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Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations

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Abstract

This review updates and extends earlier Consensus Reports related to current basic and escalating immunomodulatory treatments in multiple sclerosis (MS). The recent literature has been extracted for new evidence from randomized controlled trials, open treatment studies and reported expert opinion, both in original articles and reviews, and evaluates indications and safety issues based on published data. After data extraction from published full length publications and critically weighing the evidence and potential impact of the data, the review has been drafted and circulated within the National MS Societies and the European MS Platform to reach consensus within a very large group of European experts, combining evidence-based criteria and expert opinion where evidence is still incomplete. The review also outlines a few areas of controversy and delineates the need for future research.

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References

  1. MSTCG, et al. (2004) Escalating immunotherapy of multiple sclerosis – New aspects and practical application. J Neurol 251:1329–1339

    Google Scholar 

  2. MSTCG, et al. (2006) Symptomatic Treatment of Multiple Sclerosis. Eur Neurol 56:78–105

    Google Scholar 

  3. Goodin D, Frohman EM, Garmany GP Jr, et al. (2002) Disease modifying therapies in multiple sclerosis – Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology and the MS counsel for clinical practice guidelines. Neurology 58:169–178

    PubMed  CAS  Google Scholar 

  4. McDonald W, Compston A, Edan G, et al. (2001) Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127

    Article  PubMed  CAS  Google Scholar 

  5. Dalton C, Dalton CM, Brex PA, et al. (2002) Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol 52:47–53

    Article  PubMed  Google Scholar 

  6. Tintore M, Rovira A, Río J, et al. (2003) New diagnostic criteria for multiple sclerosis: application in first demyelinating episode. Neurology 60:27–30

    Article  PubMed  CAS  Google Scholar 

  7. Polman CH, Wolinsky JS, Reingold SC (2005) Multiple sclerosis diagnostic criteria: three years later. Mult Scler 11:5–12

    Article  PubMed  Google Scholar 

  8. 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 

  9. Wiendl H, Kieseier BC, Gold R, et al. (2006) Revision der neuen McDonalds Kriterien zur Diagnose einer MS. Nervenarzt 77:1237–1245

    Article  Google Scholar 

  10. Berger T, Rubner P, Schautzer F, et al. (2003) Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 349:139–145

    Article  PubMed  CAS  Google Scholar 

  11. Gaertner S, de Graaf KL, Greve B, Weissert R (2004) Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis. Neurology 63:2381–2383

    PubMed  CAS  Google Scholar 

  12. Lampasona V, Franciotta D, Furlan R, et al. (2004) Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects. Neurology 62:2092–2094

    PubMed  CAS  Google Scholar 

  13. Rauer S, Euler B, Reindl M, Berger T (2006) Antimyelin antibodies and the risk of relapse in patients with a primary demyelinating event. J Neurol Neurosurg Psychiatry 77:739–742

    Article  PubMed  CAS  Google Scholar 

  14. Kuhle J, Lindberg RL, Regeniter A, et al. (2007) Lack of association between antimyelin antibodies and progression to multiple sclerosis. N Engl J Med 356:371–378

    Article  PubMed  CAS  Google Scholar 

  15. Lim ET, Berger T, Reindl M, et al. (2005) Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis. Mult Scler 11:492–494

    Article  PubMed  CAS  Google Scholar 

  16. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112

    Article  PubMed  CAS  Google Scholar 

  17. Nakashima I, Fujihara K, Sato S, Itoyama Y (2006) Clinical and MRI features of Japanese MS patients with NMO-IgG. J Neurol Neurosurg Psychiatry 77:1073–1075

    Article  PubMed  CAS  Google Scholar 

  18. Paul F, Jarius S, Aktas O, et al. (2007) Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica. PLoS Med 4:e133

    Article  PubMed  CAS  Google Scholar 

  19. Matsuoka T, Matsushita T, Kawano Y, et al. (2007) Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese. Brain 130:1206–1223

    Article  PubMed  Google Scholar 

  20. Lucchinetti CF, Mandler RN, McGavern D, et al. (2002) A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 125:1450–1461

    Article  PubMed  Google Scholar 

  21. Fuhr P, Borggrefe-Chappuis A, Schindler C, Kappos L (2001) Visual and motor evoked potentials in the course of multiple sclerosis. Brain 124:2162–2168

