In addition, their analysis employed last observation carried forward to account for patients who did not have complete follow up

In addition, their analysis employed last observation carried forward to account for patients who did not have complete follow up. 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 LEQ506 1.68) and 1.58 (1.16 to 2.15). Conclusions Patients 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 LEQ506 material The online version of this article (doi:10.1186/s13075-014-0483-3) contains supplementary material, which is available to authorized users. Introduction 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 [1-5]. However, the utility of antibody level in predicting the prognosis of inflammatory arthritis, in particular rheumatoid arthritis (RA), has not been clearly established. In a recent multicentre prospective study of patients with early inflammatory arthritis (EIA), the presence of RF and/or ACPA was a significant predictor of RA diagnosis within two years, but level did not appear to be important [6]. In contrast, in a study of patients with EIA from Norway in 2010 2010, Mjaavatten et al. found that increasing levels of RF and ACPA were associated with persistent joint inflammation [7]. Other studies have failed to show consistently that either RF or ACPA antibody level is important in predicting poor outcome in patients with EIA and RA [8-10]. In addition, recent data from a subset of the Leiden Early Arthritis Clinic have shown that the avidity of ACPA may be prognostically more important than the level itself [11]. Nevertheless, 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. The presence of RF and ACPA are weighted as part of the total score according to their level; patients are said to be low positive if their level is greater than the upper limit of normal (ULN) but less than three times the ULN, and high positive if their level is at least three times the ULN. Thus, 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. The increased mortality in patients with RA has been long established [13]. It is also well recognised that the presence of RF in sera of patients FANCE with inflammatory arthritis (whether or not they meet formal classification criteria for RA) is associated with an increased risk of premature death [14-16]. In fact, this association has been demonstrated even in subjects without symptoms of LEQ506 arthritis [17]. ACPA positivity has also been shown to predict premature mortality in the Norfolk Arthritis Register [18]; however this association has yet to be confirmed in other cohorts. The aims of this study were to investigate the association between mortality and RF and/or ACPA positivity and level in patients with EIA. The term EIA includes all patients with RA early in the disease process, and studying these patients allows additional inclusion of those patients who may later go on to meet formal classification criteria for RA. It has been recognised that significant variability in antibody testing can occur between laboratories [19]. Thus, to strengthen the external validity of the study results, we investigated these questions in two large prospective cohorts of patients with EIA: the Norfolk Arthritis Register (NOAR) in the UK and the Leiden Early Arthritis Clinic (EAC) in the Netherlands. Methods Patients and setting Patients in Norfolk, UK, were recruited to NOAR between 1990 and 2009 from primary and secondary care if they were adults (16?years) and had 2 swollen joints for 4?weeks; NOAR has been described in.