Interferontherapie in der multiplen Sklerose: früh oder spät

Zusammenfassung

Für die Behandlung der schubförmig verlaufenden MS stehen inzwischen mehrere therapeutische Optionen zur Verfügung, wobei die Behandlung mit immunmodulatorischen Substanzen inzwischen zum Standard geworden ist. Auch diese Therapien sind jedoch nur partiell wirksam sowie relativ teuer und müssen über Jahre oder gar lebenslang appliziert werden. Über die therapeutischen Langzeiteffekte sowie die möglichen Nebenwirkungen einer Dauertherapie ist nach wie vor wenig bekannt. Demgegenüber zeigen prospektiv durchgeführte epidemiologische Studien immer deutlicher, dass nur ein kleiner Teil der MS-Patienten mit einem gutartigen Verlauf rechnen darf. Jüngere Therapiestudien in chronischen Phasen der Erkrankung stärken ferner die These, dass insbesondere immunmodulatorische Therapien in späteren Erkrankungsstadien nur noch begrenzt oder gar nicht mehr wirksam sind, ihre maximale Effektivität am ehesten jedoch zu Beginn - während der überwiegend inflammatorischen Phase - der Erkrankung zeigen. Darüber hinaus belegen histopathologische sowie kernspintomographische Studien, dass es bereits zu Beginn der Erkrankung zu axonalen Schädigungen kommt. Es mehren sich daher die Stimmen, die einen möglichst frühen Therapiebeginn favorisieren. Dieser Artikel diskutiert aktuelle Daten und Argumente, die für und gegen eine frühzeitige Behandlung sprechen.

Abstract

For the treatment of remitting-relapsing MS (RRMS) several different therapeutical options are now available with immunomodulatory drugs as the standard of current therapy. The treatment with immunomodulatory drugs, however, is only partially effective, relatively expensive and has to be administered for years or even life long. So far, little is known about both, long-term treatment and long-term side effects. On the other hand, long-term epidemiological studies clearly suggest that only a small percentage of patients may hope for a benign course of the disease. Moreover, recent subgroup analysis of clinical trials support the hypothesis that immunomodulatory drugs are less or not at all effective in later stages of the disease but appear to be most effective in earlier, more inflammatory driven phases. Furthermore, histopathological as well as MRI-studies indicate that axonal damage is present even in early stages of the disease. Therefore, the concept of early treatment is gaining further support. Critical voices, however, are calling this concept into question, mainly because of high cost and missing long-term data. This article discusses current data and different arguments for and against the concept of early treatment.