    Article  PubMed  CAS  Google Scholar 

  22. Kallmann BA, Fackelmann S, Toyka KV, Rieckmann P, Reiners K (2006) Early abnormalities of evoked potentials and future disability in patients with multiple sclerosis. Mult Scler 12:58–65

    Article  PubMed  CAS  Google Scholar 

  23. Kappos L, Polman CH, Freedman MS, et al. (2006) Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 67:1242–1249

    Article  PubMed  CAS  Google Scholar 

  24. Anonymus (2006) Europäische Kommission genehmigt Aktualisierung der therapeutischen Indication für Rebif® www.serono.com/content/media/downloads/2006/20060710_de.pdf

  25. Kappos L, Freedman MS, Polman CH, et al. (2007) Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 370:389–397

    Article  PubMed  CAS  Google Scholar 

  26. Rio J, Tintoré M, Nos C, et al. (2005) Interferon beta in relapsing-remitting multiple sclerosis. An eight years experience in a specialist multiple sclerosis centre. J Neurol 252:795–800

    Article  PubMed  CAS  Google Scholar 

  27. Kinkel RP, Kollman C, O’Connor P, et al. (2006) IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event. Neurology 66:678–684

    Article  PubMed  CAS  Google Scholar 

  28. Pohl D, Rostasy K, Gärtner J, Hanefeld F (2005) Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a. Neurology 64:888–890

    PubMed  CAS  Google Scholar 

  29. Ghezzi A, Amato MP, Capobianco M, et al. (2005) Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study. Mult Scler 11:420–424

    Article  PubMed  CAS  Google Scholar 

  30. Tenembaum SN, Segura MJ (2006) Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis. Neurology 67:511–513

    Article  PubMed  CAS  Google Scholar 

  31. Banwell B, Reder AT, Krupp L, et al. (2006) Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis. Neurology 66:472–476

    Article  PubMed  CAS  Google Scholar 

  32. Sandberg-Wollheim M, Frank D, Goodwin TM, et al. (2005) Pregnancy outcomes during treatment with interferon beta-1a in patients with multiple sclerosis. Neurology 65:802–806

    Article  PubMed  CAS  Google Scholar 

  33. Boskovic R, Wide R, Wolpin J, Bauer DJ, Koren G (2005) The reproductive effects of beta interferon therapy in pregnancy: a longitudinal cohort. Neurology 65:807–811

    Article  PubMed  CAS  Google Scholar 

  34. Clanet M, Radue EW, Kappos L, et al. (2002) A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS. Neurology 59:1507–1517

    PubMed  CAS  Google Scholar 

  35. Clanet M, Kappos L, Hartung HP, et al. (2004) Interferon beta-1a in relapsing multiple sclerosis: four-year extension of the European IFNbeta-1a Dose-Comparison Study. Mult Scler 10:139–144

    Article  PubMed  CAS  Google Scholar 

  36. Freedman MS, Francis GS, Sanders EA, et al. (2005) Randomized study of once-weekly interferon beta-1la therapy in relapsing multiple sclerosis: three-year data from the OWIMS study. Mult Scler 11:41–45

    Article  PubMed  CAS  Google Scholar 

  37. Vartanian T (2003) An examination of the results of the EVIDENCE, INCOMIN, and phase III studies of interferon beta products in the treatment of multiple sclerosis. Clin Ther 25:105–118

    Article  PubMed  CAS  Google Scholar 

  38. Panitch H, Goodin DS, Francis G, et al. (2002) Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology 59:1496–1506

    PubMed  CAS  Google Scholar 

  39. Panitch H, Goodin D, Francis G, et al. (2005) Benefits of high-dose, high-frequency interferon beta-1a in relapsing-remitting multiple sclerosis are sustained to 16 months: final comparative results of the EVIDENCE trial. J Neurol Sci 239:67–74

    Article  PubMed  CAS  Google Scholar 

  40. Schwid SR, Thorpe J, Sharief M, et al. (2005) Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis: the EVIDENCE Study. Arch Neurol 62:785–792

    Article  PubMed  Google Scholar 

  41. Durelli L, Verdun E, Barbero P, et al. (2002) Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet 359:1453–1460

    Article  PubMed  CAS  Google Scholar 

  42. Koch-Henriksen N, Sørensen PS, Christensen T, et al. (2006) A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis. Neurology 66:1056–1060

    Article  PubMed  CAS  Google Scholar 

  43. Bertolotto A (2004) Neutralizing antibodies to interferon beta: implications for the management of multiple sclerosis. Curr Opin Neurol 17:241–36

