Serious infections in a population-based cohort of 86,039 seniors with rheumatoid arthritis

To assess risk and risk factors for serious infections in seniors with rheumatoid arthritis (RA) using a case-control study nested within an RA cohort.

We assembled a retrospective RA cohort age ≥66 years from Ontario health administrative data across 1992-2010. Nested case-control analyses were done, comparing RA patients with a primary diagnosis of infection (based on hospital or emergency department records) to matched RA controls. We assessed independent effects of drugs, adjusting for demographics, comorbidity, and markers of RA severity.

A total of 86,039 seniors with RA experienced 20,575 infections, for a rate of 46.4 events/1,000 person-years. The most frequently occurring events included respiratory infections, herpes zoster, and skin/soft tissue infections. Factors associated with infection included higher comorbidity, rural residence, markers of disease severity, and history of previous infection. In addition, anti-tumor necrosis factor agents and disease-modifying antirheumatic drugs were associated with a several-fold increase in infections, with an adjusted odds ratio (OR) ranging from 1.2-3.5. The drug category with the greatest effect estimate was glucocorticoids, which exhibited a clear dose response with an OR ranging from 4.0 at low doses to 7.6 at high doses.

Seniors with RA have significant morbidity related to serious infections, which exceeds previous reports among younger RA populations. Rural residence, higher comorbidity, markers of disease severity, and previous infection were associated with serious infections in seniors with RA. Our results emphasize that many RA drugs may increase the risk of infection, but glucocorticoids appear to confer a particular risk.