Mediterr J Rheumatol 2018;29(1):13-6
Long-term treatment with low dose glucocorticoids in Rheumatoid Arthritis: New tricks of an old drug
Authors Information

Ioannina, Greece

  1. Hench P S, Kendall E C, Slocumb C H, Polley H F. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone: Compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis. Proc Staff Meet Mayo Clin 1949;24:181-97.
  2. EMPIRE Rheumatism Council; multi-centre controlled trial comparing cortisone acetate and acetyl salicylic acid in the long-term treatment of rheumatoid arthritis; results up to one year. Ann Rheum Dis 1955;14:353-70.
  3. A comparison of prednisolone with aspirin or other analgesics in the treatment of rheumatoid arthritis. A second report by the joint committee of the Medical Research Council and Nuffield Foundation on clinical trials of cortisone, ACTH, and other therapeutic measures in chronic rheumatic diseases. Ann Rheum Dis 1960;19:331-7.
  4. Straub R H. Rheumatoid arthritis - a neuroendocrine immune disorder: glucocorticoid resistance, relative glucocorticoid deficiency, low-dose glucocorticoid therapy, and insulin resistance. Arthritis Res Ther 2014;16:I1. doi:10.1186/ar4684.
  5. Smolen J S, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960-77.
  6. Smolen J S, Landewé R, Breedveld F C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010;69:964-75.
  7. Schenfeld J, Iles J, Trivedi M, Accortt N A. Dose relationship between oral glucocorticoids and tumor necrosis factor inhibitors and the risk of hospitalized infectious events among patients with rheumatoid arthritis. Rheumatol Int 2017;37:1075-82.
  8. Palmowski Y, Buttgereit T, Dejaco C, Bijlsma J W, Matteson E L, Voshaar M, et al. “Official View" on Glucocorticoids in Rheumatoid Arthritis: A Systematic Review of International Guidelines and Consensus Statements. Arthritis Care Res (Hoboken) 2017;69:1134-41.
  9. Mahajan T, O'Dell J R. It is the Best of Treatments, It is the Worst of Treatments: The Continuing Love-Hate Relationship With Glucocorticoids in Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 2017;69:1131–3.
  10. Roubille C, Rincheval N, Dougados M, Flipo R M, Daurès J P, Combe B. Seven-year tolerability profile of glucocorticoids use in early rheumatoid arthritis: data from the ESPOIR cohort. Ann Rheum Dis 2017;76:1797-1802.
  11. Wassenberg S, Rau R, Steinfeld P, Zeidler H, for the Low-Dose Prednisolone Therapy Study Group. Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years. Arthritis Rheum 2005;52:3371-80.
  12. Svensson B, Boonen A, Albertsson K, van der Heijde D, Keller C, Hafström I, for the BARFOT Study Group. Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate. A two-year randomized trial. Arthritis Rheum 2005;52:3360-70.
  13. van Everdingen A A, Jacobs J W G, van Reesema D R S, Bijlsma J W J. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 2002;136:1-12.
  14. Dixon W G, Abrahamowicz M, Beauchamp M E, Ray D W, Bernatsky S, Suissa S. et al. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis. Ann Rheum Dis 2012;71:1128-33.
  15. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum 2006 Feb;54(2):628-34.
  16. Doran M F, Crowson C S, Pond G R, O'Fallon W M, Gabriel S E. Predictors of infection in rheumatoid arthritis. Arthritis Rheum 2002 Sep;46(9):2294-300.
  17. Pincus T, Castrejón I, Sokka T. Long-term prednisone in doses of less than 5 mg/day for treatment of rheumatoid arthritis: personal experience over 25 years. Clin Exp Rheumatol. 2011;29:S130-8.
  18. Wassenberg S, Rau R, Steinfeld P, Zeidler H and Low-Dose Prednisolone Therapy Study Group (2005). Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: A multicenter, double-blind, placebo-controlled trial. Arthritis  Rheum 52: 3371–80. doi:10.1002/art.21421.
