OBJECTIVES: Although >50 million adults worldwide use glucocorticoids (GCs) long term, there is insufficient evidence quantifying the mortality risk. The goal of this systematic literature review was to characterize the impact of long-term GC therapy (defined as ≥3 months of GC therapy) on mortality.

METHODS: We identified relevant publications (January 2012-December 2022) describing the impact of long-term GC therapy on mortality in adults with chronic conditions, using MEDLINE, EMBASE, NICE, Cochrane, and other search engines. Outcomes were stratified by clinical consequences of GC use. The mortality rates of GC users vs nonusers were analyzed, and the association between use of GC and mortality was estimated through hazard ratios (HRs), mortality rate, and relative risk (RR) of death.

RESULTS: Of the 1300 publications found, 41 met criteria for review, and 11 met criteria for analysis. All 11 studies were observational (2 prospective, 7 retrospective, 2 case-control design). The most commonly reported condition treated with GCs was rheumatoid arthritis (RA, 43%). Other chronic conditions reported were asthma, giant cell arteritis, polymyalgia rheumatica, vasculitis, inflammatory bowel disease, and systemic lupus erythematosus. GC doses varied widely across conditions, from ≤5 mg/day to >30 mg/day. The highest mortality risk associated with GC was reported in RA (HR 4.5; 95% CI, 3.61-5.62). Lower and higher threshold ranges for HR of mortality increased with escalating doses. In studies reporting mortality RR, there was a dose-related increase in mortality risk. Mortality RR (range) for GC users were 1.47 (1.05-2.05) for the 5-mg/day dose, 1.77 (1.36-2.32) for 7-mg/day dose, and 2.05 (1.99-2.10) for aggregate GC doses.

CONCLUSIONS: Long-term GC therapy and/or use of higher GC doses increases mortality risk. The evidence collated underscores the importance of minimizing reliance on GC to manage chronic conditions.