title: Onset of clinical and MRI efficacy occurs early after fingolimod treatment initiation in relapsing multiple sclerosis.
abstract: To minimize the clinical burden associated with multiple sclerosis (MS), early control of focal and diffuse CNS disease activity is a treatment priority. A post hoc analysis was conducted to evaluate the onset of efficacy of fingolimod treatment in patients with relapsing MS. Data from patients who received fingolimod 0.5 mg or placebo during either of two 24-month, double-blind, randomized, parallel-group clinical trials (FREEDOMS and FREEDOMS II) were pooled for analysis. Efficacy outcomes were: time to first confirmed relapse; annualized relapse rate (ARR); proportions of patients free from T1 gadolinium-enhancing lesions or new/newly enlarged T2 lesions; percentage brain volume loss (BVL); and change in Multiple Sclerosis Functional Composite (MSFC) z-score from baseline to 6 months. An early benefit was seen with fingolimod (N = 783) vs. placebo (N = 773) for ARR at both 3 and 6 months (3 months, 0.32 vs. 0.52, p = 0.0015; 6 months, 0.21 vs. 0.45, p < 0.0001). Time to first relapse was also delayed with fingolimod vs. placebo from day 48 onwards. At 6 months, more patients in the fingolimod group than in the placebo group were free from new MRI activity (65.3 vs. 40.5%, p < 0.0001) and had less BVL (37.1% reduction vs. placebo, p < 0.001). MSFC z-score favored fingolimod over placebo at 6 months, with improvements noted in 9-Hole Peg Test and Paced Auditory Serial Addition Test scores. Improvements in outcomes related to relapses, MRI, disability, cognition, and BVL occurred within 6 months of treatment initiation with fingolimod.
authors.affiliation: Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital, Petersgraben 4, 4031, Basel, Switzerland. lkappos@uhbs.ch.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland.
authors.forename: Ernst-Wilhelm
authors.initials: EW
authors.lastname: Radue
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Chin
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Ritter
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Davorka
authors.initials: D
authors.lastname: Tomic
authors.affiliation: Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Lublin
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: Brain volume loss; Cognition; Early treatment; Fingolimod; MRI; Multiple sclerosis; Relapse