Low-dose glucocorticoids for rheumatoid arthritis may still carry some risk of serious infections

Reuters Health - 22-09/2020 - Even low-dose glucocorticoid treatment is associated with an increased risk of serious infection in patients with rheumatoid arthritis (RA), according to a new study.

"It was interesting to find that the risk of serious infection with a low dose of glucocorticoids (<=5mg/day) was similar to what studies have shown for biologic medications," said Dr. Michael D. George of Perelman School of Medicine at the University of Pennsylvania, in Philadelphia.

"Some patients may be hesitant to take biologics because of infection concerns but may not realize that the risk is similar to low-dose glucocorticoids (and likely substantially less than higher doses of glucocorticoids)," he told Reuters Health by email.

Glucocorticoids are widely used as bridging therapy in patients starting or changing treatment with disease-modifying antirheumatic drugs (DMARDs). But controversy remains over their long-term use because of continued uncertainty about the safety of low-dose therapy, Dr. George and colleagues note in the Annals of Internal Medicine.

They used Medicare claims data from 2006 to 2015 and data from Optum's Clinformatics Data Mart database from 2001 to 2015 to quantify the risk for infection with long-term, stable, low-dose glucocorticoids in patients with RA who were also receiving stable DMARD therapy, including biologics.

At baseline (six months after stable DMARD use), 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids, most commonly at doses of 5 mg or less per day.

During a median follow-up of 180 days and 148 days, respectively, hospitalized infection rates were 10.9 per 100 person-years in Medicare and 5.4 per 100 person-years in Optum. Rates were somewhat lower (6.4 and 3.9 per 100 person-years, respectively) when using only a primary discharge diagnosis of infection.

There were significant dose-dependent increases in the risk of hospitalized infection with glucocorticoid use in both databases. Among Medicare patients, the predicted one-year cumulative incidence of hospitalized infection increased from 8.6% with no glucocorticoid use to 11.0% for 5 mg/d or less, 14.4% for 5-10 mg/d and 17.7% for daily doses above 10 mg.

Similarly, among patients in the Optum database, the incidence increased from 4.0% with no glucocorticoid use to 5.2%, 8.1% and 10.6%, respectively.

Other factors independently associated with an increased risk for hospitalized infection included older age, prior hospitalization for infection, chronic obstructive pulmonary disease (COPD) and opioid use.

Associations between low-dose glucocorticoid use and hospitalized infection were similar in patients receiving a biologic versus a targeted synthetic DMARD and in older versus younger patients (although absolute rates were substantially higher in older patients).

"Even low doses of glucocorticoids likely carry a risk of infection," Dr. George said. "The risk is low and glucocorticoids may still be an important part of long-term treatment for some patients, but physicians need to weigh the risks and benefits of treatment when making decisions. Avoiding long-term use of higher-dose glucocorticoids, especially >10mg/day, should be a high priority."

He cautioned, "This is not a randomized study, but doing a trial to study the safety of low-dose glucocorticoids would require thousands of patients. For now, observational studies like this provide the best information we have about glucocorticoid safety."

Dr. Dana E. Orange of The Rockefeller University, in New York City, who co-authored a linked editorial, told Reuters Health by email, "This report is another piece of evidence demonstrating the risks of long-term glucocorticoids in patients with rheumatoid arthritis. The main message here is that low dose does not mean no risk."

"More than 40% of patients on stable DMARDs were also treated with glucocorticoids," she said. "It's time to develop data-driven strategies to decrease these numbers so we can limit infectious adverse events."

"Physicians might want to think twice when choosing long-term low-dose glucocorticoids instead of advancing non-biologic DMARDs to biologic or targeted synthetic DMARDs, since even low-dose glucocorticoids increase the risk of hospitalized infection," Dr. Orange said.

By Will Boggs MD

SOURCE: https://bit.ly/3mF1b7v and https://bit.ly/2RKOTfG Annals of Internal Medicine, online September 22, 2020.



Posted on 22 September 202029 September 2020