Glucocorticoids and Biologics Share Similar Infection Risk in Rheumatoid Arthritis

Continued use of low dose glucocorticoid in patients with rheumatoid arthritis also treated with stable DMARD therapy is associated with a small but significant risk of serious infection, show the results of a study published in Annals of Internal Medicine.

“The risk of infection with low dose therapy was small but similar to the risk other studies have shown with biologic therapies. For some patients the benefits of glucocorticoids may outweigh these risks, but physicians should be aware of the risks when making treatment decisions, says Michael George, a rheumatologists and assistant professor of medicine at the University of Pennsylvania, Philadelphia.

The researchers used databases to identify patients who received a stable DMARD regimen (methotrexate or a biologic or tsDMARD, with or without methotrexate) for at least six months between 2006 to 2015, and for whom there were six months of previous data―this made up the one-year baseline period.

A total of 247,297 qualifying medication courses among 172,041 patients were identified from Medicare claims data and 58,279 medication courses among 44 118 patients in the Optum deidentified Clinformatics Data Mart database, and the time to the first hospitalized infection was noted for each patient. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids, most commonly at doses ≤5 mg/day.

The researchers used inverse probability–weighted analyses, with one-year cumulative incidence predicted from weighted models, to evaluate the association between glucocorticoid dose (none, ≤5 mg/day, >5 to 10 mg/day, and >10 mg/day) and hospitalized infection.

The results showed that in rheumatoid arthritis patients receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day.

The one-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6%, compared with 11.0% in patients receiving glucocorticoid dose of 5 mg or less per day. Rates were 14.4% for glucocorticoid doses greater than 5 mg/day to 10 mg/day , and 17.7% at doses greater than 10 mg/day.

The same dose-related relationship between glucocorticoids and hospitalized infections was seen for Optum patients. The one-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0%, 5.2% for doses of of 5 mg or less per day, 8.1% for doses greater than 5 mg/day to 10 mg/d, and 10.6% for doses greater than 10 mg/day.

The most common infections were urinary infection, pneumonia, bacteremia or septicemia, and skin or soft tissue infections and rates of infection increased with higher doses of glucocorticoids.

The study highlighted that even low dose glucocorticoids may carry some risk of infection - a risk that seems similar overall to the risk with biologic therapies - so they should be tapered if possible, George said.

“Current guidelines recommend tapering glucocorticoids if possible, yet we know that frequently glucocorticoids are not tapered with many patients staying on glucocorticoids for years,” he said. “Continuing on glucocorticoids should not be the default in patients with rheumatoid arthritis, and patients should be tapered if possible. For some patients who cannot taper therapy continuing glucocorticoids may be beneficial though.

George said that the study’s findings would hopefully help rheumatologists weight the risks and benefits of steroids in comparison to other treatment options. “This data can also be useful for clinicians or are worried about infection risk with other treatments - sharing that risk may be similar with the glucocorticoids patients are on may be helpful when counselling patients,” he said.

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REFERENCE

George MD, Baker JF, Winthrop K, Hsu JY, Wu Q, Chen L, Xie F, Yun H, Curtis JR. Risk for Serious Infection With Low-Dose Glucocorticoids in Patients With Rheumatoid Arthritis : A Cohort Study. Ann Intern Med. 2020 Sep 22. doi: 10.7326/M20-1594. Epub ahead of print. PMID: 32956604.