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Intrathecal effects of daclizumab treatment of multiple sclerosis


Bielekova, B; Richert, N; Herman, M L; Ohayon, J; Waldmann, T A; McFarland, H; Martin, R; Blevins, G (2011). Intrathecal effects of daclizumab treatment of multiple sclerosis. Neurology, 77(21):1877-1886.

Abstract

OBJECTIVES:

We previously reported that daclizumab, a humanized monoclonal antibody against CD25, reduced contrast-enhancing lesions (CEL) in patients with multiple sclerosis (MS) who were suboptimal responders to interferon-β and that this response correlated with expansion of CD56(bright) NK cells. These data have been reproduced in a placebo-controlled multicenter trial (CHOICE study). The current study investigates whether daclizumab monotherapy reduces CEL in untreated patients with relapsing-remitting MS (RRMS) and the effects of daclizumab on the intrathecal immune system.
METHODS:

Sixteen patients with RRMS with high inflammatory activity were enrolled in an open-label, baseline-vs-treatment, phase II trial of daclizumab monotherapy for 54 weeks and followed by serial clinical and MRI examinations and immunologic biomarkers measured in the whole blood and CSF.
RESULTS:

The trial achieved predefined outcomes. There was an 87.7% reduction in brain CEL (primary) and improvements in Multiple Sclerosis Functional Composite (secondary), Scripps Neurologic Rating Scale, and Expanded Disability Status Scale (tertiary) outcomes. There was significant expansion of CD56(bright) NK cells in peripheral blood and CSF, with resultant decrease in T cells/NK cells and B cells/NK cells ratios and IL-12p40 in the CSF. Surprisingly, CD25 Tac epitope was equally blocked on the immune cells in the CSF and in peripheral blood.
CONCLUSIONS:

Daclizumab monotherapy inhibits formation of MS plaques in patients with RRMS and immunoregulatory NK cells may suppress activation of pathogenic immune responses directly in the CNS compartment.
CLASSIFICATION OF EVIDENCE:

The study provides Class III evidence that daclizumab reduces the number of contrast-enhancing lesions in treatment-naive patients with RRMS over a 54-week period.

OBJECTIVES:

We previously reported that daclizumab, a humanized monoclonal antibody against CD25, reduced contrast-enhancing lesions (CEL) in patients with multiple sclerosis (MS) who were suboptimal responders to interferon-β and that this response correlated with expansion of CD56(bright) NK cells. These data have been reproduced in a placebo-controlled multicenter trial (CHOICE study). The current study investigates whether daclizumab monotherapy reduces CEL in untreated patients with relapsing-remitting MS (RRMS) and the effects of daclizumab on the intrathecal immune system.
METHODS:

Sixteen patients with RRMS with high inflammatory activity were enrolled in an open-label, baseline-vs-treatment, phase II trial of daclizumab monotherapy for 54 weeks and followed by serial clinical and MRI examinations and immunologic biomarkers measured in the whole blood and CSF.
RESULTS:

The trial achieved predefined outcomes. There was an 87.7% reduction in brain CEL (primary) and improvements in Multiple Sclerosis Functional Composite (secondary), Scripps Neurologic Rating Scale, and Expanded Disability Status Scale (tertiary) outcomes. There was significant expansion of CD56(bright) NK cells in peripheral blood and CSF, with resultant decrease in T cells/NK cells and B cells/NK cells ratios and IL-12p40 in the CSF. Surprisingly, CD25 Tac epitope was equally blocked on the immune cells in the CSF and in peripheral blood.
CONCLUSIONS:

Daclizumab monotherapy inhibits formation of MS plaques in patients with RRMS and immunoregulatory NK cells may suppress activation of pathogenic immune responses directly in the CNS compartment.
CLASSIFICATION OF EVIDENCE:

The study provides Class III evidence that daclizumab reduces the number of contrast-enhancing lesions in treatment-naive patients with RRMS over a 54-week period.

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35 citations in Web of Science®
34 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:14 Jan 2012 15:14
Last Modified:05 Apr 2016 15:18
Publisher:American Academy of Neurology
ISSN:0028-3878
Publisher DOI:10.1212/WNL.0b013e318239f7ef
PubMed ID:22076546
Permanent URL: http://doi.org/10.5167/uzh-54017

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