A new study published by Kevin Winthrop MD, MPH and colleagues [1] has shown that even low doses of glucocorticoids (≤5 mg/d) are associated with a clinically important increase in the risk of hospital-acquired infection.
Long-term glucocorticoid use is common in >40% of patients with rheumatoid arthritis (RA) and the study found a statistically significant and clinically important increase in the risk of hospital-acquired infection in these patients.
This increased risk of infection shows how important it is to limit the use of glucocorticoids as much as possible, even at low doses, and it highlights why the team at Steritas covers infection as one domain of the Glucocorticoid Toxicity Index (GTI).
70 years of uncertainty about safety
Low-dose glucocorticoids for the treatment of RA and other chronic diseases have been widely used for the past 70 years, however, the safety of long-term glucocorticoid use is now more in doubt than ever before. The objective of this study was to quantify the risk of hospital-acquired infection with long-term use of low-dose glucocorticoids in patients with rheumatoid arthritis receiving stable disease-modifying antirheumatic drug (DMARD) therapy.
The study evaluated data from Medicare claims and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015, including adult patients with RA receiving stable DMARD treatment for more than 6 months. The researchers evaluated the associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospital-acquired infection using inverse probability-weighted analyses with 1-year cumulative incidence predicted from weighted models.
Associations were consistent in the 2 data sets and similar in older versus younger patients and in biologic versus non–biologic-treated patients. The approximately 2-fold greater risk for infection with more than 10 mg of glucocorticoids per day is similar to results from prior studies.
In patients with RA 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. Clinicians should therefore balance the benefits of low-dose glucocorticoids with this potential risk.
Steroid toxicity is rampant, and it can be fatal, and it is also very preventable
We recently published an interview with Dr. James T. Rosenbaum, Professor for Inflammation Research and Chief of Arthritis and Rheumatic Diseases at Oregon Health & Science University, who also urges caution in prescribing corticosteroids even at low doses and laments that their use is common. He elaborates that physicians are often more comfortable prescribing prednisone or a similar drug rather than something like methotrexate or a steroid-sparing drug or a biologic – even though those are often safer and more effective.
Dr. Rosenbaum suggests that we should reduce the dose of prednisone in chronic disease to a physiological level: “Prednisone is like a narcotic in a sense: it's easy to use, quick and convenient, but you become dependent on it and suffer from dependence in the long run. We know, for example, that steroid toxicity leads to an increased tendency to infection. Sadly, steroid toxicity is rampant, and it can be fatal, and it is also very preventable. So, bringing steroid toxicity onto the radar screen of the practicing physician is really, really important.”
References
[1] 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 Dec 1;173(11):870-878. doi: 10.7326/M20-1594. Epub 2020 Sep 22. PMID: 32956604; PMCID: PMC8073808.