Efficacy and safety of tolebrutinib in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND

Tolebrutinib is an oral, brain-penetrant Bruton's tyrosine kinase (BTK) inhibitor being investigated for multiple sclerosis (MS). Early data point to reduced relapse rates and radiological disease activity, along with a reassuring safety profile. This systematic review and meta-analysis bring together the available evidence on its clinical efficacy and adverse events.

METHODS

We searched PubMed, Web of Science, and Scopus through February 2026 using predefined eligibility criteria. Data were extracted on efficacy outcomes (disability progression and improvement, MRI activity, and brain volume change) and safety outcomes (any adverse events, serious adverse events, adverse events leading to discontinuation, headache, ALT elevation, and death). Continuous outcomes were pooled as means using reported means and standard deviations; proportional outcomes were pooled from event and total counts. Analyses were run in R using random-effects models, with data unsuitable for pooling described narratively.

RESULTS

Four publications met our inclusion criteria: three reporting four randomized controlled trials and one long-term extension study. Tolebrutinib reduced the risk of confirmed disability progression at both ≥3 and ≥6 months, and disability improvement at 6 months was numerically higher than with comparators, though not conclusively so. Pooled progression rates were 18.35% (95% CI 9.73-31.9) at ≥3 months and 14.08% (95% CI 6.78-26.95) at ≥6 months. Mean brain volume change was -0.69% (95% CI -0.73 to -0.65). Adverse events of any kind occurred in 75.98% of patients, serious adverse events in 11.26%, and discontinuation due to adverse events in 4.14%; deaths were rare.

CONCLUSION

The available trial evidence suggests that tolebrutinib may reduce confirmed disability progression in nonrelapsing secondary progressive MS and MRI inflammatory activity versus placebo in earlier-phase relapsing MS. These findings are preliminary and should not be interpreted as definitive comparative evidence; longer-term, adequately powered studies are needed to define durability, safety, and its place relative to established disease-modifying therapies.