  19. Curtis J R, Westfall A O, Allison J, Bijlsma J W, Freeman A, George V, et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum 2006;55:420-6.
  20. van der Goes M C, Jacobs J W, Boers M, Andrews T, Blom-Bakkers M A, Buttgereit F, et al. Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice. Ann Rheum Dis. 2010;69:1913-9. doi: 10.1136/ard.2009.124958.
  21. Strehl C, Bijlsma J W, de Wit M, Boers M, Caeyers N, Cutolo M, et al. Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis 2016;75:952-7. doi: 10.1136/annrheumdis-2015-208916
  22. Hoes J N, van der Goes M C, van Raalte D H, van der Zijl N J, den Uyl D, Lems W F, et al. Glucose tolerance, insulin sensitivity and β-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids. Ann Rheum Dis 2011;70:1887-94.
  23. Buckley L, Guyatt G, Fink H A, Cannon M, Grossman J, Hansen K E, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2017; doi:10.1002/art.40137
  24. Dilisio M F. Osteonecrosis following short-term, low-dose oral corticosteroids: a population-based study of 24 million patients. Orthopedics. 2014;37:e631-6. doi: 10.3928/01477447-20140626-54Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open 2014;4:e004587. doi: 10.1136/bmjopen-2013-004587.
  25. Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open 2014;4:e004587. doi: 10.1136/bmjopen-2013-004587.
  26. Safy M, Jacobs J, IJff N. On behalf of the Society for Rheumatology Research Utrecht (SRU), et al Long-term outcome is better when a methotrexate-based treatment strategy is combined with 10 mg prednisone daily: follow-up after the second Computer-Assisted Management in Early Rheumatoid Arthritis trial. Ann Rheum Dis 2017;76:1432-5. http://dx.doi.org/10.1136/annrheumdis-2016-210647.
  27. Boers M, Aletaha D, Mela C M, Baker D G, Smolen J S. Glucocorticoid Effect on Radiographic Progression in Placebo Arms of Rheumatoid Arthritis Biologics Trials. J Rheumatol 2016;43:1024-6. doi: 10.3899/jrheum.150932.
  28. Capell H A, Madhok R, Hunter J A, Porter D, Morrison E, Larkin J, et al. Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial. Ann Rheum Dis 2004;63:797-803.
  29. Kirwan J R and the Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med 1995;333:142-6.
  30. Boers M, Verhoeven A C, Markusse H M, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997;350:309-18.
  31. Dougados M, Combe B, Cantagrel A, et al. Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52-week clinical trial of sulphasalazine and methotrexate compared with the single components. Ann Rheum Dis 1999;58:220-5.
  32. Landewe R B, Boers M, Verhoeven A C, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long term structural benefits of a brief intervention. Arthritis Rheum 2002;46:347-56.
  33. Graudal N, Hubeck-Graudal T, Faurschou M, Baslund B, Jürgens G. Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta-Analysis of Randomized Trials. Arthritis Care Res (Hoboken). 2015;67:1487-95. doi: 10.1002/acr.22618.
  34. Graudal N, Jürgens G. Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons. Arthritis Rheum 2010;62:2852-63. doi: 10.1002/art.27592.
  35. Kirwan J R, Bijlsma J W J, Boers M, Shea B. Effects of glucocorticoids on radiological progression in rheumatoid arthritis. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD006356. DOI: 10.1002/14651858.CD006356.
  36. Carette S. All patients with rheumatoid arthritis should receive corticosteroids as part of their management. J Rheumatol 2007;34:656-60.
  37. Hellgren K, Baecklund E, Backlin C, Sundstrom C, Smedby K E, Askling J. Rheumatoid Arthritis and Risk of Malignant Lymphoma: Is the Risk Still Increased?. Arthritis Rheum 2017;69:700–8. doi:10.1002/art.40017.