RSS-Feed abonnieren
DOI: 10.1055/s-2003-41138
Current Disease-Modifying Therapies in Multiple Sclerosis
Publikationsverlauf
Publikationsdatum:
01. August 2003 (online)

ABSTRACT
In recent years, the usefulness of interferon beta and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis (RRMS) has been established. Interferon beta has also been shown to be efficacious in secondary-progressive multiple sclerosis (SPMS) as well as in patients with isolated syndromes at risk to develop clinically definite multiple sclerosis (MS). Mitoxantrone is another disease-modifying drug that is available for SPMS and severe cases of RRMS. The clinical utility of disease-modifying agents in MS will be reviewed with respect to the anti-inflammatory, immunomodulatory, and immunosuppressive treatments that are currently available. Symptomatic therapies will not be considered.
KEYWORDS
Multiple sclerosis - interferon beta - glatiramer acetate - mitoxantrone - glucocorticosteroids
REFERENCES
- 1 Hemmer B, Archelos J J, Hartung H P. New concepts in the immunopathogenesis of multiple sclerosis. Nature Rev Neurosci . 2002; 3 291-201
- 2 Compston A, Coles A. Multiple sclerosis. Lancet . 2002; 359 1221-1231
- 3 Rodriguez M, Siva A, Cross S A, O'Brien P C, Kurland L T. Optic neuritis: a population-based study in Olmsted County, Minnesota. Neurology . 1995; 45 244-250
- 4 Brex P A, Ciccarelli O, O'Riordan J I, Sailer M, Thompson A J, Miller D H. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med . 2002; 346 158-164
- 5 McDonald W I, Compston A, Edan G. et al . Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol . 2001; 50 121-127
- 6 Lublin F D, Reingold S C. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology . 1996; 46 907-911
- 7 Weinshenker B G, Bass B, Rice G P. et al . The natural history of multiple sclerosis: a geographically based study I: clinical course and disability. Brain . 1989; 112 133-146
- 8 Weinshenker B G, Bass B, Rice G P. et al . The natural history of multiple sclerosis: a geographically based study II: predictive value of the early clinical course. Brain . 1989; 112 1419-1428
- 9 Wiendl H, Hohlfeld R. Therapeutic approaches in multiple sclerosis: lessons from failed and interrupted treatment trials. BioDrugs . 2002; 16 183-200
- 10 Noseworthy J H, Gold R, Hartung H P. Treatment of multiple sclerosis: recent trials and future perspectives. Curr Opin Neurol . 1999; 12 279-293
- 11 Neuhaus O, Archelos J J, Hartung H P. Immunomodulation in multiple sclerosis: from immunosuppression to neuroprotection. Trends Pharmacol Sci . 2003; 24 131-138
- 12 Gold R, Buttgereit F, Toyka K V. Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders. J Neuroimmunol . 2001; 117 1-8
- 13 Thompson A J, Kennard C, Swash M. et al . Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology . 1989; 39 969-971
- 14 Rose A S, Kuzma J W, Kurtzke J F, Namerow N S, Sibley W A, Tourtellotte W W. Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH versus placebo-final report. Neurology . 1970; 20 1-59
- 15 Durelli L, Cocito D, Riccio A. et al . High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations. Neurology . 1986; 36 238-243
- 16 Milligan N M, Newcombe R, Compston D A. A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis I: clinical effects. J Neurol Neurosurg Psychiatry . 1987; 50 511-516
- 17 Sellebjerg F, Frederiksen J L, Nielsen P M, Olesen J. Double-blind, randomized, placebo-controlled study of oral, high-dose methylprednisolone in attacks of MS. Neurology . 1998; 51 529-534
- 18 Alam S M, Kyriakides T, Lawden M, Newman P K. Methylprednisolone in multiple sclerosis: a comparison of oral with intravenous therapy at equivalent high dose. J Neurol Neurosurg Psychiatry . 1993; 56 1219-1220
- 19 Barnes D. Treatment of acute relapses. In: Hawkins CP, Wolinsky JS, eds. Principles of Treatment in Multiple Sclerosis Woburn, MA: Butterworth-Heinemann 2000: 14-22
- 20 Beck R W, Cleary P A, Anderson Jr M M. et al . A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med . 1992; 326 581-588
- 21 Hickman S J, Dalton C M, Miller D H, Plant G T. Management of acute optic neuritis. Lancet . 2002; 360 1953-1962
- 22 Filippini G, Brusaferri F, Sibley W A. et al . Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev 2000;CD001331.
