Mortality in Low Dose Prednisone Save

During Monday’s release of the new ACR 2020 Pharmacologic Treatment Recommendations for the Management of Rheumatoid Arthritis, many practitioners were surprised that the new guidelines recommended against glucocorticoid initiation at disease onset. DMARD initiation alone in new disease was conditionally recommended against DMARDs with short-term glucocorticoids and strongly recommended against DMARD with long-term glucocorticoids (greater than 3 months). In practice, the glucocorticoids are often used to help get early control and low doses (<5 mg) are felt to be safe to continue as it is a physiologic steroid production. 

The ESPOIR cohort from France (abstract #1998) reports that even very low dose prednisone (1-4 mg) can have significant morbidity and mortality over time. In their cohort 65% (397 out of 608 patients) remained on low dose prednisone (mean 2.8 mg). The mean duration of glucocorticoid treatment was 44.6 months. The cohort followed 10-year outcomes of these patients to assess if increased cumulative events (death, cardiovascular disease, fracture, or severe infections) were elevated in these patients on small prednisone doses. They found that 71 of the 95 events occurred in the low dose prednisone group, demonstrating a statistically significant increase of events in those on prednisone (p=0.035). There was particularly a significant cumulative dose-effect noted in severe infections and cardiovascular disease. With each year of prednisone treatment, the risks increased up to a hazard ratio of 6.8 in those patients with 10 years of prednisone therapy. 

A major emphasis in new ACR guidelines are to avoid early initiation of glucocorticoids, in part because it often becomes difficult to wean off low levels of prednisone. This new data presented by the ESPOIR suggests that these low dose prescriptions of glucocorticoids should not be regarded as harmless, physiologic doses but may have serious long-term health effects. 

Editor's note: This article originally appeared November 10, 2020, during the 2020 ACR Convergence meeting, and is being shared again for our readers.