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Alemtuzumab: eine weitere Chance zur Therapie der Multiplen Sklerose

Alemtuzumab: a further option for treatment of multiple sclerosis

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Zusammenfassung

Alemtuzumab ist ein humanisierter monoklonaler Antikörper, der an das Zelloberflächenantigen CD52 bindet. CD52 wird auf einer Vielzahl von Zellen der lymphomonozytären Zellreihe exprimiert, nicht jedoch auf Vorläuferzellen. Alemtuzumab führt zu einer raschen und langanhaltenden Depletion von CD52-tragenden Zellen aus dem Blut. In deren Folge kommt es zu einer schrittweisen Rekonstitution, wobei anfangs aktivierte B-Lymphozyten und regulatorische T-Lymphozyten überwiegen.

Alemtuzumab ist zunächst in zwei offenen Therapiestudien an 58 und 39 Patienten mit Multipler Sklerose (MS) und danach aufgrund der sehr vielversprechenden Ergebnisse in einer ambitionierten klinischen Phase-II-Studie gegen subkutan appliziertes Interferon β-1a getestet worden. Dabei zeigte sich, dass Alemtuzumab nicht nur sehr effizient Schubrate und Behinderungsprogression reduzierte, sondern sogar zu einer Verbesserung des funktionellen Defizites führen konnte. Trotz langanhaltender Lymphopenie kam es nicht vermehrt zu schweren oder opportunistischen Infektionen. Wohl aber erlitten bis zu 30% der Patienten antikörpervermittelte Autoimmunerkrankungen, zumeist Schilddrüsenerkrankungen, aber auch immunvermittelte thrombozytopenische Purpura und Goodpasture-Syndrom.

In dieser Übersichtsarbeit werden die präklinische und klinische Entwicklung von Alemtuzumab dargestellt sowie Wirkmechanismen und die Pathogenese der Autoimmunphänomene diskutiert.

Summary

Alemtuzumab is a humanized monoclonal therapeutic antibody that targets the CD52 antigen which s expressed on most cells of the lymphoid lineage, exclusive of precursors. Alemtuzumab rapidly depletes CD52+ cells from the peripheral blood. This depletion is long-lasting, and cells repopulate in a specific pattern with B cells and regulatory T cells peaking first. Alemtuzumab was examined for clinical utility in two open-labelled intervention trials in multiple sclerosis (MS). Because of very promising results its clinical efficacy was further explored in a clinical phase-II trial using s.c. interferon beta-1a as the active comparator. Severe or opportunistic infections were surprisingly rare given the long-term lymphopenia. However, up to 30% of patients developed some antibody-mediated autoimmunity. The thyroid gland was the most frequently affected organ. Immune-mediated thrombocytopenic purpura and Goodpasture’s syndrome were additionally observed.

This review summarizes the pre-clinical and clinical development of alemtuzumab and discusses potential modes of action as well as the pathogenetic link to the treatment emergent autoimmune phenomena.

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Literatur

  1. Menge T, Hartung HP, Kieseier BC (2011) Neutralizing antibodies in interferon beta treated patients with multiple sclerosis: knowing what to do now. J Neurol 258:904–907

    Article  PubMed  Google Scholar 

  2. Menge T, Weber MS, Hemmer B et al (2008) Disease-modifying agents for multiple sclerosis: recent advances and future prospects. Drugs 68:2445–2468

    Article  PubMed  CAS  Google Scholar 

  3. Kieseier BC (2011) The mechanism of action of interferon-beta in relapsing multiple sclerosis. CNS Drugs 25:491–502

    Article  PubMed  CAS  Google Scholar 

  4. Bielekova B, Becker BL (2010) Monoclonal antibodies in MS: mechanisms of action. Neurology 74(Suppl 1):31–40

    Article  Google Scholar 

  5. Vermersch P, Kappos L, Gold R et al (2011) Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy. Neurology 76:1697–1704

