Skip to main content

Advertisement

SpringerLink
Log in

Ausschleichen und Beenden von immunsuppressiven Therapien

Systemischer Lupus erythematodes

Tapering and termination of immunosuppressive therapy

Systemic lupus erythematosus

  • Leitthema
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung

Patienten mit systemischem Lupus erythematodes (SLE) unterscheiden sich heute im Wunsch nach Absetzen der immunsuppressiven und immunmodulatorischen Therapie nicht von Patienten mit anderen rheumatischen Erkrankungen. Um sie gut zu beraten, müssen einerseits die möglichen Risiken einer Dauertherapie mit dem jeweiligen Medikament und andererseits das angenommene Risiko besonders von schweren Schüben betrachtet werden. Die Risiken einer Langzeittherapie sind für einzelne Substanzen sehr unterschiedlich. Sie reichen von hohen, inakzeptablen Risiken bei Cyclophosphamid und höher dosierten Glukokortikoiden bis zu niedrigem, normalerweise durch Langzeitvorteile ausgeglichenem Risiko bei Hydroxychloroquin. Das individuelle Risiko eines SLE-Schubs ist oft schwer abzuschätzen, aber klinische Remission und zumindest 3 Jahre Immunsuppression werden für die Lupusnephritis empfohlen. Die Dauer der Remission kann vielleicht auch kürzer sein, wenn eine mildere Erkrankung vorliegt. Diese Übersichtsarbeit versucht, die vorhandene Evidenz in die klinische Perspektive zu setzen und daraus konkrete Empfehlungen abzuleiten.

Abstract

Similar to patients with other rheumatic diseases, patients with systemic lupus erythematosus (SLE) nowadays can also have the desire to terminate immunosuppressive and immunomodulatory medications. In order to provide appropriate advice to patients, the two main issues are the risk of severe adverse events under long-term therapy with any drug and the perceived risk of a flare, in particular of severe flares. The risks of long-term therapy vary greatly between drugs, ranging from severe unacceptable risks with cyclophosphamide and higher dose glucocorticoids to low risks usually outweighed by long-term benefits with hydroxychloroquine. The individual risk of flares is often difficult to estimate but clinical remission and at least 3 years of immunosuppression are recommended for lupus nephritis. The duration of remission can also be shorter in cases of milder forms of disease. This review article tries to put the available evidence into a clinical perspective and to derive concrete recommendations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Mosca M, Tani C, Aringer M (2013) Withdrawal of therapy in non-renal systemic lupus erythematosus: is this an achievable goal? Clin Exp Rheumatol 31:71–S74

    Google Scholar 

  2. Boumpas DT, Austin HA III, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH et al (1992) Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 340:741–745

    Article  CAS  PubMed  Google Scholar 

  3. The Canadian Hydroxychloroquine Study Group (1991) A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. N Engl J Med 324:150–154

    Article  Google Scholar 

  4. Boumpas DT, Austin HA III, Vaughan EM, Yarboro CH, Klippel JH, Balow JE (1993) Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med 119:366–369

    Article  CAS  PubMed  Google Scholar 

  5. Faurschou M, Mellemkjaer L, Voss A, Keller KK, Hansen IT, Baslund B (2015) Prolonged risk of specific malignancies following cyclophosphamide therapy among patients with granulomatosis with polyangiitis. Rheumatology (Oxford) 54:1345–1350

    Article  Google Scholar 

  6. Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O’Nan P et al (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350:971–980

    Article  CAS  PubMed  Google Scholar 

  7. Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, de Ramon GE, Danieli MG et al (2010) The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis 69:61–64

    Article  CAS  PubMed  Google Scholar 

  8. Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH et al (2012) Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 71:1771–1782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Knight SR, Russell NK, Barcena L, Morris PJ (2009) Mycophenolate mofetil decreases acute rejection and may improve graft survival in renal transplant recipients when compared with azathioprine: a systematic review. Transplantation 87:785–794

    Article  CAS  PubMed  Google Scholar 

  10. Aguiar B, Santos AT, Romaozinho C, Santos L, Macario F, Alves R et al (2015) Malignancy in kidney transplantation: A 25-year single-center experience in Portugal. Transplant Proc 47:976–980

