Arthritis und Rheuma 2011; 31(04): 233-239
DOI: 10.1055/s-0037-1618077
Systemischer Lupus erythematodes
Schattauer GmbH

Systemischer Lupus erythematodes

TherapieSystemischer Lupus erythematodesTherapie
M. Aringer
1   Medizinische Klinik und Poliklinik III, Universitätsklinikum „Carl Gustav Carus“ der Technischen Universität Dresden
› Author Affiliations
Further Information

Publication History

Publication Date:
26 December 2017 (online)

Zusammenfassung

Wenn man die Therapieoptionen bei systemischem Lupus erythematodes (SLE) oberflächlich betrachtet, hat sich in den vergangenen Jahrzehnten nicht allzu viel verändert. Glukokortikoide, Cyclophosphamid, Azathioprin und Hydroxychloroquin sind (ur)alte Bekannte. Neue Zulassungen gab es in Europa bis 2011 nicht. Das hat sich in diesem Jahr mit Belimumab geändert, das in Europa und den USA zugelassen wurde. Viele weitere neue therapeutische Ansätze sind in klinischen Prüfungen. Ganz entscheidend aber hat sich zudem die Behandlungsstrategie geändert: Cyclophosphamid wird heute sehr sparsam eingesetzt, die Rolle von Azathioprin und Mycophenolat-Mofetil (MMF) ist klarer geworden. Methotrexat hat sich einen festen Platz erobert. Glukokortikoide werden möglichst rasch unter die Cushingdosis gesenkt. Antimalariamittel hingegen sind das Standardmedikament für (fast) alle SLE-Patientinnen und Patienten geworden. Daneben spielen Sonnenschutz und Vitamin D eine wichtige Rolle sowie die Kontrolle kardiovaskulärer und anderer Risikofaktoren.

Summary

A superficial look on the therapeutic options for systemic lupus erythematosus will not reveal important breakthroughs in the last decades. Glucocorticoids, cyclophosphamide, azathioprine and antimalarials have been there for ages. Until 2011, no novel therapeutic agents have been approved. This has changed in 2011. Belimumab has been approved both in the U.S. and in Europe. Many more novel therapeutic approaches are being tested in clinical trials. In addition, however, therapeutic strategies have changed dramatically: Cyclophosphamide is being used in a much reduced fashion, the role of azathioprine and mycophenolate mofetil (MMF) has been better clarified. Methotrexate has found its way into SLE standard therapy. Glucocorticoids are reduced to below 10 mg predniso(lo)ne q.d. as soon as feasible, while hydroxychloroquine has become the standard drug for essentially all SLE patients. In addition, UV protection and vitamin D both play an important role, as does the control of cardiovascular and other risk factors.

