The uncertainty about the harm-benefit balance of low-dose GC was the rationale to perform the Glucocorticoid Low-dose Outcome in RheumatoId Arthritis (GLORIA) trial. The main objectives of the GLORIA trial were to assess the effectiveness and safety of two years low-dose GC (5 mg/day prednisolone) added to standard of care in older patients with RA. This trial was targeted on older patients because they are often underrepresented or excluded from clinical trials because of the presence of multiple comorbidities, increasing frailty, and cognitive impairment. The GLORIA trial was an investigator-initiated, randomized, double-blind, placebo-controlled, multicenter, pragmatic trial in 28 clinical centers in seven European countries. Patients with a disease activity score in 28 joints (DAS28) of 2.60 or higher (3.20 or higher in first year of trial), and an age of ≥65 years were eligible to participate in the trial. Patients were allowed to use all concomitant medication, except for chronic oral GC. The primary outcome measure for benefit was disease activity measured with the time-averaged mean DAS28 and the key secondary outcome for benefit was joint damage progression measured with the Sharp/van der Heijde score. For harm the outcome was the occurrence of at least one adverse event of special interest (AESI). An AESI included serious adverse events (SAEs) according to the Good Clinical Practice definition, any adverse event (AE) leading to discontinuation of the study, symptomatic bone fracture, a myocardial infarction, cerebrovascular or peripheral arterial vascular event, and newly occurring hypertension, diabetes, infection, cataract or glaucoma requiring treatment. The conclusion about the harm-benefit balance of low-dose GC was guided with a decision tree defining the combined results as a success, tradeoff or failure. Secondary objectives of the GLORIA trial were to study the cost-effectiveness and cost-utility, to develop models to predict individualized harm and benefit, and to assess medication adherence. The 451 randomized patients in the GLORIA trial were on average 72 years, had a mean disease duration of 11 years, had mean 2.1 comorbidities, and had a baseline DAS28 of 4.5. Patients participated on average 19 months in the trial, and the trial was completed by 63% of the prednisolone group and 61% of the placebo group. Reasons for discontinuation were: AEs (both groups 14%), active disease (3 versus 4%) and other reasons (including COVID-19) (19 versus 21%). We found that add-on low-dose prednisolone had beneficial long-term effects on disease activity and joint damage progression in established RA. The disease activity (DAS28) was 0.37 points lower on prednisolone (95% Confidence Limit [CL] 0.23, p