Analysis of Peripheral Blood Mononuclear Cell Phenotypes during Treatment with Fingolimod: A 2-Year Study of a German Cohort of Patients with Relapsing-Remitting Multiple Sclerosis (P3.097)

BACKGROUND/OBJECTIVE: Fingolimod inhibits the sphingosine-1-phosphate-dependent lymphocyte egress from secondary lymphoid tissues. This inhibition results in peripheral lymphopenia. Lymphocyte counts below 0.2x109/L are defined as a criterion for therapy discontinuation. We here present data on the remaining pool of peripheral blood mononuclear cells (PBMC) in patients with RRMS over a 2-year treatment period with fingolimod. METHODS: Single center study with RRMS patients receiving 0.5 mg fingolimod on a daily oral dose. Peripheral venous blood samples were obtained at baseline, 1, 4, 6, 12, 18 and 24 months of therapy. Leucocyte surface marker expression was analysed by flow cytometric analysis (CD3, CD4, CD8, CD16, CD19, CD45RA, CD56, CCR7 surface markers were determined). Additionally, patient sera samples were studied for immunoglobulin levels (IgG, IgM, IgA, IgE). RESULTS: The relative number of CD45+, CD4+, and CD19+ positive cells decreased after 1 month of therapy, and remained at low levels for the treatment period of 24-months. Among the CD3 positive cell population, naive T cells (CCR7+/CD45RA+) were preferentially reduced, while effector memory T cells (CCR7-/CD45RA-) were relatively preserved. A mild decrease was noted for IgG and IgM levels at month 6 of therapy. CONCLUSIONS: The findings are consistent with previous observations in our cohort seen for earlier timepoints, with a preferential effect of fingolimod on the CD4+ subpopulation, and the naive T cells, while effector memory T cells are relatively spared. The mild decrease noted for Ig levels at 6 months currently is further evaluated. Biomarkers predicting clinical efficacy and/or safety signals have not yet been identified, and warrant further analyses and studies. Disclosure: Dr. Dehmel has received personal compensation for activities with Biogen as travel expense. Dr. Ingenhoven has nothing to disclose. Dr. Frenken has nothing to disclose. Dr. Hermsen has nothing to disclose. Dr. Hartung has received personal compensation for activities with from Bayer, Biogen, GeNeuro, Genzyme as speaker, committee member, consultant. Dr. Kieseier holds stock and/or stock options in Biogen, which sponsored research in which Dr. Kieseier was involved as an investigator. Dr. Warnke has received personal compensation in an editorial capacity for CML Multiple Sclerosis.