Comparing the disease course of patients with seronegative and seropositive rheumatoid arthritis fulfilling the 2010 ACR/EULAR classification criteria in a treat-to-target setting: 2-year data from the ARCTIC trial

Abstract

ObjectivesRecent studies suggest that implementation of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) leads to higher inflammatory activity in seronegative compared with seropositive patients at time of diagnosis. Our aim was to compare the disease course in seronegative and seropositive patients classified according to the 2010 criteria.MethodsDMARD-naïve patients with RA fulfilling the 2010 criteria were included in the treat-to-target ARCTIC trial and followed for 24 months. We stratified patients as seropositive (rheumatoid factor (RF)+, anticitrullinated protein antibodies (ACPA)+ or both) or seronegative (RF– and ACPA–) and compared disease activity, radiographic progression, treatment response and remission rates across groups.Results230 patients were included with mean (SD) age 51.4 (13.7) years, and 61% were female. 34 patients (15%) were seronegative. At 24 months, disease activity measures, radiographic progression and remission rates were similar between groups, despite more inflammatory activity in seronegative patients at baseline. Treatment response was slower in seronegative compared with seropositive patients. The groups received similar treatment.ConclusionOur findings suggest that among patients with RA classified according to the 2010 ACR/EULAR criteria, seronegative patients respond well to modern treatment strategies. However, treatment response was somewhat slower in seronegative patients and radiographic progression was similar in seronegative and seropositive patients. Our results indicate that seronegative RA is not a mild form of the disease and requires intensive treat-to-target therapy similar to treatment of seropositive RA.

Predictors of sustained remission in patients with early rheumatoid arthritis treated according to an aggressive treat-to-target protocol

“…The seronegative patients had the highest levels of inflammation at baseline,(7) but these patients had, nevertheless, two-year remission rates comparable to the seropositive patients suggesting good response to modern treatment. (200) Very early arthritis (defined as symptom duration less than three or six months) are highlighted as the most important factor for reaching remission, (73,74,201) and our study supports DMARD initiation within 3 months after symptom onset. As symptom onset was defined as the first swollen joint according to patient memory, there is a chance of recall bias.…”

Anti-cyclic citrullinated peptide antibodies are associated with radiographic damage but not disease activity in early rheumatoid arthritis diagnosed in 2006–2011

“…These observations are in line with our results as well as the results from previous studies (29 -34). However, when studying recent-onset patients classified according to the 2010 RA criteria, anti-CCP-positive disease does not appear to be associated with more severe outcomes (25,35).…”

“…The association remained after adjusting for response to treatment after 6 months, but it should be noted that initial treatment with biological disease-modifying anti-rheumatic drugs (bDMARDs) was rare, and hypothetically, more frequent early bDMARD use could have attenuated the radiographic damage associated with anti-CCP. A study from Norway showed that in the context of 2010 criteria-based enrolment and a strict treat-to-target protocol, anti-CCP positivity was not associated with increased radiographic damage (25). In the Swedish Swefot trial, however, where early RA patients according to ARA 1987 with inadequate response to MTX were randomized to either triple therapy or infliximab, baseline anti-CCP positivity was indeed associated with increased 2 year radiographic damage (13).…”

Use of ICD-10 diagnosis codes to identify seropositive and seronegative rheumatoid arthritis when lab results are not available

“…Indeed, a majority of RA patients (typically more than 80%) who are positive for one lab test will be positive for the other. Given the relative infrequency of discordance (i.e., RF+, anti-CCP-; or RF-, anti-CCP+), patients tend to be grouped as seronegative (both negative) or seropositive (either or both positive) in most RA outcome studies [14]. A combined approach also would avoid the need for separately representing the concept of anti-CCP antibody lab test results as part of ICD-10 coding, which avoids added complexity and administrative burden to clinicians assigning these codes.…”