Skip to main content
SpringerLink
Log in

Switching Therapies in Multiple Sclerosis

  • Leading Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

There are currently nine approved disease modifying therapies for relapsing forms of multiple sclerosis, with six distinct mechanisms of action. All have side effects, and none are cures. When a patient cannot tolerate therapy, or there is unacceptable breakthrough disease activity, the most common approach is to change drug. No universal guidelines exist for switching therapy. This overview will propose switch principles and suggestions.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. The IFNβ Multiple Sclerosis Study Group and 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;45:1277–85.

    Article  Google Scholar 

  2. Jacobs ID, Cookfair DI, Rudick RA, et al. The multiple sclerosis collaborative research group (MSCRG). Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996;39:285–94.

    Article  PubMed  CAS  Google Scholar 

  3. Johnson KP, Brooks BR, Cohen JA, et al. The copolymer 1 multiple sclerosis study group. Copolymer 1 reduces relapse rate and improves disability in relapsing/remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. Neurology. 1995;45:1268–76.

    Article  PubMed  CAS  Google Scholar 

  4. PRISMS (Prevention of relapses and disability by Interferon beta-1a subcutaneously in multiple sclerosis) study group. Randomized double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet. 1998;352:1498–504.

    Article  Google Scholar 

  5. Hartung HP, Gonsette R, Konig N, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomized, multicentre trial. Lancet. 2002;360:2018–25.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. Marriott JJ, Miyasaki JM, Gronseth G, et al. Evidence report: the efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis. Neurology. 2010;74:1463–70.

    Article  PubMed  CAS  Google Scholar 

  10. Prosperini L, Gianni C, Barletta V, et al. Predictors of freedom from disease activity in natalizumab treated patients with multiple sclerosis. J Neurol Sci. 2012;12432:1–9.

    Google Scholar 

  11. Coyle PK. Switching algorithms: from one immunomodulatory agent to another. J Neurol. 2008;255(S1):44–50.

    Article  PubMed  CAS  Google Scholar 

  12. Rio J, Tintore M, Sastre-Garriga J, et al. Change in the clinical activity of multiple sclerosis after treatment switch for suboptimal response. Eur J Neurol. 2012;19:899–904.

    Article  PubMed  CAS  Google Scholar 

  13. 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;359:1453–60.

    Article  PubMed  CAS  Google Scholar 

  14. Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta-1a treatment regiments in MS: the EVIDENCE trial. Neurology. 2002;59:1496–506.

    Article  PubMed  CAS  Google Scholar 

  15. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon on relapsing multiple sclerosis. N Engl J Med. 2010;362:404–15.

    Article  Google Scholar 

  16. Mikol DD, Barkhof F, Chang P, et al. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the Rebif vs. Glatiramer Acetate in Relapsing MS Disease (REGARD) study): a multicentre, randomized, parallel, open-label trial. Lancet. 2008;7:903–13.

    Article  CAS  Google Scholar 

  17. O’Connor P, Filippi M, Arnason B, et al. 250 μg or 500 μg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomized, multicentre study. Lancet. 2009;8:889–97.

    Article  Google Scholar 

  18. Lublin F, Cofield S, Cutter G, et al. The CombiRx trial: a multi-center, double-blind, randomized study comparing the combined use of interferon beta-1a and glatiramer acetate to either agent alone in participants with relapsing-remitting multiple sclerosis—clinical outcomes. AAN 2012; Abstract PL02.001.

  19. Press Release. Genzyme reports top-line results for TENERE study of oral Teriflunomide in relapsing multiple sclerosis. Business Wire, 20 Dec 2011.

  20. Krumbholz M, Pellkofer H, Gold R, et al. Delayed allergic reaction to Natalizumab associated with early formation of neutralizing antibodies. Arch Neurol. 2007;64(9):1331–3.

    Article  PubMed  Google Scholar 

  21. Sorensen PS, Jensen PEH, Haghikia A, et al. Occurrence of antibodies against natalizumab in relapsing multiple sclerosis patients treated with natalizumab. MSJ. 2011;17(9):1074–8.

