Interest in the numerous benefits of corticosteroid medication in the management of rheumatoid arthritis (RA) goes back to the mid-1950s, and has recently been renewed. The established evidence of their rapid symptomatic effects, along with the growing recognition of their long-lasting disease-modifying properties and preliminary data about their sub-clinical action, led us to reconsider the potential of corticosteroids in the treatment of RA, given their acceptable safety profile, especially when used at low dosages. Over time, several corticosteroid-based therapeutic approaches have been explored in order to optimize their clinical benefits, while limiting the adverse effects. Clinical data reported with initial high-dosage corticosteroid schedules with subsequent step-down schemes suggest clinical efficacy, but are not applicable to patient management in a real-life setting. Encouraging results on the clinical and sub-clinical effects of low dosages have led to a shift in usual daily practice. We present past and recent efforts to clarify the role of corticosteroids in the treatment of RA, focusing on the best approach in terms of dose and timing of corticosteroid administration. Additional information about different routes of administration, step-down schedules and adverse effects are also considered.
Native English editing, formatting and styling of the draft manuscript was provided by Mary Hines, inScience Communications, Springer Healthcare and funded by Mundipharma Pharmaceuticals srl.
Conflicts of interest
Professor Caporali took the main responsibility for the planning of the work and for the accuracy and integrity of the data reported. Professor Montecucco revised and approved the final manuscript. Dr Sakellariou and Dr Todoerti were responsible for the data search, acquisition and reporting.
- 1.Caporali R, Cimmino MA, Montecucco C, et al. Glucocorticoid treatment of polymyalgia rheumatica. Clin Exp Rheumatol. 2011;29(5 Suppl 68):S143–7.Google Scholar
- 4.OCEBM Levels of Evidence Working Group. The Oxford 2011 levels of evidence. 2012. http://www.cebm.net/index.aspx?o=5653. Accessed 2012.
- 5.The Joint Committee of the Medical Research Council and Nuffield Foundation on Clinical Trials of Cortisone, A.C.T.H., and Other Therapeutic Measures in Chronic Rheumatic Diseases. A comparison of cortisone and aspirin in the treatment of early cases of rheumatoid arthritis; a 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. Br Med J. 1954;1(4873):1223–7.Google Scholar
- 6.The Joint Committee of the Medical Research Council and Nuffield Foundation on Clinical Trials of Cortisone, A.C.T.H., and Other Therapeutic Measures in Chronic Rheumatic Diseases. A comparison of prednisolone with aspirin on other analgesics in the treatment of rheumatoid arthritis. Ann Rheum Dis. 1959;18:173–88.Google Scholar
- 7.The Joint Committee of the Medical Research Council and Nuffield Foundation on Clinical Trials of Cortisone, A.C.T.H., and Other Therapeutic Measures in Chronic Rheumatic Diseases. 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.Google Scholar
- 9.Criswell LA, Saag KG, Sems KM, et al. Moderate-term, low-dose corticosteroids for rheumatoid arthritis. Cochrane Database Syst Rev. 2000;(2):CD001158.Google Scholar
- 10.Gotzsche PC, Johansen HK. Short-term low-dose corticosteroids vs placebo and nonsteroidal anti-inflammatory drugs in rheumatoid arthritis. Cochrane Database Syst Rev. 2004;(3):CD000189.Google Scholar
- 18.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(11):3360–70.PubMedCrossRefGoogle Scholar
- 21.Pincus T, Castrejon 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(5 Suppl 68):S130–8.Google Scholar
- 25.Hafstrom I, Albertsson K, Boonen A, et al. Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study. Ann Rheum Dis. 2009;68(4):508–13.PubMedCrossRefGoogle Scholar
- 26.van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, et al. 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):1–12.PubMedCrossRefGoogle Scholar
- 29.Brown AK, Quinn MA, Karim Z, et al. Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression. Arthritis Rheum. 2006;54(12):3761–73.PubMedCrossRefGoogle Scholar
- 30.Bugatti S, Manzo A, Benaglio F, et al. Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs. Arthritis Res Ther. 2012;14(1):R34.PubMedCrossRefGoogle Scholar
- 37.Saleem B, Brown AK, Keen H, et al. Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease-modifying antirheumatic drugs: a clinical and imaging comparative study. Arthritis Rheum. 2009;60(7):1915–22.PubMedCrossRefGoogle Scholar
- 42.Gremese E, Salaffi F, Bosello SL, et al. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study. Ann Rheum Dis. 2012. [Epub ahead of print]Google Scholar
- 43.Kirwan JR, Bijlsma JW, Boers M, et al. Effects of glucocorticoids on radiological progression in rheumatoid arthritis. Cochrane Database Syst Rev. 2007;(1):CD006356.Google Scholar
- 52.Derendorf H, Ruebsamen K, Clarke L, et al. Pharmacokinetics of modified-release prednisone tablets in healthy subjects and patients with rheumatoid arthritis. J Clin Pharmacol. 2012. [Epub ahead of print]Google Scholar
- 56.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;72:204–10.Google Scholar
- 69.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(9):1288–93.PubMedCrossRefGoogle Scholar
- 71.Hetland ML, Stengaard-Pedersen K, Junker P, et al. Aggressive combination therapy with intra-articular glucocorticoid injections and conventional disease-modifying anti-rheumatic drugs in early rheumatoid arthritis: second-year clinical and radiographic results from the CIMESTRA study. Ann Rheum Dis. 2008;67(6):815–22.PubMedCrossRefGoogle Scholar
- 74.Caporali R, Conti F, Alivernini S, et al. Recommendations for the use of biologic therapy in rheumatoid arthritis: update from the Italian Society for Rheumatology I. Efficacy. Clin Exp Rheumatol. 2011;29(3 Suppl 66):S7–14.Google Scholar