Zusammenfassung
Wesentliche Fortschritte auf verschiedenen Gebieten der neuroimmunologischen Forschung haben im letzten Jahrzehnt zu einer deutlichen Erweiterung der zur Verfügung stehenden therapeutischen Möglichkeiten in der Behandlung der multiplen Sklerose geführt. Diese Fortschritte beinhalten ein verbessertes Verständnis zugrunde liegender pathogenetischer Veränderungen, biotechnologische Weiterentwicklungen, aber auch Fortentwicklungen in der Gestaltung klinischer Studien. In dieser Übersicht werden pathophysiologische Aspekte, klinische Rationale sowie die praktische Anwendung etablierter MS-Therapeutika diskutiert.
Abstract
Considerable progress in different fields of neuroimmunological research has led to a major increase in the therapeutic options available for the treatment of multiple sclerosis over the last decade. This progress not only includes advances in our understanding of the pathophysiology of MS, and biotechnological developments but also improvements in clinical trial design. Here, we will review pathophysiological aspects, clinical rationale and practical issues of current MS therapy.
Schlüsselwörter
multiple Sklerose - immunmodulatorische Therapie - Schubtherapie - Eskalationstherapie
Key words
multiple sclerosis - immunomodulatory therapy - relapse therapy - escalation therapy
Literatur
-
1
Multiple Sklerose-Therapie-Konsensus-Gruppe (MSTKG) .
Immunmodulatorische Stufentherapie der Multiplen Sklerose, Aktuelle Therapieempfehlungen (September 2006).
Nervenarzt.
2006;
77
1506-1518
-
2
Grauer O, Offenhausser M, Schmidt J. et al .
[Glucocorticosteroid therapy in optic neuritis and multiple sclerosis. Evidence from clinical studies and practical recommendations].
Nervenarzt.
2001;
72
577-589
-
3
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
-
4
Multiple Sklerose-Therapie-Konsensus-Gruppe (MSTKG) .
Immunmodulatorische Stufentherapie der Multiplen Sklerose.
Nervenarzt.
2002;
73
556-563
-
5
Song I H, Gold R, Straub R H. et al .
New glucocorticoids on the horizon: repress, don't activate!.
J Rheumatol.
2005;
32
1199-1207
-
6
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
-
7
Ruprecht K, Klinker E, Dintelmann T. et al .
Plasma exchange for severe optic neuritis: treatment of 10 patients.
Neurology.
2004;
63
1081-1083
-
8
Schilling S, Linker R A, König F B. et al .
Plasma exchange therapy for steroid-unresponsive multiple sclerosis relapses: clinical experience with 16 patients.
Nervenarzt.
2006;
77
430-438
-
9
Chan A, Gold R.
Can pathological patterns be used to guide individualized multiple sclerosis therapy?.
Nature Clin Practice Neurology.
2006;
2
72-73
-
10
Keegan M, König F, McClelland R. et al .
Multiple sclerosis pathological subtype predicts treatment response to therapeutic plasma exchange.
Lancet.
2005;
366
579-582
-
11
Linker R A, Chan A, Sommer M. et al .
Plasma exchange therapy for steroid-refractory superimposed relapses in secondary progressive multiple sclerosis.
J Neurol.
2007;
254
1288-1289
-
12
Yong V W.
Differential mechanisms of action of interferon-beta and glatiramer acetate in MS.
Neurology.
2002;
59
802-808
-
13
Kappos L, Freedman M S, Polman C H. et al .
Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study.
Lancet.
2007;
370
389-397
-
14
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
-
15
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
-
16
Stuve O, Bennett J L, Hemmer B. et al .
Pharmacological Treatment of Early Multiple Sclerosis.
Drugs.
2008;
68
73-83
-
17
Boskovic R, Wide R, Wolpin J. et al .
The reproductive effects of beta interferon therapy in pregnancy: a longitudinal cohort.
Neurology.
2005;
65
807-811
-
18
Hoffmann L A, Kumpfel T, Heer I, Hohlfeld R.
[Pregnancy and immunomodulatory therapy in multiple sclerosis patients].
Nervenarzt.
2006;
77
663-668, 670
-
19
Hartung H P, Polman C, Bertolotto A. et al .
Neutralising antibodies to interferon beta in multiple sclerosis: expert panel report.
J Neurol.
2007;
254
827-837
-
20
Hemmer B, Stuve O, Kieseier B. et al .
Immune response to immunotherapy: the role of neutralising antibodies to interferon beta in the treatment of multiple sclerosis.
Lancet Neurol.
2005;
4
403-412
-
21
Ziemssen T, Schrempf W.
Glatiramer acetate: mechanisms of action in multiple sclerosis.
Int Rev Neurobiol.
2007;
79
537-570
-
22
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. The Copolymer 1 Multiple Sclerosis Study Group [see comments].
