Disease modifying treatment of radiologically isolated syndrome: A systematic review of the use, efficacy, effectiveness, and safety
Bibliographic record
Abstract
• We reviewed the literature of treatments for radiologically isolated syndrome (RIS). • We identified 2 randomized controlled trials, and 18 observational studies. • A total of 1401 RIS patients (76% female) were included, with 21% of them receiving treatment. • Treatment was associated with a 62% reduced risk of clinical demyelinating events. • There was a 44% higher rate of adverse events in RIS treated patients. Radiologically isolated syndrome (RIS) is characterized by incidental brain lesions suggestive of demyelination without symptoms of multiple sclerosis (MS). We systematically assessed the use, benefits, and adverse effects of DMTs for RIS. MEDLINE, EMBASE, and Web of Science were searched to identify English language studies including individuals with RIS treated with a DMT. Extracted data included patient characteristics, clinical progression, and adverse events. We conducted a meta-analysis using inverse probability weighting. Risk of bias (RoB) assessments used Cochrane's RoB-2 tool and Newcastle-Ottawa cohort study scale. A total of 1012 abstracts were screened: 20 studies were included consisting of 2 RCTs, 12 observational cohort studies, and 6 case reports. A total of 1401 individuals with RIS were included; 291 (21%) received a DMT. The two RCTs randomized people with RIS to teriflunomide or dimethyl fumarate versus placebo and followed patients for at least 96 weeks. In all other studies, follow-up ranged from 2 months to 18 years; only 3 studies exceeded 5 years. DMT treatment was associated with a lower risk of a clinical demyelinating event (4 studies with different DMTs, adjusted hazard ratio = 0.37 95% confidence interval [CI]: 0.15–0.95, high certainty). There was a higher rate of adverse events in DMT treated patients with RIS versus placebo (risk ratio = 1.44, 95% CI: 1.09–1.90, moderate certainty). RoB was low for both RCTs, but high for 83% (10/12) of cohort studies. DMTs reduced the risk of a clinical demyelinating event in individuals with RIS, albeit with more adverse events compared to placebo. However, no literature addressed longer-term benefits/adverse effects.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.027 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.009 |
| Bibliometrics | 0.006 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".