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Review article: Biomedical intelligence

Vol. 144 No. 3940 (2014)

Update on multiple sclerosis treatments

  • Claire Bridel
  • Patrice H. Lalive
DOI
https://doi.org/10.4414/smw.2014.14012
Cite this as:
Swiss Med Wkly. 2014;144:w14012
Published
21.09.2014

Summary

Relapsing-remitting multiple sclerosis (RRMS) management has dramatically changed over the past decade. New drugs have arrived on the market, allowing for more individualised treatment selection. However, this diversity has increased the complexity of RRMS patient follow-up. In this review, we provide summarised information about treatment efficacy, potential side-effects, follow-up recommendations, vaccinations, and pregnancy safety issues for all currently available disease modifying therapies and those awaiting approval.

References

  1. Brinkmann, V, et al. The immune modulator FTY720 targets sphingosine 1–phosphate receptors. J Biol Chem. 2002;277(24):21453–7.
  2. Matloubian M, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004;427(6972):355–60.
  3. Kappos L, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387–401.
  4. Cohen JA, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–15.
  5. Khatri B, et al. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol. 2011;10(6):520–9.
  6. Kappos L, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006;355(11):1124–40.
  7. Singer BA. Fingolimod for the treatment of relapsing multiple sclerosis. Expert Rev Neurother. 2013;13(6):589–602.
  8. Means CK, Brown JH. Sphingosine-1–phosphate receptor signalling in the heart. Cardiovasc Res. 2009;82(2):193–200.
  9. Lindsey JW, et al. Sudden unexpected death on fingolimod. Mult Scler. 2012;18(10):1507–8.
  10. Espinosa PS, Berger JR. Delayed fingolimod-associated asystole. Mult Scler. 2011;17(11): 1387–9.
  11. Nolan R, Gelfand JM, Green AJ. Fingolimod treatment in multiple sclerosis leads to increased macular volume. Neurology. 2013;80(2):139–44.
  12. Dinkin M. Paul F. Higher macular volume in patients with MS receiving fingolimod: positive outcome or side effect? Neurology. 2013.80(2):128–9.
  13. Pilz G, et al. Tumefactive MS lesions under fingolimod: a case report and literature review. Neurology. 2013;81(19):1654–8.
  14. Paul F. Bourdette D. Tumefactive multiple sclerosis and fingolimod: Immunotherapies and unintended consequences. Neurology. 2013;81(19):1648–9.
  15. Mehling M, et al. Antigen-specific adaptive immune responses in fingolimod-treated multiple sclerosis patients. Ann Neurol. 2011;69(2):408–13.
  16. Lu E, et al. Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance. Expert Rev Neurother. 2013;13(3):251–60. quiz 261.
  17. Cherwinski HM, et al. Leflunomide interferes with pyrimidine nucleotide biosynthesis. Inflamm Res. 1995;44(8):317–22.
  18. Papadopoulou A, Kappos L, Sprenger T. Teriflunomide for oral therapy in multiple sclerosis. Expert Rev Clin Pharmacol. 2012;5(6):617–28.
  19. O’Connor P, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365(14):1293–303.
  20. Confavreux C, et al. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014.
  21. Vermersch P, et al. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler. 2013.
  22. Freedman MS, et al. Teriflunomide added to interferon-beta in relapsing multiple sclerosis: a randomized phase II trial. Neurology. 2012;78(23):1877–85.
  23. O’Connor PW, et al. A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology. 2006;66(6):894–900.
  24. Confavreux C, et al. Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years. Mult Scler. 2012;18(9):1278–89.
  25. Bar-Or A, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013;81(6):552–8.
  26. Fox RJ, et al. BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety. Curr Med Res Opin. 2013.
  27. Meissner M, et al. Dimethyl fumarate – only an anti-psoriatic medication? J Dtsch Dermatol Ges. 2012;10(11):793–801.
  28. Gold R, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012;367(12):1098–107.
  29. Fox RJ, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012;367(12):1087–97.
  30. Kappos L, et al. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet. 2008;372(9648):1463–72.
  31. Ermis U, Weis J, Schulz JB. PML in a patient treated with fumaric acid. N Engl J Med. 2013;368(17):1657–8.
  32. van Oosten BW, et al. PML in a patient treated with dimethyl fumarate from a compounding pharmacy. N Engl J Med. 2013;368(17):1658–9.
  33. Mrowietz U. Reich K. Case reports of PML in patients treated for psoriasis. N Engl J Med. 2013;369(11):1080–1.
  34. Bruck W, Wegner C. Insight into the mechanism of laquinimod action. J Neurol Sci. 2011;306(1–2):173–9.
  35. Filippi M, et al. Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage. J Neurol Neurosurg Psychiatry. 2013.
