Systemic glucocorticoids in rheumatoid arthritis

  • John R. Kirwan
  • Mark G. Perry
Part of the Progress in Inflammation Research book series (PIR)


Glucocorticoids have been therapeutic agents in rheumatology since 1948, when Philip S Hench first used compound E (later renamed cortisone) to successfully treat a patient with rheumatoid arthritis (RA) [1, 2]. Over the intervening years, opinions about glucocorticoids have varied from excitement to complete rejection. Most of the worries concerning their use have been about adverse effects. Despite this historical variability in rheumatological opinion, many patients in practice are prescribed glucocorticoids. Here we review new evidence on the mechanisms of action of glucocorticoids, outcomes of glucocorticoid treatment and adverse effects, and propose an evidence based approach to their effective use in the management of rheumatoid arthritis.


Rheumatoid Arthritis Bone Mineral Density Early Rheumatoid Arthritis Systemic Glucocorticoid Cortisone Acetate 
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  1. 1.
    Hench PS, Kendall EC, Slocumb CH et al (1949) Effects of a hormone of the adrenal cortex (17-hydroxy-ll dehydrocorticosterone: compound E) and of pituitary adrenocorticotrophic hormone on rheumatoid arthritis: Preliminary report. Proc Staff Meet Mayo Clin 24: 181–197Google Scholar
  2. 2.
    Hench PS, Kendall EC, Slocumb CH et al (1950) Effects of cortisone acetate and pituitary ACTH on rheumatoid arthritis, rheumatic fever and certain other conditions. Arch Intern Med 85: 545–666Google Scholar
  3. 3.
    Buttgereit F, Wehling M, Burmester GR (1998) A new hypothesis of modular glucocorticoid actions. Arthritis Rheum 1998; 41: 761–767CrossRefPubMedGoogle Scholar
  4. 4.
    Goulding NJ, Guyre PM (1993) Glucocorticoids, lipocortins and the immune response. Curr Opin Immunol 5: 108–113CrossRefPubMedGoogle Scholar
  5. 5.
    Ristimaki A, Narko K, Hla T (1996) Down-regulation of cytokine-induced cyclo-oxygenase-2 transcript isoforms by dexamethasone: evidence for post-transcriptional regulation. Biochem J 318 (Pt 1): 325–331PubMedGoogle Scholar
  6. 6.
    Eklund KK, Humphries DE, Xia Z, Ghildyal N, Friend DS, Gross V, Stevens RL (1997) Glucocorticoids inhibit the cytokine-induced proliferation of mast cells, the high affinity IgE receptor-mediated expression of TNF-alpha, and the IL-10-induced expression of chymases. J Immunol 158(9): 4373–4380PubMedGoogle Scholar
  7. 7.
    Fessier BJ, Paliogianni F, Hama N, Balow JE, Boumpas DT (1996) Glucocorticoids modulate CD28 mediated pathways for interleukin 2 production in human T cells: Evidence for posttranscriptional regulation. Transplantation 62(8): 1113–1118CrossRefGoogle Scholar
  8. 8.
    Buttgereit F, da Silva JA, Boers M, Burmester G-R, Cutolo M, Jacobs J, Kirwan J, Kohler L, van Riel P, Vischer T et al (2002) Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimes: current questions and tentative answers in rheumatology. Ann Rheum Dis 61: 718–722CrossRefPubMedGoogle Scholar
  9. 9.
    Oluhy RG, Newmark SR, Lauler DR et al (1975) In: DL Azarnoff (ed): Pharmacology and chemistry of adrenal glucocosteroids in steroid therapy. Philadelphia: WB SaundersGoogle Scholar
  10. 10.
    Brooks SM, Werk EE, Ackerman SJ, Sullivan I, Thrasher K (1972) Adverse effects of phenobarbital on glucocorticoid metabolism in asthmatics. N Engl J Med 286: 1125–1128PubMedCrossRefGoogle Scholar
  11. 11.
    Klinenberg JR, Mullen R (1965) Effect of glucocorticoids on blood salicylate concentrations. JAMA 194: 601–604CrossRefPubMedGoogle Scholar
  12. 12.
    Kwoh CK, Ibrahim SA (2001) Rheumatology patient and physician concordance with respect to important health and symptom status outcomes. Arthritis Care Res 45: 372–377CrossRefGoogle Scholar
  13. 13.
