Use of glucocorticoids in the treatment of rheumatoid arthritis
- James R O'Dell, MD
James R O'Dell, MD
- Section Editor — Rheumatoid Arthritis
- Bruce Professor and Vice Chairman Internal Medicine
- University of Nebraska Medical Center
- Eric L Matteson, MD, MPH
Eric L Matteson, MD, MPH
- Section Editor — Treatment Issues in Rheumatology
- Chair, Division of Rheumatology
- Professor of Medicine
- Mayo Clinic College of Medicine
- Section Editor
- Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
- Section Editor — Rheumatoid Arthritis
- Emeritus Professor of Rheumatology, Imperial College London
- Visiting Professor, Oxford University
In the early 1950s, Hench and colleagues earned a Nobel Prize in medicine and physiology for discovering the dramatic beneficial effect of cortisone on a patient incapacitated by rheumatoid arthritis (RA). Since that time, the exact role of glucocorticoids in the treatment of RA has generated considerable debate.
Glucocorticoids exert both antiinflammatory and immunosuppressive effects via several mechanisms  (see "Glucocorticoid effects on the immune system"). Among those pertinent to patients with RA are the following:
- Inhibition of prostaglandin and leukotriene synthesis
- Reductions in macrophage phagocytosis, in interleukin (IL)-1 secretion, and in the number of circulating monocytes
- Inhibition of the release of collagenase and lysosomal enzymes
These effects are mediated by intracellular glucocorticoid receptors that interact with transcription factors and thus affect gene transcription. Glucocorticoids effects may also be mediated by posttranscriptional and posttranslational mechanisms, by physicochemical interactions with biologic membranes, and by binding to membrane-bound glucocorticoid receptors.
Among patients with RA, glucocorticoids may be administered via several different modalities. These include oral (short-term, chronic, and pulse), intramuscular, intravenous, and intraarticular routes. (See "Pharmacologic use of glucocorticoids".)
- Buttgereit F, Straub RH, Wehling M, Burmester GR. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum 2004; 50:3408.
- Moreland LW, O'Dell JR. Glucocorticoids and rheumatoid arthritis: back to the future? Arthritis Rheum 2002; 46:2553.
- Guidelines for the management of rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum 1996; 39:713.
- American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002; 46:328.
- Smolen JS, Aletaha D, Keystone E. Superior efficacy of combination therapy for rheumatoid arthritis: fact or fiction? Arthritis Rheum 2005; 52:2975.
- McInnes IB, O'Dell JR. State-of-the-art: rheumatoid arthritis. Ann Rheum Dis 2010; 69:1898.
- Gøtzsche PC, Johansen HK. Meta-analysis of short-term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. BMJ 1998; 316:811.
- den Uyl D, van Raalte DH, Nurmohamed MT, et al. Metabolic effects of high-dose prednisolone treatment in early rheumatoid arthritis: balance between diabetogenic effects and inflammation reduction. Arthritis Rheum 2012; 64:639.
- Landewé RB, Boers M, Verhoeven AC, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum 2002; 46:347.
- Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 2005; 52:3381.
- Bijlsma JW, Boers M, Saag KG, Furst DE. Glucocorticoids in the treatment of early and late RA. Ann Rheum Dis 2003; 62:1033.
- Million R, Kellgren JH, Poole P, Jayson MI. Long-term study of management of rheumatoid arthritis. Lancet 1984; 1:812.
- Kirwan JR. 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.
- Strand V. Steroid withdrawal favours joint erosion in rheumatoid arthritis. Clin Exp Rheumatol 1999; 17:519.
- van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW. 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.
- McDougall R, Sibley J, Haga M, Russell A. Outcome in patients with rheumatoid arthritis receiving prednisone compared to matched controls. J Rheumatol 1994; 21:1207.
- Morrison E, Capell HA. Corticosteroids in the management of early and established rheumatoid disease. Rheumatology (Oxford) 2006; 45:1058.
- Capell HA, Madhok R, Hunter JA, 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.
- Bakker MF, Jacobs JW, Welsing PM, et al. Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis: a randomized trial. Ann Intern Med 2012; 156:329.
- Jacobs JW, van Everdingen AA, Verstappen SM, Bijlsma JW. Followup radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy or placebo. Arthritis Rheum 2006; 54:1422.
- Paulus HE, Di Primeo D, Sanda M, et al. Progression of radiographic joint erosion during low dose corticosteroid treatment of rheumatoid arthritis. J Rheumatol 2000; 27:1632.
- Svensson B, Boonen A, Albertsson K, et al. 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.
- Wassenberg S, Rau R, Steinfeld P, Zeidler H. Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 2005; 52:3371.
- Harris ED Jr, Emkey RD, Nichols JE, Newberg A. Low dose prednisone therapy in rheumatoid arthritis: a double blind study. J Rheumatol 1983; 10:713.
- Pincus T, Swearingen CJ, Luta G, Sokka T. Efficacy of prednisone 1-4 mg/day in patients with rheumatoid arthritis: a randomised, double-blind, placebo controlled withdrawal clinical trial. Ann Rheum Dis 2009; 68:1715.
- Caplan L, Wolfe F, Russell AS, Michaud K. Corticosteroid use in rheumatoid arthritis: prevalence, predictors, correlates, and outcomes. J Rheumatol 2007; 34:696.
