TY - JOUR
T1 - Three-month tapering and discontinuation of long- term, low-dose glucocorticoids in senior patients with rheumatoid arthritis is feasible and safe
T2 - Placebo-controlled double blind tapering after the GLORIA trial
AU - Almayali, Abdullah Ali Hadi
AU - Boers, Maarten
AU - Hartman, Linda
AU - Opris, Daniela
AU - Bos, Reinhard
AU - Kok, Marc R.
AU - Da Silva, Jose A.P.
AU - Griep, Ed
AU - Klaasen, Ruth
AU - Allaart, Cornelia F.
AU - Baudoin, Paul
AU - Raterman, Hennie G.
AU - Szekanecz, Zoltan
AU - Buttgereit, Frank
AU - Masaryk, Pavol
AU - Lems, Willem
AU - Smulders, Yvo
AU - Cutolo, Maurizio
AU - Ter Wee, Marieke M.
N1 - Funding Information: Follow-up study of the GLORIA trial, 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. No additional funding was obtained for this study. Publisher Copyright: © 2023 Authors. All rights reserved.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Objective The randomised placebo-controlled GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) trial evaluated the benefits and harms of prednisolone 5 mg/day added to standard care for 2 years in patients aged 65+ years with rheumatoid arthritis (RA). Here, we studied disease activity, flares and possible adrenal insufficiency after blinded withdrawal of study medication. Methods Per protocol, patients successfully completing the 2-year trial period linearly tapered and stopped blinded study medication in 3 months. We compared changes in disease activity after taper between treatment groups (one-sided testing). Secondary outcomes (two-sided tests) comprised disease flares (DAS28 (Disease Activity Score 28 joints) increase >0.6, open-label glucocorticoids or disease-modifying antirheumatic drug (DMARD) increase/switch after week 4 of tapering) and symptoms/signs of adrenal insufficiency. In a subset of patients from 3 Dutch centres, cortisol and ACTH were measured in spot serum samples after tapering. Results 191 patients were eligible; 36 met treatment-related flare criteria and were only included in the flare analysis. Mean (SD) DAS28 change at follow-up: 0.2 (1.0) in the prednisolone group (n=76) vs 0.0 (1.2) in placebo (n=79). Adjusted for baseline, the between-group difference in DAS28 increase was 0.16 (95% confidence limit -0.06, p=0.12). Flares occurred in 45% of prednisolone patients compared with 33% in placebo, relative risk (RR) 1.37 (95% CI 0.95 to 1.98; p=0.12). We found no evidence for adrenal insufficiency. Conclusions Tapering prednisolone moderately increases disease activity to the levels of the placebo group (mean still at low disease activity levels) and numerically increases the risk of flare without evidence for adrenal insufficiency. This suggests that withdrawal of low-dose prednisolone is feasible and safe after 2 years of administration.
AB - Objective The randomised placebo-controlled GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) trial evaluated the benefits and harms of prednisolone 5 mg/day added to standard care for 2 years in patients aged 65+ years with rheumatoid arthritis (RA). Here, we studied disease activity, flares and possible adrenal insufficiency after blinded withdrawal of study medication. Methods Per protocol, patients successfully completing the 2-year trial period linearly tapered and stopped blinded study medication in 3 months. We compared changes in disease activity after taper between treatment groups (one-sided testing). Secondary outcomes (two-sided tests) comprised disease flares (DAS28 (Disease Activity Score 28 joints) increase >0.6, open-label glucocorticoids or disease-modifying antirheumatic drug (DMARD) increase/switch after week 4 of tapering) and symptoms/signs of adrenal insufficiency. In a subset of patients from 3 Dutch centres, cortisol and ACTH were measured in spot serum samples after tapering. Results 191 patients were eligible; 36 met treatment-related flare criteria and were only included in the flare analysis. Mean (SD) DAS28 change at follow-up: 0.2 (1.0) in the prednisolone group (n=76) vs 0.0 (1.2) in placebo (n=79). Adjusted for baseline, the between-group difference in DAS28 increase was 0.16 (95% confidence limit -0.06, p=0.12). Flares occurred in 45% of prednisolone patients compared with 33% in placebo, relative risk (RR) 1.37 (95% CI 0.95 to 1.98; p=0.12). We found no evidence for adrenal insufficiency. Conclusions Tapering prednisolone moderately increases disease activity to the levels of the placebo group (mean still at low disease activity levels) and numerically increases the risk of flare without evidence for adrenal insufficiency. This suggests that withdrawal of low-dose prednisolone is feasible and safe after 2 years of administration.
KW - Arthritis, Rheumatoid
KW - Glucocorticoids
KW - Patient Reported Outcome Measures
UR - http://www.scopus.com/inward/record.url?scp=85168274077&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/ard-2023-223977
DO - https://doi.org/10.1136/ard-2023-223977
M3 - Article
C2 - 37541762
SN - 0003-4967
VL - 82
SP - 1307
EP - 1314
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 10
ER -