 
  • Literatur

  • 1 Bertsias G, Ioannidis JP, Boletis J. et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 2008; 67 (02) 195-205.
  • 2 Bertsias GK, Ioannidis JP, Aringer M. et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 2010; 69 (12) 2074-2082.
  • 3 Mosca M, Tani C, Aringer M. et al. European League Against Rheumatism recommendations for monitoring patients with systemic lupus erythematosus in clinical practice and in observational studies. Ann Rheum Dis 2010; 69 (07) 1269-1274.
  • 4 Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40 (09) 1725.
  • 5 Kuhn A, Sonntag M, Richter-Hintz D. et al. Phototesting in lupus erythematosus: a 15-year experience. J Am Acad Dermatol 2001; 45 (01) 86-95.
  • 6 Petri M, Kim MY, Kalunian KC. et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005; 353 (24) 2550-2558.
  • 7 Fischer-Betz R, Gromnica-Ihle E. Pregnancy and inflammatory rheumatic diseases. Z Rheumatol 2010; 69 (07) 633-641.
  • 8 Illei GG, Austin HA, Crane M. et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 2001; 135 (04) 248-257.
  • 9 Steinberg AD, Steinberg SC. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 1991; 34 (08) 945-950.
  • 10 Illei GG, Austin HA, Crane M. et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 2001; 135 (04) 248-257.
  • 11 Blumenfeld Z, Shapiro D, Shteinberg M. et al. Preservation of fertility and ovarian function and minimizing gonadotoxicity in young women with systemic lupus erythematosus treated by chemotherapy. Lupus 2000; 9 (06) 401-405.
  • 12 Contreras G, Pardo V, Leclercq B. et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med 2004; 350 (10) 971-980.
  • 13 Houssiau FA, Vasconcelos C, D'Cruz D. et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis 2010; 69 (01) 61-64.
  • 14 Abu-Shakra M, Shoenfeld Y. Azathioprine therapy for patients with systemic lupus erythematosus. Lupus 2001; 10 (03) 152-153.
  • 15 Houssiau FA, D'Cruz D, Sangle S. et al. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 2010; 69 (12) 2083-2089.
  • 16 Appel GB, Contreras G, Dooley MA. et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 2009; 20 (05) 1103-1112.
  • 17 Ginzler EM, Dooley MA, Aranow C. et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005; 353 (21) 2219-2228.
  • 18 Grootscholten C, Ligtenberg G, Hagen EC. et al. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. Kidney Int 2006; 70 (04) 732-742.
  • 19 Ginzler EM, Appel GB, Dooley MA. et al. Aspreva lupus management study (ALMS): maintenance results. Arthritis Rheum 2010; 62: S871-S872.
  • 20 Winzer M, Aringer M. Use of methotrexate in patients with systemic lupus erythematosus and primary Sjogren's syndrome. Clin Exp Rheumatol 2010; 28 (05) (Suppl. 61) S156-S159.
  • 21 Austin III HA, Illei GG, Braun MJ, Balow JE. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol 2009; 20 (04) 901-911.
  • 22 Looney RJ, Anolik JH, Campbell D. et al. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 2004; 50 (08) 2580-2589.
  • 23 Lu TY, Ng KP, Cambridge G. et al. A retrospective seven-year analysis of the use of B cell depletion therapy in systemic lupus erythematosus at University College London Hospital: the first fifty patients. Arthritis Rheum 2009; 61 (04) 482-487.
  • 24 Gunnarsson I, Sundelin B, Jonsdottir T. et al. Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis. Arthritis Rheum 2007; 56 (04) 1263-1272.
  • 25 Terrier B, Amoura Z, Ravaud P. et al. Safety and efficacy of rituximab in systemic lupus erythematosus: results from 136 patients from the French Auto-Immunity and Rituximab registry. Arthritis Rheum 2010; 62 (08) 2458-2466.
  • 26 Ng KP, Cambridge G, Leandro MJ. et al. B cell depletion therapy in systemic lupus erythematosus: long-term follow-up and predictors of response. Ann Rheum Dis 2007; 66 (09) 1259-1262.
  • 27 Merrill JT, Neuwelt CM, Wallace DJ. et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum 2010; 62 (01) 222-233.
  • 28 Furie R, Looney RJ, Rovin B. et al. Efficacy and safety of rituximab in subjects with active proliferative lupus nephritis (LN): results from the randomized, double-blind phase III LUNAR trial. Arthritis Rheum 2009; 60: S429.
  • 29 Navarra SV, Guzman RM, Gallacher AE. et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377 (9767) 721-731.
  • 30 van Vollenhoven RF, Zamani O, Wallace DJ. et al. Belimumab, a BLyS-specific inhibitor, reduces disease activity and severe flares in seropositive SLE patients: BLISS-76 study. Ann Rheum Dis 2010; 69: 74.
  • 31 Manzi S, Sanchez-Guerrero J, Merrill JT. et al. Belimumab, a BLyS-specific inhibitor, reduced disease activity across multiple organ domains: combined efficacy results from the phase 3 BLISS-52 and -76 studies. Arthritis Rheum 2010; 62: S607-S608.
  • 32 Illei GG, Shirota Y, Yarboro CH. et al. Tocilizumab in systemic lupus erythematosus: Data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum 2010; 62 (02) 542-552.
  • 33 Merrill JT, Burgos-Vargas R, Westhovens R. et al. The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2010; 62 (10) 3077-3087.
  • 34 Aringer M, Houssiau F, Gordon C. et al. Adverse events and efficacy of TNF-alpha blockade with infliximab in patients with systemic lupus erythematosus: long-term follow-up of 13 patients. Rheumatology (Oxford) 2009; 48 (11) 1451-1454.
  • 35 Vina ER, Fang AJ, Wallace DJ, Weisman MH. Chronic inflammatory demyelinating polyneuropathy in patients with systemic lupus erythematosus: prognosis and outcome. Semin Arthritis Rheum 2005; 35 (03) 175-184.
  • 36 Cervera R, Bucciarelli S, Plasin MA. et al. Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of a series of 280 patients from the „CAPS Registry“. J Autoimmun 2009; 32 (3–4) 240-245.
  • 37 Stummvoll GH, Julius U, Derfler K, Aringer M. Immunoadsorption for systemic lupus erythematosus. Atheroscler Suppl 2009; 10 (05) 110-113.
  • 38 Alexander T, Thiel A, Rosen O. et al. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood 2009; 113 (01) 214-223.