    Google Scholar 

  22. Goodin DS, Frohman EM, Hurwitz B, et al. Neutralizing antibodies to interferon beta: assessment of their clinical and radiographic impact: an evidence report. Neurology. 2007;68:977–84.

    Article  PubMed  CAS  Google Scholar 

  23. Polman CH, Bertolotto A, Deisenhammer F, et al. Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis. Lancet Neurol. 2010;9:740–50.

    Article  PubMed  CAS  Google Scholar 

  24. Havrdova E, Galetta S, Hutchinson M, et al. 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. 2009;8:254–60.

    Article  PubMed  Google Scholar 

  25. Kappos L, Radue E-W, Amato M, et al. Fingolimod treatment increases the proportion of patients who are free from disease activity in multiple sclerosis: results from a phase B, placebo controlled study (Freedoms). In: 63rd annual meeting, American Academy of Neurology 2012; PD 6.002.

  26. Cohen BA, Khan O, Jeffrey DR, et al. Identifying and treating patients with suboptimal responses. Neurology. 2004;63:S33–40.

    Article  PubMed  CAS  Google Scholar 

  27. Uitdehaag BM, Barkhof F, Coyle PK, et al. The changing face of multiple sclerosis clinical trial populations. Curr Med Res Opin. 2011;27:1529–37.

    Article  PubMed  Google Scholar 

  28. Healy BC, Glanz BI, Stankiewicz J, et al. A method for evaluating treatment switching criteria in multiple sclerosis. Mult Scler. 2010;16:1483–9.

    Article  PubMed  Google Scholar 

  29. Portaccio E, Zipoli V, Siracusa G, et al. Switching to second-line therapies in interferon-beta-treated relapsing-remitting multiple sclerosis patients. Eur Neurol. 2009;61:177–82.

    Article  PubMed  CAS  Google Scholar 

  30. Trojano M, Pellegrini F, Fuiani A, et al. New natural history of interferon-β-treated relapsing multiple sclerosis. Ann Neurol. 2007;61:300–6.

    Article  PubMed  CAS  Google Scholar 

  31. Bergamaschi R, Quaglini S, Tavazzi E, et al. Immunomodulatory therapies delay disease progression in multiple sclerosis. MSJ. 2012;. doi:10.1177/1352458512445941.

    Google Scholar 

  32. Tedeholm H, Lycke J, Skoog B, et al. Time to secondary progression in patients with multiple sclerosis who were treated with first generation immunomodulating drugs. MSJ. 2012;. doi:10.1177/1352458512463764.

    Google Scholar 

  33. Shirani A, Zhao Y, Karim ME, et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2012;308:247–56.

    Article  PubMed  CAS  Google Scholar 

  34. Freedman MS, Patry DG, Grand’Maison F, et al. Treatment optimization in multiple sclerosis. Can J Neurol Sci. 2004;31:157–68.

    PubMed  Google Scholar 

  35. Rudick RA, Polman CH. Current approaches to the identification and management of breakthrough disease in patients with multiple sclerosis. Lancet Neurol. 2009;8:545–59. (42–45).

    Article  PubMed  Google Scholar 

  36. Killestein J, Polman CH. Determinants of interferon β efficacy in patients with multiple sclerosis. Nat Rev Neurol. 2011;7(4):221–8.

    Article  PubMed  CAS  Google Scholar 

  37. Rio J, Rovira A, Tintore M, et al. Relationship between MRI lesion activity and response to IFN-β in relapsing-remitting multiple sclerosis patients. Mult Scler. 2008;14:479–84.

    Article  PubMed  CAS  Google Scholar 

  38. Prosperini L, Gallo V, Petsas N, et al. One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis. Eur J Neurol. 2009;16:1202–9.

