Glukokortikoide bei multimorbiden Rheumapatienten

Zusammenfassung

Glukokortikoide haben ihren festen Platz in der Therapie der rheumatoiden Arthritis. Ihre komplexe Wirkweise bedingt eine Reihe von Nebenwirkungen, die vor allem in der Dauertherapie oberhalb von 5 mg Prednisolon pro Tag eine Rolle spielen. In diesem höheren Dosisbereich verschlechtern sie die Prognose durch eine vermehrte Frühsterblichkeit und ein erhöhtes kardiovaskuläres Risiko. Auch ihre ungünstigen metabolischen Eigenschaften, wie die Beeinträchtigung der Glukose toleranz, sind deutlich dosisabhängig. Ihr Einsatz sollte – gemäß den Empfehlungen der S1-Leitlinie der Deutschen Gesellschaft für Rheumatologie (DGRh) – vorwiegend in der Initialphase der Erkrankung, möglichst zeitlich befristet und in geringstmöglicher Dosierung vorgenommen werden. Ihre Anwendung kann auch bei multimorbiden Patienten eine Option darstellen, wenn eine Kontrolle der entzündlichen Aktivität anders nicht erreicht werden kann.

Summary

Glucocorticoids are a cornerstone of the treatment of rheumatoid arthritis. The complex mechanism of action of these substances gives rise to a variety of side effects that occur preferentially at a dose range above 5 mg prednisolone per day. In higher dosages, they deteriorate the prognosis of the patients by causing increased mortality and an increased cardiovascular risk. In addition, higher doses of steroids worsen the glucose tolerance. According to the recommendations of the treatment guideline of the German Society of Rheumatology, glucocorticoids should be given preferentially in the early phase of arthritis, for a limited time period only, and in the smallest possible dose. However, in patients with a high level of comorbidity the application of corticosteroids is justified if the control of the inflammatory activity cannot be achieved by other means.