    Hewlett S, Smith AP, Kirwan JR (2001) Values for function in rheumatoid arthritis: patients, professionals and public. Ann Rheum Dis 60: 928–933CrossRefPubMedGoogle Scholar
  14. 14.
    Gotzsche PC, Johansen HK (1999) Short-term, low-dose corticosteroids and nons-teroidal anti-inflammatory drugs for rheumatoid arthritis. The Cochrane Library: Oxford: Update SoftwareGoogle Scholar
  15. 15.
    Criswell LC, Saag KG, Sems KM, et al (1999) Rheumatoid Arthritis (RA): Moderate-term low dose corticosteroids for rheumatoid arthritis. The Cochrane Library. Oxford: Update SoftwareGoogle Scholar
  16. 16.
    Joint Committee of the Medical Research Council and Nuffield Foundation on Clinical Trials of Cortisone A, and Other Therapeutic Measures in Chronic Rheumatic Diseases (1954) A comparison of cortisone and aspirin in the treatment of early cases of rheumatoid arthritis. Br Med J 1: 1223–1227CrossRefGoogle Scholar
  17. 17.
    Kirwan JR, Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group (1995) The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med 333: 142–146CrossRefPubMedGoogle Scholar
  18. 18.
    Boers M, Verhoven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, van Zeben D, Dijkmans BA, Peeters AJ, Jacobs P et al (1997) Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 350 (9074): 309–318CrossRefPubMedGoogle Scholar
  19. 19.
    Rau R, Wassenberg S, Zeidler H (2000) Low dose prednisolone therapy (LDPT) retards radiographically detectable destruction in early rheumatoid arthritis — preliminary results of a multicenter, randomized, parallel, double blind study. Z Rheumatol 59 (Suppl 2): II/90–96Google Scholar
  20. 20.
    Van Everdingen AA, Jacobs JWG, Siewertsz van Reesema DR, Bijlsma JWJ (2002) Low-dose prednisone therapy for patients with early active rheumatoid arthritis: Clinical Efficacy, disease-modifying properties, and side effects. A randomized, double-blind, place-bo-controlled clinical trial. Ann Intern Med 136: 1–12PubMedGoogle Scholar
  21. 21.
    Hickling P, Jacoby RK, Kirwan JR (1998) Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Br J Rheumatol 37: 930–936CrossRefPubMedGoogle Scholar
  22. 22.
    Joint Committee of the Medical Research Council and Nuffield Foundation (1957) Long term results in early cases of rheumatoid arthritis treated with either cortisone or aspirin. BMJ 1: 847–851CrossRefGoogle Scholar
  23. 23.
    Joint Committee of the Medical Research Council and Nuffield Foundation (1959) A comparison of prednisolone with aspirin or other compound analgesic in the treatment of rheumatoid arthritis. Ann Rheum Dis 18: 173–188CrossRefGoogle Scholar
  24. 24.
    Empire Rheumatism Council (1957) Multi-centre controlled trial comparing cortisone acetate and acetyl salicylic acid in the long-term treatment of rheumatoid arthritis. Ann Rheum Dis 16: 277–289CrossRefGoogle Scholar
  25. 25.
    West HF (1967) Rheumatoid arthritis. The relevance of clinical knowledge to research activities. Abstr World Med 41: 401–417Google Scholar
  26. 26.
    Carr A, Hewlett S, Hughes R, Mitchell H, Ryan S, Carr M, Kirwan J (2003) Rheumatology Outcomes: The Patient’s Perspective. J Rheumatol 30: 880–883PubMedGoogle Scholar
  27. 27.
    Kirwan J, Heiberg T, Hewlett S, Hughes R, Kvien T, Ahlmèn M, Boers M, Minnock P, Saag K, Shea B et al (2003) Outcomes from the Patient Perspective workshop at OMER-ACT 6. J Rheumatol 30: 868–872PubMedGoogle Scholar
  28. 28.
    Weusten BLAM, Jacobs JWG, Bijlsma JWJ (1993) Glucocorticoid pulse therapy in active rheumatoid arthritis. Semin Arthritis Rheum 23: 183–192CrossRefPubMedGoogle Scholar
  29. 29.
    Radia M, Furst DE (1988) Comparison of three pulse methylprednisolone regimens in the treatment of rheumatoid arthritis. J Rheumatol 15: 242–256PubMedGoogle Scholar
  30. 30.
    Shipley ME, Bacon PA, Berry H, Hazleman BL, Sturrock RD, Swinson DR, Williams IA (1988) Pulsed methylprednisolone in active early rheumatoid disease: A dose ranging study. Br J Rheumatol 15: 242–246Google Scholar
