Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: the pragmatic randomised, double-blind placebo-controlled GLORIA trial

Abstract

BackgroundLow-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear.MethodsThe 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).ResultsWe 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.ConclusionAdd-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 numberNCT02585258.

Three Months of Glucocorticoids in Rheumatoid Arthritis: A Bridge Too Short?

“…These findings also need to be viewed in light of the improved prognosis of current RA patients; the extent of damage at initial presentation and progression of such damage have strongly decreased over the last 2 decades, as the authors document in their discussion. This was confirmed in the GLORIA trial, in which it was observed that damage progression in 2 years was 0.3 units in the prednisolone group and 1.9 in the placebo group (10), similar to the rates in the Krause trial.…”

“…This included trials that continued therapy for up to 2 years. Very recently, the pragmatic Glucocorticoid Low‐dose Outcome in Rheumatoid Arthritis (GLORIA) trial compared the results of 2 years of prednisolone (5 mg/day) or placebo added to optimized standard care in senior patients with established RA (disease duration ≥11 years, age ≥65 years) (10). Even at this low dose, prednisolone reduced disease activity and joint damage progression, with the tradeoff of a 24% increased risk of an AE of special interest, mostly nonsevere infections.…”

The Effect of Anti-rheumatic Drugs on the Skeleton

“…Although many modern RA treatment strategies aim for GC free remission, GC remain important therapeutics in rheumatoid arthritis, particularly when given short-term and early in the course of the disease. The effects of low-dose GC may be much less deleterious than the effects of chronic high dose GC treatment and indeed a recently published randomized controlled trial on Glucocorticoid LOw-dose in RheumatoId Arthritis (GLORIA) [15] demonstrated no statistical difference in symptomatic fracture rates between patients with established RA treated with 5 mg of Prednisolone or placebo. Further bone health outcomes demonstrated a small but significant lumbar spine BMD loss (-1%) in the Prednisolone group but no differences in hip BMD change between the Prednisolone and placebo group after a mean treatment time of 19 months.…”

Ist die Ergänzung der Basistherapie mit tiefdosiertem Prednisolon bei älteren Patienten mit rheumatoider Arthritis vertretbar? Resultate der randomisiert-kontrollierten GLORIA-Studie

“…Das Gleichgewicht zwischen Nutzen und Risiken ist noch unklar, insbesondere für chronisch niedrig dosierte GC-Therapien. Um diese Frage zu beantworten, wurde die internationale, 1: 1 randomisierte, Placebo-kontrollierte 2-Jahres-Studie GLO-RIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) durchgeführt [6].…”