Long-term results from a phase 2 extension study of fingolimod at high and approved dose in relapsing multiple sclerosis

• Published in: Journal of neurology 2015-12, Vol.262 (12), p.2627-2634
• Main Authors: Montalban, Xavier, Comi, Giancarlo, Antel, Jack, O’Connor, Paul, de Vera, Ana, Cremer, Malika, Sfikas, Nikolaos, von Rosenstiel, Philipp, Kappos, Ludwig
• Format: Article
• Language: English
• Subjects: Double-Blind Method; Drug dosages; Electrocardiography; Fingolimod Hydrochloride - administration & dosage; Fingolimod Hydrochloride - adverse effects; Fingolimod Hydrochloride - pharmacology; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - pharmacology; Magnetic Resonance Imaging; Medicine; Medicine & Public Health; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - pathology; Neurology; Neuroradiology; Neurosciences; Original Communication; Outcome Assessment (Health Care); Patients; Questionnaires
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-015-7834-0

Fingolimod safety and efficacy data in relapsing–remitting multiple sclerosis (RRMS) are available up to 5 years, from an extension of a randomized, placebo-controlled, double-blind, phase 2 study, at a dose higher (5.0/1.25 mg) than the approved dose of 0.5 mg. The objective of the study is to present the end-of-study data (>7 years) from the open-label extension of the phase 2 study. In the core phase (6 months), patients ( N  = 281) were randomized to placebo or fingolimod 1.25/5 mg. In the extension, placebo patients were randomized to fingolimod 1.25/5 mg. All patients received open-label 1.25 mg fingolimod after month 24 and 0.5 mg after month 60. Clinical visits were performed every 3 months, expanded disability status scale (EDSS) every 6 months and magnetic resonance imaging (MRI) annually. 122 (48.8 %) patients completed the extension study; overall fingolimod exposure was 1230.7 patient-years. The most common (>10 %) reasons for study discontinuation were adverse events (19.6 %) and consent withdrawal (16.4 %). Fingolimod treatment for >7 years was associated with sustained low clinical and MRI disease activity. Over 60 % of patients remained relapse free and about 80 % were free from any MRI activity. Overall annualized relapse rate was 0.18. Long-term fingolimod treatment was not associated with new safety concerns. Long-term fingolimod was well tolerated and associated with a sustained low level of disease activity.