- 23 Wenning G K, Wietholter H, Schnauder G, Muller P H, Kanduth S, Renn W. Recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term, high-dose intravenous prednisolone therapy in patients with MS. Acta Neurol Scand . 1994; 89 270-273
- 24 Kapoor R, Miller D H, Jones S J. et al . Effects of intravenous methylprednisolone on outcome in MRI-based prognostic subgroups in acute optic neuritis. Neurology . 1998; 50 230-237
- 25 Sellebjerg F, Nielsen H S, Frederiksen J L, Olesen J. A randomized, controlled trial of oral high-dose methylprednisolone in acute optic neuritis. Neurology . 1999; 52 1479-1484
- 26 Barnes D, Hughes R A, Morris R W. et al . Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet . 1997; 349 902-906
- 27 Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol . 2000; 47 707-717
- 28 Barkhof F, Hommes O R, Scheltens P, Valk J. Quantitative MRI changes in gadolinium-DTPA enhancement after high-dose intravenous methylprednisolone in multiple sclerosis. Neurology . 1991; 41 1219-1222
- 29 Oliveri R L, Valentino P, Russo C. et al . Randomized trial comparing two different high doses of methylprednisolone in MS: a clinical and MRI study. Neurology . 1998; 50 1833-1836
- 30 Goodin D S, Frohman E M, Garmany Jr P G. 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
- 31 Weinshenker B G. Plasma exchange for severe attacks of inflammatory demyelinating diseases of the central nervous system. J Clin Apheresis . 2001; 16 39-42
- 32 Keegan M, Pineda A A, McClelland R L, Darby C H, Rodriguez M, Weinshenker B G. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology . 2002; 58 143-146
- 33 Weinshenker B G, O'Brien P C, Petterson T M. et al . A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol . 1999; 46 878-886
- 34 Jacobs L D, Beck R W, Simon J H. et al . Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med . 2000; 343 898-904
- 35 Comi G, Filippi M, Barkhof F. et al . Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet . 2001; 357 1576-1582
- 36 Beck R W, Chandler D L, Cole S R. et al . Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses. Ann Neurol . 2002; 51 481-490
- 37 Fazekas F, Barkhof F, Filippi M. et al . The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis. Neurology . 1999; 53 448-456
- 38 McFarland H F, Barkhof F, Antel J, Miller D H. The role of MRI as a surrogate outcome measure in multiple sclerosis. Mult Scler . 2002; 8 40-51
- 39 Barkhof F, Filippi M, Miller D H. et al . Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain . 1997; 120 2059-2069
- 40 Tintore M, Rovira A, Martinez M J. et al . Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. AJNR Am J Neuroradiol . 2000; 21 702-706
- 41 Dalton C M, Brex P A, Miszkiel K A. et al . Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol . 2002; 52 47-53
- 42 Brex P A, O'Riordan J I, Miszkiel K A. et al . Multisequence MRI in clinically isolated syndromes and the early development of MS. Neurology . 1999; 53 1184-1190
- 43 Optic Neuritis Study Group. The 5-year risk of MS after optic neuritis: experience of the optic neuritis treatment trial. Neurology . 1997; 49 1404-1413
- 44 Corboy J R, Goodin D S, Frohman E M. Disease-modifying therapies for multiple sclerosis. Curr Treat Options Neurol . 2003; 5 35-54
- 45 CHAMPS Study Group. MRI predictors of early conversion to clinically definite MS in the CHAMPS placebo group. Neurology . 2002; 59 998-1005
- 46 PRISMS Study Group. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology . 2001; 56 1628-1636
- 47 Coyle P K, Hartung H P. Use of interferon beta in multiple sclerosis: rationale for early treatment and evidence for dose- and frequency-dependent effects on clinical response. Mult Scler . 2002; 8 2-9
