Seropositivity for both rheumatoid factor and anti-citrullinated protein antibody was associated with increased mortality, compared with single positivity or seronegativity in patients with early inflammatory arthritis in two large, independent observational cohorts.
However, higher levels of the antibodies did not appear to be associated with early deaths as the influence of increasing antibody level was not consistent in the two cohorts, Dr. Jennifer H. Humphreys of the University of Manchester (England) and her colleagues reported (Arthritis Res. Ther. 2014 Dec. 4 [doi:10.1186/s13075-014-0483-3]).
Dr. Jennifer H. Humphreys
Among 3,053 patients in the Norfolk Arthritis Register (NOAR) cohort and 1,909 in the Leiden Early Arthritis Clinic (EAC) cohort, double antibody positivity – which occurred in 35% and 42% of patients in the cohorts, respectively – was associated with excess mortality (adjusted hazard ratios, 1.35 and 1.57). However, when antibody status was negative, low-positive, or high-positive, findings in one cohort were not replicated in the other. For example, there was a marked difference in rheumatoid factor high and low positivity in the NOAR cohort (adjusted HRs of 0.80 and 1.49, respectively), but not in the EAC cohort (adjusted HRs of 1.62 and 1.63, respectively), the investigators said.
Median patient age at symptom onset was 56 years in NOAR and 54 years in EAC, and 65% and 63% of subjects in the cohorts, respectively, were women. They were followed for a mean of 11.8 years and 8.5 years, until death or censor date, and analyses were adjusted for age, sex, smoking status, inflammatory markers, and year of enrollment.
The findings suggest that in patients presenting with early rheumatoid arthritis, mortality risk may be better assessed by the number of positive antibodies than by the antibody levels, the investigators concluded.
NOAR is funded by Arthritis Research UK grants, as is Dr. Humphreys. The current study was also funded by the European Community Seventh Framework Program FP7 and a Vidi grant of the Netherlands Organization for Scientific Research. The authors reported having no other disclosures.