Glucocorticoids associated with increased infection risk even at low doses

Patients taking glucocorticoids for rheumatoid arthritis had a significant, dose-dependent increased risk for infections requiring hospitalization, and the results should be considered in prescribing for these patients, according to an accompanying editorial.

Glucocorticoids are associated with an increased risk for infection, even at doses as low as 5 mg or less per day, a study found.

The retrospective study used Medicare and commercial claims data to compare patients with rheumatoid arthritis who had been receiving stable doses of disease-modifying anti-rheumatic drugs (DMARDs), including biologics, for six months according to whether they were receiving glucocorticoids. They recorded associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalizations for infections. Results were published Sept. 22 by Annals of Internal Medicine.

The cohort included 247,297 observations among 172,041 patients in Medicare and 58,279 observations among 44,118 patients in the commercial database. After six months of stable DMARD use, 47.1% of Medicare patients and 39.5% of commercially insured patients were receiving glucocorticoids. The one-year cumulative incidence of hospitalization for infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg/d or lower, 14.4% (95% CI, 13.8% to 15.1%) for a dose of more than 5 to 10 mg/d, and 17.7% (95% CI, 16.5% to 19.1%) for a dose of more than 10 mg/d (P<0.001 vs. no glucocorticoids for all comparisons).

The one-year cumulative incidence of hospitalized infection in patients in the commercial database not receiving glucocorticoids was 4.0% versus 5.2% (95% CI, 4.7% to 5.8%) for a glucocorticoid dose of 5 mg/d or lower, 8.1% (95% CI, 7.0% to 9.3%) for a dose of more than 5 to 10 mg/d, and 10.6% (95% CI, 8.5% to 13.2%) for a dose of more than 10 mg/d (P<0.001 vs. no glucocorticoids for all comparisons).

According to the study authors, glucocorticoids may continue to be an important part of treatment for many patients, especially if other treatments are not fully controlling rheumatoid arthritis, but these findings should help physicians better understand potential risk. Even patients on the lowest dose had about a 30% increase in the risk of infection, they noted. Patients receiving higher-dose glucocorticoids (>10 mg/d) had more than twice the risk of serious infection as patients not receiving glucocorticoids, although few patients were on these doses.

Physicians should consider this information when weighing the benefits and risks of treatment for patients with rheumatoid arthritis, an accompanying editorial noted. “This finding is highly relevant to the clinical community who have been treating some patients with low-dose GCs [glucocorticoids] instead of advancing nonbiologic DMARDs to biologic or targeted synthetic DMARDs, thinking that low-dose GCs may not increase risk for infection,” it said. “We would be cautious in extrapolating these results to other conditions where patients are given low-dose GCs. It is well recognized that patients with [rheumatoid arthritis] are at increased risk for serious infections due to disease-associated immune dysregulation, which may not be the case in other conditions.”