- 48 Yong V W, Chabot S, Stuve O, Williams G. Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology . 1998; 51 682-689
- 49 Yong V W. Differential mechanisms of action of interferon-beta and glatiramer acetate in MS. Neurology . 2002; 59 802-808
- 50 Kieseier B C, Seifert T, Giovannoni G, Hartung H P. Matrix metalloproteinases in inflammatory demyelination: targets for treatment. Neurology . 1999; 53 20-25
- 51 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, placebo-controlled trial. Neurology . 1993; 43 655-661
- 52 Paty D W, Li D K. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis 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
- 53 The IFNB 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 1277-1285
- 54 Simon J H, Jacobs L D, Campion M. et al . Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. Ann Neurol . 1998; 43 79-87
- 55 Rudick R A, Goodkin D E, Jacobs L D. et al . Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology . 1997; 49 358-363
- 56 Jacobs L D, Cookfair D L, Rudick R A. et al . Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol . 1996; 39 285-294
- 57 PRISMS Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet . 1998; 352 1498-1504
- 58 Li D K, Paty D W. Magnetic resonance imaging results of the PRISMS trial-a randomized, double-blind, placebo-controlled study of interferon-beta 1a in relapsing-remitting multiple sclerosis: prevention of relapses and disability by interferon-beta 1a subcutaneously in multiple sclerosis. Ann Neurol . 1999; 46 197-206
- 59 The Once Weekly Interferon for MS Study Group. Evidence of interferon beta-1a dose response in relapsing-remitting MS: the OWIMS Study. Neurology . 1999; 11 679-686
- 60 Clanet M, Radue E W, Kappos L. et al . A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS. Neurology . 2002; 59 1507-1517
- 61 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 randomised multicentre study (INCOMIN). Lancet . 2002; 359 1453-1460
- 62 Benatar M. Interferon beta-1a and beta-1b for treatment of multiple sclerosis. Lancet . 2002; 360 1428-1429
- 63 Panitch H, Goodin D S, Francis G. et al . Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE Trial. Neurology . 2002; 59 1496-1506
- 64 Lublin F D. When marketing and science intersect: do patients with MS benefit?. Neurology . 2002; 59 1480-1481
- 65 Polman C, Kappos L, White R. et al . Neutralizing antibodies during treatment of secondary progressive MS with interferon beta-1b. Neurology . 2003; 60 37-43
- 66 Pozzilli C, Antonini G, Bagnato F. et al . Monthly corticosteroids decrease neutralizing antibodies to IFNbeta1 b: a randomized trial in multiple sclerosis. J Neurol . 2002; 249 50-56
- 67 Neuhaus O, Farina C, Wekerle H, Hohlfeld R. Mechanisms of action of glatiramer acetate in multiple sclerosis. Neurology . 2001; 56 702-708
- 68 Johnson K P, Brooks B R, Cohen J A. 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. Neurology . 1995; 45 1268-1276
- 69 Johnson K P, Brooks B R, Cohen J A. et al . Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group. Neurology . 1998; 50 701-708
- 70 Comi G, Filippi M, Wolinsky J S. 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. European/Canadian Glatiramer Acetate Study Group. Ann Neurol . 2001; 49 290-297
- 71 Wolinsky J S, Comi G, Filippi M, Ladkani D, Kadosh S, Shifroni G. Copaxone's effect on MRI-monitored disease in relapsing MS is reproducible and sustained. Neurology . 2002; 59 1284-1286
- 72 Johnson K P, Brooks B R, Ford C C. et al . Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group. Mult Scler . 2000; 6 255-266
- 73 Ziemssen T, Neuhaus O, Hohlfeld R. Risk-benefit assessment of glatiramer acetate in multiple sclerosis. Drug Saf . 2001; 24 979-990
