• Michael D George, Joshua F Baker, Kevin Winthrop, Jesse Y Hsu, Qufei Wu, Lang Chen, Fenglong Xie, Huifeng Yun, and Jeffrey R Curtis.
• University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania (M.D.G., J.Y.H., Q.W.).
• Ann. Intern. Med. 2020 Dec 1; 173 (11): 870-878.

BackgroundLow-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain.ObjectiveTo quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy.DesignRetrospective cohort study.SettingMedicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015.PatientsAdults with RA receiving a stable DMARD regimen for more than 6 months.MeasurementsAssociations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models.Results247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). The 1-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0% versus 5.2% (CI, 4.7% to 5.8%) for glucocorticoid dose of 5 mg or less per day, 8.1% (CI, 7.0% to 9.3%) for greater than 5 to 10 mg/d, and 10.6% (CI, 8.5% to 13.2%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids).LimitationPotential for residual confounding and misclassification of glucocorticoid dose.ConclusionIn 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 balance the benefits of low-dose glucocorticoids with this potential risk.Primary Funding SourceNational Institute of Arthritis and Musculoskeletal and Skin Diseases.

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