Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: the pragmatic randomised, double-blind placebo-controlled GLORIA trial. Issue 7 (31st May 2022)

• Record Type: Journal Article
• Authors: Boers, Maarten; Hartman, Linda; Opris-Belinski, Daniela; Bos, Reinhard; Kok, Marc R; Da Silva, Jose AP; Griep, Eduard N; Klaasen, Ruth; Allaart, Cornelia F; Baudoin, Paul; Raterman, Hennie G; Szekanecz, Zoltan; Buttgereit, Frank; Masaryk, Pavol; Klausch, L Thomas; Paolino, Sabrina; Schilder, Annemarie M; Lems, Willem F; Cutolo, Maurizio
• Other Names: author non-byline.; Middelink LM author non-byline.; Dekker V author non-byline.; van den Bulk N author non-byline.; Pinto RMA author non-byline.; Doerwald L author non-byline.; Manger S author non-byline.; Redol J author non-byline.; Prinsen K author non-byline.; Scholte-Voshaar M author non-byline.; Jansen TLTA author non-byline.; Codreanu C author non-byline.; Molenaar E author non-byline.; van Laar JM author non-byline.; Ruiterman YPM author non-byline.; Boonen AERCH author non-byline.; Boonen AERCH author non-byline.; Micaelo M author non-byline.; Costa J author non-byline.; Sieburg M author non-byline.; Spoorenberg JPL author non-byline.; Prothmann U author non-byline.; Saavedra MJ author non-byline.; Silva I author non-byline.; Nurmohamed MT author non-byline.; Jacobs JWG author non-byline.; Tas SW author non-byline.; Bijlsma JWJ author non-byline.; Christensen R author non-byline.; Smulders YM author non-byline.; Ralston SH author non-byline.; van der Heijde DMFM author non-byline.; Marsman AF author non-byline.; Lems WF author non-byline.; Rusthoven C author non-byline.; Bakkers M author non-byline.; Frazão Mateus E author non-byline.; Mendes G author non-byline.; Elling-Audersch C author non-byline.; Borucki D author non-byline.; Celano A author non-byline.; Corduta P author non-byline.; Constantinescu O author non-byline.; Richards P author non-byline.; Aanerud GJ author non-byline.;
• Is Part Of: Annals of the rheumatic diseases. Volume 81:Issue 7(2022)
• Page Start: 925
• Page End: 936
• Publication Date: 2022-05-31
• Subjects: glucocorticoids -- arthritis, rheumatoid -- therapeutics -- osteoporosis; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2021-221957
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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 .