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

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 beta-1a (sc IFN beta-1a) versus placebo. This post hoc analysis evaluated the effect of sc IFN beta-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 magnetic resonance imaging data from FCDE patients who received sc IFN beta-1a 44 mu g once or three times weekly, or placebo in the REFLEX trial. Patients were grouped according to McDonald MS status (converter/non-converter) or treatment (sc IFN beta-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. 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 sc IFN beta-1a-treated patients (ratio: 0.95). Patients treated with sc IFN beta-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 sc IFN beta-1a in an FCDE population.