Neurology.
1995;
45
1268-1276
-
23
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
-
24
Filippi M, Rovaris M, Rocca M A. et al .
Glatiramer acetate reduces the proportion of new MS lesions evolving into „black holes”.
Neurology.
2001;
57
731-733
-
25
Filippi M, Wolinsky J S, Comi G.
Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: a multicentre, double-blind, randomised, placebo-controlled study.
Lancet Neurol.
2006;
5
213-220
-
26
Wolinsky J S, Narayana P A, O'Connor P. et al .
Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial.
Ann Neurol.
2007;
61
14-24
-
27
Polman C H, O'Connor P W, Havrdova E. et al .
A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.
N Engl J Med.
2006;
354
899-910
-
28
Krumbholz M, Pellkofer H, Gold R. et al .
Delayed allergic reaction to natalizumab associated with early formation of neutralizing antibodies.
Arch Neurol.
2007;
64
1331-1333
-
29
Hellwig K, Schimrigk S, Fischer M. et al .
Allergic and non-allergic delayed infusion reactions during natalizumab therapy.
Arch Neurol.
2008, im Druck;
-
30
Calabresi P A, Giovannoni G, Confavreux C. et al .
The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL.
Neurology.
2007;
69
1391-1403
-
31
Chan A, Weilbach F X, Toyka K V, Gold R.
Mitoxantrone induces cell death in peripheral blood leucocytes of multiple sclerosis patients.
Clin Exp Immunol.
2005;
139
152-158
-
32
Kopadze T, Dehmel T, Hartung H P. et al .
Inhibition by mitoxantrone of in vitro migration of immunocompetent cells: a possible mechanism for therapeutic efficacy in the treatment of multiple sclerosis.
Arch Neurol.
2006;
63
1572-1578
-
33
Duddy M, Niino M, Adatia F. et al .
Distinct Effector Cytokine Profiles of Memory and Naive Human B Cell Subsets and Implication in Multiple Sclerosis.
J Immunol.
2006;
178
6092-6099
-
34
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
-
35
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 [see comments].
J Neurol Neurosurg Psychiatry.
1997;
62
112-118
-
36
Debouverie M, Vandenberghe N, Morrissey S P. et al .
Predictive parameters of mitoxantrone effectiveness in the treatment of multiple sclerosis.
Mult Scler.
2004;
10
407-412
-
37
Le Page E, Leray E, Taurin G. et al .
Mitoxantrone as induction treatment in aggressive relapsing remitting Multiple Sclerosis: treatment response factors in a 5-year follow-up observational study of 100 consecutive patients.
J Neurol Neurosurg Psychiatry.
2008;
79
52-56
-
38
Morrissey S P, Le Page E, Edan G.
Mitoxantrone in the treatment of multiple sclerosis.
Int MS J.
2005;
12
74-87
-
39
Goffette S, van P V, Vanoverschelde J L. et al .
Severe delayed heart failure in three multiple sclerosis patients previously treated with mitoxantrone.
J Neurol.
2005;
252
1217-1222
-
40
Ramtahal J, Jacob A, Das K, Boggild M.
Sequential maintenance treatment with glatiramer acetate after mitoxantrone is safe and can limit exposure to immunosuppression in very active, relapsing remitting multiple sclerosis.
J Neurol.
2006;
253
1160-1164
-
41
Correale J, Rush C, Amengual A, Goicochea M T.
Mitoxantrone as rescue therapy in worsening relapsing-remitting MS patients receiving IFN-beta.
J Neuroimmunol.
2005;
162
173-183
-
42
Edan G, Comi G, Lebrun D. et al .
The French-Italian Mitoxantrone-Interferon-beta trial: a 3-year randomized study.
Multiple Sclerosis.
2007;
13, Suppl 2
S22-S23
-
43
Soelberg S P.
Intravenous polyclonal human immunoglobulins in multiple sclerosis.
Neurodegener Dis.
2008;
5
8-15
-
44
Haas J, Hommes O R.
A dose comparison study of IVIG in postpartum relapsing-remitting multiple sclerosis.
Mult Scler.
2007;
13
900-908
-
45
Hommes O R, Sorensen P S, Fazekas F. et al .
Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial.
Lancet.
2004;
364
1149-1156
-
46
Palace J, Rothwell P.
New treatments and azathioprine in multiple sclerosis [letter].
Lancet.
1997;
350
261
-
47
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
-
48
Gold R, Jawad A, Miller D H. et al .
Expert opinion: guidelines for the use of natalizumab in multiple sclerosis patients previously treated with immunomodulating therapies.
J Neuroimmunol.
2007;
187
156-158
PD Dr. med. A. Chan
Neurologische Klinik
Ruhr-Universität Bochum
St. Josef-Hospital
Gudrunstr. 56
44791 Bochum
Email: andrew.chan@rub.de