    Article  PubMed  CAS  Google Scholar 

  39. Bermel RA, You X, Foulds P, et al. Predictors of long-term outcome in multiple sclerosis patients treated with interferon beta. Ann Neurol. 2013;73:95–103.

    Google Scholar 

  40. Leray E, Yaouang J, Le Page E, et al. Evidence for a two-stage disability progression in multiple sclerosis. Brain. 2010;133:1900–13.

    Article  PubMed  Google Scholar 

  41. Durelli L, Barbero P, Bergui M, et al. MRI activity and neutralizing antibody as predictors of response to interferon β treatment in multiple sclerosis. J Neurol Neurosurg Psych. 2008;79:646–51.

    Article  CAS  Google Scholar 

  42. Trojano M, Pellegrini F, De Stat M, et al. Real-life impact of early interferon β therapy in relapsing multiple sclerosis. Ann Neurol. 2009;66:513–20.

    Article  PubMed  CAS  Google Scholar 

  43. Prosperini L, Borriello G, De Giglio L, et al. Management of breakthrough disease in patients with multiple sclerosis: when an increasing of Interferon beta dose should be effective? BMC Neurol. 2011;11(26):1–6.

    Google Scholar 

  44. Rieckmann P. Concepts of induction and escalation therapy in multiple sclerosis. J Neurol Sci. 2009;277(S1):S42–5.

    Article  PubMed  CAS  Google Scholar 

  45. Castillo-Trivino T, Mowry EM, Gajofatto A, et al. Switching multiple sclerosis patients with breakthrough disease to second-line therapy. PLoS ONE. 2011;6:1–5.

    Article  Google Scholar 

  46. Cree BA, Al-Sabbagh A, Bennett R, et al. Response to interferon beta-1a treatment in African American multiple sclerosis patients. Arch Neurol. 2005;62:1681–3.

    Article  PubMed  Google Scholar 

  47. Gajofatto A, Bacchetti P, Grimes B, et al. Switching first-line disease-modifying therapy after failure: impact on the course of relapsing-remitting multiple sclerosis. Mult Scler. 2009;15:50–8.

    Article  PubMed  CAS  Google Scholar 

  48. Putzki N, Kollia K, Woods S, et al. Natalizumab is effective as second line therapy in the treatment of relapsing remitting multiple sclerosis. Eur J Neurol. 2009;16:424–6.

    Article  PubMed  CAS  Google Scholar 

  49. Carra A, Onaha P, Luetic G, et al. Therapeutic outcome 3 years after switching of immunomodulatory therapies in patients with relapsing-remitting multiple sclerosis in Argentina. Eur J Neurol. 2008;15:386–93.

    Article  PubMed  CAS  Google Scholar 

  50. Havla J, Gerdes LA, Meinl I, et al. De-escalation from natalizumab in multiple sclerosis: recurrence of disease activity despite switching to glatiramer acetate. J Neurol. 2011;258:1665–9.

    Article  PubMed  CAS  Google Scholar 

  51. Prosperini L, Gianni C, Leonardi L, et al. Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis. Mult Scler. 2012;18:64–71.

    Article  PubMed  CAS  Google Scholar 

  52. Belachew S, Phan-Ba R, Bartholome E, et al. Natalizumab induces a rapid-improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis. Eur J Neurol. 2011;18:240–5.

    Article  PubMed  CAS  Google Scholar 

  53. Cree BA, Stuart WH, Tornatore CJ, et al. Efficacy of natalizumab therapy in patients of African descent with relapsing multiple sclerosis: analysis of AFFIRM and SENTINEL data. Arch Neurol. 2011;68:464–8.

    Article  PubMed  Google Scholar 

  54. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associate progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366:1870–80.

    Article  PubMed  CAS  Google Scholar 

  55. Centonze D, Rossi S, Rinaldi F, et al. Severe relapses under fingolimod treatment prescribed after natalizumab. Neurology. 2012;79:2004–6.

