Design: Two identical phase 3, randomised, double-blind, double-dummy, active-comparator trials
Population: 2,007 adults aged 18–55 with relapsing multiple sclerosis
Primary outcome: Annualised relapse rate up to 30 months
Effect: Rate ratio 0.65 (0.45–0.93) and 0.69 (0.49–0.97) vs teriflunomide

REMODEL-1 and REMODEL-2 were identical double-blind, double-dummy phase 3 trials in 2,007 adults with relapsing multiple sclerosis across 46 countries. Patients received oral remibrutinib, a BTK inhibitor, 100 mg twice daily, or teriflunomide 14 mg once daily, for up to 30 months.

The annualised relapse rate was lower with remibrutinib in both trials: 0.073 vs 0.112 (rate ratio 0.65, 95% CI 0.45–0.93) and 0.080 vs 0.116 (0.69, 0.49–0.97). Discontinuation for adverse events was less frequent (3.1% vs 5.8%), and hair thinning was less common. The authors report no liver safety concerns, which matters because earlier drugs in this class raised them.

Teriflunomide is a modest comparator, and relapse rate is not disability progression. Whether remibrutinib slows disability, and how it compares with high-efficacy infusions, is not answered here. The trials are funded by the manufacturer and still in follow-up.

Expect oral BTK inhibitors to enter the multiple sclerosis conversation as alternatives to older oral agents.
Relapse benefit was shown against teriflunomide, not against high-efficacy infusion therapies.
Liver monitoring will remain part of any BTK inhibitor plan until longer safety data accumulate.
Disability outcomes were not reported in this analysis.

Why it matters

A new oral mechanism has beaten an established oral comparator in phase 3, which will reshape first-line discussions.

The statistics, in plain English

A rate ratio of 0.65 means about 35% fewer relapses per patient-year. The confidence intervals stay below 1.0 in both trials but their upper ends (0.93 and 0.97) are close to it, so the true benefit could be smaller.