    Article  PubMed  CAS  Google Scholar 

  6. Cohen JA, Barkhof F, Comi G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362:402–415

    Article  PubMed  CAS  Google Scholar 

  7. Kappos L, Radue EW, O’Connor P et al (2010) A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362:387–401

    Article  PubMed  CAS  Google Scholar 

  8. Aktas O, Kury P, Kieseier B et al (2010) Fingolimod is a potential novel therapy for multiple sclerosis. Nat Rev Neurol 6:373–382

    Article  PubMed  CAS  Google Scholar 

  9. Brinkmann V, Billich A, Baumruker T et al (2010) Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 9:883–897

    Article  PubMed  CAS  Google Scholar 

  10. Hale G, Rye PD, Warford A et al (1993) The glycosylphosphatidylinositol-anchored lymphocyte antigen CDw52 is associated with the epididymal maturation of human spermatozoa. J Reprod Immunol 23:189–205

    Article  PubMed  CAS  Google Scholar 

  11. Xia MQ, Tone M, Packman L et al (1991) Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone. Eur J Immunol 21:1677–1684

    Article  PubMed  CAS  Google Scholar 

  12. Buggins AG, Mufti GJ, Salisbury J et al (2002) Peripheral blood but not tissue dendritic cells express CD52 and are depleted by treatment with alemtuzumab. Blood 100:1715–1720

    PubMed  CAS  Google Scholar 

  13. Ratzinger G, Reagan JL, Heller G et al (2003) Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation. Blood 101:1422–1429

    Article  PubMed  CAS  Google Scholar 

  14. Coles AJ, Cox A, Le Page E et al (2006) The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol 253:98–108

    Article  PubMed  Google Scholar 

  15. Rowan WC, Hale G, Tite JP et al (1995) Cross-linking of the CAMPATH-1 antigen (CD52) triggers activation of normal human T lymphocytes. Int Immunol 7:69–77

    Article  PubMed  CAS  Google Scholar 

  16. Hederer RA, Guntermann C, Miller N et al (2000) The CD45 tyrosine phosphatase regulates Campath-1H (CD52)-induced TCR-dependent signal transduction in human T cells. Int Immunol 12:505–516

    Article  PubMed  CAS  Google Scholar 

  17. Coles AJ, Compston DA, Selmaj KW et al (2008) Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 359:1786–1801

    Article  PubMed  Google Scholar 

  18. Hu Y, Turner MJ, Shields J et al (2009) Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology 128:260–270

    Article  PubMed  CAS  Google Scholar 

  19. Stauch D, Dernier A, Sarmiento ME et al (2009) Targeting of natural killer cells by rabbit antithymocyte globulin and campath-1H: similar effects independent of specificity. PLoS ONE 4:e4709

    Article  PubMed  Google Scholar 

  20. Zent CS, Secreto CR, LaPlant BR et al (2008) Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab. Leuk Res 32:1849–1856

    Article  PubMed  CAS  Google Scholar 

  21. Bologna L, Gotti E, Manganini M et al (2011) Mechanism of action of type II, glycoengineered, anti-CD20 monoclonal antibody GA101 in B-chronic lymphocytic leukemia whole blood assays in comparison with rituximab and alemtuzumab. J Immunol 186:3762–3769

    Article  PubMed  CAS  Google Scholar 

  22. Chakraverty R, Orti G, Roughton M et al (2010) Impact of in vivo alemtuzumab dose before reduced intensity conditioning and HLA-identical sibling stem cell transplantation: pharmacokinetics, GVHD, and immune reconstitution. Blood 116:3080–3088

    Article  PubMed  CAS  Google Scholar 

  23. Coles AJ (2010) Leukocyte dynamics following alemtuzumab treatment in relapsing-remitting multiple sclerosis in a Phase 2 Study (CAMMS223). Neurology 74:A553 (Abstr)

    Article  Google Scholar 

  24. Thompson SA, Jones JL, Cox AL et al (2010) B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis. J Clin Immunol 30:99–105

