Cellular composition of peripheral blood mononuclear cells during 4 years long-term treatment with fingolimod (P5.364)

Objective: Aim of thison-going study is a long term assessment of changes in the cellular compositionof peripheral blood mononuclear cells (PBMCs) with a focus on CD4+ and CD8+ Tcell subpopulations, as well as B cells, monocytes and NK cells at month 48 orlater (M48) compared to month 6 (M6) and baseline after treatment initiation with fingolimod. Background: Fingolimodinhibits the sphingosine-1-phosphate-dependent egress from secondary lymphoid tissues resulting in lymphopenia. Design/Methods: Extension study at M48 aiming to including a minimum of 120 patients of the initial study(CFTY720DDE01); the latter was a M6 open-label, multi-center, single-arm study, including 445 patients with relapsing remitting MS treated with fingolimod. Leukocyte surface expression markers of PBMCs were analysed by flow cytometry (CD3, CD4, CD8, CD14, CD19, CD45RA, CD56, CCR6, CCR7). Results: Preliminary analysis of 98 patients (62.6% female) with mean age of 39.7 years, mean EDSS of 2.8, and treatment duration with fingolimod of ≥48 months. Flow cytometry revealed that the predominant decrease of naiveCCR7+ CD45RA+ T cells within the CD4 or CD8 subpopulation noted at M6 of the initial study persisted at M48; CD4: −83 % (95% CI −90% to −76%); CD8: −93 % (95%CI −90 to −96.0), results reported as mean % change from baseline. A spreviously noted at M6, effect or memory (CCR7-/CD45RA-) T cells were relatively preserved (M48: CD4: +72% (95% CI +60% to +84%); CD8: −10% (−31% to +10%)). While the relative number of B cells among lymphocytes where also decreasing (M48: −56%(−65% to −46%)), CD14+ monocytes and CD56+ NK cells relatively increased. Conclusions: Changes to the cellular composition of PBMCs, previously noted at M6 of therapy with fingolimod, persist during continued therapy at M48. Study Supported by: Study support:Novartis (CFTY720DDE01E1). Disclosure: Dr. Dehmel has received personal compensation for activities with Biogen. Dr. Heininger has nothing to disclose. Dr. Pleiser has nothing to disclose. Dr. Seibert has nothing to disclose. Dr. Putzki has received personal compensation for activities with Novartis Pharma AG as an employee. Dr. Kieseier holds stock and/or stock options in Biogen. Dr. Aktas has received personal compensation for activities with Bayer, Biogen, Chugai, Genzyme, Novartis, Roche, Teva, and MedImmune as an advisor. Dr. has received personal compensation in an editorial capacity for CML Multiple Sclerosis. Dr. Hartung has received personal compensation from Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme as a speaker and consultant.