Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system. It is characterized by inflammation and damage to the protective covering of nerve fibers called myelin. Over time, this damage can disrupt the normal flow of electrical signals along nerve fibers, leading to a wide range of symptoms such as fatigue, difficulty walking, muscle weakness, numbness or tingling in the limbs, coordination problems, bladder and bowel dysfunction, cognitive changes, and mood disturbances.
Researchers conducted a trial to evaluate the impact of therapeutic intervention in preventing the first symptom manifestation in a specific early phase of MS called radiologically isolated syndrome (RIS). RIS refers to the earliest detectable pre-clinical stage of MS, where individuals have incidental brain MRI anomalies consistent with central nervous system demyelination but do not yet exhibit clinical symptoms typical of MS.
The trial was conducted at 12 MS centers in the United States and involved a randomized, double-blinded, placebo-controlled design. Participants were randomly assigned to receive either oral dimethyl fumarate (DMF) 240 mg twice daily or a placebo and were followed up for 96 weeks. The study's primary endpoint was the time to onset of clinical symptoms attributable to a central nervous system demyelinating event.
The study results showed that treatment with DMF significantly reduced the risk of a first clinical demyelinating event during the 96-week study period, compared to a placebo. The risk reduction was highly significant in the statistical analysis, with a hazard ratio of 0.18, indicating a substantial benefit of DMF in preventing the onset of clinical symptoms in people with RIS.
While some adverse reactions were observed with DMF treatment, including moderate adverse events in 32% of participants, severe events were similar between the DMF and placebo groups. This suggests that the overall safety profile of DMF was acceptable in this study population.
This clinical trial is significant as it is the first randomized clinical trial to demonstrate the benefit of a disease-modifying therapy in preventing a first acute clinical event in people with RIS. These findings have implications for early intervention strategies in individuals with RIS to delay or prevent the development of MS symptoms potentially. Further research and long-term follow-up studies are needed to confirm these findings and better understand the optimal treatment approach for individuals with RIS.
This clinical trial provides evidence of the potential benefit of therapeutic intervention with DMF in preventing the first symptom manifestation in people with RIS, which represents the earliest detectable pre-clinical phase of MS. Early intervention in MS is an active area of research, and findings from studies like this may help guide future treatment strategies for individuals at risk of developing MS.