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Treatment of progressive multiple sclerosis in adults

Author
Michael J Olek, DO
Section Editor
Francisco González-Scarano, MD
Deputy Editor
John F Dashe, MD, PhD

INTRODUCTION

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) that is a leading cause of disability in young adults. The course of MS is variable. For some, MS is a disease with one or two acute neurologic episodes and no further evidence of disease activity. In others, it is a chronic relapsing or progressive disease, with an unpredictable clinical course that may span 10 to 20 years, during which time neurologic disability accumulates.

This topic will discuss treatment of progressive forms of MS. The treatment of relapsing forms of MS is discussed separately. (See "Disease-modifying treatment of relapsing-remitting multiple sclerosis in adults".)

Other aspects of MS are reviewed elsewhere:

(See "Pathogenesis and epidemiology of multiple sclerosis".)

(See "Clinical course and classification of multiple sclerosis".)

                               
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Literature review current through: Sep 2017. | This topic last updated: Apr 14, 2017.
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References
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  1. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014; 83:278.
  2. Willis MA, Fox RJ. Progressive Multiple Sclerosis. Continuum (Minneap Minn) 2016; 22:785.
  3. Goodin DS, Frohman EM, Garmany GP Jr, 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.
  4. Goodkin DE, Rudick RA, VanderBrug Medendorp S, et al. Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann Neurol 1995; 37:30.
  5. Filippini G, Del Giovane C, Vacchi L, et al. Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev 2013; :CD008933.
  6. Calabresi PA. B-Cell Depletion - A Frontier in Monoclonal Antibodies for Multiple Sclerosis. N Engl J Med 2017; 376:280.
  7. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med 2017; 376:209.
  8. FDA approves new drug to treat multiple sclerosis. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm549325.htm (Accessed on March 30, 2017).
  9. Ocrevus - Highlights of prescribing information. https://www.gene.com/download/pdf/ocrevus_prescribing.pdf (Accessed on March 30, 2017).
  10. Casetta I, Iuliano G, Filippini G. Azathioprine for multiple sclerosis. Cochrane Database Syst Rev 2007; :CD003982.
  11. Sipe JC, Romine JS, Koziol JA, et al. Cladribine in treatment of chronic progressive multiple sclerosis. Lancet 1994; 344:9.
  12. Rice GP, Filippi M, Comi G. Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial. Cladribine MRI Study Group. Neurology 2000; 54:1145.
  13. Filippi M, Rovaris M, Iannucci G, et al. Whole brain volume changes in patients with progressive MS treated with cladribine. Neurology 2000; 55:1714.
  14. Goodkin DE, Kinkel RP, Weinstock-Guttman B, et al. A phase II study of i.v. methylprednisolone in secondary-progressive multiple sclerosis. Neurology 1998; 51:239.
  15. La Mantia L, Milanese C, Mascoli N, et al. Cyclophosphamide for multiple sclerosis. Cochrane Database Syst Rev 2007; :CD002819.
  16. Hauser SL, Dawson DM, Lehrich JR, et al. Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med 1983; 308:173.
  17. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. The Canadian Cooperative Multiple Sclerosis Study Group. Lancet 1991; 337:441.
  18. Weiner HL, Mackin GA, Orav EJ, et al. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. Neurology 1993; 43:910.
  19. Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group. Ann Neurol 1990; 27:591.
  20. Rudge P, Koetsier JC, Mertin J, et al. Randomised double blind controlled trial of cyclosporin in multiple sclerosis. J Neurol Neurosurg Psychiatry 1989; 52:559.
  21. Lublin F, Miller DH, Freedman MS, et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet 2016; 387:1075.
  22. 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.
  23. La Mantia L, Vacchi L, Di Pietrantonj C, et al. Interferon beta for secondary progressive multiple sclerosis. Cochrane Database Syst Rev 2012; 1:CD005181.
  24. Rojas JI, Romano M, Ciapponi A, et al. Interferon beta for primary progressive multiple sclerosis. Cochrane Database Syst Rev 2009; :CD006643.
  25. Leary SM, Miller DH, Stevenson VL, et al. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 2003; 60:44.
  26. Montalban X. Overview of European pilot study of interferon beta-Ib in primary progressive multiple sclerosis. Mult Scler 2004; 10 Suppl 1:S62; discussion 62.
  27. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS. Lancet 1998; 352:1491.
  28. Panitch H, Miller A, Paty D, et al. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 2004; 63:1788.
  29. Kappos L, Weinshenker B, Pozzilli C, et al. Interferon beta-1b in secondary progressive MS: a combined analysis of the two trials. Neurology 2004; 63:1779.
  30. Cohen JA, Antel JP. Does interferon beta help in secondary progressive MS? Neurology 2004; 63:1768.
  31. 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.
  32. Hughes RA. Interferon beta 1a for secondary progressive multiple sclerosis. J Neurol Sci 2003; 206:199.
  33. Li DK, Zhao GJ, Paty DW, University of British Columbia MS/MRI Analysis Research Group. The SPECTRIMS Study Group. Randomized controlled trial of interferon-beta-1a in secondary progressive MS: MRI results. Neurology 2001; 56:1505.
  34. Cohen JA, Cutter GR, Fischer JS, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 2002; 59:679.
  35. Andersen O, Elovaara I, Färkkilä M, et al. Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 2004; 75:706.