    Article  PubMed  CAS  Google Scholar 

  44. Sorensen P, Koch-Henriksen N, Ross C, et al. (2005) Appearance and disappearance of neutralizing antibodies during interferon beta therapy. Neurology 65:33–39

    Article  PubMed  CAS  Google Scholar 

  45. Sorensen PS, et al. (2003) Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet 362:1184–1191

    Article  PubMed  CAS  Google Scholar 

  46. Sorensen PS, Ross C, Clemmesen KM, et al. (2005) Guidelines on use of anti-IFN-beta antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN-beta antibodies in multiple sclerosis. Eur J Neurol 12:817–827

    Article  PubMed  CAS  Google Scholar 

  47. Polman C, Kappos L, White R, et al. (2003) Neutralizing antibodies during treatment of secondary progressive MS with interferon beta-1b. Neurology 60:37–43

    Article  PubMed  CAS  Google Scholar 

  48. Francis GS, Rice GP, Alsop JC (2005) Interferon beta-1a in MS: results following development of neutralizing antibodies in PRISMS. Neurology 65:48–55

    Article  PubMed  CAS  Google Scholar 

  49. Kappos L, Clanet M, Sandberg-Wollheim M, et al. (2005) Neutralizing antibodies and efficacy of interferon beta-1a: a 4-year controlled study. Neurology 65:40–47

    Article  PubMed  CAS  Google Scholar 

  50. Koch M, Mostert JP, de Vries JJ, De Keyser J (2007) Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 68:1163–1164

    Article  PubMed  Google Scholar 

  51. Hemmer B, Stüve O, Kieseier B, Schellekens H, Hartung HP (2005) Immune response to immunotherapy: the role of neutralizing antibodies to interferon beta in the treatment of multiple sclerosis. Lancet Neurol 4:403–412

    Article  PubMed  CAS  Google Scholar 

  52. Khan O, Khan OA, Tselis AC, Kamholz JA, Garbern JY, Lewis RA, Lisak RP, et al. (2001) A prospective, open-label treatment trial to compare the effect of IFNbeta-1a (Avonex), IFNbeta-1b (Betaseron), and glatiramer acetate (Copaxone) on the relapse rate in relapsing – remitting multiple sclerosis: results after 18 months of therapy. Mult Scler 7:349–353

    PubMed  CAS  Google Scholar 

  53. Haas J, Firzlaff M (2005) Twenty-four-month comparison of immunomodulatory treatments – a retrospective open label study in 308 RRMS patients treated with beta interferons or glatiramer acetate (Copaxone). Eur J Neurol 12:425–431

    Article  PubMed  CAS  Google Scholar 

  54. Vallittu AM, Peltoniemi J, Elovaara I, et al. (2005) The efficacy of glatiramer acetate in beta-interferon-intolerant MS patients. Acta Neurol Scand 112:234–237

    Article  PubMed  CAS  Google Scholar 

  55. Flechter S, Vardi J, Pollak L, Rabey JM (2002) Comparison of glatiramer acetate (Copaxone) and interferon beta-1b (Betaferon) in multiple sclerosis patients: an open-label 2-year follow-up. J Neurol Sci 197:51–55

    Article  PubMed  CAS  Google Scholar 

  56. Cohen JA, Rovaris M, Goodman AD, Ladkani D, Wynn D, Filippi M; 9006 Study Group (2007) Randomized, double-blind, dose-comparison study of glatiramer acetate in relapsing-remitting MS. Neurology 68:939–944

    Article  PubMed  CAS  Google Scholar 

  57. Ramtahal J, Jacob A, Das K, Boggild M (2006) Sequential maintenance treatment with glatiramer acetate after mitoxantrone is safe and can limit exposure to immunosuppression in very active, relapsing remitting multiple sclerosis. J Neurol 253:1160–1164

    Article  PubMed  CAS  Google Scholar 

  58. Ziemssen T (2004) Neuroprotection and glatiramer acetate: the possible role in the treatment of multiple sclerosis. Adv Exp Med Biol 541:111–134

    PubMed  CAS  Google Scholar 

  59. Aharoni R, Eilam R, Domev H, et al. (2005) The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice. Proc Natl Acad Sci USA 102:19045–19050

