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Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis.

Publication ,  Journal Article
Grove, RA; Shackelford, S; Sopper, S; Pirruccello, S; Horrigan, J; Havrdova, E; Gold, M; Graff, O
Published in: Eur J Neurol
July 2013

BACKGROUND AND PURPOSE: Firategrast is an orally bioavailable alpha4 beta1/alpha4 beta7 integrin antagonist designed to reduce trafficking of lymphocytes into the central nervous system (CNS). This could decrease multiple sclerosis (MS) activity, but may compromise CNS immune surveillance. We aimed to quantitate the effect of firategrast treatment on cerebrospinal fluid (CSF) lymphocyte count and the extent/speed of recovery after its discontinuation. METHODS: Forty-six subjects with relapsing forms of MS were treated for up to 24 weeks with open-label firategrast, 900 (females) or 1200 (males) mg twice daily. CSF and blood cell counts, and lymphocyte composition were determined using flow cytometry. RESULTS: Median (n, range) CSF lymphocyte counts (cells/µl) at weeks 0, 24, 28 and 36 were: 5.3 (44, 0.3-70.2), 3.3 (31, 0.0-99.0), 3.0 (32, 0.0-58.2) and 3.5 (29, 0.0-274.8). CD4+, CD8+ T- and CD19+ B-lymphocyte counts followed a similar pattern. Minimal changes were observed for CD3-CD16+CD56+ natural killer cells. Median CD4 : CD8 ratios were: 2.9 (41, 1.1-10.9), 2.2 (29, 0.6-5.9), 3.8 (28, 1.6-9.0) and 3.8 (21, 2.1-9.4). Blood lymphocyte counts were elevated at weeks 4 and 24, consistent with the mechanism of firategrast, and returned to baseline when firategrast was discontinued. There were minimal changes in CD4 : CD8 ratios. CONCLUSIONS: Firategrast treatment was associated with modest decreases in median CSF total, CD4, CD8 and CD19 lymphocyte counts. The generally small magnitude of decreases suggests that sufficient numbers of lymphocytes can access the subarachnoid space, preserving CNS immune surveillance.

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Published In

Eur J Neurol

DOI

EISSN

1468-1331

Publication Date

July 2013

Volume

20

Issue

7

Start / End Page

1032 / 1042

Location

England

Related Subject Headings

  • Treatment Outcome
  • Neurology & Neurosurgery
  • Multiple Sclerosis, Relapsing-Remitting
  • Middle Aged
  • Male
  • Lymphocyte Count
  • Leukocyte Count
  • Integrins
  • Integrin alpha4beta1
  • Humans
 

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Grove, R. A., Shackelford, S., Sopper, S., Pirruccello, S., Horrigan, J., Havrdova, E., … Graff, O. (2013). Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis. Eur J Neurol, 20(7), 1032–1042. https://doi.org/10.1111/ene.12097
Grove, R. A., S. Shackelford, S. Sopper, S. Pirruccello, J. Horrigan, E. Havrdova, M. Gold, and O. Graff. “Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis.Eur J Neurol 20, no. 7 (July 2013): 1032–42. https://doi.org/10.1111/ene.12097.
Grove RA, Shackelford S, Sopper S, Pirruccello S, Horrigan J, Havrdova E, et al. Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis. Eur J Neurol. 2013 Jul;20(7):1032–42.
Grove, R. A., et al. “Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis.Eur J Neurol, vol. 20, no. 7, July 2013, pp. 1032–42. Pubmed, doi:10.1111/ene.12097.
Grove RA, Shackelford S, Sopper S, Pirruccello S, Horrigan J, Havrdova E, Gold M, Graff O. Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis. Eur J Neurol. 2013 Jul;20(7):1032–1042.
Journal cover image

Published In

Eur J Neurol

DOI

EISSN

1468-1331

Publication Date

July 2013

Volume

20

Issue

7

Start / End Page

1032 / 1042

Location

England

Related Subject Headings

  • Treatment Outcome
  • Neurology & Neurosurgery
  • Multiple Sclerosis, Relapsing-Remitting
  • Middle Aged
  • Male
  • Lymphocyte Count
  • Leukocyte Count
  • Integrins
  • Integrin alpha4beta1
  • Humans