Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-naïve patients classified according to the 2010 ACR/EULAR criteria

Abstract

ObjectivesTo compare the presentation of seropositive and seronegative early rheumatoid arthritis (RA) in disease-modifying antirheumatic drug (DMARD)-naïve patients classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria.MethodsAll patients had symptom duration from first swollen joint <2 years and were DMARD naïve with an indication for DMARD treatment. Patients were stratified as seropositive (positive rheumatoid factor (RF)+ and/or anticitrullinated peptide antibody (ACPA)+) or seronegative (RF− and ACPA−), and disease characteristics were compared between groups.ResultsA total of 234 patients were included, and 36 (15.4%) were seronegative. Ultrasonography (US) scores for joints (median 55 vs 25, p<0.001) and tendons (median 3 vs 0, p<0.001), number of swollen joints (median 17 vs 8, p<0.001), disease activity score (DAS; mean 3.9 vs 3.4, p=0.03) and physician global assessment (mean 49.1 vs 38.9, p=0.006) were significantly higher in seronegative patients compared with seropositive. Total van der Heijde-modified Sharp score, Richie Articular Index and patient-reported outcome measures were similar between groups.ConclusionsSeronegative patients had higher levels of inflammation, assessed both clinically and by US, than seropositive patients. These differences may reflect the high number of involved joints required for seronegative patients to fulfil the 2010 ACR/EULAR classification criteria for RA.Trial registration numberNCT01205854; Pre-results.

Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present

“…The association between the presence of additional autoantibodies and longer symptom duration is in line with a previous publication 13. It was recently reported that seronegative individuals have higher joint counts at presentation 5. We found in addition that increasing numbers of autoantibodies are associated with lower tender joint counts (and swollen joint counts in EAC).…”

“…Seropositive patients also have a worse disease outcome with more radiological damage over time 4. In contrast, seronegative patients have recently been described to have more joint inflammation at initial presentation 5. Even though novel autoantibodies may be discovered in the future, seropositive and seronegative RA as defined at the moment is likely to differ in underlying pathophysiology and phenotype 5 6…”

What is rheumatoid arthritis? Considering consequences of changed classification criteria

“…Although it is not directly evaluated in the study of Nordberg et al ,5 the results of this study suggest that the increase in sensitivity is largely confined to patients who are ACPA positive because patients who are ACPA negative now require more inflamed/involved joints to be classified as RA than those who are ACPA positive. Further studies are needed to verify this.…”

“…The study of Nordberg et al 5 makes us think about the consequences of the novel criteria for the phenotype of RA. According to the 1987 criteria, the characteristic phenotype of RA consists of symmetric polyarthritis of small joints with morning stiffness (ignoring the features of long-standing disease nodules and erosions).…”

The role of autoantibodies in the pathophysiology of rheumatoid arthritis

“…More recently, antibodies against other posttranslationally modified proteins, i.e., carbamylated [2] and acetylated proteins were identified [3]. Seropositive RA is associated with increased radiographic progression and joint damage [27], while seronegative RA patients have higher inflammation parameters at presentation [28]. Furthermore, not only positivity for a single autoantibody but rather the conjoined presence of multiple autoantibodies might be relevant for characterizing distinct phenotypes of RA patients [29].…”