta C-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.