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Even low-dose steroids increase DMARD infection risk



– Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.

Dr. Michael George, University of Pennsylvania, Philadelphia

Dr. Michael George

Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.

“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.

The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.

There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.

After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.

Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.

“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”

The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.

“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.

Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.

Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.

The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.

SOURCE: George M et al. ACR 2019, Abstract 848

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