Long-term low dose glucocorticoid therapy in rheumatoid arthritis: a systematic review with meta-analysis on...

Glucocorticoids (GCs) are widely used as first-line therapy in rheumatoid arthritis (RA) due to their rapid onset of action and strong efficacy. However, inappropriate use is associated with significant adverse effects. Long-term treatment with low doses has been considered relatively safe for most RA patients, although its cardiovascular (CV) impact remains controversial.

A systematic literature review was conducted using PubMed to evaluate the CV effects of long-term (≥12 months) low-dose GC therapy (<7.5 mg/day prednisone equivalent) in RA patients. Studies published between 2010 and 15 March 2026 were screened independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2 tool for randomised controlled trials. A meta-analysis was performed to estimate pooled hazard ratios (HRs) with 95% confidence intervals.

Ten studies were included in the review, of which five provided adjusted HRs suitable for meta-analysis. Long-term GC exposure even to low doses was associated with an increased risk of CV events (pooled HR 1.37; 95%CI 1.03-1.81; p=0.01). Substantial heterogeneity was observed among studies. Egger's test did not indicate significant publication bias.

Current evidence suggests that while short-term low-dose GC therapy may be relatively safe in selected RA patients, prolonged use and higher cumulative doses are associated with a slight increased CV risk, particularly in individuals with existing risk factors or comorbidities.