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

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