No Effect on Incidence of Infection After Therapy Switch to Fingolimod

Background: Fingolimod is a once-daily, oral treatment for relapsing forms of multiple sclerosis (MS) that sequesters lymphocytes in the secondary lymphoid organs. In phase 3 studies, fingolimod did not adversely affect infection rates.

Objectives: To investigate the relationship between peripheral lymphocyte counts and infections in patients switching from standard-of-care disease-modifying therapy (DMT) to fingolimod 0.5 mg.

Methods: Eligible patients for the phase 4, multicenter, 6-month study to Evaluate Patient OutComes (EPOC; NCT01216072) had relapsing MS, were fingolimod-naive, and had received ≥6 months’ continuous treatment with a standard DMT (interferon β or glatiramer acetate) before study initiation. Patients were assigned 3:1 to open-label fingolimod 0.5 mg or standard DMT (with no washout) for 6 months. Safety assessments included CD4/CD8 counts and infection reporting. The last post-baseline lymphocyte count assessment was used to analyze 1) lymphocyte count by infection occurrence and 2) infection incidence by lymphocyte count category.

Results: 783 patients switched from DMT to fingolimod 0.5 mg at randomization; 245 continued with a standard DMT (GA, 34.3%; IFNb, 65.6%). Infections were reported by 236 (30.1%) and 68 (27.8%) patients in the fingolimod and DMT groups, respectively. The most common infections were upper respiratory (6.5%), nasopharyngitis (5.5%), and urinary tract (5.1%) in the fingolimod group, and nasopharyngitis (5.3%), sinusitis (4.9%) and urinary tract (4.1%) in the DMT group. At week 24, mean total lymphocyte counts in fingolimod-treated patients who had vs had not reported an infection were 440 cells/mL vs 430 cells/mL (P=0.778), mean CD4+ counts were 72.3 vs 78.1 cells/mL (P=0.751), and mean CD8+ counts were 136.9 vs 121.4 cells/mL (P=0.259). Lymphocyte counts did not significantly differ by occurrence or non-occurrence of specific infection types. In patients with total lymphocyte counts <200, 200-400, >400-600, and >600 cells/mL, the incidence of infection was 33%, 28%, 31%, and 35%.

Conclusions: The overall incidence of infection was similar in the fingolimod and DMT groups in EPOC; this is reminiscent of similar infection rates across treatment groups in the longer duration trials, FREEDOMS and TRANSFORMS. The results of this study do not show a relationship between lymphocyte count, or lymphocyte subset counts, and infection rates. These findings may be explained by the preservation of lymphocyte function during fingolimod treatment (Mehling, et al. Neurology 2008; 71; 1261), including that of naive and central memory T lymphocytes retained in the lymph nodes and that of effector memory T lymphocytes.