- 74 Zivadinov R, Rudick R A, De Masi R. et al . Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS. Neurology . 2001; 57 1239-1247
- 75 Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B. Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group. Lancet . 1997; 349 589-593
- 76 Achiron A, Gabbay U, Gilad R. et al . Intravenous immunoglobulin treatment in multiple sclerosis: effect on relapses. Neurology . 1998; 50 398-402
- 77 Sorensen P S, Wanscher B, Jensen C V. et al . Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis. Neurology . 1998; 50 1273-1281
- 78 Lewanska M, Siger-Zajdel M, Selmaj K. No difference in efficacy of two different doses of intravenous immunoglobulins in MS: clinical and MRI assessment. Eur J Neurol . 2002; 9 565-572
- 79 Sorensen P S, Fazekas F, Lee M. Intravenous immunoglobulin G for the treatment of relapsing-remitting multiple sclerosis: a meta-analysis. Eur J Neurol . 2002; 9 557-563
- 80 Hartung H P, Gonsette R, Konig N. et al . Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet . 2002; 360 2018-2025
- 81 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
- 82 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; 244 153-159
- 83 Ghalie R G, 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
- 84 Ghalie R G, Edan G, Laurent M. et al . Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS. Neurology . 2002; 59 909-913
- 85 Yudkin P L, Ellison G W, Ghezzi A. et al . Overview of azathioprine treatment in multiple sclerosis. Lancet . 1991; 338 1051-1055
- 86 Miller D H, Khan O A, Sheremata W A. et al . Controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med . 2003; 348 15-23
- 87 von Andrian H U, Engelhardt B. Alpha4 integrins as therapeutic targets in autoimmune disease. N Engl J Med . 2003; 348 68-72
- 88 European Study Group on Interferon beta-1b in Secondary Progressive MS. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet . 1998; 352 1491-1497
- 89 Goodkin D E. the North American Study Group on Interferon beta-1b in Secondary Progressive MS. Interferon beta-1b in secondary progressive MS: clinical and MRI results of a 3-year randomized controlled trial. Neurology . 2000; 54 2352
- 90 SPECTRIMS Study Group. Randomized controlled trial of interferon- beta-1a in secondary progressive MS: clinical results. Neurology . 2001; 56 1496-1504
- 91 Cohen J A, Cutter G R, Fischer J S. et al . Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology . 2002; 59 679-687
- 92 Weiner H L, Mackin G A, Orav E J. et al . Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. Neurology . 1993; 43 910-918
- 93 The Canadian Cooperative Multiple Sclerosis Study Group. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet . 1991; 337 441-446
- 94 Goodkin D E, Rudick R A, 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 30-40
- 95 Goodkin D E, Rudick R A, VanderBrug Medendorp S, Daughtry M M, Van Dyke C. Low-dose oral methotrexate in chronic progressive multiple sclerosis: analyses of serial MRIs. Neurology . 1996; 47 1153-1157
- 96 Kappos L, Patzold U, Dommasch D. et al . Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis: results of the German multicenter study. Ann Neurol . 1988; 23 56-63
- 97 Rudge P, Koetsier J C, Mertin J. et al . Randomised double blind controlled trial of cyclosporin in multiple sclerosis. J Neurol Neurosurg Psychiatry . 1989; 52 559-565
- 98 The Multiple Sclerosis Study Group. Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. Ann Neurol . 1990; 27 591-605
- 99 Leary S M, Miller D H, Stevenson V L, Brex P A, Chard D T, Thompson A J. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology . 2003; 60 44-51