    Article  PubMed  CAS  Google Scholar 

  60. Khan O, Shen Y, Caon C, et al. (2005) Axonal metabolic recovery and potential neuroprotective effect of glatiramer acetate in relapsing-remitting multiple sclerosis. Mult Scler 11:646–651

    Article  PubMed  CAS  Google Scholar 

  61. Wolinsky JS, Narayana PA, O’Connor P, et al. (2007) Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 61:14–24

    Article  PubMed  CAS  Google Scholar 

  62. Filippi M, Wolinsky JS, Comi G (2006) Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: a multicentre, double-blind, randomised, placebo-controlled study. Lancet Neurol 5:213–220

    Article  PubMed  CAS  Google Scholar 

  63. Simmons DL (2005) Anti-adhesion therapies. Curr Opin Pharmacol 5:398–404

    Article  PubMed  CAS  Google Scholar 

  64. Ropper AH (2006) Selective treatment of multiple sclerosis. N Engl J Med 354:965–967

    Article  PubMed  CAS  Google Scholar 

  65. Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, et al. (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356:63–66

    Article  PubMed  CAS  Google Scholar 

  66. Theien BE, Vanderlugt CL, Eagar T, et al. (2001) Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis. J Clin Invest 107:995–1006

    Article  PubMed  CAS  Google Scholar 

  67. Miller D, Khan OA, Sheremata WA, et al. (2003) A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348:15–23

    Article  PubMed  CAS  Google Scholar 

  68. Rudick RA, Stuart WH, Calabresi PA, et al. (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354:911–923

    Article  PubMed  CAS  Google Scholar 

  69. Polman CH, O’Connor PW, Havrdova E, et al. (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910

    Article  PubMed  CAS  Google Scholar 

  70. Ransohoff RM (2005) Natalizumab and PML. Nat Neurosci 8:1275

    Article  PubMed  CAS  Google Scholar 

  71. Yousry TA, Major EO, Ryschkewitsch C, et al. (2006) Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 354:924–933

    Article  PubMed  CAS  Google Scholar 

  72. Khalili K, White MK (2006) Human demyelinating disease and the polyomavirus JCV. Mult Scler 12:133–142

    Article  PubMed  CAS  Google Scholar 

  73. Mullen JT, Vartanian TK, Atkins MB (2008) Melanoma complicating treatment with natalizumab for multiple sclerosis. N Engl J Med 358:647–648

    Article  PubMed  CAS  Google Scholar 

  74. BI GmbH BI (2008) http://www.biogenidec.com/site/products-on-the-market.html

  75. European Medicines Agency (EMEA) (2008) EPARs for authorised medicinal products for human use. http://www.emea.europa.eu/humandocs/Humans/EPAR/tysabri/tysabri.htm

  76. Ghalie R, Edan G, Laurent M, et al. (2002) Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS. Neurology 59:909–913

    Article  PubMed  CAS  Google Scholar 

  77. Ghalie R, RG, Mauch E, Edan G, et al. (2002) A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis. Mult Scler 8:441–445

    Article  PubMed  CAS  Google Scholar 

  78. Cocco E, Marchi P, Sardu C, et al. (2007) Mitoxantrone treatment in patients with early relapsing-remitting multiple sclerosis. Mult Scler 13:975–980

    Article  PubMed  CAS  Google Scholar 

  79. Scott LJ, Figgitt DP (2004) Mitoxantrone: a review of its use in multiple sclerosis. CNS Drugs 18:379–396

    Article  PubMed  CAS  Google Scholar 

  80. Kappos L, Bates D, Hartung HP, et al. (2007) Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. Lancet Neurol 6:431–441

    Article  PubMed  Google Scholar 

  81. Gold R, Jawad A, Miller DH, et al. (2007) Expert opinion: Guidelines for the use of natalizumab in multiple sclerosis patients previously treated with immunomodulating therapies. J Neuroimmunol 187:156–158

    Article  PubMed  CAS  Google Scholar 

  82. O’Connor PW, Goodman A, Willmer-Hulme AJ, et al. (2004) Randomized multicenter trial of natalizumab in acute MS relapses: clinical and MRI effects. Neurology 62:2038–2043

    PubMed  CAS  Google Scholar 

  83. O’Connor PW, Li D, Freedman MS, et al. (2006) A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology 66:894–900

    Article  PubMed  CAS  Google Scholar 

  84. Kappos L, Antel J, Comi G, et al. (2006) Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med 355:1124–1140

    Article  PubMed  CAS  Google Scholar 

  85. Sipe JC (2005) Cladribine for multiple sclerosis: review and current status. Expert Rev Neurother 5:721–727

    Article  PubMed  CAS  Google Scholar 

  86. Rose JW, Burns JB, Bjorklund J, et al. (2007) Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results. Neurology 69:785–789

