Skip to main content
SpringerLink
Log in

Disease-Modifying Therapy

  • Chapter
  • First Online:
Handbook of Multiple Sclerosis

  • 1843 Accesses

Abstract

Since 1993 eight disease-modifying agents have been approved by regulatory agencies to treat relapsing–remitting multiple sclerosis (RR MS). In addition, a sizable number of agents are used off label alone or in combination.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Dhib-Jalbut S. Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology. 2002;58(Suppl 4):S3-S9.

    Google Scholar 

  2. Bornstein MB, Miller A, Slagle S, et al. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med. 1987;317:408-414.

    Google Scholar 

  3. Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing–remitting multiple sclerosis: results of a phase III multicenter, doubleblind, placebo-controlled trial. Neurology. 1995;45:1268-1276.

    Google Scholar 

  4. Comi G, Filippi M, Wolinsky JS, et al. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis. Ann Neurol. 2001;49:290-297.

    Google Scholar 

  5. Filippi M, Rovaris M, Rocca MA, et al. Glatiramer acetate reduces the proportion of new MS lesions evolving into “black holes”. Neurology. 2001;57:731-733.

    Google Scholar 

  6. Comi G, Martinelli V, Rodegher M, et al. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:1503-1511.

    Google Scholar 

  7. The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing–remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebocontrolled trial. Neurology. 1993;43:655-661.

    Google Scholar 

  8. Paty DW, Li DKB; the UBC MS/MRI Study Group. Interferon beta-1b is effective in relapsing–remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology. 1993;43:662-667.

    Google Scholar 

  9. IFNB Multiple Sclerosis Study Group, The University of British Columbia MS/MRI Analysis Group. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology. 1995;45:1277-1285.

    Google Scholar 

  10. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996;39:285-294.

    Google Scholar 

  11. Rudick RA, Goodkin DE, Jacobs LD, et al. Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. Neurology. 1997;49:358-363.

    Google Scholar 

  12. Simon JH, Jacobs LD, Campion M, et al. Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. Ann Neurol. 1998;43:79-87.

    Google Scholar 

  13. PRISMS Study Group. Randomized double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet. 1998;352:1498-1504.

    Google Scholar 

  14. Li DKB, Paty DW; the UBC MS/MRI Analysis Research Group, the PRISMS Study Group. Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebocontrolled study of interferon-beta1a in relapsing–remitting multiple sclerosis. Ann Neurol. 1999;46:197-206.

    Google Scholar 

  15. PRISMS Study Group. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology. 2001;56:1628-1636.

    Google Scholar 

  16. Ransohoff RM. Natalizumab for multiple sclerosis. N Eng J Med. 2007;356:2622-2629.

    Google Scholar 

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

    Google Scholar 

  18. Miller DH, Soon D, Fernando KT, et al. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology. 2007;68:1390-1401.

    Google Scholar 

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

    Google Scholar 

  20. Calabresi PA, Giovannoni G, Confavreux C, et al. The incidence and significance of antinatalizumab antibodies. Results from AFFIRM and SENTINEL. Neurology. 2007;69:1391-1403.

    Google Scholar 

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

    Google Scholar 

  22. Khatri BO, Man S, Giaovannoni G, et al. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function. Neurology. 2009;72:402-409.

    Google Scholar 

  23. Bozic C, Richman S, Plavina T, et al. Anti-John Cunnigham virus antibody prevalence in multiple sclerosis patients: Baseline results of STRATIFY-1. Ann Neurol. 2011;70:742-750.

    Google Scholar 

  24. Kappos L, Bates D, Hartung HP, et al. Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. Lancet Neurol. 2007;6:431-441.

    Google Scholar 

  25. Millefiorini E, Gasperini C, Pozzilli C, et al. Randomized placebo-controlled trial of mitoxantrone in relapsing–remitting multiple sclerosis: 24-month clinical and MRI outcome. J Neurol. 1997;44:153-159.

    Google Scholar 

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

    Google Scholar 

  27. van de Wyngaeert FA, Beguin C, D’Hooghie MB, et al. A double-blind clinical trial of mitoxantrone versus methylprednisolone in relapsing, secondary progressive multiple sclerosis. Acta Neurol Belg. 2001;101:210-216.

    Google Scholar 

  28. Hartung HP, Gonsette R, the MIMS Study Group. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, randomised, multicentre trial. Lancet. 2002;360:2018-2025.

    Google Scholar 

  29. Krapf H, Morrissey SP, Zenker O, et al. Effect of mitoxantrone on MRI in progressive MS. Results of the MIMS trial. Neurology. 2005; 65:690-695.

    Google Scholar 

  30. Cohen BA, Mikol DD. Mitoxantrone treatment of multiple sclerosis. Safety considerations. Neurology. 2004;63(Suppl 6):S28-S32.

