Longterm Fingolimod Treatment of Multiple Sclerosis Induces Phenotypical Immunsenescence (P2.082)

OBJECTIVE: To determine changes of lymphocyte counts (CD4 and CD8 T cells, B cells and their subtypes) in the peripheral blood of patients with multiple sclerosis treated for an extended period with fingolimod (MSFin) compared to healthy controls (HC). BACKGROUND: Fingolimod induces profound short-term changes in circulating lymphocyte composition, but long-term effects are less well characterized. DESIGN/METHODS: Lymphocyte differentiation of whole-blood samples was performed by multiparameter FACS. MSFin (n=9, mean age: 44.67±7.58years, sex: 5F/4M, continuously treated for 51-64 months) were compared to HC (n=15, mean age: 47.87±9.30years, sex: 9F/6M). RESULTS: Absolute counts of CD4 and CD8 T cells and B cells were very low in MSFin (CD4: 48.33±61.34/μl vs. 856.73±249.19/μl; CD8: 97.89±79.39/μl vs. 394.33±172.97/μl; CD19: 8.00±6.06/μl vs. 187.13±123.42/μl). Among T cells, MSFin had a striking decrease of recent thymic emigrants (RTEs; 1.82±0.97[percnt] vs. 19.20±8.12[percnt]) and naive T cells (0.92±1.14[percnt] vs. 28.55±8.43[percnt]), while the percentage of effector (36.99±14.69[percnt] vs. 28.15±13.00[percnt]) and effector memory T cells (65.49±19.79[percnt] vs. 37.43±7.40[percnt]) was accordingly higher. Regulatory T cells (CD25high) were decreased in MSFin (28.4±22.7/μl vs. 648.00±178.00μl). Among B cells, in contrast, the percentage of immature B cells was increased, while naive and memory B cells were reduced. CONCLUSIONS: Fingolimod induces, in the long term, phenotypic changes similar to immunsenescence in elderly persons. As one consequence, such patients should be evaluated for completeness of vaccinations. While few severe infections have been reported with fingolimod treatment, surveillance for possible reactivation of chronic infections should continue. Disclosure: Dr. Schwanitz has nothing to disclose. Dr. Boldt has nothing to disclose. Dr. Stoppe has nothing to disclose. Dr. Orthgiess has nothing to disclose. Dr. Borte has nothing to disclose. Dr. Sack has nothing to disclose. Dr. Then Bergh has received personal compensation for activities with Biogen Idec, Novartis, Merck Serono, and Sanofi-Aventis Pharmaceuticals, Inc. as a speaker and/or advisory board member.