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Empfehlungen zum Einsatz von Belimumab beim systemischen Lupus erythematodes

Recommendation for use of belimumab for systemic lupus erythematosus

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Zusammenfassung

Die zentrale Rolle der B-Lymphozyten in der Pathogenese des systemischen Lupus erythematodes (SLE) hat in den letzten Jahren das Interesse insbesondere auf spezifischere, B-Zell-gerichtete Therapien gelenkt. Belimumab ist ein monoklonaler Antikörper gegen den B-Lymphozytenstimulator BLyS, der 2011 als Zusatztherapie bei erwachsenen Patienten mit SLE zugelassen wurde. Auf Basis des aktuellen Kenntnisstands wird der Einsatz von Belimumab bei Patienten mit klinisch und serologisch aktivem SLE trotz einer individuell angepassten Standardtherapie empfohlen. Diese besteht in der Regel aus Antimalariamitteln, einem Immunsuppressivum (z. B. Azathioprin) und/oder Glukokortikoiden. Auch die Notwendigkeit von regelmäßig höheren Dosierungen von ≥ 7,5 mg Prednisolonäquivalent/Tag kann eine mögliche Indikation für Belimumab darstellen. Aufgrund fehlender Daten kann der Einsatz bei einer aktiven Nieren- und/oder ZNS-Beteiligung zurzeit nicht empfohlen werden.

Abstract

The central role of B-lymphocytes in the pathogenesis of systemic lupus erythematosus (SLE) has turned the attention particularly to more specific B-cell targeted therapies in recent years. Belimumab is a monoclonal antibody against the B-lymphocyte stimulator BlyS and was approved in 2011 as additional therapy for adult patients with SLE. Based upon the available data, treatment with belimumab is recommended in patients with clinically and serologically active SLE despite individually adjusted standard therapy. The standard therapy usually consists of antimalarial agents, an immunosuppressive drug (e.g. azathioprine) and/or steroids. Even the necessity for regular higher dosages of ≥ 7.5 mg prednisolone equivalents/day could be a feasible medical indication for belimumab. Due to lacking data the use of belimumab is not recommended for the purpose of treating severe active SLE with renal or central nervous system involvement until efficacy has been shown for these indications.

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Literatur

  1. Moore PA, Belvedere O, Orr A et al (1999) BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science 285(5425):260–263

    Article  PubMed  CAS  Google Scholar 

  2. Baker KP, Edwards BM, Main SH et al (2003) Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum 48(11):3253–3265

    Article  PubMed  CAS  Google Scholar 

  3. Dörner T, Burmester GR (2008) New approaches of B-cell-directed therapy: beyond rituximab. Curr Opin Rheumatol 20:263–268

    Article  PubMed  Google Scholar 

  4. Isenberg DA (2008) Treating patients with lupus with B-cell depletion. Lupus 17:400–404

    Article  PubMed  CAS  Google Scholar 

  5. Mackay F, Woodcock SA, Lawton P et al (1999) Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med 190(11):1697–1710

    Article  PubMed  CAS  Google Scholar 

  6. Groom J, Kalled SL, Cutler AH et al (2002) Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren’s syndrome. J Clin Invest 109(1):59–68

    PubMed  CAS  Google Scholar 

  7. Gross JA, Johnston J, Mudri S et al (2000) TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 404(6781):995–999

    Article  PubMed  CAS  Google Scholar 

  8. Ramanujam M, Wang X, Huang W et al (2006) Similarities and differences between selective and nonselective BAFF blockade in murine SLE. J Clin Invest 116(3):724–734

    Article  PubMed  CAS  Google Scholar 

  9. Halpern WG, Lappin P, Zanardi T et al (2006) Chronic administration of belimumab, a BLyS antagonist, decreases tissue and peripheral blood B-lymphocyte populations in cynomolgus monkeys: pharmacokinetic, pharmacodynamic, and toxicologic effects. Toxicol Sci 91(2):586–599

