Background Rheumatoid arthritis (RA) is associated with a risk of premature mortality. Chronic inflammation is one of the factors explaining this risk, but limited data exist on the importance of disease activity early in the disease.
Objectives To investigate the relationship between disease activity over the first two and five years of RA and risk of mortality.
Methods Between 1993 and 1999, 839 patients were included in the BARFOT early RA inception cohort. 805 of these, mean age 56.6 (15.3) years, 64% women, 59% RF-positive, had attended the pre-defined follow-up visits for at least 2 years and formed the patient material. Disease activity was assessed with DAS28 at baseline, 1, 2 and 5 years and remission was defined as DAS28 <2.6. The patients were grouped in those with remission at all time-points (sustained remission), at some time-point (intermittent remission), and those never in remission (persistent disease activity). The outcome was all-cause mortality that was identified through linkage with the nationwide Causes of Death Registry until 2011. The relative hazard ratios (HR) and 95% CI adjusted for age, gender, smoking and treatment strategy were calculated using Cox proportional-hazards models. Since an association between seropositivity and increased mortality has been suggested we also performed analyses stratified by presence of rheumatoid factor (RF).
Results After two years, 185 patients had achieved sustained remission, 193 intermittent remission and 427 had persistent disease activity. Of these 805 patients, 202 died during the following observation period, 19.6%, 25.9% and 27.2% in the respective group. The HR for mortality for those with persistent disease activity was 1.7 times higher (1.1-2.4), and for those in intermittent remission 1.6 times higher (1.02-2.4) than for those in sustained remission. Within RF-positive patients, the respective HRs were 1.8 (1.2-2.7) and 1.6 (1.02-2.4); and within RF-negative patients 1.5 (0.9-2.4) and 1.6 (1.02-2.4).
705 patients were followed for 5 years and 120 had achieved sustained remission, 126 patients had remission on two occasions, 157 on one and 302 had persistent disease activity. 141 patients died during the following observation period, 14.4%, 18.3%, 21.7% and 22.2% in the respective group. Compared to those in sustained remission, the HR for mortality for those with persistent disease activity was 1.9 times higher (1.1-3.3), for those who achieved remission at one assessment 1.8 times higher (1.03-3.3), and for those in remission at two assessments 1.5 times higher (0.8-2.7). Within RF-positive patients, the respective HRs were 1.8 (1.0-3.2), 1.8 (1.0-3.3), and 1.4 (0.8-2.7); and within RF-negative patients 2.2 (1.2-4.2), 1.9 (1.1-3.5), and 1.5 (0.8-2.8).
Additional adjustments for baseline CRP, ESR and DAS28 did not change the results.
Conclusions Persistent disease activity and intermittent remission during the first years after diagnosis of RA augment the risk of mortality over 10 years of follow-up, independent of age, gender, smoking and anti-rheumatic treatment regime. Unfavorable survival prognosis associated with failure to achieve remission involved both RF-positive and RF-negative patients with RA.
Disclosure of Interest None declared
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