    Article  PubMed  CAS  Google Scholar 

  25. Hale G, Bright S, Chumbley G et al (1983) Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. Blood 62:873–882

    PubMed  CAS  Google Scholar 

  26. Hale G, Cobbold SP, Waldmann H et al (1987) Isolation of low-frequency class-switch variants from rat hybrid myelomas. J Immunol Methods 103:59–67

    Article  PubMed  CAS  Google Scholar 

  27. Riechmann L, Clark M, Waldmann H et al (1988) Reshaping human antibodies for therapy. Nature 332:323–327

    Article  PubMed  CAS  Google Scholar 

  28. Keating MJ, Flinn I, Jain V et al (2002) Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 99:3554–3561

    Article  PubMed  CAS  Google Scholar 

  29. Hale G, Jacobs P, Wood L et al (2000) CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells. Bone Marrow Transplant 26:69–76

    Article  PubMed  CAS  Google Scholar 

  30. Hale G, Cobbold S, Novitzky N et al (2001) CAMPATH-1 antibodies in stem-cell transplantation. Cytotherapy 3:145–164

    Article  PubMed  CAS  Google Scholar 

  31. Kottaridis PD, Milligan DW, Chopra R et al (2001) In vivo CAMPATH-1H prevents GvHD following nonmyeloablative stem-cell transplantation. Cytotherapy 3:197–201

    Article  PubMed  CAS  Google Scholar 

  32. Weissenbacher A, Boesmueller C, Brandacher G et al (2010) Alemtuzumab in solid organ transplantation and in composite tissue allotransplantation. Immunotherapy 2:783–790

    Article  PubMed  CAS  Google Scholar 

  33. Hanaway MJ, Woodle ES, Mulgaonkar S et al (2011) Alemtuzumab induction in renal transplantation. N Engl J Med 364:1909–1919

    Article  PubMed  CAS  Google Scholar 

  34. Levitsky J, Thudi K, Ison MG et al (2011) Alemtuzumab induction in non-hepatitis C positive liver transplant recipients. Liver Transpl 17:32–37

    Article  PubMed  Google Scholar 

  35. Calne R, Moffatt SD, Friend PJ et al (1999) Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients. Transplantation 68:1613–1616

    Article  PubMed  CAS  Google Scholar 

  36. Mathieson PW, Cobbold SP, Hale G et al (1990) Monoclonal-antibody therapy in systemic vasculitis. N Engl J Med 323:250–254

    Article  PubMed  CAS  Google Scholar 

  37. Lockwood CM, Thiru S, Stewart S et al (1996) Treatment of refractory Wegener’s granulomatosis with humanized monoclonal antibodies. QJM 89:903–912

    Article  PubMed  CAS  Google Scholar 

  38. Lim SH, Hale G, Marcus RE et al (1993) CAMPATH-1 monoclonal antibody therapy in severe refractory autoimmune thrombocytopenic purpura. Br J Haematol 84:542–544

    Article  PubMed  CAS  Google Scholar 

  39. Watts RA, Isaacs JD, Hale G et al (1993) CAMPATH-1H in inflammatory arthritis. Clin Exp Rheumatol 11(Suppl 8):165–167

    Google Scholar 

  40. Isaacs JD, Hale G, Waldmann H et al (1995) Monoclonal antibody therapy of chronic intraocular inflammation using Campath-1H. Br J Ophthalmol 79:1054–1055

    Article  PubMed  CAS  Google Scholar 

  41. Isaacs JD, Hazleman BL, Chakravarty K et al (1996) Monoclonal antibody therapy of diffuse cutaneous scleroderma with CAMPATH-1H. J Rheumatol 23:1103–1106

    PubMed  CAS  Google Scholar 

  42. Killick SB, Marsh JC, Hale G et al (1997) Sustained remission of severe resistant autoimmune neutropenia with Campath-1H. Br J Haematol 97:306–308