    Google Scholar 

  31. De Castro S, Cartoni D, Millefiorini E, et al. Noninvasive assessment of mitoxantrone cardiotoxicity in relapsing remitting multiple sclerosis. J Clin Pharmacol. 1995;35:627-632.

    Google Scholar 

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

    Google Scholar 

  33. Strotmann JM, Spindler M, Weilbach FX, et al. Myocardial function in patients with multiple sclerosis treated with low-dose mitoxantrone. Am J Cardiol. 2002;89:1222-1225.

    Google Scholar 

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

    Google Scholar 

  35. Brassat D, Recher C, Waubant E, et al. Therapy-related acute myeloblastic leukemia after mitoxantrone treatment in a patient with MS. Neurology. 2002;59:954-955.

    Google Scholar 

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

    Google Scholar 

  37. Cohen JA, Chun J. Mechanisms of fingolimod’s efficacy and adverse effects in multiple sclerosis. Ann Neurol. 2011;69:759-777.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  40. Sorensen PS, Deisenhammer F, Dudac P, et al. 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. 2005;12:817-827.

    Google Scholar 

  41. Goodin DS, Frohman EM, Garmany GP, et al. Disease modifying therapies in multiple sclerosis. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002;58:169-178.

    Google Scholar 

  42. The Once Weekly Interferon for MS Study Group (OWIMS). Evidence of interferon beta-1a dose response in relapsing–remitting MS. The OWIMS study. Neurology. 1999;53:679-686.

    Google Scholar 

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

    Google Scholar 

  44. Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon b-1a treatment regimens in MS. The EVIDENCE trial. Neurology. 2002;59:1496-1506.

    Google Scholar 

  45. Schwid SR, Thorpe J, Sharief M, et al. Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis. The EVIDENCE study. Arch Neurol. 2005;62:785-792.

    Google Scholar 

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

    Google Scholar 

  47. Goodin DS, Frohman EM, Hurwitz B, et al. Neutralizing antibodies to interferon beta: assessment of their clinical impact and radiographic impact: an evidence report. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2007;68:977-984.

    Google Scholar 

  48. Mikol DD, Barkhof F, Chang P, et al. Comparison of subcutaneous beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol. 2008;7:903-914.

    Google Scholar 

  49. O’Connor P, Filippi M, Arnason B, et al. 250 mg or 500 mg interferon beta-1b versus 20 mg glatiramer acetate in relapsing–remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol. 2009;8:889-897.

    Google Scholar 

  50. Rudick RA, Polman CH. Current approaches to the identification and management of breakthrough disease in patients with multiple sclerosis. Lancet Neurol. 2009;8:545-559.

    Google Scholar 

  51. Cohen JA, Imrey PB, Calabresi PA, et al. Results of the Avonex Combination Trial (ACT) in relapsing–remitting MS. Neurology. 2009;72:535-541.

    Google Scholar 

  52. Cohen JA, Confavreux C. Combination therapy in multiple sclerosis. In: Cohen JA, Rudick RA, eds. Multiple Sclerosis Therapeutics, 3rd Edition. London, UK: Informa Healthcare; 2007:681-697.

    Google Scholar 

  53. Jacobs LD, Beck RW, Simon JH, et al. Intramuscular Interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med. 2000;343:898-904.

    Google Scholar 

  54. Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomized study. Lancet. 2001;357:1576-1582.

    Google Scholar 

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

    Google Scholar 

  56. Comi G, Martinelli V, Rodegher M, et al. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:1503-1511.

    Google Scholar 

  57. Trapp BD, Nave K-A. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci. 2008;31:247-269.

    Google Scholar 

  58. Kappos L, Polman C, Pozzilli C, et al. Final analysis of the European multicenter trial on INFbeta-1b in secondary-progressive MS. Neurology. 2001;57:1969-1975.

    Google Scholar 

  59. Cohen JA, Cutter GR, Fischer JS, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology. 2002;59:679-687.

    Google Scholar 

  60. The North American Study Group on Interferon Beta-1b in Secondary Progressive MS. Interferon beta-1b in secondary progressive MS: results from a three-year controlled study. Neurology. 2004;63:1788-1795.

    Google Scholar 

  61. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-beta-1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of interferon-beta-1a in secondary progressive MS. Clinical results. Neurology. 2001;56:1496-1504.

    Google Scholar 

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

    Google Scholar 

  63. Hawker K, O’Connor P, Freedman MS, et al. Rituximab in patients with primary progressive multiple sclerosis. Results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009;66:460-471.

    Google Scholar 

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

    Google Scholar 

  65. Ahrens N, Salama A, Haas J. Mycophenolate-mofetil in the treatment of refractory multiple sclerosis. J Neurol. 2001;248:713-714.

