title: Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial.
abstract: OBJECTIVE
  To assess long-term safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  Patients completing FTY720 Research Evaluating Effects of Daily Oral Therapy in MS (FREEDOMS) were eligible for this dose-blinded, parallel-group extension study, continuing fingolimod 0.5 mg/day or 1.25 mg/day, or switching from placebo to either dose, randomized 1:1. Efficacy variables included annualized relapse rate (ARR), brain volume loss (BVL), and confirmed disability progression (CDP). Between-group analyses were conducted in the intent-to-treat (ITT) population from FREEDOMS baseline to end of study. Within-group analyses compared years 0-2 (FREEDOMS) and years 2-4 (extension) in the extension ITT population.
  
  
  RESULTS
  Of 1,272 patients (FREEDOMS ITT population), 1,033 were eligible, and 920 enrolled in the extension study (continuous-fingolimod: 0.5 mg [n = 331], 1.25 mg [n = 289]; placebo-fingolimod: 0.5 mg [n = 155], 1.25 mg [n = 145]); 916 formed the extension ITT population (n = 330; n = 287; n = 154; n = 145) and 773 (84%) completed. In the continuous-fingolimod groups, ARR was lower (p < 0.0001), BVL was reduced (p < 0.05), and proportionately more patients were free from 3-month CDP (p < 0.05) than in a group comprising all placebo-fingolimod patients. Within each placebo-fingolimod group, ARR was lower (p < 0.001, both) and BVL was reduced after switching (p < 0.01, placebo-fingolimod 0.5 mg). Rates and types of adverse events were similar across groups; no new safety issues were reported.
  
  
  CONCLUSIONS
  Efficacy benefits of fingolimod during FREEDOMS were sustained during the extension; ARR and BVL were reduced after switching.
  
  
  METHODS
  This study provides Class IV evidence that long-term fingolimod treatment is well-tolerated and reduces relapse rates, disability progression, and MRI effects in patients with RRMS.
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland. lkappos@uhbs.ch.
authors: Ludwig
authors: L
authors: Kappos
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Paul
authors: P
authors: O'Connor
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Ernst-Wilhelm
authors: EW
authors: Radue
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Chris
authors: C
authors: Polman
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Reinhard
authors: R
authors: Hohlfeld
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Krzysztof
authors: K
authors: Selmaj
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Shannon
authors: S
authors: Ritter
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Rolf
authors: R
authors: Schlosshauer
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Philipp
authors: P
authors: von Rosenstiel
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Lixin
authors: L
authors: Zhang-Auberson
authors: From the Department of Neurology (L.K.), University Hospital, Basel, Switzerland; St. Michael's Hospital (P.O.'C.), Toronto, Canada; Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Department of Neurology (C.P.), VU University Medical Center, Amsterdam, Netherlands; Ludwig-Maximilians University of Munich and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany; Department of Neurology (K.S.), Medical University of Lodz, Poland; Novartis Pharmaceuticals Corporation (S.R., G.F.), East Hanover, NJ; and Novartis Pharma AG (R.S., P.v.R., L.Z.-A.), Basel, Switzerland.
authors: Gordon
authors: G
authors: Francis
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011409:Propylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D012008:Recurrence; D016037:Single-Blind Method; D013110:Sphingosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine