Finite-course ocrelizumab in relapsing multiple sclerosis: Results of two prospective open-label trials with matched...

Whether continuous anti-CD20 therapy is required for durable disease control in relapsing multiple sclerosis (MS) is uncertain.

To determine if two standard courses of ocrelizumab can sustain clinical and radiological remission and to compare outcomes with patients who continue standard-interval dosing (SID).

We pooled two single-center, prospective, open-label trials (NCT03853746, NCT04261790). Nineteen adults with active relapsing MS received two ocrelizumab courses (300 mg × 2 followed 6 months later by 600 mg) and were followed for up to 46 months. Fifty-two SID recipients were propensity-matched (⩽1:3). The primary endpoint was time to disease reactivation, analyzed with restricted mean survival time (RMST) computed to a common truncation time (τ = 46 months). We also included a post-hoc comparative analysis with a retrospectively identified standard interval-dosing (SID) cohort.

Disease reactivation occurred in 6/19 (32%) discontinuation participants and 0/52 propensity-score-matched controls. RMST to reactivation was 40.5 months with finite dosing versus 46.0 months with SID (difference -5.5 months; 95% confidence interval [CI] -9.8 to -1.3; p = 0.011). Peripheral CD19+ B-cell repopulation (⩾1% or ⩾40 cells/μL) did not predict reactivation.

Most patients remained clinically stable for more than 3 years after only two ocrelizumab courses. These hypothesis-generating findings warrant larger randomized or prospectively harmonized studies of finite-course anti-CD20 therapy as a de-escalation strategy in MS.

ClinicalTrials.gov NCT03853746 and NCT04261790.