    Article  PubMed  CAS  Google Scholar 

  87. Bielekova B, Richert N, Howard T, et al. (2004) Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proc Nat Acad Sci USA 101:8705–8708

    Article  PubMed  CAS  Google Scholar 

  88. Rose JW, Watt HE, White AT, Carlson NG (2004) Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol 56:864–867

    Article  PubMed  CAS  Google Scholar 

  89. Hauser SL, Waubant E, Arnold DL, et al. (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 358:676–688

    Article  PubMed  CAS  Google Scholar 

  90. Bar-Or A, Calabresi PA, Arnold D, et al. (2008) Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol 63:395–400

    Article  PubMed  CAS  Google Scholar 

  91. 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 

  92. Coles AJ, et al. (2007) Efficacy of Alemtuzumab in Treatment-Naive Relapsing-Remitting Multiple Sclerosis: Analysis after Two Years of Study CAMMS223 Neurology (Suppl 1) 68:A100

    Article  Google Scholar 

  93. 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 

  94. Markovic-Plese S, Bielekova B, Kadom N, et al. (2003) Longitudinal MRI study: the effects of azathioprine in MS patients refractory to interferon beta-1b. Neurology 60:1849–1851

    PubMed  CAS  Google Scholar 

  95. Pulicken M, Bash CN, Costello K, et al. (2005) Optimization of the safety and efficacy of interferon beta 1b and azathioprine combination therapy in multiple sclerosis. Mult Scler 11:169–174

    Article  PubMed  CAS  Google Scholar 

  96. Calabresi PA, Wilterdink JL, Rogg JM, et al. (2002) An open-label trial of combination therapy with interferon beta-1a and oral methotrexate in MS. Neurology 58:314–317

    PubMed  CAS  Google Scholar 

  97. Jeffery DR (2004) Use of combination therapy with immunomodulators and immunosuppressants in treating multiple sclerosis. Neurology 63(Suppl 6):S41–S46

    PubMed  CAS  Google Scholar 

  98. Smith DR, Weinstock-Guttman B, Cohen JA, et al. (2005) A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta. Mult Scler 11:573–582

    Article  PubMed  CAS  Google Scholar 

  99. Jeffery DR, Chepuri N, Durden D, Burdette J (2005) A pilot trial of combination therapy with mitoxantrone and interferon beta-1b using monthly gadolinium-enhanced magnetic resonance imaging. Mult Scler 11:296–301

    Article  PubMed  CAS  Google Scholar 

  100. Perini P, Calabrese M, Tiberio M, et al. (2006) Mitoxantrone versus cyclophosphamide in secondary-progressive multiple sclerosis: A comparative study. J Neurol 253:1034–1040

    Article  PubMed  CAS  Google Scholar 

  101. Sorensen PS (2003) Treatment of multiple sclerosis with intravenous immunoglobulin: review of clinical trials. Neurol Sci 24(Suppl 4):S227–S230

    Article  PubMed  Google Scholar 

  102. Achiron A, Kishner I, Sarova-Pinhas I, et al. (2004) Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Arch Neurol 61:1515–1520

    Article  PubMed  Google Scholar 

  103. Hommes OR, Sørensen PS, Fazekas F, et al. (2004) Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial. Lancet 364:1149–1156

    Article  PubMed  CAS  Google Scholar 

  104. Sorensen PS, Haas J, Sellebjerg F, et al. (2004) IV immunoglobulins as addon treatment to methylprednisolone for acute relapses in MS. Neurology 63:2028–2033

    PubMed  CAS  Google Scholar 

  105. Stangel M, Gold R (2005) Intravenous Immunoglobulins in MS. Int MS J 12:5–10,4

    PubMed  CAS  Google Scholar 

  106. Haas J, Hommes OR (2007) A dose comparison study of IVIG in postpartum relapsing-remitting multiple sclerosis. Mult Scler 13:900–908

    Article  PubMed  CAS  Google Scholar 

  107. Achiron A, Kishner I, Dolev M, et al. (2004) Effect of intravenous immunoglobulin treatment on pregnancy and postpartum-related relapses in multiple sclerosis. J Neurol 251:1133–1137

