Fingolimod for the treatment of relapsing multiple sclerosis

Abstract

Fingolimod is the first oral agent approved in the USA for the treatment of relapsing forms of multiple sclerosis. Fingolimod is a sphingosine 1-phosphate receptor modulator that binds to sphingosine 1-phosphate receptors on lymphocytes, resulting in a downregulation of the receptor and a reversible sequestration of lymphocytes in lymphoid tissue. Effector memory T cells are not sequestered so that immune surveillance may be minimally affected. Two large-scale Phase III clinical trials have demonstrated the efficacy of fingolimod compared with placebo and intramuscular interferon β-1a in relapsing–remitting multiple sclerosis. Due to its mechanism of action, fingolimod administration may be associated with first-dose bradycardia and macular edema. Therefore, patients should be observed for 6 h at the time of their first dose and undergo ophthalmologic evaluation prior to treatment initiation and at 3–4 months after initiation.

Keywords::

• administration recommendations
• efficacy
• fingolimod
• immunomodulatory
• mechanism of action
• oral
• relapsing–remitting multiple sclerosis
• safety
• sphingosine 1-phosphate receptor

Acknowledgements

The authors would like to thank Fran Karo, PhD, and Amy Zannikos, PharmD, of Oxford PharmaGenesis for their editorial assistance.

Financial & competing interests disclosure

Douglas R Jeffery has received honoraria for speaking and consulting and research support from Novartis, Bayer, Biogen-Idec, GSK, Teva, Acorda, Serono and Pfizer. Kathy Tobias is an employee of Novartis. Anthony T Reder is on the advisory board for/has acted as a consultant for Novartis. Bianca Weinstock-Guttman has participated in speaker’s bureaus and served as a consultant for Biogen Idec, Teva Neurosciences, EMD Serono, Pfizer, and Acorda. She also has received grant/research support from the agencies listed above as well as Novartis and Shire. Clyde E Markowitz has research funding from Biogen-Idec, EMD Serono, Bayer, Teva, Novartis and ONO. He has served as a consultant for Biogen-Idec, EMD Serono, Bayer, Teva, Novartis, Pfizer/Wyeth and Sanofi-Aventis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Editorial assistance was provided by Fran Karo, PhD, and Amy Zannikos, PharmD, of Oxford PharmaGenesis. Funding for this assistance was provided by Novartis.