  36. Noseworthy JH, O'Brien PC, Weinshenker BG, et al. IV immunoglobulin does not reverse established weakness in MS. Neurology 2000; 55:1135.
  37. Hommes OR, Sørensen PS, Fazekas F, et al. Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial. Lancet 2004; 364:1149.
  38. Pöhlau D, Przuntek H, Sailer M, et al. Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study. Mult Scler 2007; 13:1107.
  39. Gray OM, McDonnell GV, Forbes RB. A systematic review of oral methotrexate for multiple sclerosis. Mult Scler 2006; 12:507.
  40. Olek MJ, Hohol MJ, Weiner HL. Methotrexate in the treatment of multiple sclerosis. Ann Neurol 1996; 39:684.
  41. Hartung HP, Gonsette R, König N, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002; 360:2018.
  42. 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.
  43. 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; 244:153.
  44. Martinelli Boneschi F, Vacchi L, Rovaris M, et al. Mitoxantrone for multiple sclerosis. Cochrane Database Syst Rev 2013; :CD002127.
  45. 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.
  46. Ramkumar B, Chadha MK, Barcos M, et al. Acute promyelocytic leukemia after mitoxantrone therapy for multiple sclerosis. Cancer Genet Cytogenet 2008; 182:126.
  47. Bosca I, Pascual AM, Casanova B, et al. Four new cases of therapy-related acute promyelocytic leukemia after mitoxantrone. Neurology 2008; 71:457.
  48. Martinelli V, Cocco E, Capra R, et al. Acute myeloid leukemia in Italian patients with multiple sclerosis treated with mitoxantrone. Neurology 2011; 77:1887.
  49. Marriott JJ, Miyasaki JM, Gronseth G, et al. Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2010; 74:1463.
  50. Chan A, Lo-Coco F. Mitoxantrone-related acute leukemia in MS: an open or closed book? Neurology 2013; 80:1529.
  51. Goodin DS, Arnason BG, Coyle PK, et al. The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003; 61:1332.
  52. Boster A, Edan G, Frohman E, et al. Intense immunosuppression in patients with rapidly worsening multiple sclerosis: treatment guidelines for the clinician. Lancet Neurol 2008; 7:173.
  53. Goodin DS, Cohen BA, O'Connor P, et al. Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2008; 71:766.
  54. Biogen reports top-line results from phase 3 study evaluating natalizumab in secondary progressive MS. http://media.biogen.com/press-release/corporate/biogen-reports-top-line-results-phase-3-study-evaluating-natalizumab-seconda (Accessed on March 21, 2016).
  55. Gordon PA, Carroll DJ, Etches WS, et al. A double-blind controlled pilot study of plasma exchange versus sham apheresis in chronic progressive multiple sclerosis. Can J Neurol Sci 1985; 12:39.
  56. Khatri BO, McQuillen MP, Harrington GJ, et al. Chronic progressive multiple sclerosis: double-blind controlled study of plasmapheresis in patients taking immunosuppressive drugs. Neurology 1985; 35:312.
  57. Cortese I, Chaudhry V, So YT, et al. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011; 76:294.
  58. 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.
  59. Novartis BAF312 reduces the risk of disability progression in pivotal phase III study in secondary progressive MS patients. https://www.novartis.com/news/media-releases/novartis-baf312-reduces-risk-disability-progression-pivotal-phase-iii-study (Accessed on March 30, 2017).
  60. UPDATE: Positive results announced from clinical trial of BAF-312 (siponimod) in secondary progressive MS. http://www.nationalmssociety.org/About-the-Society/News/Positive-Results-Announced-from-Clinical-Trial-of (Accessed on March 30, 2017).
  61. Mancardi G, Saccardi R. Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol 2008; 7:626.
  62. Fassas A, Kimiskidis VK, Sakellari I, et al. Long-term results of stem cell transplantation for MS: a single-center experience. Neurology 2011; 76:1066.
  63. Mancardi GL, Sormani MP, Di Gioia M, et al. Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience. Mult Scler 2012; 18:835.
  64. Sullivan KM, Muraro P, Tyndall A. Hematopoietic cell transplantation for autoimmune disease: updates from Europe and the United States. Biol Blood Marrow Transplant 2010; 16:S48.
  65. Burt RK, Loh Y, Cohen B, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol 2009; 8:244.
  66. Uccelli A, Laroni A, Freedman MS. Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol 2011; 10:649.
  67. Connick P, Kolappan M, Crawley C, et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol 2012; 11:150.
  68. Rice CM, Kemp K, Wilkins A, Scolding NJ. Cell therapy for multiple sclerosis: an evolving concept with implications for other neurodegenerative diseases. Lancet 2013; 382:1204.
  69. Reston JT, Uhl S, Treadwell JR, et al. Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review. Mult Scler 2011; 17:204.
  70. Popat U, Krance R. Haematopoietic stem cell transplantation for autoimmune disorders: the American perspective. Br J Haematol 2004; 126:637.
  71. Hough RE, Snowden JA, Wulffraat NM. Haemopoietic stem cell transplantation in autoimmune diseases: a European perspective. Br J Haematol 2005; 128:432.
  72. Sedel F, Bernard D, Mock DM, Tourbah A. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis. Neuropharmacology 2016; 110:644.
  73. Sedel F, Papeix C, Bellanger A, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Mult Scler Relat Disord 2015; 4:159.
  74. Tourbah A, Lebrun-Frenay C, Edan G, et al. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study. Mult Scler 2016; 22:1719.
  75. Chataway J, Schuerer N, Alsanousi A, et al. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet 2014; 383:2213.