Fingolimod Therapy for Multiple Sclerosis

Mary A. Willis, MD; Jeffrey A. Cohen, MD


Semin Neurol. 2013;33(1):37-44. 

In This Article

Abstract and Introduction


Because of its potent efficacy and oral route of administration, the approval of fingolimod as treatment for relapsing-remitting multiple sclerosis (MS) was highly anticipated. The therapeutic and adverse effects are mediated by modulation of sphingosine 1-phosphate receptors. Fingolimod inhibits the egress of lymphocytes from lymph nodes and may also have direct effects on the central nervous system. The clinical trials that led to the approval of fingolimod demonstrated benefit on relapses, disability progression, magnetic resonance imaging (MRI) activity, and brain volume loss in treatment-naïve and previously treated patients with relapsing-remitting MS. The use of fingolimod in clinical practice has been limited by concerns for cardiac effects, infection, and macular edema as well as the relative lack of long-term safety data for this drug with a novel mechanism of action. Additional clinical trial and postmarketing data suggest that fingolimod is a safe, effective, and well-tolerated treatment option when patients are selected and monitored appropriately.


Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) most often characterized by relapsing-remitting (RR) symptoms at the onset, followed by secondary progression. Inflammatory tissue damage mediated by autoreactive T cells is thought to initiate lesion formation. Variable remyelination and axonal loss result in accumulation of physical and cognitive disability. All currently approved disease-modifying therapies aim to prevent clinical relapses and limit magnetic resonance imaging (MRI) changes by modulating the inflammatory response in some way.

Until recently, all therapeutic options for RRMS required parenteral administration. Despite excellent long-term safety profiles, patient compliance with first-line drugs—interferon beta (IFNβ) and glatiramer acetate (GA)—is limited by modest efficacy, frequent injections, and bothersome side effects. The U.S. Food and Drug Administration (FDA) approval of fingolimod (FTY720; Gilenya, Novartis, Basel, Switzerland) in September 2010, the first oral disease-modifying therapy, generated much interest among both patients and physicians.

The role of fingolimod in MS treatment continues to evolve. In this review, we describe the immunologic and CNS effects of fingolimod and the clinical trial evidence for its efficacy. We then discuss the issues to be considered in safe use of fingolimod for patients with RRMS.