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24 - Neutralizing antibodies directed against biologic agents to treat multiple sclerosis

from Section II - Clinical trial methodology

Published online by Cambridge University Press:  05 December 2011

By
Per Soelberg Sørensen
Edited by
Jeffrey A. Cohen  and
Richard A. Rudick
Jeffrey A. Cohen
Affiliation:
Cleveland Clinic
Richard A. Rudick
Affiliation:
Cleveland Clinic
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Summary

In vitro, two different classes of antibodies are recognized according to the assay used to identify them: binding antibodies (BAbs) and neutralizing antibodies (NAbs). There is emerging agreement that NAbs are correlated with reduced therapeutic efficacy of IFNβ. None of the pivotal trials in relapsing-remitting multiple sclerosis (MS) showed an effect of NAbs on disease progression. Among the therapeutic monoclonal antibodies natalizumab, alemtuzumab, and daclizumab are humanized monoclonal antibodies, whereas rituximab is a mouse-human chimeric antibody. NAbs are associated with reduction of the therapeutic effect of IFNβ, and patients with persistent high titers of NAbs should be switched to an alternative therapy. Patients with low or intermediate titers should have their IFN bioactivity measured with an in vivo mRNA MxA induction test. Patients with repeated abrogation of the mRNA MxA response to IFN injections should be switched to another therapy.

Keywords

multiple sclerosisnormal appearing brain tissueblood-brain-barriergray mattermagnetic resonance imagingbrain atrophy
Type
Chapter
Information
Multiple Sclerosis Therapeutics , pp. 287 - 299
Publisher: Cambridge University Press
Print publication year: 2011

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