Journal of Neurology

, Volume 253, Supplement 6, pp vi45–vi51 | Cite as

Rationale and experience with combination therapies in multiple sclerosis

Article

Abstract

Standard immunomodulatory therapies for multiple sclerosis reduce relapses by around thirty percent and possibly slow progression of disability. In many patients, use of such treatments allows the disease process to be stabilised and quality of life to be improved. However in patients experiencing frequent severe relapses, for whom prognosis is often poor, they may not be sufficiently efficacious. Emerging therapies such as natalizumab, alemtuzumab or mitoxantrone may be more effective in such patients but have potentially greater side-effects that limit their use as maintenance therapies. Combining current immunomodulatory treatments with emerging therapies may offer the potential to treat patients with active disease successfully and safely. In particular, the use of induction therapy with mitoxantrone followed by maintenance treatment with glatiramer acetate appears to be of interest. In a cohort of over 60 patients receiving this combination in routine clinical practice, disease activity as measured by relapses is rapidly suppressed and the benefit sustained for over five years. With current, anti-inflammatory, therapies decisions on switching and combining therapies need to be made early in the disease course in order to optimise benefit for patients and minimise the risk of accumulating irreversible disability.

Key words

multiple sclerosis combination therapy beta-interferon glatiramer acetate mitoxantrone 