    Article  CAS  PubMed  Google Scholar 

  11. Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D et al (2011) Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 365:1886–1895

    Article  CAS  PubMed  Google Scholar 

  12. Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D et al (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Grootscholten C, Ligtenberg G, Hagen EC, van den Wall Bake AW, de Glas-Vos JW, Bijl M et al (2006) Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. Kidney Int 70:732–742

    Article  CAS  PubMed  Google Scholar 

  14. Fischer-Betz R, Specker C, Brinks R, Aringer M, Schneider M (2013) Low risk of renal flares and negative outcomes in women with lupus nephritis conceiving after switching from mycophenolate mofetil to azathioprine. Rheumatology (Oxford) 52:1070–1076

    Article  CAS  Google Scholar 

  15. Bertsias G, Ioannidis JP, Boletis J, Bombardieri S, Cervera R, Dostal C et al (2008) 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 67:195–205

    Article  CAS  PubMed  Google Scholar 

  16. Ginzler EM, Wofsy D, Isenberg D, Gordon C, Lisk L, Dooley MA (2010) Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial. Arthritis Rheum 62:211–221

    Article  CAS  PubMed  Google Scholar 

  17. Keysser G (2011) Methotrexate toxicity. Myths and facts. Z Rheumatol 70:108–113

    Article  CAS  PubMed  Google Scholar 

  18. Yazici Y (2010) Long-term safety of methotrexate in the treatment of rheumatoid arthritis. Clin Exp Rheumatol 28:65–S67

    Google Scholar 

  19. Winzer M, Aringer M (2010) Use of methotrexate in patients with systemic lupus erythematosus and primary Sjogren’s syndrome. Clin Exp Rheumatol 28:156–S159

    Google Scholar 

  20. Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE et al (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377:721–731

    Article  CAS  PubMed  Google Scholar 

  21. Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzova D et al (2011) A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum 63:3918–3930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ginzler EM, Wallace DJ, Merrill JT, Furie RA, Stohl W, Chatham WW et al (2014) Disease control and safety of belimumab plus standard therapy over 7 years in patients with systemic lupus erythematosus. J Rheumatol 41:300–309

    Article  CAS  PubMed  Google Scholar 

  23. Bruce IN, Urowitz M, van Vollenhoven R, Aranow C, Fettiplace J, Oldham M et al (2016) Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care. Lupus 25:699–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Aringer M, Burkhardt H, Burmester GR, Fischer-Betz R, Fleck M, Graninger W et al (2012) Current state of evidence on ’off-label’ therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland–a consensus report. Lupus 21:386–401

    Article  CAS  PubMed  Google Scholar 

  25. Ryden-Aulin M, Boumpas D, Bultink I, Callejas Rubio JL, Caminal-Montero L, Castro A et al (2016) Off-label use of rituximab for systemic lupus erythematosus in Europe. Lupus Sci Med 3:e000163

    Article  PubMed  PubMed Central  Google Scholar 

  26. Aguiar R, Araujo C, Martins-Coelho G, Isenberg D (2016) Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years. Arthritis Care Res (Hoboken). doi:10.1002/acr.22921

    Google Scholar 

  27. Reddy V, Martinez L, Isenberg DA, Leandro MJ, Cambridge G (2016) Pragmatic treatment of patients with Systemic Lupus Erythematosus with rituximab: Long-term effects on serum immunoglobulins. Arthritis Care Res (Hoboken). doi:10.1002/acr.22993

    Google Scholar 

  28. van Vollenhoven RF, Fleischmann RM, Furst DE, Lacey S, Lehane PB (2015) Longterm safety of rituximab: final report of the Rheumatoid Arthritis Global Clinical Trial Program over 11 years. J Rheumatol 42:1761–1766

    Article  PubMed  Google Scholar 

  29. Cobo-Ibanez T, Loza-Santamaria E, Pego-Reigosa JM, Marques AO, Rua-Figueroa I, Fernandez-Nebro A et al (2014) Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: A systematic review. Semin Arthritis Rheum 44(2):175–185

