Anti-rheumatic Drug Use and Risk of Serious Infections in Rheumatoid Arthritis

Objectives: To assess the risk of severe infections associated with the use of traditional disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoid agents in rheumatoid arthritis (RA).

Methods: Our study was a case-control design nested within a cohort of 23 733 RA patients studied between 1 January 1980 and 31 December 2003. Matching on age and gender, and adjusting for comorbidity and physician use, conditional logistic regression was used to estimate the effect of specific drugs on the rate ratio (RR) for infections requiring hospitalization.

Results: The risk for all infections requiring hospitalization appeared to be most elevated with current exposures to cyclophosphamide [RR: 3.26, 95% confidence interval (CI): 2.28-4.67] and systemic glucocorticoid agents (RR: 2.56, 95% CI: 2.29-2.85); azathioprine was associated with a moderate increased risk (RR: 1.52, 95% CI: 1.18-1.97). There was a suggestion of increased risk of pneumonia due to methotrexate (RR: 1.16, 95% CI: 1.02-1.33). The results were similar for the period before and after the introduction of anti-tumour necrosis factor (TNF) agents. The RR point estimate for anti-TNF agents suggested about a 2-fold increased risk for all infections, but the estimate was imprecise.

Conclusions: In this large cohort of RA patients, the most heightened risk of serious infections was seen with the use of glucocorticoid agents and immunosuppressive DMARDs. Assessments of infection risk related to newer and emerging therapies should carefully consider concomitant medication exposures, including traditional DMARDs and glucocorticoid therapy.