Correlation between brain volume loss and clinical and MRI outcomes in multiple sclerosis.
- Radue EW From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH.
- Barkhof F From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH.
- Kappos L From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH. ludwig.kappos@usb.ch.
- Sprenger T From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH.
- Häring DA From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH.
- de Vera A From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH.
- von Rosenstiel P From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH.
- Bright JR From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH.
- Francis G From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH.
- Cohen JA From the Medical Image Analysis Centre (E.-W.R.), University Hospital, University of Basel, Switzerland; Image Analysis Center (F.B.), VU Medical Centre, Amsterdam, the Netherlands; Departments of Medicine and Clinical Research, Neurology (L.K., T.S.) and Radiology (T.S.), Division of Neuroradiology, University Hospital, Basel, Switzerland; Novartis Pharma AG (D.A.H., A.d.V., P.v.R.), Basel, Switzerland; Oxford PharmaGenesis Ltd. (J.R.B.), Tubney, Oxford, UK; Novartis Pharmaceuticals Corporation (G.F.), East Hanover, NJ; and Neurological Institute (J.A.C.), Cleveland Clinic, OH.
- 2015-01-30
Published in:
- Neurology. - 2015
Brain
Double-Blind Method
Female
Fingolimod Hydrochloride
Humans
Immunosuppressive Agents
Longitudinal Studies
Magnetic Resonance Imaging
Male
Multiple Sclerosis
Organ Size
Propylene Glycols
Sphingosine
Treatment Outcome
English
OBJECTIVE
We investigated the determinants and clinical correlations of MRI-detected brain volume loss (BVL) among patients with relapsing-remitting multiple sclerosis from the phase 3 trials of fingolimod: FREEDOMS, FREEDOMS II, and TRANSFORMS.
METHODS
Post hoc analyses were conducted in the intent-to-treat populations from each trial and in a combined dataset of 3,635 patients from the trials and their extensions. The relationship between brain volume changes and demographic, clinical, and MRI parameters was studied in pairwise correlations (Pearson) and in multiple regression models. The relative frequency of confirmed disability progression was evaluated in the combined dataset by strata of concurrent BVL at up to 4 years.
RESULTS
Increasing age, disease duration, T2 lesion volume, T1-hypointense lesion volume, and disability were associated with reduced brain volume (p < 0.001, all). The strongest individual baseline predictors of on-study BVL were T2 lesion volume, gadolinium-enhancing lesion count, and T1-hypointense lesion volume (p < 0.01, all). During each study, BVL correlated most strongly with cumulative gadolinium-enhancing lesion count, new/enlarged T2 lesion count (p < 0.001, both), and number of confirmed on-study relapses (p < 0.01). Over 4 years in the combined dataset (mean exposure to study drug, 2.4 years), confirmed disability progression was most frequent in patients with greatest BVL.
CONCLUSIONS
Rate of BVL in patients during the fingolimod trials correlated with disease severity at baseline and new disease activity on study, and was associated with worsening disability.
We investigated the determinants and clinical correlations of MRI-detected brain volume loss (BVL) among patients with relapsing-remitting multiple sclerosis from the phase 3 trials of fingolimod: FREEDOMS, FREEDOMS II, and TRANSFORMS.
METHODS
Post hoc analyses were conducted in the intent-to-treat populations from each trial and in a combined dataset of 3,635 patients from the trials and their extensions. The relationship between brain volume changes and demographic, clinical, and MRI parameters was studied in pairwise correlations (Pearson) and in multiple regression models. The relative frequency of confirmed disability progression was evaluated in the combined dataset by strata of concurrent BVL at up to 4 years.
RESULTS
Increasing age, disease duration, T2 lesion volume, T1-hypointense lesion volume, and disability were associated with reduced brain volume (p < 0.001, all). The strongest individual baseline predictors of on-study BVL were T2 lesion volume, gadolinium-enhancing lesion count, and T1-hypointense lesion volume (p < 0.01, all). During each study, BVL correlated most strongly with cumulative gadolinium-enhancing lesion count, new/enlarged T2 lesion count (p < 0.001, both), and number of confirmed on-study relapses (p < 0.01). Over 4 years in the combined dataset (mean exposure to study drug, 2.4 years), confirmed disability progression was most frequent in patients with greatest BVL.
CONCLUSIONS
Rate of BVL in patients during the fingolimod trials correlated with disease severity at baseline and new disease activity on study, and was associated with worsening disability.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1212/WNL.0000000000001281
- PMID 25632085
- Persistent URL
- https://folia.unifr.ch/global/documents/124363
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