Frederik Barkhof1, Remko de Jong2, Nikolaos Sfikas3, Ana de Vera3, Gordon Francis4, Jeffrey Cohen5. 1. Image Analysis Center, VU University Medical Center, The Netherlands f.barkhof@vumc.nl. 2. Image Analysis Center, VU University Medical Center, The Netherlands. 3. Novartis Pharma AG, Switzerland. 4. Novartis Pharmaceuticals Corporation, USA. 5. Neurological Institute, Cleveland Clinic Foundation, USA.
Abstract
BACKGROUND:Patients with multiple sclerosis (MS) lose brain volume (BV) faster than healthy individuals. OBJECTIVE: Our purpose, within the 12-month phase 3 TRANSFORMS study, was to examine the effect of treatment on BV loss in patient subgroups, establish correlations between baseline normalized BV (NBV) and baseline disease parameters, to identify variables predictive of baseline NBV and on-study percentage BV change (PBVC), and to establish correlations between on-study PBVC and on-study efficacy outcomes. METHODS: Patients received fingolimod 0.5 mg or 1.25 mg, or intramuscular (IM) interferon β-1a (IFNβ-1a) for 12 months. The effect of treatment on PBVC was examined in patient demographic, disease and magnetic resonance imaging (MRI) characteristic subgroups. Pearson's correlation analyses and a stepwise linear regression model were used to identify variables predictive of NBV and PBVC. RESULTS: Fingolimod reduced BV loss over 12 months versus IFNβ-1a IM in all patient subgroups assessed, including individuals with or without gadolinium (Gd)-enhancing lesions at baseline. Baseline T1 hypointense lesion volume had the strongest correlation with baseline NBV. Baseline Gd-enhancing T1 lesion count was most predictive of change in PBVC over 12 months. CONCLUSIONS: Our results improve understanding of the contributions of different baseline demographic, clinical and MRI characteristics to NBV, including factors that may be predictive of future BV loss.
RCT Entities:
BACKGROUND:Patients with multiple sclerosis (MS) lose brain volume (BV) faster than healthy individuals. OBJECTIVE: Our purpose, within the 12-month phase 3 TRANSFORMS study, was to examine the effect of treatment on BV loss in patient subgroups, establish correlations between baseline normalized BV (NBV) and baseline disease parameters, to identify variables predictive of baseline NBV and on-study percentage BV change (PBVC), and to establish correlations between on-study PBVC and on-study efficacy outcomes. METHODS:Patients received fingolimod 0.5 mg or 1.25 mg, or intramuscular (IM) interferon β-1a (IFNβ-1a) for 12 months. The effect of treatment on PBVC was examined in patient demographic, disease and magnetic resonance imaging (MRI) characteristic subgroups. Pearson's correlation analyses and a stepwise linear regression model were used to identify variables predictive of NBV and PBVC. RESULTS:Fingolimod reduced BV loss over 12 months versus IFNβ-1a IM in all patient subgroups assessed, including individuals with or without gadolinium (Gd)-enhancing lesions at baseline. Baseline T1 hypointense lesion volume had the strongest correlation with baseline NBV. Baseline Gd-enhancing T1 lesion count was most predictive of change in PBVC over 12 months. CONCLUSIONS: Our results improve understanding of the contributions of different baseline demographic, clinical and MRI characteristics to NBV, including factors that may be predictive of future BV loss.
Authors: F L Scott; B Clemons; J Brooks; E Brahmachary; R Powell; H Dedman; H G Desale; G A Timony; E Martinborough; H Rosen; E Roberts; M F Boehm; R J Peach Journal: Br J Pharmacol Date: 2016-04-28 Impact factor: 8.739