Long-term results from a phase 2 extension study of fingolimod at high and approved dose in relapsing multiple sclerosis.
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.
Neurology-Neuroimmunology Department & Neurorehabilitation Unit, Edif. Cemcat, Vall d'Hebron University Hospital, 119-129, 08035, Barcelona, Spain. xavier.montalban@cem-cat.org.
Xavier
X
Montalban
Department of Neurology, Vita-Salute San Raffaele, University, Milan, Italy.
Giancarlo
G
Comi
Department of Neurology and Neurosurgery, Montreal Neurological Institute University, 3801, Room 111, Montreal, Canada.
Jack
J
Antel
St. Michael's Hospital, 30 Bond St, Toronto, ON, M5B 1W8, Canada.
Paul
P
O'Connor
Novartis Pharma AG, Basel, Switzerland.
Ana
A
de Vera
Novartis Pharma AG, Basel, Switzerland.
Malika
M
Cremer
Novartis Pharma AG, Basel, Switzerland.
Nikolaos
N
Sfikas
Novartis Pharma AG, Basel, Switzerland.
Philipp
P
von Rosenstiel
Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital, Basel, Switzerland.
Ludwig
L
Kappos
D004311:Double-Blind Method; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D017063:Outcome Assessment, Health Care
D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
Disease-modifying therapy; Fingolimod; Long term; Phase 2; Relapsing–remitting multiple sclerosis; Sphingosine 1-phosphate receptor modulator