Literatur

• 1 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
• 2 Hawkins S A, McDonnell G V. Benign multiple sclerosis? Clinical course, long-term follow-up, and assessment of prognostic factors.  J Neurol Neurosurg Psychiatry. 1999;  67 148-152
• 3 Runmarker B, Andersen O. Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up.  Brain. 1993;  116 117-134
• 4 Weinshenker B G, Rice G P, Noseworthy J H. et al . The natural history of multiple sclerosis: a geographically based study. 3. Multivariate analysis of predictive factors and models of outcome.  Brain. 1991;  114 1045-1056
• 5 Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in Multiple Sclerosis.  N Engl J Med. 2000;  343 1430-1438
• 6 Achiron A, Barak Y. Multiple sclerosis - from probable to definite diagnosis: a 7-year prospective study.  Arch Neurol. 2000;  57 974-979
• 7 O'Riordan J I, Thompson A J, Kingsley D PE. et al . The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up.  Brain. 1998;  121 495-503
• 8 Sailer M, O'Riordan J I, Thompson A J. et al . Quantitative MRI in patients with clinically isolated syndroms suggestive of demyelinisation.  Neurology. 1999;  52 599-606
• 9 Brex P A, Ciccarelli O, O'Riordan J I. et al . A longitudinal study of abnormalities on MRI and disability from multiple sclerosis.  N Engl J Med. 2002;  346 158-164
• 10 Furgeson B, Matyzak M K, Esiri M M. et al . Axonal damage in acute multiple sclerosis lesions.  Brain. 1997;  120 393-399
• 11 Kornek B, Storch M K, Weissert R. et al . Multiple Sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions.  Am J Pathol. 2000;  157 267-276
• 12 Trapp B D, Peterson J, Ransohoff R M. et al . Axonal transection in the lesions of multiple sclerosis.  N Engl J Med. 1998;  338 278-285
• 13 Bitch A, Schuchardt J, Bunkowski S. et al . Acute axonal injury in multiple sclerosis.  Brain. 2000;  123 1289-1292
• 14 Poser C M, Paty D W, Scheinberg L. et al . New diagnostic criteria for multiple sclerosis: guidelines for research protocols.  Ann Neurol. 1983;  13 227-231
• 15 Chang A, Tourtellotte W W, Rudnick R, Trapp B D. Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis.  N Eng J Med. 2002;  346 165-173
• 16 McFarland H F, Frank J A, Albert P S. et al . Using gadolinium-enhanced magnetic resonance imaging lesions to monitor disease activity in multiple sclerosis.  Annals of Neurol. 1992;  32 758-766
• 17 Rudick R A, Coofair D L, Simonian N. et al . Cerebrospinal fluit abnormalities in a phase III trial of Avonex (IFNβ-1a) for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group.  J Neuroimmunol. 1999;  93 8-14
• 18 Simon J H, Jacobs L D, Campion M K. et al . A longitudinal study of brain atrophy in relapsing multiple sclerosis.  Neurology. 1999;  53 139-148
• 19 Rudick R A, Fisher E, Lee J C. et al . Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group.  Neurology. 1999;  53 1698-1704
• 20 Fisher E, Rudick R A, Cutter G. et al . Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients.  Mult Scler. 2000;  6 373-377
• 21 Brex P A, Jenkins R, Fox N C. et al . Detection of ventricular enlargement in patients at the earliest clinical stage of MS.  Neurology. 2000;  54 1689-1691
• 22 Arnold D L. Magnetic resonance spectroscopy: imaging axonal damage in MS.  J Neuroimmunology. 1999;  98 2-6
• 23 Bjartmar C, Kidd G, Mork S. et al . Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl-aspartate in chronic multiple sclerosis patients.  Ann Neurol. 2000;  48 893-901
• 24 De Stefano N, Narayanan S, Francis G S. et al . Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability.  Arch Neurol. 2001;  58 65-70
• 25 Brex P A, Gomez-Anson B, Parker G J. et al . Proton MR spectroscopy in clinically isolated syndromes suggestive of multiple sclerosis.  J Neurol Sci. 1999;  166 16-22
• 26 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;  28 898-904
• 27 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
• 28 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
• 29 Kappos L. and the European Study group on Interferon beta-1b in secondary - progressive MS . Placebo-controlled multicentre randomized trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis.  Lancet. 1998;  352 1491-1497
• 30 Molyneux P D, Kappos L, Polman C. et al . The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study group on interferon beta-1b in secondary progressive multiple sclerosis.  Brain. 2000;  123 2256-2263
• 31 Goodkin D E. and the Northamerican 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 randomised controlled trial.  Neurology. 2000;  54 2352
• 32 Secondary progressive efficacy trial of recombinant interferon-beta-1a in MS study group . Randomized controlled trial of interferon-beta-1a in secondary progressive MS - clinical results.  Neurology. 2001;  56 1496-1504
• 33 Cohen J A, Goodman A D, Heidenreich F R. et al . Benefit of interferon (beta)-1a on MSFC progression in secondary progressive MS.  Neurology. 2002;  59 679-687
• 34 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 1277-1285
• 35 MS-Therapie Konsensus Gruppe (MSTKG) . Immunmodulatorische Stufentherapie der multiplen Sklerose.  Nervenarzt. 1999;  70 371-386
• 36 MS-Therapie Konsensus Gruppe (MSTKG) . Immunmodulatorische Stufentherapie der multiplen Sklerose. 1. Ergänzung: Dezember 2000.  Nervenarzt. 2001;  72 150-157
• 37 MS-Therapie Konsensus Gruppe (MSTKG) . Immunmodulatorische Stufentherapie der multiplen Sklerose. Neue Aspekte und praktische Umsetzung.  Nervenarzt. 2002;  73 556-563
• 38 Goodin D S, Frohman E M, Garmany G P. 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