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Evolution from a first clinical demyelinating event to multiple sclerosis in the REFLEX trial: Regional susceptibility in the conversion to multiple sclerosis at disease onset and its amenability to subcutaneous interferon beta-1a

Battaglini, Marco; Vrenken, Hugo; Tappa Brocci, Ricardo; Gentile, Giordano; Luchetti, Ludovico; Versteeg, Adriaan; Freedman, Mark S; ... De Stefano, Nicola; + view all (2022) Evolution from a first clinical demyelinating event to multiple sclerosis in the REFLEX trial: Regional susceptibility in the conversion to multiple sclerosis at disease onset and its amenability to subcutaneous interferon beta-1a. European Journal of Neurology 10.1111/ene.15314. (In press). Green open access

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Abstract

BACKGROUND AND PURPOSE: In the REFLEX trial (ClinicalTrials.gov identifier: NCT00404352), patients with a first clinical demyelinating event (FCDE) displayed significantly delayed onset of multiple sclerosis (MS; McDonald criteria) when treated with subcutaneous interferon β-1a (scIFNβ-1a) versus placebo. This post hoc analysis evaluated the effect of scIFNβ-1a on spatio-temporal evolution of disease activity, assessed by changes in T2 lesion distribution, in specific brain regions of such patients and its relationship with conversion to MS. METHODS: Post hoc analysis of baseline and 24-month MRI data from FCDE patients who received scIFNβ-1a 44 μg once or three times weekly, or placebo in the REFLEX trial. Patients were grouped according to McDonald MS status (converter/non-converter) or treatment (scIFNβ-1a/placebo). For each patient group, a baseline lesion probability map (LPM) and longitudinal new/enlarging and shrinking/disappearing LPMs were created. Lesion location/frequency of lesion occurrence were assessed in the white matter (WM). RESULTS: At Month 24, lesion frequency was significantly higher in the anterior thalamic radiation (ATR) and corticospinal tract (CST) of converters versus non-converters (p<0.05). Additionally, the overall distribution of new/enlarging lesions across the brain at Month 24 was similar in placebo- and scIFNβ-1a-treated patients (ratio: 0.95). Patients treated with scIFNβ-1a versus placebo showed significantly lower new lesion frequency in specific brain regions (cluster corrected): ATR (p=0.025), superior longitudinal fasciculus (p=0.042), CST (p=0.048), and inferior longitudinal fasciculus (p=0.048). CONCLUSIONS: T2 lesion distribution in specific brain locations predict conversion to McDonald MS and show significantly reduced new lesion occurrence after treatment with scIFNβ-1a in an FCDE population.

Type: Article
Title: Evolution from a first clinical demyelinating event to multiple sclerosis in the REFLEX trial: Regional susceptibility in the conversion to multiple sclerosis at disease onset and its amenability to subcutaneous interferon beta-1a
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/ene.15314
Publisher version: https://doi.org/10.1111/ene.15314
Language: English
Additional information: Copyright © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: First clinical demyelinating event, interferon-beta, lesions, white matter tracts
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10146617
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