To conduct a systematic review and meta-analysis on the conversion rate of radiologically isolated syndrome (RIS) to multiple sclerosis (MS) and the effects of disease-modifying therapy (DMT).

RIS is often considered a preclinical stage of MS. Accordingly, definition of the conversion rate and associated factors will guide the selection of patients that will possibly benefit from DMT.

This review is registered at PROSPERO (CRD42023457264). Three databases (Embase, PubMed, and Web of Science) were searched from 2009 to August 2023. The primary outcome was the proportion of RIS patients progressing to MS with a 95% confidence interval (CI).

Six hundred and sixty-three (663) articles were screened and 37 met inclusion criteria (35 observational studies and 2 randomized clinical trials). A total of 1,061 patients were included, comprising 765 females (72.10%) and a mean age of 37.9 years (95% CI 35.4-40.5). Follow-up time ranged from 1 to 13 years. Headache was the most common reason for undergoing an MRI scan (46.92%), and 11.55% of patients had a family history of MS. Approximately 26.6% (95% CI 23.1-30.2%) of RIS patients converted to MS regardless of follow-up time. At 1 year, 19.4% (95% CI 9.0-29.8%) of patients had converted and at 5 years, 33.3% (95% CI 29.2-37.3) did so. Myelitis was the most common first acute demyelinating event (42.37%), followed by optic neuritis (19.49%). Around 10.38% of RIS patients developed primary progressive MS. Intervention with moderate-efficacy DMT in 88 RIS patients (44 on dimethyl fumarate and 44 on teriflunomide) led to a 70% reduction (hazard ratio 0.30, 95% CI 0.15-0.59) in the conversion rate at 96 weeks compared to placebo.   

Approximately a quarter of RIS patients will convert to MS, and DMT seems to significantly reduce this rate. However, future research is needed to properly identify high-risk patients that would benefit from DMT.