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Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis
Author(s) -
Grove R. A.,
Shackelford S.,
Sopper S.,
Pirruccello S.,
Horrigan J.,
Havrdova E.,
Gold M.,
Graff O.
Publication year - 2013
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12097
Subject(s) - medicine , cerebrospinal fluid , multiple sclerosis , cd8 , lymphocyte , cd19 , immunology , flow cytometry , immune system , gastroenterology
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). CD 4+, CD 8+ T‐ and CD 19+ B‐lymphocyte counts followed a similar pattern. Minimal changes were observed for CD 3− CD 16+ CD 56+ natural killer cells. Median CD 4 : CD 8 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 CD 4 : CD 8 ratios. Conclusions Firategrast treatment was associated with modest decreases in median CSF total, CD 4, CD 8 and CD 19 lymphocyte counts. The generally small magnitude of decreases suggests that sufficient numbers of lymphocytes can access the subarachnoid space, preserving CNS immune surveillance.