Review
Long-term low dose glucocorticoid therapy in rheumatoid arthritis: a systematic review with meta-analysis on cardiovascular effects
E. Gotelli1, R. Campitiello2, E. Hysa3, S. Soldano4, C. Pizzorni5, S. Paolino6, A. Sulli7, V. Smith8, M. Cutolo9
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialty, University of Genova; and IRCCS AOM Ospedale Policlinico San Martino, Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialties, University of Genova; and Department of Experimental Medicine, University of Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialties, University of Genova; and Department of Experimental Medicine, University of Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialties, University of Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialty, University of Genova; and IRCCS AOM Ospedale Policlinico San Martino, Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialty, University of Genova; and IRCCS AOM Ospedale Policlinico San Martino, Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialty, University of Genova; and IRCCS AOM Ospedale Policlinico San Martino, Genova, Italy.
- Department of Rheumatology, Ghent University Hospital, University of Ghent; Department of Internal Medicine, Ghent University Hospital, University of Ghent; and Unit for Molecular Immunology and Inflammation, Flemish Institute for Biotechnology, Inflammation Research Center, Ghent, Belgium.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialty, University of Genova; and IRCCS AOM Ospedale Policlinico San Martino, Genova, Italy. mcutolo@unige.it
CER19981
2026 Vol.44, N°7
PI 1279, PF 1288
Review
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Received: 31/03/2026
Accepted : 29/05/2026
In Press: 07/07/2026
Published: 14/07/2026
Abstract
OBJECTIVES:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.