Schlüsselwörter

Glukokortikoide - rheumatoide Arthritis - kardiovaskuläres Risiko

Keywords

Glucocorticoids - rheumatoid arthritis - cardiovascular risk

• Literatur

• 1 Todoerti M, Scire CA, Boffini N. et al. Early disease control by low-dose prednisone comedication may affect the quality of remission in patients with early rheumatoid arthritis. Annals of the New York Academy of Sciences 2010; 1193: 139-145.
• 2 Graudal N, Jurgens 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 and rheumatism 2010; 62: 2852-2863.
• 3 Pincus T, Swearingen CJ, Luta G. et al. Efficacy of prednisone 1-4 mg/day in patients with rheumatoid arthritis: a randomised, double-blind, placebo controlled withdrawal clinical trial. Annals of the rheumatic diseases 2009; 68: 1715-1720.
• 4 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. Annals of internal medicine 2012; 156: 329-339.
• 5 Kirwan JR. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. The New England journal of medicine 1995; 333: 142-146.
• 6 Rau R. [Use of glucocorticoids in rheumatoid arthritis. Inhibition of disease progression versus risk of steroid osteoporosis]. Zeitschrift fur Rheumatologie 2001; 60: 485-491.
• 7 Burt MG, Willenberg VM, Petersons CJ. et al. Screening for diabetes in patients with inflammatory rheumatological disease administered long-term prednisolone: a cross-sectional study. Rheumatology (Oxford) 2012; 51: 1112-1119.
• 8 Matsumoto K, Yamasaki H, Akazawa S. et al. High-dose but not low-dose dexamethasone impairs glucose tolerance by inducing compensatory failure of pancreatic beta-cells in normal men. The Journal of clinical endocrinology and metabolism 1996; 81: 2621-2626.
• 9 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 and rheumatism 2012; 64: 639-646.
• 10 Hoes JN, van der Goes MC, van Raalte DH. et al. Glucose tolerance, insulin sensitivity and beta-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids. Annals of the rheumatic diseases 2011; 70: 1887-1894.
• 11 Metsios GS, Stavropoulos-Kalinoglou A, Veldhuijzen van Zanten JJ. et al. Rheumatoid arthritis, cardiovascular disease and physical exercise: a systematic review. Rheumatology (Oxford) 2008; 47: 239-248.
• 12 Panoulas VF, Douglas KM, Stavropoulos-Kalinoglou A. et al. Long-term exposure to medium-dose glucocorticoid therapy associates with hypertension in patients with rheumatoid arthritis. Rheumatology (Oxford) 2008; 47: 72-75.
• 13 Georgiadis AN, Papavasiliou EC, Lourida ES. et al. Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment - a prospective, controlled study. Arthritis research & therapy 2006; 8: R82.
• 14 Boers M, Nurmohamed MT, Doelman CJ. et al. Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis. Annals of the rheumatic diseases 2003; 62: 842-845.
• 15 Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Annals of internal medicine 2004; 141: 764-770.
• 16 Ajeganova S, Svensson B, Hafstrom I. Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial. BMJ open. 2014 4. e004259 DOI:
• 17 Huerta C, Johansson S, Wallander MA. et al. Risk factors and short-term mortality of venous thromboembolism diagnosed in the primary care setting in the United Kingdom. Archives of internal medicine 2007; 167: 935-943.
• 18 Bartl R, Bartl C, Gradinger R. [Drug-induced osteopathies. Drugs, pathogenesis, forms, diagnosis, prevention and therapy]. Zeitschrift fur Rheumatologie 2010; 69: 135-150 quiz 151
• 19 Van Staa TP, Leufkens HG, Abenhaim L. et al. Use of oral corticosteroids and risk of fractures. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2000; 15: 993-1000.
• 20 Weinstein RS. Glucocorticoid-induced osteoporosis and osteonecrosis. Endocrinology and metabolism clinics of North America 2012; 41: 595-611.
• 21 Pereira RM, Freire de Carvalho J. Glucocorticoid-induced myopathy. Joint, bone, spine: revue du rhumatisme 2011; 78: 41-44.
• 22 Winthrop KL. Infections and biologic therapy in rheumatoid arthritis: our changing understanding of risk and prevention. Rheumatic diseases clinics of North America 2012; 38: 727-745.
• 23 Dixon WG, Abrahamowicz M, Beauchamp ME. 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. Annals of the rheumatic diseases 2012; 71: 1128-1133.
• 24 Au K, Reed G, Curtis JR. et al. High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis. Annals of the rheumatic diseases. 2011 70. 785-791 DOI:
• 25 Jick SS, Lieberman ES, Rahman MU. et al. Glucocorticoid use, other associated factors, and the risk of tuberculosis. Arthritis and rheumatism 2006; 55: 19-26.
• 26 Miller AO, Brause BD. Perioperative infection in the patient with rheumatic disease. Current rheumatology reports 2013; 15: 379.
• 27 Listing J, Kekow J, Manger B. et al. Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFalpha inhibitors and rituximab. Ann Rheum Dis. doi: [Epub ahead of print]
• 28 Kroot EJ, van Leeuwen MA, van Rijswijk MH. et al. No increased mortality in patients with rheumatoid arthritis: up to 10 years of follow up from disease onset. Annals of the rheumatic diseases 2000; 59: 954-958.
• 29 Furtado RN, Oliveira LM, Natour J. Polyarticular corticosteroid injection versus systemic administration in treatment of rheumatoid arthritis patients: a randomized controlled study. The Journal of rheumatology 2005; 32: 1691-1698.
• 30 Hetland ML, Ostergaard M, Ejbjerg B. et al. Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis: impact of joint area, repeated injections, MRI findings, anti-CCP, IgM-RF and CRP. Annals of the rheumatic diseases 2012; 71: 851-856.
• 31 Grigor C, Capell H, Stirling A. et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 2004; 364: 263-269.