Abstract
AbstractObjectivesFingolimod (FTY) potentially inhibits the disease activity of multiple sclerosis (MS), but induces severe lymphocytopenia that might be related viral infections, including progressive multifocal leukoencephalopathy. We use a reduced dosage of FTY treatment to avoid its cessation because of lymphocytopenia. FTY inhibits the egress of CD62L+ cells from lymph nodes, and the number of CD4+CD62L+ cells, a major population of CD62L+ cells, in blood is a maker to evaluate the strength of FTY action in patients with MS treated by intermittent drug holidays of FTY.MethodsA total of 24 Japanese patients with MS were treated with variable dosages of FTY initially based on the number of lymphocytes, and then changed to CD4+CD62L+ cell counts as a marker. Fluorescence‐activated cell sorting analysis was used to evaluate the number of CD4+CD62L+ cells in fresh blood of 21 MS patients treated with FTY for 30–94 months, including the mean period of 27.5 months of daily administration.ResultsThe CD4+CD62L+ cell counts and the proportion of patients with <2% CD4+CD62L+ cells in total lymphocytes declined from 12 ± 13 cells/mm3 (median 8 cells/mm3) to 31 ± 4 cells/mm3 (median 27 cells/mm3) and 61.5% to 0%, respectively, after further dosage reduction. Their annual relapse rates were kept to <0.03, even after inducing CD4+CD62L+ counts as a monitoring marker. The target range of CD4+CD62L+cells on reduction of FTY dosage was 10–80 cells/mm3.ConclusionsIt is critical to monitor CD4+CD62L+ cells rather than total lymphocyte count to avoid excessive FTY administration.
Published Version
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