This study aims to analyze the efficacy of teriflunomide (Aubagio®) in extending the time to a seminal acute or progressive demyelinating event in a cohort of Radiologically isolated syndrome (RIS) subjects within Europe and Turkey.

RIS subjects present with MRI features highly typical for multiple sclerosis (MS) without clinical symptomatology suggestive of central nervous system (CNS) demyelination. They are possibly exposed to disease-modifying therapies despite the lack of evidence-based medical literature. Earlier treatment intervention may prevent the onset of a first clinical event, reducing the risk for new lesion development and incomplete recovery due to permanent neurological impairment.

This Phase III study enrolled 124 subjects and randomized 89 who fulfill the 2009 RIS Criteria (NCT03122652). Study participants were randomized 1:1 to teriflunomide (14 mg daily) or placebo. The primary outcome measure was time to a first acute or progressive event from study entry. Clinical examinations as defined within this protocol were performed at scheduled visits and during or immediately following clinical exacerbations. All MRI and clinical data, including seminal events, were independently adjudicated by defined committees. Standardized MRI studies of the brain and spinal cord are performed at weeks 0, 48, 96, and clinical events.

One hundred twenty-four subjects were screened, but 35 subjects were not randomized. Of the 89 randomized RIS subjects, 63 (70.8%) were female with mean age: 39.8 years (y), and age at index MRI: 38 y). Index MRI motives were headache (47%), follow-up other neurological disease (18%), dizziness/vertigo (13.5%), ophthalmology (7%), miscellaneous (14.5%).

MRI characteristics (T2 lesions number and location, gadolinium-enhancing lesions, brain volume) and non-conventional MRI were prospectively collected and correlated with demographics characteristics and the occurrence of a clinical event.

The result of this study investigating the impact of early treatment of teriflunomide in RIS will be published at the end of 2022.