    Google Scholar 

  66. Frohman EM, Brannon K, Racke MK, et al. Mycophenolate mofetil in multiple sclerosis. Clin Neuropharmacol. 2004;27:80-83.

    Google Scholar 

  67. Ness JM, Chabas D, Sadovnick AD, et al. Clinical features of children and adolescents with multiple sclerosis. Neurology. 2007;68(Suppl 2):S37-S45.

    Google Scholar 

  68. Waldman AT, Gorman MP, Rensel MR, et al. Management of pediatric central nervous system demyelinating disorders: consensus of united states neurologists. J Child Neurol. 2011;26:675-682.

    Google Scholar 

  69. Weinshenker BG. Neuromyelitis optica is distinct from multiple sclerosis. Arch Neurol. 2007;64:899-901.

    Google Scholar 

  70. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum antibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364:2106-2112.

    Google Scholar 

  71. Mandler RN, Ahmed W, Dencoff JE. Devic’s neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology. 1998;51:1219-1220.

    Google Scholar 

  72. Weinstock-Guttman B, Ramanathan M, Lincoff N, et al. Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease). Arch Neurol. 2006;63:957-963.

    Google Scholar 

  73. Cree BAC, Lamb S, Morgan K, et al. An open label study of the effects of rituximab in neuromyelitis optica. Neurology. 2005;64:1270-1272.

    Google Scholar 

  74. Jacob A, Weinshenker BG, Violich I, et al. Treatment of neuromyelitis optica with rituximab. Retrospective analysis of 25 patients. Arch Neurol. 2008;65:1443-1448.

    Google Scholar 

  75. Jacob A, Matiello M, Weinshenker BG, et al. Treatment of neuromyelitis optica with mycophenolate mofetil. Arch Neurol. 2009;66:1128-1133.

    Google Scholar 

  76. Cohen JA. Emerging therapies for relapsing multiple sclerosis. Arch Neurol. 2009;66:821-828.

    Google Scholar 

  77. Kappos L, Gold R, Miller DH, et al. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebocontrolled phase IIb study. Lancet. 2008;372:1463-72.

    Google Scholar 

  78. Biogen Idec. Biogen Idec announces positive top-line results from the first phase 3 trial investigating oral BG-12 (DIMETHYL FUMARATE) in multiple sclerosis. www.biogenidec.com/.press_release_details.aspx?ID=5981&ReqId=1548648. Accessed March 9, 2012.

  79. Biogen Idec. Biogen Idec announces positive top-line results from second phase 3 trial investigating oral bg-12 (dimethyl fumarate) in multiple sclerosis. www.biogenidec.com/.press_release_details.aspx?ID=5981&ReqId=1621631. Accessed March 9, 2012.

  80. Tallantyre E, Evangelou N, Constantinescu CS. Spotlight on teriflunomide. Int MS J. 2008;15:62-68.

    Google Scholar 

  81. O’Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365:1293-303.

    Google Scholar 

  82. Comi G. Oral laquinimod reduced relapse rate and delayed progression of disability in ALLEGRO, a placebo-controlled phase III trial for relapsing-remitting multiple sclerosis. Neurology. 2011;76(Suppl 4):7PP.001.

    Google Scholar 

  83. TevaPharma. Results of Phase III Bravo trial. www.tevapharm.com/en-US/Media/News/Pages/Bravo.aspx. Accessed March 9, 2012.

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

    Google Scholar 

  85. Klotz L, Meuth SG, Wiendl H, et al. Immune mechanisms of new therapeutic strategies in multiple sclerosis- a focus on alemtuzumab. Clin Immunol. 2012;142:25-30.

    Google Scholar 

  86. Coles A, Brinar V, Arnold DL, et al. Efficacy and Safety Results from CARE-MS I: a Phase 3 study comparing alemtuzumab and interferon beta-1a. Abstract presented at ECTRIMS 2011.

    Google Scholar 

  87. Genzyme. Genzyme announces successful Phase III results for alemtuzumab in multiple sclerosis. www.businesswire.com/news/genzyme/20111113005072/en. Last updated November 14, 2011. Accessed March 9, 2012.

Download references

Author information

Authors and Affiliations

  1. Cleveland Clinic, Cleveland, OH, USA

    Jeffrey A. Cohen

  2. Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, USA

    Alexander Rae-Grant

Authors
  1. Jeffrey A. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander Rae-Grant
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springher Healthcare

About this chapter

Cite this chapter

Cohen, J.A., Rae-Grant, A. (2012). Disease-Modifying Therapy. In: Handbook of Multiple Sclerosis. Springer Healthcare, Tarporley. https://doi.org/10.1007/978-1-907673-50-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-907673-50-4_5

  • Published:

  • Publisher Name: Springer Healthcare, Tarporley

  • Print ISBN: 978-1-908517-49-4

  • Online ISBN: 978-1-907673-50-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation