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  • Three-month tapering and discontinuation of long- term, low-dose glucocorticoids in senior patients with rheumatoid arthritis is feasible and safe: placebo-controlled double blind tapering after the GLORIA trial

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Rheumatoid arthritis
Three-month tapering and discontinuation of long- term, low-dose glucocorticoids in senior patients with rheumatoid arthritis is feasible and safe: placebo-controlled double blind tapering after the GLORIA trial
  1. Abdullah Ali Hadi Almayali1,
  2. Maarten Boers1,
  3. Linda Hartman1,2,
  4. Daniela Opris3,
  5. Reinhard Bos4,
  6. Marc R Kok5,
  7. Jose AP Da Silva6,
  8. Ed Griep7,
  9. Ruth Klaasen8,
  10. Cornelia F Allaart9,
  11. Paul Baudoin10,
  12. Hennie G Raterman11,
  13. Zoltan Szekanecz12,
  14. Frank Buttgereit13,
  15. Pavol Masaryk14,
  16. Willem Lems2,
  17. Yvo Smulders15,
  18. Maurizio Cutolo16,
  19. Marieke M ter Wee1
  1. 1 Department of Epidemiology & Data Science, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
  2. 2 Amsterdam Rheumatology and Immunology Center, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
  3. 3 Rheumatology, Carol Davila University of Medicine and Pharmacy, Bucuresti, Romania
  4. 4 Department of Rheumatology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands
  5. 5 Department of Rheumatology and Clinical Immunology, Maasstad Hospital, Rotterdam, The Netherlands
  6. 6 Rheumatology Department, University of Coimbra Faculty of Medicine, Coimbra, Portugal
  7. 7 Department of Rheumatology, Antonius Hospital, Sneek, The Netherlands
  8. 8 Department of Rheumatology, Meander Medical Centre, Amersfoort, The Netherlands
  9. 9 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  10. 10 Rheumatology, Reumazorg Flevoland, Emmeloord, The Netherlands
  11. 11 Department of Rheumatology, Northwest Clinics, Alkmaar, The Netherlands
  12. 12 Department of Rheumatology, University of Debrecen, Debrecen, Hungary
  13. 13 Department of Rheumatology and Clinical Immunology, Charite University Hospital Berlin, Berlin, Germany
  14. 14 Rheumatology, National Institute of Rheumatic Diseases, Piestany, Slovakia
  15. 15 Department of Internal Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
  16. 16 Department of Internal Medicine, Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Genova, Italy
  1. Correspondence to Mr Abdullah Ali Hadi Almayali, Department of Epidemiology & Data Science, Amsterdam UMC Locatie VUmc, Amsterdam, 1007, The Netherlands; ab.almayali{at}gmail.com

Abstract

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.

  • Arthritis, Rheumatoid
  • Glucocorticoids
  • Patient Reported Outcome Measures

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/ard-2023-223977

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • Handling editor Josef S Smolen

    • Contributors The corresponding author as guarantor accepts full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish. He affirms that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned (and, if relevant, registered) have been explained. All authors meet the ICMJE criteria.

    • Funding 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.

    • Competing interests AAHA: None declared. MB: Novartis, Pfizer. LH: None declared. DO-B: AbbVie, Boehringer Ingelheim, Sandoz, EwoPharma, BMS, Alfą Sigma, Pfizer, Eli Lilly, Nordic Pharma. RB: UCB, Galapagos, Pfizer, Janssen. MRK: None declared. JAPdS: None declared. ENG: None declared. RK: None declared. CA: None declared. PB: None declared. HR: AbbVie, Amgen, Galapagos, Novartis, Amgen. ZS: AbbVie, Bristol-Myers, Pfizer, MSD, Lilly, Novartis, Gedeon Richter. FB: AbbVie, AstraZeneca, Gruenenthal, Horizon Therapeutics, Mundipharma, Pfizer, Roche. PM: None declared. WL: Pfizer, Galapagos, Lilly, Amgen, UCB. YS: None declared. MC: BMS, AMGEN, Pfizer, Celgene, Horizon. MMtW: None declared.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.