Safety and efficacy of reduced fingolimod dosage treatment

Abstract

Background: Oral fingolimod is a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes. Fingolimod reduces relapse rate and delays disability progression in patients with relapsing forms of multiple sclerosis (MS). Elevation of liver function tests (LFTs) and reduction in peripheral-blood lymphocyte counts were among the most common adverse events reported in phase II, phase III, and extension studies. Objective: To describe eight patients in whom fingolimod dose was reduced to every other day (n=6) or every third day (n=2) due to increased LFTs more than 3 times the upper limit of normal (ULN) (n=2) or decreased lymphocyte count by ≤0.2×109/L (n=6). Results: Fingolimod dose reduction resulted in reversal of laboratory abnormalities. Clinically, none of the 8 patients developed clinical relapses, but five patients had new lesions on magnetic resonance imaging (MRI), one of whom with disability progression, and one patient converted to secondary progressive MS (SPMS). Conclusion: Reducing the frequency of fingolimod administration can reverse laboratory abnormalities but may have a negative impact on drug efficacy. © 2015 Elsevier B.V.