    Article  PubMed  CAS  Google Scholar 

  108. Haas J (2000) High dose IVIG in the post partum period for prevention of exacerbations in MS. Mult Scler 6(Suppl 2):S18–S20 and S33

    PubMed  CAS  Google Scholar 

  109. Hartung H, Gonsette R, König N, et al. (2002) Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. The Lancet 360:2018–2025

    Article  Google Scholar 

  110. Krapf H, Morrissey SP, Zenker O, et al. (2005) Effect of mitoxantrone on MRI in progressive MS: results of the MIMS trial. Neurology 65:690–695

    Article  PubMed  CAS  Google Scholar 

  111. Avasarala JR, Cross AH, Clifford DB, et al. (2003) Rapid onset mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis. Mult Scler 9:59–62

    Article  PubMed  CAS  Google Scholar 

  112. Paul F, Dörr J, Würfel J, Vogel HP, Zipp F (2007) Early mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 78:198–200

    Article  PubMed  CAS  Google Scholar 

  113. Edan G, Miller D, Clanet M, et al. (1997) Therapeutic effect of mitoxantrone combined with methylsprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry 62:112–118

    Article  PubMed  CAS  Google Scholar 

  114. Le Page E, Leray E, Taurin G, et al. (2008) Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients. J Neurol Neurosurg Psychiatry 79:52–56

    Article  PubMed  Google Scholar 

  115. Confavreux C, Saddier P, Grimaud J, et al. (1996) Risk of cancer from azathioprine therapy in multiple sclerosis: a case-control study. Neurology 46:1607–1612

    PubMed  CAS  Google Scholar 

  116. Massacesi L, Parigi A, Barilaro A, et al. (2005) Efficacy of azathioprine on multiple sclerosis new brain lesions evaluated using magnetic resonance imaging. Arch Neurol 62:1843–1847

    Article  PubMed  Google Scholar 

  117. Vermersch P, Stojkovic T, de Seze J (2005) Mycophenolate mofetil and neurological diseases. Lupus 14 (Suppl 1):S42–S45

    Article  PubMed  CAS  Google Scholar 

  118. Frohman EM, Brannon K, Racke MK, Hawker K (2004) Mycophenolate mofetil in multiple sclerosis. Clin Neuropharmacol 27:80–83

    Article  PubMed  CAS  Google Scholar 

  119. Rowin J, Amato AA, Deisher N, Cursio J, Meriggioli MN (2006) Mycophenolate mofetil in dermatomyositis: is it safe? Neurology 66:1245–1247

    Article  PubMed  CAS  Google Scholar 

  120. Vollmer T, et al. (2004) Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 363:1607–1608

    Article  PubMed  CAS  Google Scholar 

  121. Ruprecht K, Klinker E, Dintelmann T, Rieckmann P, Gold R (2004) Plasma exchange for severe optic neuritis: treatment of 10 patients. Neurology 63:1081–1083

    PubMed  CAS  Google Scholar 

  122. Lehmann HC, Hartung HP, Hetzel GR, Stüve O, Kieseier BC (2006) Plasma exchange in neuroimmunological disorders: Part 1: Rationale and treatment of inflammatory central nervous system disorders. Arch Neurol 63:930–935

    Article  PubMed  Google Scholar 

  123. Comi G, Martino G (2006) MS treatment: New perspectives. Clin Neurol Neurosurg 108:339–345

    Article  PubMed  Google Scholar 

  124. Tomassini V, Paolillo A, Russo P, et al. (2006) Predictors of long-term clinical response to interferon beta therapy in relapsing multiple sclerosis. J Neurol 253:287–293

    Article  PubMed  CAS  Google Scholar 

  125. Filippi M, Rocca MA, Arnold DL, et al. (2006) EFNS guidelines on the use of neuroimaging in the management of multiple sclerosis. Eur J Neurol 13:313–325

    Article  PubMed  CAS  Google Scholar 

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Correspondence to H. Wiendl or K. V. Toyka FRCP.

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Appendix

Multiple Sclerosis Therapy Consensus Group (MSTCG)

Austria. U. Baumhackl (St. Pölten), T. Berger (Innsbruck), F. Deisenhammer (Innsbruck), F. Fazekas (Graz), M. Freimüller (Hermagor), H. Kollegger (Vienna), W. Kristoferitsch (Vienna), H. Lassmann (Vienna), H. Markut (Vöcklabruck), S. Strasser-Fuchs (Graz), K. Vass (Vienna).

