Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis
Article first published online: 18 FEB 2013
© 2013 The Author(s) European Journal of Neurology © 2013 EFNS
European Journal of Neurology
Volume 20, Issue 7, pages 1032–1042, July 2013
How to Cite
Grove, R. A., Shackelford, S., Sopper, S., Pirruccello, S., Horrigan, J., Havrdova, E., Gold, M. and Graff, O. (2013), Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis. European Journal of Neurology, 20: 1032–1042. doi: 10.1111/ene.12097
- Issue published online: 10 JUN 2013
- Article first published online: 18 FEB 2013
- Manuscript Accepted: 11 DEC 2012
- Manuscript Received: 11 MAY 2012
- Czech Ministry of Education
- GlaxoSmithKline. Grant Number: 0021620849
- integrin antagonists;
- multiple sclerosis;
- progressive multifocal leukoencephalopathy
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.
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.
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.
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.