References

  1. 1.
    Adelman B, Sandrock A, Panzara MA (2005) Natalizumab and progressive multifocal leukoencephalopathy. N Engl J Med 353:432–433PubMedCrossRefGoogle Scholar
  2. 2.
    Calabresi PA, Wilterdink JL, Rogg JM, Mills P, Webb A, Whartenby KA (2002) An open-label trial of combination therapy with interferon beta-1a and oral methotrexate in MS. Neurology 58:314–317PubMedGoogle Scholar
  3. 3.
    Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale G, Miller D, Waldmann H, Compston A (1999) Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol 46:296–304PubMedCrossRefGoogle Scholar
  4. 4.
    Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA (2006) The window of therapeutic opportunity in multiple sclerosis Evidence from monoclonal antibody therapy. J Neurol 253:98–108PubMedCrossRefGoogle Scholar
  5. 5.
    Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343:1430–1438PubMedCrossRefGoogle Scholar
  6. 6.
    Correale J, Rush C, Amengual A, Goicochea MT (2005) Mitoxantrone as rescue therapy in worsening relapsing-remitting MS patients receiving IFN-beta. J Neuroimmunol 162:173–183PubMedCrossRefGoogle Scholar
  7. 7.
    De Stefano N, Guidi L, Stromillo ML, Bartolozzi ML, Federico A (2003) Imaging neuronal and axonal degeneration in multiple sclerosis. Neurol Sci 24(Suppl 5):S283–S286PubMedCrossRefGoogle Scholar
  8. 8.
    Farina C, Weber MS, Meinl E, Wekerle H, Hohlfeld R (2005) Glatiramer acetate in multiple sclerosis: update on potential mechanisms of action. Lancet Neurol 4:567–575PubMedCrossRefGoogle Scholar
  9. 9.
    Fernandez O, Guerrero M, Mayorga C, Munoz L, Lean A, Luque G, Hervas M, Fernandez V, Capdevila A, de Ramon E (2002) Combination therapy with interferon beta-1b and azathioprine in secondary progressive multiple sclerosis. A two-year pilot study. J Neurol 249:1058–1062PubMedCrossRefGoogle Scholar
  10. 10.
    Ford CC, Johnson KP, Lisak RP, Panitch HS, Shifronis G, Wolinsky JS; Copaxone Study Group (2006) A prospective open-label study of glatiramer acetate: over a decade of continuous use in multiple sclerosis patients. Mult Scler 12:309–320PubMedCrossRefGoogle Scholar
  11. 11.
    Fox EJ (2004) Mechanism of action of mitoxantrone. Neurology 63(Suppl 6):S15–S18PubMedGoogle Scholar
  12. 12.
    Hartung HP, Bar-Or A, Zoukos Y (2004) What do we know about the mechanism of action of disease-modifying treatments in MS? J Neurol 251(Suppl 5):v12–v29PubMedCrossRefGoogle Scholar
  13. 13.
    Giovannoni G, Goodman A (2005) Neutralizing anti-IFN-beta antibodies: how much more evidence do we need to use them in practice? Neurology 65:6–8PubMedCrossRefGoogle Scholar
  14. 14.
    Gonsette RE (2004) A comparison of the benefits of mitoxantrone and other recent therapeutic approaches in multiple sclerosis. Expert Opin Pharmacother 5:747–765PubMedCrossRefGoogle Scholar
  15. 15.
    Hobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A (2001) The Multiple Sclerosis Impact Scale (MSIS-29): a new patient-based outcome measure. Brain 124(Pt 5):962–973PubMedCrossRefGoogle Scholar
  16. 16.
    Hobart JC, Riazi A, Lamping DL, Fitzpatrick R, Thompson AJ (2005) How responsive is the Multiple Sclerosis Impact Scale (MSIS-29)? A comparison with some other self report scales. J Neurol Neurosurg Psychiatry 76:1539–1543PubMedCrossRefGoogle Scholar
  17. 17.
    Jacob A, Rashid S, Ramtahal J, Mahavish K, Young C, Boggild M (2005) Long-term adherence to first disease-modifying drug and reasons for discontinuation in 194 patients with relapsing-remitting multiple sclerosis. Multiple Sclerosis 11:P597Google Scholar
  18. 18.
    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 11:296–301PubMedCrossRefGoogle Scholar
  19. 19.
    Kappos L, Achtnichts L, Dahlke F, Kuhle J, Naegelin Y, Sandbrink R, Lindberg RL (2005) Genomics and proteomics: role in the management of multiple sclerosis. J Neurol 252(Suppl 3):iii21–iii27PubMedCrossRefGoogle Scholar
  20. 20.
    Lus G, Romano F, Scuotto A, Accardo C, Cotrufo R (2004) Azathioprine and interferon beta(1a) in relapsing-remitting multiple sclerosis patients: increasing efficacy of combined treatment. Eur Neurol 51:15–20PubMedCrossRefGoogle Scholar
  21. 21.
    Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910PubMedCrossRefGoogle Scholar
  22. 22.
    Pryce G, O’Neill JK, Croxford JL, Amor S, Hankey DJ, East E, Giovannoni G, Baker D (2005) Autoimmune tolerance eliminates relapses but fails to halt progression in a model of multiple sclerosis. J Neuroimmunol 165:41–52PubMedCrossRefGoogle Scholar
  23. 23.
    Pulicken M, Bash CN, Costello K, Said A, Cuffari C, Wilterdink JL, Rogg JM, Mills P, Calabresi PA (2005) Optimization of the safety and efficacy of interferon beta 1b and azathioprine combination therapy in multiple sclerosis. Mult Scler 11:169–174PubMedCrossRefGoogle Scholar
  24. 24.
    Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, Panzara MA, Sandrock AW; SENTINEL Investigators (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354:911–923PubMedCrossRefGoogle Scholar
  25. 25.
    Stuve O, Marra CM, Jerome KR, Cook L, Cravens PD, Cepok S, Frohman EM, Phillips JT, Arendt G, Hemmer B, Monson NL, Racke MK (2006) Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann Neurol 59:743–747PubMedCrossRefGoogle Scholar
  26. 26.
    Waldmann H, Hale G (2005) CAMPATH: from concept to clinic. Philos Trans R Soc Lond B Biol Sci 360:1707–1711PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  1. 1.Walton Centre for Neurology and NeurosurgeryFazakerley, Liverpool, L9 7LJUK

Personalised recommendations