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January 05, 2010; 74 (1 Supplement 1) Articles

Mitoxantrone and cytotoxic drugs' mechanisms of action

Timothy Vollmer, Thomas Stewart, Nancy Baxter
First published December 28, 2009, DOI: https://doi.org/10.1212/WNL.0b013e3181c97f5a
Timothy Vollmer
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Thomas Stewart
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Nancy Baxter
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Mitoxantrone and cytotoxic drugs' mechanisms of action
Timothy Vollmer, Thomas Stewart, Nancy Baxter
Neurology Jan 2010, 74 (1 Supplement 1) S41-S46; DOI: 10.1212/WNL.0b013e3181c97f5a

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Abstract

Evidence has suggested that early, aggressive intervention may improve both short- and long-term outcomes in patients with multiple sclerosis (MS). Cytotoxic agents may offer advantages in this setting, particularly when used as an induction or add-on therapy with immunomodulators. Immunosuppression is the mechanism of action common to all cytotoxic drugs; individual subtleties in immunoregulatory actions are likely of minor importance. In the United States, mitoxantrone is currently the only cytotoxic agent approved for the treatment of MS (secondary-progressive, progressive-relapsing, and worsening relapsing-remitting forms). Therapies in phase III development include cyclophosphamide, mycophenolate mofetil, cladribine, and teriflunomide. All these drugs have exhibited efficacy in controlled clinical trials, although the degree of benefit with respect to MRI and clinical endpoints has varied both within and among the various agents. Further investigations are needed to determine whether cytotoxic drugs represent a substantial improvement over treatments that have a more targeted impact on the immune system.

Glossary

ACTH=
adrenocorticotropic hormone;
CIS=
clinically isolated syndrome;
EDSS=
Expanded Disability Status Scale;
CI=
confidence interval;
GA=
glatiramer acetate;
RRMS=
relapsing-remitting MS;
MS=
multiple sclerosis;
MSFC=
Multiple Sclerosis Functional Composite;
IFN=
interferon;
IL=
interleukin.
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  • Article
    • Abstract
    • Glossary
    • INTRODUCTION
    • Efficacy of cytotoxic agents in MS
    • TOXICITIES OF CYTOTOXIC DRUGS IN MS
    • MECHANISMS OF ACTION OF CYTOTOXIC DRUGS IN MS
    • KEY LEARNINGS FROM STUDIES OF CYTOTOXIC DRUGS IN MS
    • CONCLUSION
    • DISCLOSURE
    • Footnotes
    • REFERENCES
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