  31. 31.
    Needs CJ, Smith M, Boutagy J et al (1988) Comparison of methylprednisolone (1 gram IV) with prednisolone (1 gram orally) in rheumatoid arthritis: a pharmokinetic and clinical study. J Rheumatol 15: 224–228PubMedGoogle Scholar
  32. 32.
    Choy EHS, Kingsley G, Corkhill MM, Panayi GS (1993) Intramuscular methylprednisolone is superior to pulse oral methylprednisolone during the induction phase of chrysotherapy. Br J Rheumatol 32: 734–739CrossRefPubMedGoogle Scholar
  33. 33.
    Conn D, Tomkins RB, Nichols WL (1988) Glucocorticoids in the management of vasculitis—a double edged sword? J Rheumatol 15: 1181–1183PubMedGoogle Scholar
  34. 34.
    Saag KG, Kirwan JR (2002) Glucocorticoid therapy in rheumatoid arthritis. In: GC Tsokos (ed): Modern Therapeutics of Rheumatoid Disease. Humana Press, New JerseyGoogle Scholar
  35. 35.
    Harris ED, Emkey RD, Nichols JE, Newberg A (1983) Low dose prednisone therapy in rheumatoid arthritis: A double blind study. J Rheumatol 10: 713–721PubMedGoogle Scholar
  36. 36.
    Million R, Poole P, Kellgren JH, Jayson MI (1984) Long-term study management of rheumatoid arthritis. Lancet 1: 812–816CrossRefPubMedGoogle Scholar
  37. 37.
    Dujovne CA, Azarnoff DL (1975) Clinical complications of corticosteroid therapy: a selected review. In: DL Azarnoff (ed): Steroid Therapy. WB Saunders, London, 27–41Google Scholar
  38. 38.
    Cooper C, Kirwan JR (1990) The risk of local and systemic corticosteroid administration. Baillière’s Clin Rheumatol 4: 305–332CrossRefGoogle Scholar
  39. 39.
    A working group of The Royal College of Physicians, The Bone and Tooth Society of Great Britain, and the National Osteoporosis Society (2002) Glucocorticoid-induced osteoporosis: Guidelines for prevention and treatment. Royal College of Physicians, LondonGoogle Scholar
  40. 40.
    ACR ad hoc committee on glucocorticoid-induced osteoporosis (2001) Recommendations for the Prevention and Treatment of Glucocorticoid-induced osteoporosis. Arthritis Rheum 44: 1496–1503CrossRefGoogle Scholar
  41. 41.
    Zeidler H, Rau R, Steinfield P (1999) Efficacy and safety of low dose prednisolone therapy in early rheumatoid arthritis. Arthritis Rheum 42: S271Google Scholar
  42. 42.
    Capell HA, Madhok R, Hunter JA, Porter D, Morrison E, Larkin J et al (2004) 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 63(7): 797–803CrossRefPubMedGoogle Scholar
  43. 43.
    Kirwan JR, Hallgren R, Mielants H, Wollheim F, Bjorck E, Persson T et al (2004) A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis. Ann Rheum Dis 63(6): 688–695CrossRefPubMedGoogle Scholar
  44. 44.
    Choy EH, Kingsley G, Khoshaba B, Pipitone N, Dolan L, Pitt P et al (2004) Randomised placebo-controlled trial of intramuscular (IM) depot methylprednisolone in patient with established rheumatoid arthritis. Rheumatology 43(S2): ii44–45Google Scholar
  45. 45.
    Haugeberg G, Strand A, Kvien TK, Kirwan JR (2004) Reduced loss of hand bone mass in patients with early rheumatoid arthritis treated with prednisolone — results from a randomised placebo-controlled trial. Ann Rheum Dis 63(S1): 86Google Scholar
  46. 46.
    Kirwan JR, Boers M, Low dose prednisolone for treatment of RA. Ann Rheum Dis; in press Google Scholar
  47. 47.
    Jensen T, Klarlund M, Hansen M, Jensen KE, Podenphant J, Hansen TM et al. (2004) Bone loss in unclassified polyarthritis and early rheumatoid arthritis is better detected by digital x ray radiogrammetry than dual x ray absorptiometry: relationship with disease activity and radiographic outcome. Ann Rheum Dis 63: 15–22CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2005

Authors and Affiliations

  • John R. Kirwan
    • 1
  • Mark G. Perry
    • 1
  1. 1.Academic Rheumatology, Bristol Royal InfirmaryUniversity of BristolBristolUK

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