Belgium. C. Sindic (Brussels), M.B. D’hooghe (Melsbroek)

Croatia. S. Podobnik (Sarkanji)

Czech Republic. E. Havrdova (Prague)

Finland. I. Elovaara (Tampere)

France. M. Clanet (Toulouse), C. Confavreux (Lyon), G. Edan (Rennes), C, Lubetzki (Paris)

Germany. H. Altenkirch (Berlin), S. Bamborschke (Bernau), K. Baum (Hennigsdorf), A. Bayas (Augsburg), R. Benecke (Rostock), W. Brück (Göttingen), M. Buttmann (Würzburg), A. Chan (Bochum), M. Daumer (Munich), D. Dommasch (Bielefeld), W.G. Elias (Hamburg), E. Fasshauer (Halle), P. Flachenecker (Bad Wildbad), R. Gold (Bochum), J. Haas (Berlin), G. Haferkamp (Hanover), P. Haller (Osnabrück), H.-P. Hartung (Düsseldorf), C.Heesen (Hamburg), M. Heibel (Hachen), F. Heidenreich (Hannover), B. Hemmer (München), T. Henze (Niddenau), R. Hohlfeld (Munich), R. W. C. Janzen (Frankfurt/Main), G. Japp (Königstein), S. Jung (Dillingen), E. Jügelt (Sundern/Hachen), B. Kallmann (Bamberg), B. C. Kieseier (Düsseldorf), C. Kleinschnitz (Würzburg), J. Köhler (Hamburg), W. Köhler (Wermsdorf), W. Kölmel (Erfurt), N. König (Berg), G. Lehrieder (Bad Windsheim), V. Leussink (Düsseldorf), K. Lowitzsch (Ludwigshafen), M. Mäurer (Erlangen), U. Manegold (Göttingen), A. Melms (Tübingen), J. Mertin (Amtzell), S.G. Meuth (Würzburg), O. Neuhaus (Sigmaringen), P. Oschmann (Bayreuth), H.-F. Petereit (Cologne), M. Pette (Dresden), D. Pöhlau (Asbach), D. Pohl (Paris), P. Rieckmann (Würzburg/Vancouver), K. Ruprecht (Homburg), M. Sailer (Magdeburg), H. Schipper (Bernburg), S. Schmidt (Bonn), G. Schock (Gera), M. Schulz (Ueckermünde), S. Schwarz (Mannheim), G. Schwendemann (Bremen), D. Seidel (Isselburg), N. Sommer (Marburg/Göppingen), M. Stangel (Hannover), E. Stark (Offenbach), A. Steinbrecher (Regensburg), G. Stoll (Würzburg), K. V. Toyka (Würzburg), H. Tumani (Ulm), R. Voltz (Cologne), F. Weber (Munich), F. Weilbach (Bad Kissingen), H. Wiendl (Würzburg), H. Wiethölter (Stuttgart), B. Wildemann (Heidelberg), U. K. Zettl (Rostock), T. Ziemssen (Dresden), F. Zipp (Berlin), R. Zschenderlein (Berlin).

Greece. A. Orologas (Thessaloniki) Hungary. A. Guseo (Székesfehérvár)

Iceland. S. Bergmann (Reykjavik)

Italy. M. Pugliatti (Sassari)

Norway. K.-M. Myhr (Bergen)

Spain. G. Izquierdo (Sevilla),

Switzerland. C. Bassetti (Zurich), K. Beer (St. Gallen), S. Beer (Valens), U. Buettner (Aarau), M. Chofflon (Geneva), A. Gass (Basel/Mannheim), N. Goebels (Zurich), M. Götschi-Fuchs (Knoblisbühl), L. Kappos (Basel), J. Kesselring (Valens), H.-P. Ludin (St. Gallen), H. Mattle (Bern), M. Schluep (Lausanne), C. Vaney (Montana-Vermala).

U.K. D. Bates (Newcastle u. Tyne)

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Multiple Sclerosis Therapy Consensus Group (MSTCG)., Wiendl, H., Toyka, K.V. et al. Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations. J Neurol 255, 1449–1463 (2008). https://doi.org/10.1007/s00415-008-0061-1

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  • DOI: https://doi.org/10.1007/s00415-008-0061-1

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