Salazar-Camelo A, Vega L, Fadlallah Y, Bou Rjeily N, Balshi A, Morris B, Ghajarzadeh M, Mowry EM, Waubant E, Nourbakhsh B. Finite-course ocrelizumab in relapsing multiple sclerosis: Results of two prospective open-label trials with matched controls. Mult Scler. 2025 Sep 19:13524585251375350. doi: 10.1177/13524585251375350. Epub ahead of print. PMID: 40970353.
Background: Whether continuous anti-CD20 therapy is required for durable disease control in relapsing multiple sclerosis (MS) is uncertain.
Objective: 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).
Methods: 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.
Results: 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.
Conclusion: 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.
Many years ago we made the suggestion that the action of CD20 was maintained for months.longer than the typical dosing.. Pharma are never going to do these studies as it is not in their financial interest. They want to sell drugs.
Here they gave two doses and waited, I think to mimic alemtuzumab and cladribine three doses would be the most similar. Here there was reactivation in those getting two doses. 68 percent didn’t reactivate when they matched people on standard dosing the found no-one reactivated and here I would say this is very odd. In the ocrelizumab trial there was a relapse in 19.6 percent of people in opera I (Hauser etc al 2017) in 96 weeks. However in the study it took 3 and a half years to relapse.
Source: multiple-sclerosis-research.org