Clinical management of seronegative and seropositive rheumatoid arthritis: A comparative study

Both rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are associated with poor radiologic outcomes in patients with rheumatoid arthritis (RA). In general, RA patients positive for RF or ACPA (SPRA) are considered to manifest an aggressive disease course compared with seronegative RA patients (SNRA). However, the relationship between seropositivity and measures of disease severity other than radiologic outcome is disputed. In this study, we sought to compare the clinical presentations and treatment outcomes of SNRA and SPRA patients. A total of 241 patients diagnosed with DMARD-naïve RA under either 1987 American College of Rheumatology (ACR) criteria or 2010 ACR/European League Against Rheumatism (EULAR) criteria were identified (40 with SNRA and 201 with SPRA). We investigated the disease activity measures including ESR, CRP, patient VAS, 28 tender/swollen joint count (28 TJC, 28 SJC) and DAS28 as well as radiologic outcomes at baseline, 1 and 2 years after conventional treatment with DMARD. Age, sex and disease duration were similar between SNRA and SPRA. However, the baseline 28 TJC (4.7±2.9 vs. 3.3±2.7, p = 0.004), 28 SJC (4.3±3.0 vs. 2.9±2.3, p = 0.001) and DAS28 (5.1±1.0 vs. 4.7±1.0, p = 0.043) components were significantly higher in SNRA than in SPRA. Over 2 years of similar treatment with DMARDs, all disease activity measures significantly improved in both groups. Comparison among populations matched for baseline disease activity showed that ΔDAS28 at 1 year was greater in SNRA than in SPRA (-2.84±1.32 vs. -3.70±1.29, p = 0.037) in high disease activity population (DAS28-ESR>5.1). Radiologic outcomes at baseline and at 1- or 2-year follow-up were similar between the 2 groups. In conclusion, SNRA patients manifested more active disease at baseline, but showed a better response to treatment compared with SPRA. SNRA does not appear to be a benign subtype of RA.