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Background: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear.Methods: The GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) pragmatic double-blind randomised trial compared 2 years of prednisolone, 5 mg/day, to placebo in patients aged 65+ with active RA. We allowed all cotreatments except long-term open label GC and minimised exclusion criteria, tailored to seniors. Benefit outcomes included disease activity (disease activity score; DAS28, coprimary) and joint damage (Sharp/van der Heijde, secondary). The other coprimary outcome was harm, expressed as the proportion of patients with ≥1 adverse event (AE) of special interest. Such events comprised serious events, GC-specific events and those causing study discontinuation. Longitudinal models analysed the data, with one-sided testing and 95% confidence limits (95% CL).Results: We randomised 451 patients with established RA and mean 2.1 comorbidities, age 72, disease duration 11 years and DAS28 4.5. 79% were on disease-modifying treatment, including 14% on biologics. 63% prednisolone versus 61% placebo patients completed the trial. Discontinuations were for AE (both, 14%), active disease (3 vs 4%) and for other (including covid pandemic-related disease) reasons (19 vs 21%); mean time in study was 19 months. Disease activity was 0.37 points lower on prednisolone (95% CL 0.23, p<0.0001); joint damage progression was 1.7 points lower (95% CL 0.7, p=0.003). 60% versus 49% of patients experienced the harm outcome, adjusted relative risk 1.24 (95% CL 1.04, p=0.02), with the largest contrast in (mostly non-severe) infections. Other GC-specific events were rare.Conclusion: Add-on low-dose prednisolone has beneficial long-term effects in senior patients with established RA, with a trade-off of 24% increase in patients with mostly non-severe AE; this suggests a favourable balance of benefit and harm.Trial Registration Number: NCT02585258. [ABSTRACT FROM AUTHOR]

Objective: High adalimumab serum concentrations do not result in better response in patients with rheumatoid arthritis (RA), suggesting overexposure. We investigated whether patients with adalimumab concentrations >8 µg/mL can prolong their dosing interval by 50% without a clinically relevant change in disease activity.Methods: Consecutive patients with RA, treated with adalimumab 40 mg every other week for at least 28 weeks, were approached for this randomised, open-label, non-inferiority trial. Patients with adalimumab trough concentrations >8 µg/mL were randomly (1:1) assigned to dose-interval prolongation of once every 3 weeks or continuation of every other week. Primary outcome was the change in disease activity score of 28 joints (ΔDAS28-ESR) after 28 weeks, with a non-inferiority margin of 0.6 points.Results: In total, 147 patients were screened. Fifty-five patients had concentrations >8 µg/mL and were randomised. Mean ΔDAS28 after 28 weeks was -0.14±SD 0.61 in the prolongation group and 0.30±0.52 in the continuation group. Mean difference was significantly in favour of the prolongation group: 0.44 (95% CI 0.12 to 0.76, p=0.01).Conclusions: Adalimumab-treated patients with RA with trough concentrations >8 µg/mL can prolong their standard dosing interval to once every 3 weeks without loss of disease control.Trial Registration Number: NTR3509; Results. [ABSTRACT FROM AUTHOR]