    Article  CAS  PubMed  Google Scholar 

  30. Iaccarino L, Bartoloni E, Carli L, Ceccarelli F, Conti F, de Vita S et al (2015) Efficacy and safety of off-label use of rituximab in refractory lupus: data from the Italian Multicentre Registry. Clin Exp Rheumatol 33:449–456

    PubMed  Google Scholar 

  31. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P et al (2003) Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 82:299–308

    Article  Google Scholar 

  32. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF (2016) Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 123:1386–1394

    Article  PubMed  Google Scholar 

  33. Costedoat-Chalumeau N, Dunogue B, Morel N, Le Guern V, Guettrot-Imbert G (2014) Hydroxychloroquine: a multifaceted treatment in lupus. Presse Med 43:e167–e180

    Article  PubMed  Google Scholar 

  34. Ruiz-Irastorza G, Khamashta MA (2008) Hydroxychloroquine: the cornerstone of lupus therapy. Lupus 17:271–273

    Article  CAS  PubMed  Google Scholar 

  35. van Vollenhoven RF, Aranow C, Bertsias G, Bonfa E, Cervera R, Costedoat-Chalumeau N, Dörner T, Houssiau F, Lertsrom K, Moran E, Mosca M, Navarra S, Petri M, Urowitz M, Voskuijl A, Voss A, Ward M, Werth V, Schneider M (2015) Remission in SLE: Consensus findings from a large international panel on definitions of remission in SLE (DORIS). Ann Rheum Dis 74(Suppl 2):103 (Abstract)

    Article  Google Scholar 

  36. Huscher D, Thiele K, Gromnica-Ihle E, Hein G, Demary W, Dreher R et al (2009) Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis 68:1119–1124

    Article  CAS  PubMed  Google Scholar 

  37. Ruiz-Arruza I, Ugarte A, Cabezas-Rodriguez I, Medina JA, Moran MA, Ruiz-Irastorza G (2014) Glucocorticoids and irreversible damage in patients with systemic lupus erythematosus. Rheumatology (Oxford) 53:1470–1476

    Article  CAS  Google Scholar 

  38. Moya FB, Pineda Galindo LF, García de la Peña M (2016) Impact of chronic glucocorticoid treatment on cardiovascular risk profile in patients with Systemic Lupus Erythematosus. J Clin Rheumatol 22:8–12

    Article  PubMed  Google Scholar 

  39. Listing J, Gerhold K, Zink A (2013) The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford) 52:53–61

    Article  CAS  Google Scholar 

  40. Carli L, Tani C, Spera V, Vagelli R, Vagnani S, Mazzantini M et al (2016) Risk factors for osteoporosis and fragility fractures in patients with systemic lupus erythematosus. Lupus Sci Med 3:e000098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tani C, Carli L, Vagelli R, Signorini V, Vagnani S, Totti D, Tristano M, Mosca M (2016) Glucocorticoids withdrawal in systemic lupuserythematosus: myth or reality? Ann Rheum Dis 75(Suppl 2):290 (Abstract)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Klinik und Poliklinik III, Universitätsklinikum und Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Deutschland

    M. Aringer & N. Leuchten

  2. Poliklinik für Rheumatologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland

    R. Fischer-Betz

  3. Bereich Rheumatologie, Medizinische Klinik und Poliklinik III, Universitätsklinikum und Medizinische Fakultät Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland

    M. Aringer

Authors
  1. M. Aringer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Leuchten
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Fischer-Betz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Aringer.

Ethics declarations

Interessenkonflikt

M. Aringer: Advisory Boards GSK, Roche. N. Leuchten und R. Fischer-Betz geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Additional information

Redaktion

P.M. Villiger, Bern

U. Müller-Ladner, Bad Nauheim

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aringer, M., Leuchten, N. & Fischer-Betz, R. Ausschleichen und Beenden von immunsuppressiven Therapien. Z Rheumatol 76, 27–32 (2017). https://doi.org/10.1007/s00393-016-0258-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-016-0258-0

Schlüsselwörter

Keywords

Search

Navigation