    Article  PubMed  Google Scholar 

  56. Daelman L, Maitrot A, Maarouf A, et al. Severe multiple sclerosis reactivatrion under fingolimod 3 months after natalizumab withdrawal. MSJ. 2012;18:1647–9.

    CAS  Google Scholar 

  57. Havla J, Tackenberg B, Hellwig K, et al. Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis. J Neurol. 2012;. doi:10.1007/s00415-012-6808-8.

    PubMed  Google Scholar 

  58. Jander S, Turowski B, Kieseler BC, et al. Emerging tumefactive multiple sclerosis after switching therapy from natalizumab to fingolimod. MSJ. 2012;18:1650–2.

    Google Scholar 

  59. Rinaldi F, Seppi D, Calabrese M, et al. Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: clinical and magnetic resonance imaging findings. MSJ. 2012;18:1640–3.

    CAS  Google Scholar 

  60. Muller H, Hofer S, Kaneider N, et al. The immunomodulators FTY720 interferes with effector functions of human monocyte-derived dendritic cells. Eur J Immunol. 2005;35:533–45.

    Article  PubMed  Google Scholar 

  61. Bourdette D, Gilden D. Fingolimod and multiple sclerosis. Four cautionary tales (Ed.). Neurology. 2012;79:1942–3.

    Article  PubMed  Google Scholar 

  62. Rieckmann P, Heidenreich F, Sailer M, et al. Treatment de-escalation after Mitoxantrone therapy: results of a phase IV, multicentre, open-label, randomized study of subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis. Ther Adv Neurlo Disord. 2012;5:3–12.

    Article  CAS  Google Scholar 

  63. Zecca C, Meier S, Tschuor S, et al. Natalizumab de-escalation to interferon-beta-1b in multiple sclerosis: a randomized, controlled, pilot trial (abstract). ECTRIMS, 12 Oct 2012.

  64. Yeh EA, Waubant E, Krupp LB, et al. Multiple sclerosis therapies in pediatric patients with refractory multiple sclerosis. Arch Neurol. 2011;68:437–44.

    Article  PubMed  Google Scholar 

  65. Ghezzi A, Banwell B, Boyko A, et al. The management of multiple sclerosis in children: a European view. Mult Scler. 2010;16(10):1258–67.

    Article  PubMed  Google Scholar 

  66. Demoruelle MK, Deane KD. Treatment strategies in early rheumatoid arthritis and prevention of rheumatoid arthritis. Curr Rheumatol Rep. 2012;14:472–80.

    Article  PubMed  CAS  Google Scholar 

  67. Axtell RC, de Jong BA, Boniface K, et al. T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis. Nat Med. 2010;16:406–12.

    Article  PubMed  CAS  Google Scholar 

  68. Sellebjerg F, Hedegaard CJ, Krakauer M, et al. Glatiramer acetate antibodies, gene expression and disease activity in multiple sclerosis. MSJ. 2012;18(3):305–13.

    CAS  Google Scholar 

  69. Grossman I, Avidan N, Singer C, et al. Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers. Pharmacogenet Genomics. 2007;17:657–66.

    Article  PubMed  CAS  Google Scholar 

  70. Bushnell SE, Zhao Z, Stebbins CC, et al. Serum IL-17F does not predict poor response to IM IFNβ-1a in relapsing-remitting MS. Neurol. 2012;79(6):531–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

No funding was received for this article. Personal compensation for consultative and educational activities was received from: Bayer, Biogen-Idec, EMD Serono, Genzyme/Sanofi-Aventis, Novartis, Roche, and Teva.

Author information

Authors and Affiliations

  1. Department of Neurology, Stony Brook University Medical Center, HSC T12-020, Stony Brook, NY, 11794-8121, USA

    Patricia K. Coyle

Authors
  1. Patricia K. Coyle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patricia K. Coyle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coyle, P.K. Switching Therapies in Multiple Sclerosis. CNS Drugs 27, 239–247 (2013). https://doi.org/10.1007/s40263-013-0042-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40263-013-0042-5

Keywords

Search

Navigation