TY - JOUR
T1 - Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+
T2 - The pragmatic randomised, double-blind placebo-controlled GLORIA trial
AU - Boers, Maarten
AU - Hartman, Linda
AU - Opris-Belinski, Daniela
AU - Bos, Reinhard
AU - Kok, Marc R.
AU - da Silva, Jose A. P.
AU - Griep, Eduard N.
AU - Klaasen, Ruth
AU - Allaart, Cornelia F.
AU - Baudoin, Paul
AU - Raterman, Hennie G.
AU - Szekanecz, Zoltan
AU - Buttgereit, Frank
AU - Masaryk, Pavol
AU - Klausch, L. Thomas
AU - Paolino, Sabrina
AU - Schilder, Annemarie M.
AU - Lems, Willem F.
AU - Cutolo, Maurizio
N1 - Funding Information: The trial is part of a larger project funded by the European Union's Horizon 2020 research and innovation program under grant agreement Number 634886. Funding Information: Funding The trial is part of a larger project funded by the European Union’s Horizon 2020 research and innovation program under grant agreement Number 634886. The funder had no role in the design, collection, analysis or interpretation of the data, the writing of the report or the decision to publish. Publisher Copyright: © Author(s) (or their employer(s)) 2022.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - 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.
AB - 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.
KW - arthritis
KW - glucocorticoids
KW - osteoporosis
KW - rheumatoid
KW - therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85132198667&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/annrheumdis-2021-221957
DO - https://doi.org/10.1136/annrheumdis-2021-221957
M3 - Article
C2 - 35641125
SN - 0003-4967
VL - 81
SP - 925
EP - 936
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 7
ER -