George MD, Baker JF, Winthrop K, et al. Risk for Serious Infection With Low-Dose Glucocorticoids in Patients With Rheumatoid Arthritis : A Cohort Study. Ann Intern Med. 2020 Sep 22. doi: 10.7326/M20-1594.
Abstract

BACKGROUND: Low-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.

OBJECTIVE: To 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.

DESIGN: Retrospective cohort study.

SETTING: Medicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015.

PATIENTS: Adults with RA receiving a stable DMARD regimen for more than 6 months.

MEASUREMENTS: Associations 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.

RESULTS: 247 297 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).

LIMITATION: Potential for residual confounding and misclassification of glucocorticoid dose.

CONCLUSION: 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 balance the benefits of low-dose glucocorticoids with this potential risk.

PRIMARY FUNDING SOURCE: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Ratings by Clinicians (at least 3 per Specialty)
Specialty Score
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Infectious Disease
Rheumatology
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

Retrospective data. It's surprising still that even at low dose prednisone, under 10 mg, there was an increased incidence of hospitalized infection. Is this association from the direct immunosuppression effect or underlying disease severity that requires use of higher immunosuppression?