    Article  PubMed  CAS  Google Scholar 

  10. Cheema GS, Roschke V, Hilbert DM, Stohl W (2001) Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum 44(6):1313–1319

    Article  PubMed  CAS  Google Scholar 

  11. Stohl W, Metyas S, Tan SM et al (2003) B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum 48(12):3475–3486

    Article  PubMed  Google Scholar 

  12. Petri M, Stohl W, Chatham W et al (2008) Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum 58(8):2453–2459

    Article  PubMed  CAS  Google Scholar 

  13. Cancro MP, D’Cruz DP, Khamashta MA (2009) The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Invest 119(5):1066–1073

    Article  PubMed  CAS  Google Scholar 

  14. Navarra SV, Guzmán RM, Gallacher AE et al (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377(9767):721–731

    Article  PubMed  CAS  Google Scholar 

  15. Furie R, Petri M, Zamani O 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(12):3918–3930

    Article  PubMed  CAS  Google Scholar 

  16. Wallace DJ, Stohl W, Furie RA et al (2009) A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum 61(9):1168–1178

    Article  PubMed  CAS  Google Scholar 

  17. Furie R, Petri MA, Wallace DJ et al (2009) Novel evidence-based systemic lupus erythematosus responder index. Arthritis Rheum 61(9):1143–1151

    Article  PubMed  CAS  Google Scholar 

  18. Vollenhoven RF van, Petri MA, Cervera R et al (2012) Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis 71(8):1343–1349

    Article  PubMed  Google Scholar 

  19. Manzi S, Sánchez-Guerrero J, Merrill JT et al (2012) Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis 71(11):1833–1838

    Article  PubMed  CAS  Google Scholar 

  20. Petri M, Furie R, Merrill J et al (2009) Four-year experience of belimummab, a BLys-specific inhibitor in SLE patients. Arthritis Rheum 60:S774

    Google Scholar 

  21. Stohl W, Hiepe F, Latinis KM et al (2012) Belimumab reduces autoantibodies, normalizes low complement, and reduces select B-cell populations in patients with systemic lupus erythematosus. Arthritis Rheum 64(7):2328–2337

    Article  PubMed  CAS  Google Scholar 

  22. Rote-Hand-Brief zu Benlysta® (Belimumab). GlaxoSmithKline GmbH u. Co. KG vom 05.03.2012

  23. Wallace D, Navarra S, Gallacher A et al (2010) Safety profile of belimumab, a BLyS-specific inhibitor, in patients with active systemic lupus erythematosus (SLE): pooled data from phase 2 and 3 studies. Arthritis Rheum 62:S491

    Article  Google Scholar 

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Interessenkonflikt

Die korrespondierende Autorin weist für sich und ihren Koautor auf folgende Beziehungen hin: Dr. Fischer-Betz: Vorträge und Beratungstätigkeit für Abbott, Actelion, Chugai, Essex, GSK, Roche, Swedish Orphan Biovitrum, Pfizer, UCB, Wyeth. Prof. Dr. M. Schneider: Forschungsunterstützung, Vorträge und Beratungstätigkeit für Abbott, Actelion, Chugai, Essex, GSK, Merck Serono, Roche, Pfizer, UCB, Wyeth.

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  1. Klinik für Endokrinologie, Diabetologie und Rheumatologie, Rheumazentrum Rhein-Ruhr, Heinrich Heine Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland

    R. Fischer-Betz MD & M. Schneider MD PhD

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  1. R. Fischer-Betz MD
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Kommission Pharmakotherapie der DGRh

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Correspondence to R. Fischer-Betz MD.

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Fischer-Betz, R., Schneider, M. & Kommission Pharmakotherapie der DGRh. Empfehlungen zum Einsatz von Belimumab beim systemischen Lupus erythematodes. Z. Rheumatol. 72, 462–467 (2013). https://doi.org/10.1007/s00393-013-1212-z

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  • DOI: https://doi.org/10.1007/s00393-013-1212-z

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