    Article  PubMed  CAS  Google Scholar 

  43. Reiff A (2005) A review of Campath in autoimmune disease: biologic therapy in the gray zone between immunosuppression and immunoablation. Hematology 10:79–93

    Article  PubMed  CAS  Google Scholar 

  44. Risitano AM, Selleri C, Serio B et al (2010) Alemtuzumab is safe and effective as immunosuppressive treatment for aplastic anaemia and single-lineage marrow failure: a pilot study and a survey from the EBMT WPSAA. Br J Haematol 148:791–796

    Article  PubMed  CAS  Google Scholar 

  45. Gomez-Almaguer D, Solano-Genesta M, Tarin-Arzaga L et al (2010) Low-dose rituximab and alemtuzumab combination therapy for patients with steroid-refractory autoimmune cytopenias. Blood 116:4783–4785

    Article  PubMed  CAS  Google Scholar 

  46. Waldmann H, Hale G (2005) CAMPATH: from concept to clinic. Philos Trans R Soc Lond B Biol Sci 360:1707–1711

    Article  PubMed  CAS  Google Scholar 

  47. Coles AJ, Wing MG, Molyneux P et al (1999) Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol 46:296–304

    Article  PubMed  CAS  Google Scholar 

  48. Moreau T, Thorpe J, Miller D et al (1994) Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis. Lancet 344:298–301

    Article  PubMed  CAS  Google Scholar 

  49. Coles A, Deans J, Compston A (2004) Campath-1H treatment of multiple sclerosis: lessons from the bedside for the bench. Clin Neurol Neurosurg 106:270–274

    Article  PubMed  Google Scholar 

  50. Hirst CL, Pace A, Pickersgill TP et al (2008) Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis. J Neurol 255:231–238

    Article  PubMed  CAS  Google Scholar 

  51. Fox E (2010) Sustained positive effects of alemtuzumab on diverse neurological functions in relapsing-remitting multiple sclerosis patients. Neurology 74:A417–A418 (Abstr)

    Article  Google Scholar 

  52. Coles AJ, Fox E, Vladic A et al (2011) Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol 10:338–348

    Article  PubMed  CAS  Google Scholar 

  53. Havrdova E, Galetta S, Hutchinson M et al (2009) Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol 8:254–260

    Article  PubMed  Google Scholar 

  54. Wingerchuk D (2010) Efficacy of alemtuzumab in highly active relapsing-remitting multiple sclerosis patients in the CAMMS223 Trial. Mult Scler 16:141 (Abstr)

    Google Scholar 

  55. Coles AJ (2010) Alemtuzumab long-term safety and efficacy: five years of the CAMMS223 Trial. Mult Scler 16:134 (Abstr)

    Google Scholar 

  56. Twyman C, Study G (2011) More alemtuzumab relapsing-remitting multiple sclerosis patients are free of clinical disease activity at five years. Neurology 76:A563–A564 (Abstr)

    Article  Google Scholar 

  57. Hartung HP, Aktas O (2011) Evolution of multiple sclerosis treatment: next generation therapies meet next generation efficacy criteria. Lancet Neurol 10:293–295

    Article  PubMed  Google Scholar 

  58. Giovannoni G, Comi G, Cook S et al (2010) A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med 362:416–426

    Article  PubMed  CAS  Google Scholar 

  59. Jones JL, Anderson JM, Phuah CL et al (2010) Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain 133:2232–2247

    Article  PubMed  Google Scholar 

  60. Jones JL, Coles AJ (2009) Spotlight on alemtuzumab. Int MS J 16:77–81

    PubMed  CAS  Google Scholar 

  61. Turner M, LaMorte M, Stockman A et al (2011) Analysis of innate immune cells following alemtuzumab treatment in human cd52 transgenic mice. Neurology 76:A140 (Abstr)

    Google Scholar 

  62. Brinar V, Study G (2011) Alemtuzumab and thyroid autoimmunity in relapsing-remitting multiple sclerosis patients in CAMMS223. Neurology 76:A246 (Abstr)