  36. Tur C. Oral laquinimod for multiple sclerosis: beyond the anti-inflammatory effect. J Neurol Neurosurg Psychiatry. 2013.
  37. Bruck W, Vollmer T. Multiple sclerosis: Oral laquinimod for MS-bringing the brain into focus. Nat Rev Neurol. 2013;9(12):664–5.
  38. Comi G, et al. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med. 2012;366(11):1000–9.
  39. Vollmer TL, et al. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. J Neurol. 2014;261(4):773–83.
  40. Comi G, et al. Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet. 2008;371(9630):2085–92.
  41. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology. 1993;43(4):655–61.
  42. Paty, DW, Li DK. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology. 1993;43(4):662–7.
  43. Jacobs LD, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996;39(3):285–94.
  44. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet. 1998;352(9139):1498–504.
  45. Johnson KP, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995;45(7):1268–76.
  46. Kappos, L, et al. Long-term subcutaneous interferon beta-1a therapy in patients with relapsing-remitting MS. Neurology. 2006;67(6):944–53.
  47. Sandberg-Wollheim M, et al. The risk of malignancy is not increased in patients with multiple sclerosis treated with subcutaneous interferon beta-la: analysis of data from clinical trial and post-marketing surveillance settings. Mult Scler. 2011;17(4):431–40.
  48. Schwid SR, Decker MD, Lopez-Bresnahan M. Immune response to influenza vaccine is maintained in patients with multiple sclerosis receiving interferon beta-1a. Neurology. 2005;65(12):1964–6.
  49. Olberg HK, et al. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult Scler. 2014.
  50. Weber-Schoendorfer C, Schaefer C. Multiple sclerosis, immunomodulators, and pregnancy outcome: a prospective observational study. Mult Scler. 2009;15(9):1037–42.
  51. Sandberg-Wollheim M, et al. Pregnancy outcomes in multiple sclerosis following subcutaneous interferon beta-1a therapy. Mult Scler. 2011;17(4):423–30.
  52. Niino M, et al. Natalizumab effects on immune cell responses in multiple sclerosis. Ann Neurol. 2006;59(5):748–54.
  53. Rudick RA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med, 2006;354(9):911–23.
  54. Polman CH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899–910.
  55. Langer-Gould A, et al. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med. 2005;353(4):375–81.
  56. Kleinschmidt-DeMasters BK, Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med. 2005;353(4):369–74.
  57. Miller DH, et al. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology. 2007;68(17):1390–401.
  58. Plavina, T.e.a., in The 27th annual meeting of the consortium of multiple sclerosis centers. 2013: Orlando Florida.
  59. Calabresi PA, et al. The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL. Neurology. 2007;69(14):1391–403.
  60. Deisenhammer, F. Neutralizing antibodies to interferon-beta and other immunological treatments for multiple sclerosis: prevalence and impact on outcomes. CNS Drugs. 2009;23(5):379–96.
  61. Kleiter I, et al. Failure of natalizumab to prevent relapses in neuromyelitis optica. Arch Neurol. 2012;69(2):239–5.
  62. Barnett MH, et al. Massive astrocyte destruction in neuromyelitis optica despite natalizumab therapy. Mult Scler, 2012;18(1):108–12.
  63. Kitley J, et al. Catastrophic brain relapse in seronegative NMO after a single dose of natalizumab. J Neurol Sci. 2014;339(1–2):223–5.
  64. Vagberg M, Kumlin U, Svenningsson A. Humoral immune response to influenza vaccine in natalizumab-treated MS patients. Neurol Res. 2012;34(7):p.730–3.
  65. Houtchens MK, Kolb CM, Multiple sclerosis and pregnancy: therapeutic considerations. J Neurol. 2013;260(5):1202–14.
  66. Freedman MS, Kaplan JM, Markovic-Plese S. Insights into the Mechanisms of the Therapeutic Efficacy of Alemtuzumab in Multiple Sclerosis. J Clin Cell Immunol. 2013;4(4).
  67. Cohen JA, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819–28.
  68. Coles AJ, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786–801.
  69. Coles AJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–39.
  70. Coles AJ, et al. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet. 1999;354(9191):1691–5.
  71. Cossburn M, et al. Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Neurology. 2011;77(6):573–9.
  72. Fox EJ, et al. A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis. Eur J Neurol. 2012;19(2):307–11.
  73. McCarthy CL, et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013;81(10):872–6.
  74. Kappos L, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011;378(9805):1779–87.
  75. Gold R, et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet. 2013;381(9884):2167–75.