Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial.
- Kappos L 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.
- O'Connor P 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.
- Radue EW 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.
- Polman C 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.
- Hohlfeld R 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.
- Selmaj K 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.
- Ritter S 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.
- Schlosshauer R 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.
- von Rosenstiel P 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.
- Zhang-Auberson L 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.
- Francis G 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.
- 2015-03-22
Published in:
- Neurology. - 2015
Adolescent
Adult
Brain
Disability Evaluation
Disease Progression
Female
Fingolimod Hydrochloride
Humans
Immunosuppressive Agents
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting
Propylene Glycols
Recurrence
Single-Blind Method
Sphingosine
Treatment Outcome
Young Adult
English
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.
CONCLUSION
Efficacy benefits of fingolimod during FREEDOMS were sustained during the extension; ARR and BVL were reduced after switching.
CLASSIFICATION OF EVIDENCE
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.
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.
CONCLUSION
Efficacy benefits of fingolimod during FREEDOMS were sustained during the extension; ARR and BVL were reduced after switching.
CLASSIFICATION OF EVIDENCE
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1212/WNL.0000000000001462
- PMID 25795646
- Persistent URL
- https://folia.unifr.ch/global/documents/18091
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