    Google Scholar 

  63. Cossburn M, Pace AA, Jones J et al (2011) Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Neurology 77:573–579

    Article  PubMed  CAS  Google Scholar 

  64. Walsh M, Chaudhry A, Jayne D (2008) Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-1H). Ann Rheum Dis 67:1322–1327

    Article  PubMed  CAS  Google Scholar 

  65. Hauser SL, Dawson DM, Lehrich JR et al (1983) Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med 308:173–180

    Article  PubMed  CAS  Google Scholar 

  66. Broadley SA, Deans J, Sawcer SJ et al (2000) Autoimmune disease in first-degree relatives of patients with multiple sclerosis – A UK survey. Brain 123:1102–1111

    Article  PubMed  Google Scholar 

  67. Weetman A (2009) Immune reconstitution syndrome and the thyroid. Best Pract Res Clin Endocrinol Metab 23:693–702

    Article  PubMed  CAS  Google Scholar 

  68. Aster RH, Curtis BR, McFarland JG et al (2009) Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management. J Thromb Haemost 7:911–918

    Article  PubMed  CAS  Google Scholar 

  69. Pedchenko V, Bondar O, Fogo AB et al (2010) Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med 363:343–354

    Article  PubMed  CAS  Google Scholar 

  70. Ooi JD, Phoon RK, Holdsworth SR et al (2009) IL-23, not IL-12, directs autoimmunity to the Goodpasture antigen. J Am Soc Nephrol 20:980–989

    Article  PubMed  CAS  Google Scholar 

  71. Ooi JD, Holdsworth SR, Kitching AR (2008) Advances in the pathogenesis of Goodpasture’s disease: from epitopes to autoantibodies to effector T cells. J Autoimmun 31:295–300

    Article  PubMed  CAS  Google Scholar 

  72. Hsiao LT, Liu JH, Yen CC et al (2001) Relapse of Graves‘ disease after successful allogeneic bone marrow transplantation. Bone Marrow Transplant 28:1151–1153

    Article  PubMed  CAS  Google Scholar 

  73. Gilquin J, Viard JP, Jubault V et al (1998) Delayed occurrence of Graves‘ disease after immune restoration with HAART. Highly active antiretroviral therapy. Lancet 352:1907–1908

    Article  PubMed  CAS  Google Scholar 

  74. Daikeler T, Tyndall A (2007) Autoimmunity following haematopoietic stem-cell transplantation. Best Pract Res Clin Haematol 20:349–360

    Article  PubMed  CAS  Google Scholar 

  75. Abbi KK, Rizvi SM, Sivik J et al (2010) Guillain-Barre syndrome after use of alemtuzumab (Campath) in a patient with T-cell prolymphocytic leukemia: a case report and review of the literature. Leuk Res 34:e154–e156

    Article  PubMed  Google Scholar 

  76. Cheng KL, Brody J, Warshall CE et al (2010) Paroxysmal nocturnal hemoglobinuria following alemtuzumab immunosuppressive therapy for myelodysplastic syndrome and complicated by recurrent life-threatening thrombosis despite anticoagulation: successful intervention with eculizumab and fondaparinux. Leuk Res 34:e85–e87

    Article  PubMed  Google Scholar 

  77. Anoop P, Wotherspoon A, Matutes E (2010) Severe liver dysfunction from hepatitis C virus reactivation following alemtuzumab treatment for chronic lymphocytic leukaemia. Br J Haematol 148:484–486

    Article  PubMed  Google Scholar 

  78. Buyck HC, Prentice HG, Griffiths PD et al (2010) The risk of early and late CMV DNAemia associated with Campath use in stem cell transplant recipients. Bone Marrow Transplant 45:1212–1219

    Article  PubMed  CAS  Google Scholar 

  79. Carpenter B, Haque T, Dimopoulou M et al (2010) Incidence and dynamics of Epstein-Barr virus reactivation after alemtuzumab-based conditioning for allogeneic hematopoietic stem-cell transplantation. Transplantation 90:564–570

    Article  PubMed  CAS  Google Scholar 

  80. Weisser M (2011) Impfungen unter immunsuppressiver Therapie chronisch entzündlicher Erkrankungen. Internist 52:277–282

    Article  PubMed  CAS  Google Scholar 

  81. Cheuk DK, Chiang AK, Lee TL et al (2011) Vaccines for prophylaxis of viral infections in patients with hematological malignancies. Cochrane Database Syst Rev:CD006505

    Google Scholar 

  82. Chou JF, Kernan NA, Prockop S et al (2011) Safety and immunogenicity of the live attenuated varicella vaccine following T replete or T cell-depleted related and unrelated allogeneic hematopoietic cell transplantation (alloHCT). Biol Blood Marrow Transplant (in press)

  83. Oxman MN (2010) Zoster vaccine: current status and future prospects. Clin Infect Dis 51:197–213

    Article  PubMed  Google Scholar 

  84. Fisher JP, Bate J, Hambleton S (2011) Preventing varicella in children with malignancies: what is the evidence? Curr Opin Infect Dis 24:203–211

    Article  PubMed  Google Scholar 

  85. Hackett CB, Wall D, Fitzgerald SF et al (2011) Varicella-zoster virus immunity in dermatological patients on systemic immunosuppressant treatment. Br J Dermatol 164:1387–1389

    Article  PubMed  CAS  Google Scholar 

  86. Lobermann M, Borso D, Hilgendorf I et al (2011) Immunization in the adult immunocompromised host. Autoimmun Rev

  87. www.en.sanofi.com/binaries/20110711_CARE-MSI-RESULTS_en_tcm28–33024.pdf; www.businesswire.com/news/genzyme/20110710005114/en

  88. Razonable RR (2010) Immune-based therapies for cytomegalovirus infection. Immunotherapy 2:117–130

    Article  PubMed  CAS  Google Scholar 

  89. Xia MQ, Hale G, Lifely MR et al (1993) Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem J 293:633–640

    PubMed  CAS  Google Scholar 

  90. Warnke C, Kieseier BC, Zettl U et al (2009) Alemtuzumab als neue Therapieoption der Multiplen Sklerose – Hoffnung und Risiken beim Einsatz des monoklonalen Antikörpers. Nervenarzt 80:468–474

    Article  PubMed  CAS  Google Scholar 

  91. Menge T, Schloot NC, Schott M et al (2009) Interferon beta treatment does not induce organ-specific autoantibodies in multiple sclerosis. Neurology 73:900–902

    Article  PubMed  CAS  Google Scholar 

  92. Polman CH, Reingold SC, Edan G et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the „McDonald Criteria“. Ann Neurol 58:840–846

    Article  PubMed  Google Scholar 

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Interessenkonflikte

Der korrespondierende Autor weist auf folgende Beziehungen hin: T. M. erhielt Honorare und Reisekostenzuschüsse von Bayer Healthcare, Biogen Idec, Merck Serono. CW hat keine Interessenkonflikte. B.C.K, O.A. und H.-P.H. erhielten in der Vergangenheit nach Genehmigung durch den Ärztlichen Direktor des Universitätsklinikums Düsseldorf und den Rektor der Heinrich-Heine-Universität Vortrags- bzw. Beratungshonorare der Hersteller der im Artikel erwähnten Präparate: (Bayer Schering, Biogen Idec, Merck-Serono, Novartis, TEVA/Sanofi Aventis) sowie Genentech (H.-P.H.).

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  1. Neurologische Klinik, Universitätsklinikum Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland

    T. Menge, B.C. Kieseier, C. Warnke, O. Aktas & H.-P. Hartung

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  1. T. Menge
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Menge, T., Kieseier, B., Warnke, C. et al. Alemtuzumab: eine weitere Chance zur Therapie der Multiplen Sklerose. Nervenarzt 83, 487–501 (2012). https://doi.org/10.1007/s00115-011-3393-5

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