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

In 30 seconds

This systematic review and meta-analysis assessed tolebrutinib’s efficacy and safety in multiple sclerosis, drawing on four publications covering four randomised controlled trials and one long-term extension study. The review found evidence of reduced confirmed disability progression, with pooled progression rates of 18.35% (95% CI 9.73-31.9) at ≥3 months and 14.08% (95% CI 6.78-26.95) at ≥6 months. Disability improvement at 6 months was numerically higher than with comparators but inconclusive. The authors also report reduced MRI inflammatory activity versus placebo in earlier-phase relapsing MS, while emphasising that the evidence remains preliminary.

Key findings

• Pooled confirmed disability 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.
• Disability improvement at 6 months was numerically higher with tolebrutinib than with comparators, but the difference was not conclusive.
• Any adverse event occurred in 75.98% of patients, serious adverse events in 11.26%, and adverse events led to discontinuation in 4.14%; deaths were rare.
• Mean brain volume change was -0.69% (95% CI -0.73 to -0.65).

Why it matters

Disability progression and MRI inflammatory activity are clinically relevant outcomes in MS, and the findings suggest potential activity across nonrelapsing secondary progressive and earlier-phase relapsing disease. The pooled safety estimates also provide an initial overview of adverse events. However, the evidence base is limited, and the results do not establish durable benefit or comparative effectiveness against established disease-modifying therapies.

What to keep in mind

Only four publications were included, and the authors describe the findings as preliminary. Longer-term, adequately powered studies are needed to establish durability, safety, and comparative effectiveness.