Infections, Drugs, and RA.......... | Arthritis Information

Virtually all RA studies looking at the causes of mortality have shown increased risk of infection. In some studies the excess death rate from infection was 5.5-fold for RA patients compared with controls³. However, a more germane question in the era of biologics is: What percentage of patients with RA are hospitalized with infections? This question, which more cogently addresses the ambulatory life experience of the RA patient currently being treated, has been reviewed many times. Doran, et al found a significantly increased risk of infection in patients with RA⁴, but other studies have not shown the same outcomes^5,6. This may be due to differences in patient populations (not controlled for severity) and in control groups (not controlled for age, sex, comorbidities). However, there is a belief among practicing rheumatologists that RA patients not only have increased risk of infection, but also increased severity when infected, particularly when taking disease modifying antirheumatic drugs, and especially biologic therapies. However, it is only recently that these discrepancies are being teased out and dissected as to why. Is it disease severity? Is it drug therapy? Is it one particular drug?

In this issue of The Journal Smitten, et al describe their retrospective study from 1999 to 2006 including 24,530 RA patients and 500,000 controls, in which individuals with RA were observed to have an increased risk of being hospitalized for an infection⁷. In a nested case-control analysis, oral corticosteroid use was associated with a dose related increase, and the biologic therapies were associated with only a slightly increased risk. Patients treated with hydroxychloroquine and methotrexate had a decreased risk of hospitalized infections.

The advantages of this study are the large number of patients in the RA group and the number of patients who had received at least one biologic (24%). When one further dissects the RA group, those with infections, not surprisingly, were more likely to be older, diabetic, have chronic lung diseases, and to have been previously hospitalized; however, the use of biologics only slightly increased the risk of hospitalized infection (relative risk 1.21; 95% CI 1.02–1.43). Interestingly, methotrexate use and hydroxychloroquine use were associated with decreased risk, and other non-biologics had no association.

What is surprising is that the risk of infection was most associated with increasing doses of steroids, but even at doses ≤ 5 mg/day the risk of hospitalization for infections increased (RR = 1.32; 95% CI 1.06–1.63). This risk is slightly higher than the risk of infection with biologic therapies!