Journal Article

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

Borucki, D, Baudoin, Paul, Lems, Willem F, van Laar, JM, Griep, Eduard N, Spoorenberg, JPL, Cutolo, Maurizio, Jansen, TLTA, Masaryk, Pavol, Opris-Belinski, Daniela, Saavedra, MJ, Manger, S, Bos, Reinhard, Tas, SW, Ruiterman, YPM, Da Silva, Jose AP, Richards, P, Marsman, AF, Allaart, Cornelia F, Silva, I, Doerwald, L, Prinsen, K, Bijlsma, JWJ, Christensen, R, Pinto, RMA, Micaelo, M, Ralston, SH, Hartman, Linda, Paolino, Sabrina, Smulders, YM, Rusthoven, C, Molenaar, E, Schilder, Annemarie M, Costa, J, Boers, Maarten, Prothmann, U, Raterman, Hennie G, Constantinescu, O, Lems, WF, Redol, J, Codreanu, C, Boonen, AERCH, van der Heijde, DMFM, Aanerud, GJ, van den Bulk, N, Scholte-Voshaar, M, Corduta, P, Kok, Marc R, Dekker, V, Szekanecz, Zoltan, Sieburg, M, Mendes, G, Jacobs, JWG, Frazão Mateus, E, Klaasen, Ruth, Klausch, L Thomas, Buttgereit, Frank, Bakkers, M, Elling-Audersch, C, Celano, A, Middelink, LM, Nurmohamed, MT

2022

Overview

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 number NCT02585258.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited,BMJ Publishing Group
• Subject: Aged / Antirheumatic Agents - therapeutic use / arthritis, rheumatoid / Arthritis, Rheumatoid - drug therapy / Bias / Clinical medicine / Comorbidity / Double-Blind Method / Double-blind studies / Drug dosages / Drug Therapy, Combination / Fractures / Glucocorticoids / Glucocorticoids - therapeutic use / Humans / Long-term effects / Methotrexate - therapeutic use / Osteoporosis / Patients / Placebos / Population / Prednisolone / Prednisolone - therapeutic use / Rheumatoid Arthritis / Statistical analysis / therapeutics / Treatment Outcome