Glucocorticoids boost infection risk among patients with RA receiving DMARDs
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Glucocorticoids are associated with a dose-dependent increase in the risk for serious infections among patients with rheumatoid arthritis receiving DMARDs, according to data published in the Annals of Internal Medicine.
“Glucocorticoids are used very commonly in the treatment of RA,” Michael D. George, MD, of the University of Pennsylvania, told Healio Rheumatology. “Even though most recommendations suggest tapering patients off glucocorticoids, a large number of patients remain on glucocorticoids chronically. This is likely due, at least in part, to continued controversy over the risk of low-dose glucocorticoids, with some physicians considering low-dose glucocorticoids to be ‘physiologic.’”
To examine the association between long-term, low-dose glucocorticoid treatment and the risk for infection leading to hospitalization among patients with RA who receive DMARD therapy, George and colleagues conducted a retrospective cohort study of Medicare claims data and the Optum Clinformatics Data Mart database.
Focusing on data from 2006 to 2015, from adults with RA treated with stable DMARDs for more than 6 months, the researchers identified 247,297 observations across 172,041 patients in Medicare. From the Optum database, the researchers included 58,279 observations from 44,118 patients.
Among the included patients, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids after 6 months of stable DMARD therapy. Links between glucocorticoid dose and infection were evaluated using inverse probability–weighted analyses, with 1-year cumulative incidence predicted from weighted models. Glucocorticoid doses were grouped by none, 5 mg per day or less, between 5 and 10 mg per day, and more than 10 mg per day.
According to the researchers, the 1-year cumulative incidence of serious infection among Medicare patients not receiving glucocorticoids was 8.6%, compared with 11% (95% CI, 10.6% to 11.5%) for those receiving glucocorticoid doses of 5 mg or less per day, 14.4% (95% CI, 13.8% to 15.1%) for doses between 5 and 10 mg per day, and 17.7% (95% CI, 16.5% to 19.1%) for those greater than 10 mg per day.
In the Optum database, the cumulative incidence of serious infection was 4% for patients not receiving glucocorticoids, compared with 5.2% (95% CI, 4.7% to 5.8%) for those treated with 5 mg or less per day, 8.1% (95% CI, 7% to 9.3%) for doses between 5 and 10 mg per day, and 10.6% (95% CI, 8.5% to 13.2%) for those greater than 10 mg per day.
“The main message is that even low doses of glucocorticoids likely carry a risk of infection,” 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 at more than 10 mg per day, should be a high priority.”
“It was interesting to find that the risk of serious infection with a low dose of glucocorticoids — 5 mg per day — was similar to what studies have shown for biologic medications,” he added. “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.”
According to George, the findings support investigating alternatives to long-term glucocorticoid use.
“These findings support recommendations to attempt to taper patients with rheumatoid arthritis off glucocorticoids if possible and to use other medications to control disease,” he said. “If patients are unable to achieve good disease control with other medications, then physicians should be aware that there is likely some risk even with low-dose glucocorticoids and should weigh the risks and benefits of treatment when making decisions with patients.”
Perspective
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Alone, glucocorticoids and DMARDs, including biologics, each pose an increased risk for infection. When used together, the risk of infection increases. For some patients, adding glucocorticoids to their treatment regimen for short-term use is the bridge that gets them to achieve minimal disease activity, which improves their quality of life among other things. But how often does short-term evolve into long-term use?
It is so important to find a happy medium: Achieve low/minimal disease activity while doing what is safest for our patients. Titrating glucocorticoid doses is very important and should be done by a patient’s prescribing doctor. It is also important to educate clinic and infusion staff to advise patients on when to hold any immunosuppressive medications if patients have active infections, are receiving vaccinations, or need to receive vaccinations prior to starting specific treatments.
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