- Buttgereit F, Doering G, Schaeffler A, et al. Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial. Lancet 2008; 371:205.
- Buttgereit F, Mehta D, Kirwan J, et al. Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2). Ann Rheum Dis 2013; 72:204.
- Perry MG, Kirwan JR, Jessop DS, Hunt LP. Overnight variations in cortisol, interleukin 6, tumour necrosis factor alpha and other cytokines in people with rheumatoid arthritis. Ann Rheum Dis 2009; 68:63.
- Delayed-release prednisone (Rayos). Med Lett Drugs Ther 2012; 54:94.
- Saag KG, Koehnke R, Caldwell JR, et al. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 1994; 96:115.
- Laan RF, van Riel PL, van de Putte LB, et al. Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med 1993; 119:963.
- Buckley LM, Leib ES, Cartularo KS, et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996; 125:961.
- Michel BA, Bloch DA, Fries JF. Predictors of fractures in early rheumatoid arthritis. J Rheumatol 1991; 18:804.
- Van Staa TP, Leufkens HG, Abenhaim L, et al. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000; 15:993.
- Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 1990; 112:352.
- Smith MD, Ahern MJ, Roberts-Thomson PJ. Pulse methylprednisolone therapy in rheumatoid arthritis: unproved therapy, unjustified therapy, or effective adjunctive treatment? Ann Rheum Dis 1990; 49:265.
- Iglehart IW 3rd, Sutton JD, Bender JC, et al. Intravenous pulsed steroids in rheumatoid arthritis: a comparative dose study. J Rheumatol 1990; 17:159.
- Corkill MM, Kirkham BW, Chikanza IC, et al. Intramuscular depot methylprednisolone induction of chrysotherapy in rheumatoid arthritis: a 24-week randomized controlled trial. Br J Rheumatol 1990; 29:274.
- Choy EH, Kingsley GH, Corkill MM, Panayi GS. Intramuscular methylprednisolone is superior to pulse oral methylprednisolone during the induction phase of chrysotherapy. Br J Rheumatol 1993; 32:734.
- Radia M, Furst DE. Comparison of three pulse methylprednisolone regimens in the treatment of rheumatoid arthritis. J Rheumatol 1988; 15:242.
- Weiss MM. Corticosteroids in rheumatoid arthritis. Semin Arthritis Rheum 1989; 19:9.
- Blyth T, Hunter JA, Stirling A. Pain relief in the rheumatoid knee after steroid injection. A single-blind comparison of hydrocortisone succinate, and triamcinolone acetonide or hexacetonide. Br J Rheumatol 1994; 33:461.
- Chakravarty K, Pharoah PD, Scott DG. A randomized controlled study of post-injection rest following intra-articular steroid therapy for knee synovitis. Br J Rheumatol 1994; 33:464.
- Furtado RN, Oliveira LM, Natour J. Polyarticular corticosteroid injection versus systemic administration in treatment of rheumatoid arthritis patients: a randomized controlled study. J Rheumatol 2005; 32:1691.
- HOLLANDER JL, JESSAR RA, BROWN EM Jr. Intra-synovial corticosteroid therapy: a decade of use. Bull Rheum Dis 1961; 11:239.
- Roberts WN, Babcock EA, Breitbach SA, et al. Corticosteroid injection in rheumatoid arthritis does not increase rate of total joint arthroplasty. J Rheumatol 1996; 23:1001.
- Jain R, Lipsky PE. Treatment of rheumatoid arthritis. Med Clin North Am 1997; 81:57.
- Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum 1996; 39:723.
- Conn DL. Resolved: Low-dose prednisone is indicated as a standard treatment in patients with rheumatoid arthritis. Arthritis Rheum 2001; 45:462.
- Strand V, Simon LS. Low dose glucocorticoids in early rheumatoid arthritis. Clin Exp Rheumatol 2003; 21:S186.
- Choy EH, Kingsley GH, Khoshaba B, et al. A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs. Ann Rheum Dis 2005; 64:1288.
- Hoes JN, Jacobs JW, Boers M, et al. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 2007; 66:1560.
- Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. American College of Rheumatology Task Force on Osteoporosis Guidelines. Arthritis Rheum 1996; 39:1791.
- Hougardy DM, Peterson GM, Bleasel MD, Randall CT. Is enough attention being given to the adverse effects of corticosteroid therapy? J Clin Pharm Ther 2000; 25:227.
- Chantler IW, Davie MW, Evans SF, Rees JS. Oral corticosteroid prescribing in women over 50, use of fracture prevention therapy, and bone densitometry service. Ann Rheum Dis 2003; 62:350.
- Blalock SJ, Norton LL, Patel RA, Dooley MA. Patient knowledge, beliefs, and behavior concerning the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 2005; 53:732.
- Yilmaz L, Ozoran K, Gündüz OH, et al. Alendronate in rheumatoid arthritis patients treated with methotrexate and glucocorticoids. Rheumatol Int 2001; 20:65.
- Morrison E, Crosbie D, Capell HA. Attitude of rheumatoid arthritis patients to treatment with oral corticosteroids. Rheumatology (Oxford) 2003; 42:1247.