Efficacy of interferon beta-1b as a first-line treatment in patients with Radiologically Isolated Syndrome: a controlled, randomized, multicenter, double-blind clinical trial

Abstract

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), and it’s the most common demyelinating disease of young adults. The onset of MS ranges from 10 to 59 years, but the majority of cases occur between the ages of 20 and 40 years. Radiologically Isolated Syndrome (RIS) is defined as incidental Magnetic Resonance Imaging (MRI) identified white matter anomalies within the central nervous system (CNS) suggestive of MS in healthy people without typical signs and symptoms associated with CNS demyelination and with normal neurological findings, after exclusion of other possible aetiologies. Although some individuals did not exhibit progression over a lengthy follow-up period, most patients will progress clinically or radiologically in the initial years of the follow-up (83.3%), so all patients with RIS should be considered as having a high risk of developing MS. Thus, for many patients, RIS represents the earliest visible manifestation of demyelinating disease, or a preclinical stage of MS. Among the different treatments approved for the treatment of relapsing forms of MS, the one with the best efficacy is interferon beta-1b (IFN β-1b), because it reduces relapse rates, decreases disability progression and also reduces clinical activity in the MRI. That’s why this drug would be the best option for treatment of RIS patients, specifically the Betaseron presentation, which is the one that has more clinical experience. A statistical significant and clinically relevant result in this study would change the management of these patients, thus avoiding many new cases of MS and reducing economic impact of this disease in our society. AIMS: To determine the efficacy of IFN β-1b on reducing the proportion of RIS patients experiencing a first clinical event of MS. DESIGN: A controlled, randomized, multicentre, double-blind and placebo-controlled clinical trial conducted between September 2015 and April 2019. METHODS: The clinical trial will enroll 522 patients with RIS. Patients will be randomized to receive 1 ml of subcutaneous IFN β-1b at doses of 0.25 mg or 1 ml of placebo every other day for 18 months. During the treatment period and 6 months more (24 months), clinical assessments, laboratory analysis as well as MRI will be performed. The main outcome is the proportion of patients with RIS experiencing a first clinical event of MS in each group, identified by anamnesis and neurological exploration based in functional systems, and secondary outcomes include radiological progression (defined by the prevention of new MRI lesions or reducing or avoiding the enlargement of pre-existing lesions on MRI), disability progression (measured by the EDSS) and description of adverse events