Abstract
IntroductionThis study aimed to investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA).MethodsData from the Norfolk Arthritis Register (NOAR) and Leiden Early Arthritis Clinic (EAC) cohorts were used. At baseline, patients had demographic data and smoking status recorded; RF, ACPA and inflammatory markers were measured in the local laboratories. Patients were flagged with national death registers until death or censor date. Antibody status was stratified as negative, low or high positive by RF and ACPA levels individually. In addition, patients were grouped as seronegative, RF positive, ACPA positive or double antibody (RF and ACPA) positive. Cox regression models explored associations between antibody status and mortality adjusting for age, sex, smoking status, inflammatory markers and year of enrolment.ResultsA total of 4962 patients were included, 64% were female. Median age at onset was 56 (NOAR) and 54 (EAC) years. In NOAR and EAC respectively, 35% and 42% of patients were ACPA/RF positive. When antibody status was stratified as negative, low or high positive, there were no consistent findings between the two cohorts. Double antibody positivity was associated with excess mortality in both cohorts compared to seronegative patients: NOAR and EAC respective adjusted HR (95% confidence interval) 1.35 (1.09 to 1.68) and 1.58 (1.16 to 2.15).ConclusionsPatients with EIA who are seropositive for both RF and ACPA have increased mortality compared to those who are single positive or seronegative. Antibody level in seropositive patients was not consistently associated with excess mortality.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0483-3) contains supplementary material, which is available to authorized users.
Highlights
This study aimed to investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA)
Antibody level is included in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) [12], which aim to identify those patients with EIA with poor prognosis sufficient to require intervention with disease modifying therapy
In two well established observational cohorts of EIA and its sub-population of patients with RA, we have shown that RF and ACPA positivity are predictors of excess mortality, and that the presence of both antibodies was a stronger predictor of mortality than single antibody positivity
Summary
This study aimed to investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA). In patients with inflammatory arthritis, the autoantibodies rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) have been associated with poor outcomes, such as increased disease activity, radiographic progression and disability [1,2,3,4,5]. The utility of antibody level in predicting the prognosis of important in predicting poor outcome in patients with EIA and RA [8,9,10]. Antibody level is included in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA [12], which aim to identify those patients with EIA with poor prognosis sufficient to require intervention with disease modifying therapy. Patients with high antibody levels are more likely to fulfil the criteria, and it would be interesting to investigate whether these cut-offs are appropriate in predicting other adverse outcomes, such as mortality
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