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Efficacy, duration of use and safety of glucocorticoids: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis
  1. Sytske Anne Bergstra1,
  2. Alexandre Sepriano1,2,
  3. Andreas Kerschbaumer3,
  4. Désirée van der Heijde1,
  5. Roberto Caporali4,
  6. Christopher John Edwards5,
  7. Patrick Verschueren6,
  8. Savia de Souza7,
  9. Janet E Pope8,
  10. Tsutomu Takeuchi9,10,
  11. Kimme L Hyrich11,12,
  12. Kevin L Winthrop13,
  13. Daniel Aletaha3,
  14. Tanja A Stamm14,15,
  15. Jan W Schoones16,
  16. Josef S Smolen3,17,
  17. Robert B M Landewé18,19
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal
  3. 3Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Wien, Austria
  4. 4University of Milan, Milan and Department of Rheumatology, ASST PINI-CTO, Milano, Italy
  5. 5NIHR Southampton Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  6. 6Department of rheumatology, KU Leuven University Hospitals Leuven, Leuven, Belgium
  7. 7EULAR Patient Research Partner Network, Zurich, Switzerland
  8. 8University of Western Ontario, Schulich School of Medicine, London, Ontario, Canada
  9. 9Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Graduate School of Medicine, Shinjuku-ku, Japan
  10. 10Saitama Medical University, Iruma-gun, Saitama, Japan
  11. 11Centre for Epidemiology Versus Arthritis, The University of Manchester, Manchester, UK
  12. 12NIHR Manchester Biomedical Research Centre, Manchester University NHS Trust, UK
  13. 13Oregon Health and Science University, Portland, Oregon, USA
  14. 14Section for Outcomes Research, Centre for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Wien, Austria
  15. 15Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria
  16. 16Walaeus Library, Leiden University Medical Center, Leiden, The Netherlands
  17. 172nd Department of Medicine, Hietzing Hospital, Wien, Austria
  18. 18Amsterdam Rheumatology Center, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  19. 19Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, The Netherlands
  1. Correspondence to Sytske Anne Bergstra, Department of Rheumatology, Leiden University Medical Center, Leiden, 2333 ZA, Netherlands; s.a.bergstra{at}lumc.nl

Abstract

This systematic literature review (SLR) regarding the efficacy, duration of use and safety of glucocorticoids (GCs), was performed to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA). Studies on GC efficacy were identified from a separate search on the efficacy of disease-modifying antirheumatic drugs (DMARDs). A combined search was performed for the duration of use and safety of GCs in RA patients. Dose-defined and time-defined GC treatment of any dose and duration (excluding intra-articular GCs) prescribed in combination with other DMARDs were considered. Results are presented descriptively. Two included studies confirmed the efficacy of GC bridging as initial therapy, with equal efficacy after 2 years of initial doses of 30 mg/day compared with 60 mg/day prednisone. Based on a recently performed SLR, in clinical trials most patients starting initial GC bridging are able to stop GCs within 12 (22% patients continued on GCs) to 24 months (10% patients continued on GCs). The safety search included 12 RCTs and 21 observational studies. Well-known safety risks of GC use were confirmed, including an increased risk of osteoporotic fractures, serious infections, diabetes and mortality. Data on cardiovascular outcomes were Inconsistent. Overall, safety risks increased with increasing dose and/or duration, but evidence on which dose is safe was conflicting. In conclusion, this SLR has confirmed the efficacy of GCs in the treatment of RA. In clinical trials, most patients have shown to be able to stop GCs within 12–24 months. Well-known safety risks of GC use have been confirmed, but with heterogeneity between studies.

  • Glucocorticoids
  • Epidemiology
  • Arthritis, Rheumatoid

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Footnotes

  • Handling editor David S Pisetsky

  • Twitter @AlexSepriano, @Janetbirdope

  • Contributors SAB extracted the data for the SLR; JWS developed the search strategies; SAB wrote the first version of the manuscript and all authors revised the manuscript critically for important intellectual content and gave final approval of the version to be published.

  • Funding This work was supported by the European Alliance of Associations for Rheumatology.

  • Competing interests SAB: received an ASPIRE grant from Pfizer. AS: received speaker/consulting fees from UCB, Novartis and Lilly. AK: Speakers bureau, Consultancy: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, Janssen, Merck Sharp and Dohme, Novartis, UCB und Pfizer. JWS: received grants from Abbvie, Astra-Zeneca, Janssen, Lilly, Novartis, Roche and honoraria from Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB. DvdH: received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma and is Director of Imaging Rheumatology bv. RC received consulting fees from Abbvie, BMS, Amgen, Celltrion, Eli-Lilly, Fresenius-Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB Pharma. CJE Has received fees from Abbvie, Astra Zeneca, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Galapagos, GSK, Janssen, Eli Lilly, Pfizer, Roche, Sanofi for advisory boards, speakers bureau and research support. PV received consulting fees from Abbvie, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Sidekick Health, UCB and speaker’s fees from Eli Lilly, Galapagos, MSD and Roularta. Holds the Pfizer Chair Early RA Management at KU Leuven. SdS: none. JEP received research grants from AbbVie, Frensenius Kabi, Mallinckrodt Pharmaceuticals, Pfizer, Seattle Genetics and consulting fees from AbbVie, Amgen, Astra Zeneca, BI, BMS, Celltrion, EMERALD, Frensenius Kabi, Galapagos, GSK, Janssen, Lilly, Mallinckrodt Pharmaceuticals, Medexus, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sandoz, Samsung, Sobi, Viatris. TT received grants from AbbVie GK, Astellas, Asahi Kasei, Chugai, Daiichi Sankyo, Eisai, Takeda, Mitsubishi Tanabe, Nippon Kayaku, and speakers/consulting fees from AbbVie GK, Astellas, Chugai, Daiichi Sankyo, Eli Lilly Japan, Eisai, Gilead, Mitsubishi Tanabe, Pfizer Japan. KLH received speaker’s fees from Abbvie and research grants from Pfizer and BMS. KLW received research grants from Pfizer, BMS, and GSK, and scientific consulting fees from UCB, Abbvie, BMS, Galapagos, Gilead, Lilly, GSK, Roche, and Novartis. DA has received grants and/or speaker/consulting fees from Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, SoBi, Sanofi, Sandoz, and Roche. TAS has received grant/research support from AbbVie and Roche, has been a consultant for AbbVie and Sanofi Genzyme, and has been a paid speaker for AbbVie, Novartis, Roche, Sanofi, and Takeda. JSS: none. RBML: received consulting fees from AbbVie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Roche, UCB and is Director of Rheumatology Consultancy bv. JSS, DvdH, KLH, KLW, DD and RBML are members of the Editorial Board of ARD.

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

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