Intrathecal effects of daclizumab treatment of multiple sclerosis

B. Bielekova, N. Richert, M. L. Herman, J. Ohayon, T. A. Waldmann, H. McFarland, R. Martin, G. Blevins

Research output: Contribution to journalArticle

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-± and that this response correlated with expansion ofCD56bright 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-remittingMS(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 CD56bright 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.

Original languageEnglish (US)
Pages (from-to)1877-1886
Number of pages10
JournalNeurology
Volume77
Issue number21
DOIs
StatePublished - Nov 22 2011
Externally publishedYes

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Multiple Sclerosis
Natural Killer Cells
Therapeutics
Interleukin-12 Subunit p40
Antibodies, Monoclonal, Humanized
Interferons
Nervous System
Multicenter Studies
daclizumab
Cells
Epitopes
Immune System
B-Lymphocytes
Biomarkers
Placebos
T-Lymphocytes
Brain
Lesion
Blood

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Bielekova, B., Richert, N., Herman, M. L., Ohayon, J., Waldmann, T. A., McFarland, H., ... Blevins, G. (2011). Intrathecal effects of daclizumab treatment of multiple sclerosis. Neurology, 77(21), 1877-1886. https://doi.org/10.1212/WNL.0b013e318239f7ef

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.

In: Neurology, Vol. 77, No. 21, 22.11.2011, p. 1877-1886.

Research output: Contribution to journalArticle

Bielekova, B, Richert, N, Herman, ML, Ohayon, J, Waldmann, TA, McFarland, H, Martin, R & Blevins, G 2011, 'Intrathecal effects of daclizumab treatment of multiple sclerosis', Neurology, vol. 77, no. 21, pp. 1877-1886. https://doi.org/10.1212/WNL.0b013e318239f7ef
Bielekova B, Richert N, Herman ML, Ohayon J, Waldmann TA, McFarland H et al. Intrathecal effects of daclizumab treatment of multiple sclerosis. Neurology. 2011 Nov 22;77(21):1877-1886. https://doi.org/10.1212/WNL.0b013e318239f7ef
Bielekova, B. ; Richert, N. ; Herman, M. L. ; Ohayon, J. ; Waldmann, T. A. ; McFarland, H. ; Martin, R. ; Blevins, G. / Intrathecal effects of daclizumab treatment of multiple sclerosis. In: Neurology. 2011 ; Vol. 77, No. 21. pp. 1877-1886.
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