High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis

Objective To determine the relationship of disease activity to infections in patients with rheumatoid arthritis (RA). Methods From the CORRONA database, the incidence of physician-reported infections in RA patients on stable disease-modifying antirheumatic drug, biological, and corticosteroid therapy for at least 6 months was ascertained. Two composite measures of disease activity were defined: clinical disease activity index (CDAI) and disease activity score 28 (DAS28). Incident rate ratios (IRR) were calculated using generalised estimating equation Poisson regression models adjusted for demographics, medications and clinical factors. Results Of 1 6242 RA patients, 6242 were on stable therapy for at least 6 months and were eligible for analysis. 2282 infections were reported in the cohort, followed over 7290 patient-years. After controlling for possible confounders, disease activity was associated with an increased rate of infections. Each 0.6 unit increase in DAS28 score corresponded to a 4% increased rate of outpatient infections (IRR 1.04, p=0.01) and a 25% increased rate of infections requiring hospitalisation (IRR 1.25, p=0.03). There was a dichotomy in the relationship between infections and CDAI scores. For CDAI < 10 (mild disease activity) patients had a 12% increased rate of outpatient infections with each 5 unit increase in CDAI score (IRR 1.12, p=0.003). At CDAI scores >= 10, there was no further increase in the rate of outpatient infections associated with higher disease activity. The relationship of CDAI to hospitalised infections showed similar trends to outpatient data but did not reach statistical significance after multivariate analysis (CDAI < 10: IRR 1.56, p=0.08). Conclusions In this large cohort of RA patients, higher disease activity was associated with a higher probability of developing infections.