Adverse Effects and Withdrawal Symptoms of Prolonged Glucocorticoid Therapy in Chronic Rheumatoid Arthritis and Systemic Lupus Erythematosus: A Systematic Review.

Abstract

The objective of this systematic review was to assess adverse effects and long-term withdrawal symptoms of prolonged glucocorticoid (GC) therapy in patients with rheumatic diseases, e.g., rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The review synthesizes evidence from randomized controlled trials (RCTs), clinical trials, and observational cohorts in order to evaluate the safety and tolerability of long-term GC use and the effect of GC withdrawal strategies. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A complete literature search on PubMed, Scopus, and Google Scholar was performed using both text words and controlled vocabulary. Only RCTs and clinical trials published in English from January 1, 2020, to October 31, 2025, were included. Only RCTs and observational cohort studies were considered. RCT's methodological quality was assessed using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool and non-randomized studies by the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. ROBVIS software (University of Bristol, Bristol, United Kingdom) was used to visualize the RoB. A total of 10 studies of low to moderate RoBs were considered to synthesize evidence. In conclusion, the balance of evidence strongly supports the European Alliance of Associations for Rheumatology (EULAR) recommendations to taper and discontinue GCs whenever clinically feasible. Although there is actual danger of disease flare, the evidence suggests less long-term organ damage, particularly in SLE, and prevention of multi-system adverse events, indicating a clear clinical advantage for attempting GC withdrawal. This reinforces the significance of discontinuation as a cornerstone of standard care. The findings support a gradual process of tapering as a safer and more efficient solution than sudden withdrawal. Thus, clinicians need to take into account the individual patient factors to increase the likelihood of successful discontinuation.