Rheumatoid factor and anti-citrullinated protein antibody positivity, but not level, are associated with increased mortality in patients with rheumatoid arthritis: results from two large independent cohorts.

INTRODUCTION: 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). METHODS: Data 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. RESULTS: A 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). 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.

Demographic and disease-related predictors of abnormal lung function in patients with established inflammatory polyarthritis and a comparison with the general population.

OBJECTIVES: To identify demographic and clinical predictors of obstructive lung disease (OLD) and restrictive lung disease (RLD) in patients with established inflammatory polyarthritis (IP) and to compare the prevalence of respiratory symptoms in patients with IP and the general population. METHOD: A total of 421 patients with IP underwent a spirometry test 15 years after inclusion in the Norfolk Arthritis Register (NOAR). Logistic regression analyses were performed to assess the predictive ability of demographic and clinical characteristics obtained at inclusion in NOAR and to assess their association with OLD or RLD at 15 years (age- and gender-adjusted). In addition, the prevalence of OLD and RLD was compared with a matched population (1:4) of people participating in the European Prospective Investigation of Cancer-Norfolk, a representative sample of the general population in Norfolk, UK. RESULTS: In this IP population, current smoking was the strongest predictor for OLD and functional disability for RLD. In the comparison study, 11.6% had OLD in the IP population and 4.9% in the general population (adjOR 2.01, 95% CI 1.26 to 3.22). The prevalence of RLD was not statistically different between the IP population and the general population (14.6% vs 17.5%; adjOR 0.76, 95% CI 0.53 to 1.10). CONCLUSIONS: OLD, but not RLD, is more prevalent in the IP population than in the general population. Functional disability is especially associated with RLD whereas smoking is associated with OLD. The latter finding, and the known association between smoking and a poor disease prognosis, underlines the importance of smoking cessation in patients with IP.